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[ CAS No. 154350-29-5 ] {[proInfo.proName]}

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Chemical Structure| 154350-29-5
Chemical Structure| 154350-29-5
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Product Details of [ 154350-29-5 ]

CAS No. :154350-29-5 MDL No. :MFCD08705286
Formula : C3H7NO2S Boiling Point : -
Linear Structure Formula :- InChI Key :WMSPXQIQBQAWLL-UHFFFAOYSA-N
M.W : 121.16 Pubchem ID :15765418
Synonyms :

Calculated chemistry of [ 154350-29-5 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 7
Num. arom. heavy atoms : 0
Fraction Csp3 : 1.0
Num. rotatable bonds : 1
Num. H-bond acceptors : 3.0
Num. H-bond donors : 1.0
Molar Refractivity : 26.09
TPSA : 68.54 ?2

Pharmacokinetics

GI absorption : High
BBB permeant : No
P-gp substrate : No
CYP1A2 inhibitor : No
CYP2C19 inhibitor : No
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -7.41 cm/s

Lipophilicity

Log Po/w (iLOGP) : 0.04
Log Po/w (XLOGP3) : -0.52
Log Po/w (WLOGP) : 0.46
Log Po/w (MLOGP) : -1.35
Log Po/w (SILICOS-IT) : -0.55
Consensus Log Po/w : -0.38

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 2.0
Bioavailability Score : 0.55

Water Solubility

Log S (ESOL) : -0.2
Solubility : 76.9 mg/ml ; 0.634 mol/l
Class : Very soluble
Log S (Ali) : -0.45
Solubility : 42.9 mg/ml ; 0.354 mol/l
Class : Very soluble
Log S (SILICOS-IT) : 0.0
Solubility : 122.0 mg/ml ; 1.0 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.42

Safety of [ 154350-29-5 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P280-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H332-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 154350-29-5 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 154350-29-5 ]

[ 154350-29-5 ] Synthesis Path-Downstream   1~10

  • 1
  • [ 154350-29-5 ]
  • tert-butyl ((2R,6S,13aS,14aR,16aS,Z)-14a-((cyclopropylsulfonyl)carbamoyl)-5,16-dioxo-2-((3-(thiophen-2-yl)quinoxalin-2-yl)oxy)-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-yl)carbamate [ No CAS ]
YieldReaction ConditionsOperation in experiment
71% The title compound from Example 2 (21.0 mg, 0.031 mmol) and carbonyldiimidazole (6.0 mg, 0.037 mmol) were dissolved in 0.7 ml anhydrous DMF and the resulting solution was heated to 40 C. for 1 hour. Cyclopropylsulfonamide (8.0 mg, 0.06 mmol) was added to the reaction followed by DBU (7.0 mg, 0.046 mmol). The reaction mixture was stirred at 40 C. for 10 hour. LCMS showed the formation of the desired product. The reaction was cooled down and 10 ml ethyl acetate was added to the solution. The mixture was washed with saturated aqueous NaHCO3 solution, water and brine. The organic layer was dried over anhydrous sodium sulfate. The organic phase was then filtered, concentrated in vacuo and subsequently purified by flash chromatography (ethyl acetate/hexanes 1:1) to give 17.0 mg (71%) of the title compound. MS (ESI) m/z 779.2 (M+H)+. 1H-NMR (500 MHz, CD3Cl): δ 10.24 (1H, s), 8.10 (1H, s), 8.00 (1H, d, J=8.0 Hz), 7.82 (1H, d, J=8.0 Hz), 7.60 (2H, m), 7.49 (1H, d, J=5.0 Hz), 7.16 (1H, s), 6.91 (1H, s), 6.09 (1H, s), 5.67 (1H, m), 5.12 (1H, m), 4.98 (1H, t, J=8.0 Hz), 4.70 (1H, t, J=8.0 Hz), 4.62 (2H, s), 4.33 (1H, m), 4.10 (1H, m), 2.92 (1H, m), 2.75 (2H, m), 2.58 (2H, m), 2.28 (1H, m), 1.91 (2H, m), 1.60-0.80 (20H, m). 13C-NMR (125 MHz, CD3Cl, 200-40 ppm region): δ 177.1, 173.5, 168.1, 155.2, 152.5, 140.7, 139.8, 139.1, 136.5, 130.5, 130.4, 129.7, 128.7, 128.3, 127.6, 127.1, 124.8, 80.1, 75.8, 59.7, 53.5, 52.3, 44.8.
  • 2
  • [ 154350-29-5 ]
  • Cyclopropanesulfonic acid 4-[(R)-4-(7-methoxy-1-oxo-3,4-dihydro-1H-isoquinolin-2-ylmethyl)-2,5-dioxo-imidazolidin-4-ylethynyl]-benzoylamide [ No CAS ]
YieldReaction ConditionsOperation in experiment
48% Example 1570 Compound 1570 A was prepared from Compound 400 and 4-iodobenzoic acid by sequential application of the procedures given in Parts H and I in Example 400. Solid carbonyl diimidazole (19 mg, 0.12 mmol) was added in one portion to a stirred solution of Compound 1570A in THF (200 mL). The solution was stirred at 70 0C for 1.5 h, and was subsequently allowed to cool to rt. Solid <strong>[154350-29-5]cyclopropanesulfonamide</strong> (17 mg, 0.14 mmol) and DBU (43 mL, 43 mg, 0.29 mmol) were added sequentially and the reaction mixture was stirred at rt for 18 h. The solvent was evaporated and the residue was dissolved in DCM (50 mL). The solution was washed sequentially with 0.1 N aq hydrochloric acid (~25 mL), water (~25 mL) and brine (~25 mL). The organic phase was dried over anhydrous MgSCM, filtered and concentrated under reduced pressure to afford an off-white solid. The crude product was purified by PTLC (3:1 EtOAc-hexanes + 1% HCO2H) to afford the desired Compound 1570 (24 mg, 48% yield) as a beige solid.
  • 3
  • [ 154350-29-5 ]
  • C41H50N6O8S [ No CAS ]
YieldReaction ConditionsOperation in experiment
51% The title compound from Example 2 (2c) (6.0 mg, 0.01 mmol) and carbonyldiimidazole (2.0 mg, 0.01 mmol) were dissolved in 0.75 ml anhydrous DMF and the resulting solution was heated to 40 0C for 1 h. Cyclopropylsulfonamide (3.6 mg, 0.03 mmol) was added to the reaction followed by DBU (4.5 mg, 0.03 mmol). The reaction mixture was stirred at 40 0C, until completion was confirmed by MS analysis. The reaction was diluted with 10 ml ethyl acetate and extracted with saturated aqueous with NaHCO3 (2 x 2 mL) and brine (1 x 2 mL). The organic phase was dried over anhydrous Na2SO4, filtered, and then concentrated in vacuo. The residue was purified by silica gel flash chromatography using gradient elution with MeOH in DCM (1%→2%→5%) affording affording pyridazinone 4a. (4.0 mg, 51 %) MS (ESI) m/z = 787.3 (M+H)+.
  • 4
  • [ 154350-29-5 ]
  • C38H46N6O8S3 [ No CAS ]
YieldReaction ConditionsOperation in experiment
51% The title compound from Example 2 (6.0 mg) and carbonyldiimidazole (2.0 mg) were dissolved in 0.75 ml anhydrous DMF and the resulting solution was heated to 40 0C for 1 h. Cyclopropylsulfonamide (3.6 mg) was added to the reaction followed by DBU (4.5 mg). The reaction mixture was stirred at 40 0C, until completion was confirmed by MS analysis. The reaction was diluted with 10 ml ethyl acetate and extracted with saturated aqueous with NaHCCh (2 x 2 mL) and brine (1 x 2 mL). The organic phase was dried over anhydrous Na2SO4, filtered, and then concentrated in vacuo. The residue was purified by silica gel flash chromatography using gradient elution with MeOH in DCM (1%- >2%- >5%) affording the title compound. (4.0 mg, 51 %) MS (ESI) m/z = 811.42 (M+H)+.
  • 5
  • [ 139631-62-2 ]
  • [ 154350-29-5 ]
YieldReaction ConditionsOperation in experiment
100% With ammonia; In tetrahydrofuran; at 0 - 20℃; for 24h;Product distribution / selectivity; II. Preparation of P1' Intermediates 1. Preparation of Cyclopropylsulfonamide Method 1 (of 2): To a solution of 100 mL of THF cooled to 0 C. was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF, the solution warmed to room temperature overnight and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained, applied on to 30 g plug of SiO2 (eluted with 30% to 60% ethyl acetate/hexanes) to afford 3.45 g (100%) of cyclopropyl sulfonamide as a white solid. 1H NMR (methanol-d4) δ 0.94-1.07 (m, 4H), 2.52-2.60 (m, 1H); 13C NMR (methanol-d4) δ 5.92, 33.01.
100% With ammonia; In tetrahydrofuran; at 20℃;Product distribution / selectivity; To a solution of 100 mL of THF cooled to 0 C. was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF, the solution warmed to room temperature overnight and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained, applied on to 30 g plug of SiO2 (eluted with 30% to 60% ethyl acetate/hexanes) to provide 3.45 g (100%) of cyclopropyl sulfonamide as a white solid. 1H NMR (Methanol-d4) δ 0.94-1.07 (m, 4H), 2.52-2.60 (m, 1H); 13C NMR (methanol-d4) δ 5.92, 33.01. Anal. Calcd. For C3H7NO2S: C, 29.74; H, 5.82; N, 11.56. Found: C, 29.99; H, 5.89, N, 11.50.
100% With ammonia; In tetrahydrofuran; at 0 - 20℃; To a solution of 100 mL of THF cooled to 0 C. was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF. The solution was warmed to room temperature overnight and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained and poured onto a 30 g plug of SiO2 (eluted with 30% to 60% ethyl acetate/hexanes) to provide 3.45 g (100%) of cyclopropylsulfonamide as a white solid. 1H NMR (methanol-d4) δ 0.94-1.07 (m, 4H), 2.52-2.60 (m, 1H); 13C NMR (methanol-d4) δ 5.92, 33.01.
100% With ammonia; In tetrahydrofuran; at 0 - 20℃;Product distribution / selectivity; To a solution of 100 mL of THF cooled to 0 C. was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF, the solution warmed to rt overnite and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained, applied on to 30 g plug of SiO2 (eluted with 30% to 60% EtOAc/Hexanes) to afford 3.45 g (100%) of cyclopropyl sulfonamide as a white solid. 1H NMR (Methanol-d4) δ 0.94-1.07 (m, 4H), 2.52-2.60 (m, 1H); 13C NMR (methanol-d4) δ 5.92, 33.01.
100% With ammonia; In tetrahydrofuran; at 0 - 20℃; To a solution of 100 mL of THF cooled to 0 C was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g(28. 45 mmol) of cyclopropylsulfonyl chloride (purchased from ArrayBiopharma) in 50mL of THF, the solution warmed to rtovernite and stirred one additional day. The mixture was concentrated until 1-2mL of solvent remained, applied onto 30 g plug ofSi02 (eluted with 30% to 60% EtOAc/Hexanes) to afford 3.45g (100%) of cyclopropyl sulfonamide as a whitesolid.'H NMR (Methanol-d4) 0.94-1. 07 (m, 4H), 2.52-2. 60 (m,1H); 13C NMR(methanol-d4)8 5.92, 33.01.
100% With ammonia; In tetrahydrofuran; at 0 - 20℃; Method A: To a solution of 100 mL of TUF cooled to 0 C. was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF, the solution warmed to rt overnite and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained, applied onto 30 g plug of SiO2 (eluted with 30% to 60% EtOAc/Hexanes) to afford 3.45 g (100%) of cyclopropylsulfonamide as a white solid.
100% With ammonia; In tetrahydrofuran; at 0 - 20℃;Product distribution / selectivity; To a solution of 100 mL of THF cooled to 0 C was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF, the solution warmed to rt overnite and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained, applied onto 30 g plug of Si02 (eluted with 30% to 60% EtOAc/Hexanes) to afford 3. 45g (100%) of cyclopropyl sulfonamide as a white solid NMR (Methanol-d4) 8 0.94-1. 07 (m, 4H), 2.52-2. 60 (m, 1H) ; 13C NMR (methanol-d4) 8 5.92, 33.01.
100% With ammonia; In tetrahydrofuran; at 20℃;Product distribution / selectivity; Method A:; O NH3 ( sat ) THF O^ ^ -S I l -Cl ? n _ h I ^ S -NHO 0 0C to rt OTo a solution of 100 mL of THF cooled to 0 0C was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF, the solution warmed to rt overnite and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained, applied on to 30 g plug of SiO2 (eluted with 30% to 60% EtOAc/Hexanes) to afford 3.45g (100%) of cyclopropyl sulfonamide as a white solid. 1H NMR (Methanol^) δ 0.94-1.07 (m, 4H), 2.52-2.60 (m, IH); 13C NMR (methanol^) δ 5.92, 33.01.
100% With ammonia; In tetrahydrofuran; at 0 - 20℃;Product distribution / selectivity; To a solution of 100 mL of THF cooled to 0 C. was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF, the solution warmed to rt overnite and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained, applied on to 30 g plug of SiO2 (eluted with 30% to 60% EtOAc/Hexanes) to afford 3.45 g (100%) of cyclopropyl sulfonamide as a white solid. 1H NMR (Methanol-d4) δ 0.94-1.07 (m, 4H), 2.52-2.60 (m, 1H); 13C NMR (methanol-d4) δ 5.92, 33.01.
100% With ammonia; In tetrahydrofuran; at 0 - 20℃; for 24h;Product distribution / selectivity; Method A To a solution of 100 mL of THF cooled to 0 C. was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF, the solution warmed to it overnite and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained, applied on to 30 g plug of SiO2 (eluted with 30% to 60% EtOAc/Hexanes) to afford 3.45 g (100%) of cyclopropyl sulfonamide as a white solid. 1H NMR (Methanol-d4) δ 0.94-1.07 (m, 4H), 2.52-2.60 (m, 1H); 13C NMR (methanol-d4) δ 5.92, 33.01.
100% With ammonia; In tetrahydrofuran; at 0 - 20℃;Product distribution / selectivity; To a solution of 100 mL of THF cooled to 0 C. was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF, the solution warmed to rt overnight and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained, applied on to 30 g plug of SiO2 (eluted with 30% to 60% EtOAc/Hexanes) to afford 3.45 g (100%) of cyclopropyl sulfonamide as a white solid. 1H NMR (Methanol-d4) δ 0.94-1.07 (m, 4H), 2.52-2.60 (m, 1H); 13C NMR (methanol-d4) δ 5.92, 33.01.
100% With ammonia; In tetrahydrofuran; at 0 - 20℃; To a solution of 100 mL of THF cooled to 0 C. was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF, the solution warmed to rt overnite and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained, applied on to 30 g plug of SiO2 (eluted with 30% to 60% EtOAc/Hexanes) to afford 3.45 g (100%) of cyclopropyl sulfonamide as a white solid. 1H NMR (Methanol-d4) δ 0.94-1.07 (m, 4H), 2.52-2.60 (m, 1H); 13C NMR (methanol-d4) δ 5.92, 33.01.
100% With ammonia; In tetrahydrofuran; at 0 - 20℃;Product distribution / selectivity; Method 2 To a solution of 100 mL of THF cooled to 0 C. was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF. The solution was warmed to room temperature overnight and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained and poured onto a 30 g plug of SiO2 (eluted with 30% to 60% ethyl acetate/hexanes) to provide 3.45 g (100%) of cyclopropylsulfonamide as a white solid. 1H NMR (methanol-d4) δ 0.94-1.07 (m, 4H), 2.52-2.60 (m, 1H); 13C NMR (methanol-d4) δ 5.92, 33.01.
100% With ammonia; In tetrahydrofuran; at 0 - 20℃;Product distribution / selectivity; To a solution of 100 mL of THF cooled to 0 0C was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF, the solution warmed to rt overnite and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained, applied on to 30 g plug of SiO2 (eluted with 30% to 60% EtOAc/Hexanes) to afford 3.45g (100%) of cyclopropyl sulfonamide as a white solid. 1H NMR (Methanol^) δ 0.94-1.07 (m, 4H), 2.52-2.60 (m, IH); 13C NMR (methanol^) δ 5.92, 33.01.
95% With ammonia; In dichloromethane; at -78 - 20℃; for 3.25h; Example 27Synthesis of new sulfonamides[0529] Preparation of compound 3: compound 1 (1Og, 71mmol) was dissolved in dry DCM (150ml) under nitrogen. The resulting solution was bubbled through NH3 for 15 minutes at -78 -C, then it was allowed to rise to room temperature and stirred for 3 h. Before filtration, the Filtrate was concentrated to provide compound 2 as white solid 8.2 g (yield
> 90% With ammonia; In 1,4-dioxane; at 20℃; for 72h; Cyclopropylsulfonyl chloride (5 g, 35.56 mmol) was dissolved in 0.5 M ammonia in dioxane (200 ml, 100 mmol) at RT. The reaction was stirred at RT for 3 days. The large amount of precipitation was filtered and discarded. The clear filtrate was evaporated in vacuo and the white residue was dried on vacuum for 24 hours to give the cyclopropylsulfonamide (>90%). 1H-NMR (500 MHz, CD3Cl): δ 4.62 (2H, s), 2.59 (1H, m), 1.20 (2H, m), 1.02 (2H, m).
89% With ammonia; In tetrahydrofuran; at 0 - 20℃; for 17h; Ammonia gas was bubbled through THF (355 mL) at 0 C. for 20 min. Neat cyclopropylsulfonyl chloride (1a, 15 g, 0.11 mol) was dropwise added to the solution. The resulting solution was allowed to warm to room temperature and stirred for 17 h. The resulting suspension was filtered through a plug of silica gel, eluting with ethyl acetate. The filtrate was concentrated in vacuo to afford 11.5 g (89%) of cyclopropylsulfonamide 1b. 1H NMR (300 MHz, CD3OD): δ 2.63-2.53 (m, 1H), 1.09-0.95 (m, 4H).
87% With ammonia; In tetrahydrofuran; at 0 - 20℃; [00279] Ammonia gas was bubbled through a gas dispersion tube into THF (40 mL) cooled to 0 0C for 5 minutes. To this solution at 0 0C was added cyclopropylsulfonylchloride (1 gram, 7.1 mmol). The reaction was stirred at room temperature overnight, then filtered through a plug of silica gel, followed by elution with EtOAc to yield 750 mg (6.19 mmol, EPO <DP n="294"/>87%) of cyclopropylsulfonamide. 1H-NMR (500 MHz, Methanol-d4): 4.79 (s, 2H), 2.59-2.54 (m, IH), 1.06-0.96 (m, 4H).
74% With ammonia; In 1,4-dioxane; at 20℃; for 72h; Example 46 Compound of Formula IV, wherein Step 46a: Cyclopropylsulfonyl chloride (1.4 g, 10 mmol) was dissolved in 0.5 M ammonia in dioxane (50 ml, 25 mmol) at RT. The reaction was kept at RT for 3 days. The large amount of precipitation was filtered and discarded. The clear filtrate was evaporated in vacuo and the white residue was dried on vacuum for 24 hours to give the cyclopropylsulfonamide (0.88 g, 74%). 1H-NMR (500 MHz, CD3Cl): δ 4.62 (2H, s), 2.59 (1H, m), 1.20 (2H, m), 1.02 (2H, m).
74% With ammonia; In 1,4-dioxane; at 20℃; for 72h; Cyclopropylsulfonyl chloride (1.4g, 10 mmol) was dissolved in 0.5 M ammonia in dioxane (50 ml, 25 mmol) at rt. The reaction was stirred at rt for 72 h. The precipitate was filtered and discarded. The clear filtrate was evaporated in vacuo and the white residue was dried on vacuum for 24 h to give cyclopropylsulfonamide (0.88 g, 74%).1H NMR (500 MHz, CD3Cl): δ 4.62 (2H, s), 2.59 (IH, m), 1.20 (2H, m), 1.02 (2H, m).
74% With ammonia; In 1,4-dioxane; at 20℃; for 72h; Cyclopropylsulfonyl chloride (1.4g, 10 mmol) was dissolved in 0.5 M ammonia in dioxane (50 ml, 25 mmol) at rt. The reaction was stirred at rt for 72 h. The precipitate was filtered and discarded. The clear filtrate was evaporated in vacuo and the white residue was dried on vacuum for 24 h to give cyclopropylsulfonamide (0.88 g, 74%).1H NMR (500 MHz, CD3Cl): δ 4.62 (2H, s), 2.59 (IH, m), 1.20 (2H, m), 1.02 (2H, m).
74% With ammonia; In 1,4-dioxane; at 20℃; for 72h; Cyclopropylsulfonyl chloride (1.4 g, 10 mmol) was dissolved in 0.5 M ammonia in dioxane (50 ml, 25 mmol) at RT. The reaction was kept at RT for 3 days. The large amount of precipitation was filtered and discarded. The clear filtrate was evaporated in vacuo and the white residue was dried on vacuum for 24 hours to give the cyclopropylsulfonamide (0.88 g, 74%). 1H-NMR (500 MHz, CD3Cl): δ 4.62 (2H, s), 2.59 (1H, m), 1.20 (2H, m), 1.02 (2H, m).
74% With ammonia; In 1,4-dioxane; at 20℃; for 72h; Cyclopropylsulfonyl chloride (IAg, 10 mmol) was dissolved in 0.5 M ammonia in dioxane (50 ml, 25 mmol) at RT. The reaction was kept at RT for 3 days. The large amount of precipitation was filtered and discarded. The clear filtrate was evaporated in vacuo and the white residue was dried on vacuum for 24 hours to give the cyclopropylsulfonamide (0.88 g, 74%). 1H- NMR (500 MHz, CD3Cl): δ 4.62 (2H, s), 2.59 (IH, m), 1.20 (2H, m), 1.02 (2H, m).
74% With ammonia; In 1,4-dioxane; at 20℃; for 72h; Step 3A: Cyclopropylsulfonyl chloride (1.4g, 10 mmol) was dissolved in 0.5 M ammonia in dioxane (50 ml, 25 mmol) at RT. The reaction was kept at RT for 3 days. The large amount of precipitation was filtered and discarded. The clear filtrate was <n="44"/>evaporated in vacuo and the white residue was dried on vacuum for 24 hours to give the cyclopropylsulfonamide (0.88 g, 74%). 1H-NMR (500 MHz, CD3Cl): δ 4.62 (2H, s), 2.59 (IH, m), 1.20 (2H, m), 1.02 (2H, m).
52% With ammonium hydroxide; In methanol; at 20℃; for 16h; General procedure: Standard Procedure D for the Preparation of Sulfonamides (0054) A solution of sulfonyl chloride in methanol and ammonium hydroxide solution was stirred at 0 C. or room temperature. After the reaction was complete, methanol was removed under reduced pressure. The solution was extracted with ethyl acetate. The combined organic layers were dried over MgSO4(s), filtered, and concentrated to give the desired products without further purification. Step 1. Cyclopropanesulfonamide Following standard procedure D, cyclopropanesulfonyl chloride (0.400 mL, 3.95 mmol), methanol (3.0 mL), and ammonium hydroxide solution (15 mL) were used to carry out the reaction. After the reaction was stirred at room temperature for 16 h and work up, cyclopropanesulfonamide (0.249 g, 52%) was obtained as a white solid. 1H NMR (DMSO-d6, 300 MHz) δ 6.78 (br s, 2H), 2.50-2.46 (m, 1H), 0.89-0.86 (m, 4H).
3.45 g (100%) In tetrahydrofuran; ammonia; Preparation of cyclopropyl sulfonamide To a solution of 100 mL of THF cooled to 0 C. was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF, the solution warmed to rt overnite and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained, applied onto 30 g plug of SiO2 (eluted with 30% to 60% EtOAc/Hexanes) to afford 3.45 g (100%) of cyclopropyl sulfonamide as a white solid. 1H NMR (Methanol-d4) δ 0.94-1.07 (m, 4H), 2.52-2.60 (m, 1H); 13C NMR (methanol-d4) δ 5.92, 33.01.
1.70 g (99%) In tetrahydrofuran; ammonia; Preparation of Cyclopropyl Sulfonamide Moiety for Use in Step 2e: To a solution of 20 mL THF cooled to 0 C. was bubbled in gaseous ammonia until saturation was reached. To this solution was added 2 g (5.69 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma). The solution was warmed to room temperature over two hours and the crude solution was filtered through a plug of silica gel eluding the product with ethyl acetate. The fractions were concentrated in vacuo to yield 1.70 g (99%) of cyclopropyl sulfonamide as a white solid: 1H NMR (d4-MeOH, 500 MHz) δ 0.94-1.07 (m, 4H), 2.52-2.60 (m, 1H).
3.45 g (100%) In tetrahydrofuran; ammonia; Method 2 To a solution of 100 mL of THF cooled to 0 C. was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5 g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF. The solution was warmed to room temperature overnight and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained and poured onto a 30 g plug of SiO2 (eluted with 30% to 60% ethyl acetate/hexanes) to provide 3.45 g (100%) of cyclopropylsulfonamide as a white solid. 1H NMR (methanol-d4) δ 0.94-1.07 (m, 4H), 2.52-2.60 (m, 1H); 13C NMR (methanol-d4) δ 5.92, 33.01.
3.45 g (100%) In tetrahydrofuran; ammonia; Method 2 To a solution of 100 mL of THF cooled to 0 C. was bubbled in gaseous ammonia until saturation was reached. To this solution was added a solution of 5g (28.45 mmol) of cyclopropylsulfonyl chloride (purchased from Array Biopharma) in 50 mL of THF. The solution was warmed to room temperature overnight and stirred one additional day. The mixture was concentrated until 1-2 mL of solvent remained and poured onto a 30 g plug of SiO2 (eluted with 30% to 60% ethyl acetate/hexanes) to provide 3.45 g (100%) of cyclopropylsulfonamide as a white solid. 1H NMR (methanol-d4) δ 0.94-1.07 (m, 4H), 2.52-2.60 (m, 1H); 13C NMR (methanol-d4) δ 5.92, 33.01.
With ammonia; In dichloromethane; at 0 - 20℃; To a solution of cyclopropylmagnesium bromide (0 5 M 20 mL, 10 0 mmol) in anhydrous THF (10 mL) at about -100C is added a solution of SO; in THF (~ 16 wt%, 4 8 mL, 12 mmo.) slowiy over 10 mm at -10 to -5C Tne reaction mixture is warmed to ambient temperature over 0 5h, and then NCS (2 O g 15 mmo.) is added at about -5 to 0C The reaction mixture is warmed up to ambient temperature and diluted with 50 mL oi methyl terl-buty. ether To tne reaction mixture ι≤ added 50 mL water and the mixture is stirred for 5 mm The organic layer is washed with 50 mL of bnne The organic layer is concentrated and the resultant cyclopropylsuifony. chloride is dissolved in CH2Ci2 (total volume was about 50 mL) and ammonia gas is bubbled in at about O'C for about 5 mm and the mixture is slowly warmed up to ambient temperature and stored at that temperature for 2 h The mixture is filtered through Cehte to remove the solid (NH4C.), and the filtrate is concentrated to obtain a crude cyclopropyisulfonamide solid (~ 1 2g) Re-cryslailization of the crude product from EtOAc/hexane produces cyclopropyisuifonarnide 42 in 80% overall yield.
7.03 g With ammonia; In tetrahydrofuran; for 16h; Cyclopropanesulfonamide A mixture of 50 ml of 25% aqueous ammonia solution and 50 ml of THF was initially charged, and then 10.00 g of cyclopropanesulfonyl chloride in 10 ml of THY were slowly added dropwise and the mixture was stirred for 16 hours. After concentration by rotary evaporation and coevaporation with toluene, the residue was extracted by stirring with 100 ml of ethyl acetate and the solids were filtered off. The organic phase was dried over Na2SO4 and concentrated by rotary evaporation. This gave the product (7.03 g) with a molecular weight of 121.2 g/mol (C3H7NO2S); MS (ESI): m/e=122 (M+H+).
7.03 g With ammonium hydroxide; In tetrahydrofuran; water; for 16h; Cyclopropanesulfonamide A mixture of 50 ml of 25% aqueous ammonia solution and 50 ml of THF was initially charged, and then 10.00 g of cyclopropanesulfonyl chloride in 10 ml of THF were slowly added dropwise and the mixture was stirred for 16 hours. After concentration by rotary evaporation and coevaporation with toluene, the residue was extracted by stirring with 100 ml of ethyl acetate and the solids were filtered off. The organic phase was dried over Na2SO4 and concentrated by rotary evaporation. This gave the product (7.03 g) with a molecular weight of 121.2 g/mol (C3H7NO2S); MS (ESI): m/e=122 (M+H+).
7.03 g In tetrahydrofuran; water; for 16h; A mixture of 50 ml of 25% aqueous ammonia solution and 50 ml of THF was initially charged, and then 10.00 g of cyclopropanesulfonyl chloride in 10 ml of THF were slowly added dropwise and the mixture was stirred for 16 hours. After concentration by rotary evaporation and coevaporation with toluene, the residue was extracted by stirring with 100 ml of ethyl acetate and the solids were filtered off. The organic phase was dried over Na2SO4 and concentrated by rotary evaporation. This gave the product (7.03 g) with a molecular weight of 121.2 g/mol (C3H7NO2S); MS (ESI): m/e=122 (M+H+).
With ammonia; In tetrahydrofuran; at 0 - 20℃; [0314] Ammonia gas was bubbled through a gas dispersion tube into THF (40 mL) cooled to 0 0C for 5 minutes. To this solution at 00C was added cyclopropylsulfonylchloride (1 gram, 7.1 mmol). The reaction was stirred at room temperature overnight, then filtered through a plug of silica gel, followed by elution with EtOAc to yield 750 mg (6.19 mmol) of cyclopropylsulfonamide. 1H-NMR (500 MHz, Methanol-d4): 4.79 (s, 2H), 2.59-2.54 (m, IH), 1.06-0.96 (m, 4H).

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  • 6
  • [ 154350-29-5 ]
  • [ 630421-48-6 ]
YieldReaction ConditionsOperation in experiment
92% A solution of the product of Step 1 (2.62 g, 11.5 mmol) and CDI (2.43 g, 15.0 mmol) in THF (40 mL) was heated to reflux for 50 minutes under nitrogen. The solution was cooled to room temperature and transferred by cannula to a solution of <strong>[154350-29-5]cyclopropylsulfonamide</strong> (1.82 g, 15.0 mmol) in THF (10 mL). To the resulting solution was added DBU (2.40 mL, 16.1 mmol) and stirring was continued for 20 hours. The mixture was quenched with 1N HCl to pH 1 and THF was concentrated in vacuo. The suspension was extracted with ethyl acetate (2*50 mL) and the combined organic extracts were dried (Na2SO4), filtered, and concentrated. Purification by recystallization from hexanes-ethyl acetate (1:1) provided the desired product (2.4 g) as a white solid. The mother liquor was purified by a Biotage 40S column (eluted 9% acetone in dichloromethane) to give a second batch of the desired product (1.1 g). Both batches were combined (total yield 92%). 1H NMR (DMSO-d6) δ 0.96-1.10 (m, 4H), 1.22 (dd, J=5.5, 9.5 Hz, 1H), 1.39 (s, 9H), 1.70 (t, J=5.5 Hz, 1H), 2.19-2.24 (m, 1H), 2.90 (m, 1H), 5.08 (d, J=10 Hz, 1H), 5.23 (d, J=17 Hz, 1H), 5.45 (m, 1H), 6.85, 7.22 (s, NH (rotamers); LC-MS (retention time: 1.70 minutes, method B), MS m/z 331 (M++H).
  • 7
  • [ 154350-29-5 ]
  • [ 24424-99-5 ]
  • [ 681808-26-4 ]
YieldReaction ConditionsOperation in experiment
99% Stage lc:oI IBocHN-SI Io[0182] Cyclopropanesulfonamide (5.0 g, 41.26 mmol, 1.0 eq.), triethylamine (8.62 g, 61.90 mmol, 1.5 eq.) and dichloromethane (50 mL) were charged in a 100 mL round bottom flask. Di-te/t-butyldicarbonate (10.8 g, 49.52 mmol, 1.2 eq.) and N,N- dimethylaminopyridine (252 mg, 2.06 mmol, 0.05 eq.) were added portion wise and the reaction mixture stirred at ambient temperature for 48 hours. The solvent was removed in vacuo and the residue diluted with water (20 mL). The aqueous phase was acidified to pH = 1 with 1M hydrochloric acid, and extracted with ethyl acetate (3 x 100 mL). The organic extracts were combined, washed with water (100 mL) and brine (100 mL), dried over magnesium sulfate, filtered and the solvent removed in vacuo to give 9.1 g (99% yield) of the title compound as a white solid. 1H NMR (500 MHz, CDC13) δ ppm 7.14 (br. s., 1 H) 2.90 (tt, 7=8.09, 4.73 Hz, 1 H) 1.50 - 1.54 (m, 9 H) 1.35 - 1.40 (m, 2 H) 1.09 - 1.15 (m, 2 H). LC-MS: purity 100% (UV), tR 1.62 min m/z [M+Na]+ 243.95 (MET/CR/1278).
96% With dmap; triethylamine; In dichloromethane; at 20℃;Cooling with ice; To an iced slurry of <strong>[154350-29-5]cyclopropanesulfonamide</strong> (1.21 g, 9.99 mmol), Triethylamine (2.95 mL, 20.97 mmol), and 4-Dimethylaminopyridine (0.061 g, 0.499 mmol) in CH2Cl2 (50 mL) was added solution of Di-tert-butyl dicarbonate (2.423 mL, 10.99 mmol) in DCM (10 mL) dropwise. The formed solution was stirred at room temperature overnight, Removed the solvent in vacuo. The residual oil was taken up in EtOAc and washed with 1M HCl and brine. Dried over MgSO4, filtered, and concentrated. The residue was purified by Biotage column, eluted with gradient 5%50% acetone-hexane to yield the desired produce tert-butyl cyclopropylsulfonylcarbamate (2.17 g, 9.61 mmol, 96% yield) as a viscous oil, which solidified upon standing on bench. 1H NMR (400 MHz, CDCl3) ppm 1.11-1.13 (m, 2H) 1.37-1.39 9m, 2H) 1.53 (s, 9H), 2.89-2.92 (m, 1H) 7.00-7.05 (b, NH).
94% With dmap; triethylamine; In dichloromethane; at 20℃; Step 4:; To the solid <strong>[154350-29-5]cyclopropanesulfonamide</strong> 2d4 (1.51 g ; 12.46 mmol) was added insequence: di-t-butyl-dicarbonate (3.26 g ; 14.95 mmol) dissolved in anhydrousdichloromethane (15 ml_), triethylamine (2.6 ml; 18.65 mmol) anddimethylaminopyridine (76 mg; 0.622 mmol). The resulting solution was stirred atroom temperature overnight and subsequently evaporated to near dryness. Theresidue was diluted with EtOAc, washed with 1N aq. HCI (3x) and brine (1x), dried(MgSO4), filtered and evaporated to dryness to provide the Boc-<strong>[154350-29-5]cyclopropylsulfonamide</strong> product 2d5 as a white solid (2.6 g ; 94%).
94% With dmap; triethylamine; In dichloromethane; at 20℃; To the solid <strong>[154350-29-5]cyclopropanesulfonamide</strong> 2d4 (1.51 g; 12.46 mmol) was added in sequence: di-t-butyl-dicarbonate (3.26 g; 14.95 mmol) dissolved in anhydrous dichloromethane (15 mL), triethylamine (2.6 mL; 18.65 mmol) and dimethylaminopyridine (76 mg; 0.622 mmol). The resulting solution was stirred at room temperature overnight and subsequently evaporated to near dryness. The residue was diluted with EtOAc, washed with 1 N aq. HCl (3×) and brine (1×), dried (MgSO4), filtered and evaporated to dryness to provide the Boc-<strong>[154350-29-5]cyclopropylsulfonamide</strong> product 2d5 as a white solid (2.6 g; 94%).
94% With dmap; triethylamine; In dichloromethane; at 18 - 22℃; Step D; To the solid <strong>[154350-29-5]cyclopropanesulfonamide</strong> 4A4 (1.51 g ; 12.46 mmol) was added in sequence: di-t-butyl-dicarbonate (3.26 g ; 14.95 mmol) dissolved in anhydrous dichloromethane (15 mL), triethylamine (2.6 mL; 18.65 mmol) and dimethylaminopyridine (76 mg; 0.622 mmol). The resulting solution was stirred at room temperature overnight and subsequently evaporated to near dryness. The residue was diluted with EtOAc, washed with 1 N aq. HCI (3x) and brine (1x), dried EPO <DP n="44"/>(MgSO4), filtered and evaporated to dryness to provide the Boc- <strong>[154350-29-5]cyclopropylsulfonamide</strong> product 4A5 as a white solid (2.6 g ; 94%).
93% With dmap; triethylamine; In dichloromethane; for 5.08333h; Compound 2 (4g, 33 mmol) was suspended in dry DCM (100 mL) containing Et3N (5 mL, 36.3 mmol) and DMAP (0.4g , 3.3 mmol). A solution of (Boc)20 (8.3g, 38 mmol) in dry DCM (50 mL) was added dropwise with stirring over 5 min. after 5h, the solution was concentrated in vacuo and the residue treated with EtOAc (30OmL) and IN HCl. The EtOAc layer was washed successively with water (40 mLl) and brine (40 mL), dried (Na2SO4), and concentrated to leave a solid. Heating with hexane (30 mL), cooling to room temperature, and filtration provide compound 3 as a white solid 6.8 g (yield 93%).
88% With dmap; triethylamine; In dichloromethane; To a solution of <strong>[154350-29-5]cyclopropanesulfonamide</strong> (6 g, 50 mmol) in DCM (50 ml) were added triethylamine (7.5 ml, 74 mmol) followed by DMAP (0.3 g, 7.5 mmol) and di-tert-butyl dicarbonate (13 g, 59 ml) and the reaction was left stirring overnight. The solvent was removed; water, 2N HCl (40 ml) and ethyl acetate were added. The organic layer was washed with brine, dried over magnesium sulfate and evaporated to give Boc-<strong>[154350-29-5]cyclopropanesulfonamide</strong> as a white solid, used on the next step without further purification. Yield 9.73 g (88%).
87% With dmap; triethylamine; In dichloromethane; at 0 - 20℃; for 3.5h; Step 1: Preparation of Boc-cyclopropane sulfonyl amide 50. To a solution of <strong>[154350-29-5]cyclopropanesulfonamide</strong>, TEA (13.9 mL), and DMAP (1.11 g, 0.1 eq.) (10.72 g, leq.) in DCM (160 mL) was added a solution of BoC2O (21.88 g, 0.8 eq.) in DCM (10OmL) was added dropwise at 0 0C over 30 min. The mixture was then allowed to warm up to room temperature and stirred for 3 hrs. The solution was washed with IN HCl, water and brine, dried over Na2SO4, filtered, and concentrated under reduced pressure to yield after trituration in hexane compound 50 as a white solid in 87% yield.1H NMR (CDCl3, 400 MHz): δ 0.92-0.96 (td, J = 6.5 and 1.50 Hz, 2H), 1.51 (s, 9H), 1.60- 1.64 (td, 7 = 6.46 and 1.50 Hz, 2H), 1.25 (m, IH), 6.99 (brs, IH).
85% With dmap; triethylamine; In dichloromethane; at 20℃;Product distribution / selectivity; C.5) Alternative Preparation of Cyclopropylsulfonylamine tert-butyl carbamate To a solution of <strong>[154350-29-5]cyclopropylsulfonamide</strong> (6.0 g, 50.0 mmol) in CH2Cl2 (50 mL) was added BOC2O (13.0 g, 59.0 mmol), triethylamine (7.5 mL, 74 mmol), and 4-DMAP (0.30 g, 2.5 mmol). The reaction mixture was stirred overnight at room temperature, diluted with ethyl acetate (300 mL), partitioned with 1 N HCl (3*100 mL), dried over MgSO4, filtered, and concentrated in vacuo to provide 9.3 g (85%) of cyclopropylsulfonylamine tert-butylcarbamate.
85% With dmap; triethylamine; In dichloromethane; at 20℃;Product distribution / selectivity; Step ii) To a solution of <strong>[154350-29-5]cyclopropylsulfonamide</strong> (6.0 g, 50.0 mmol) in CH2Cl2 (50 mL) was added BOC2O(13.0 g, 59.0 mmol), Et3N (7.5 mL, 74 mmol), and 4-DMAP (0.30 g, 2.5 mmol). The reaction mixture was stirred overnite at rt, diluted with EtOAc (300 mL), partitioned with 1 N HCl (3*100 mL), dried over MgSO4 and concentrated in vacuo to afford 9.3 g (85%) of cyclopropylsulfonylamine tert-butylcarbamate as a white solid having identical data to its preparation in Step IIc.
With dmap; triethylamine; In dichloromethane; at 0 - 20℃; Step a: tert-butyl (cyciopropyisuifonyi)carbamate To a mixture of 15 g (124 mmof) cyclopropanβsulfo nic acid amide, 25.9 mL (186 mmol) triethylamine and 0.8 g (6.2 mmol) DMAP in 150 ml DCM was added 32.4 g (149 mmol) Boc- anhydride at OC. The mixture was slowly warmed to RT and stirred for 48 h. After dilution with DCM the mixture was washed with 1 N aq. HCi solution. The organic layer was dried over Na2SO4 and concentrated in vacuo to yield the title compound which was used in the next step without further purification. LC-MS (method E): Rt = 1.254 min; MIz = 220.2 [M-H].
2.66 g With dmap; triethylamine; In dichloromethane; for 16h; N-tert-Butyloxycarbonyl<strong>[154350-29-5]cyclopropanesulfonamide</strong> 1.46 g of <strong>[154350-29-5]cyclopropanesulfonamide</strong> were initially charged in a mixture of 30 ml of dichloromethane and 1.67 ml of triethylamine, and then 2.63 g of di-tert-butyl dicarbonate and 0.15 g of 4-dimethylaminopyridine were added and the mixture was stirred for 16 hours. The reaction solution was washed with 1 N aqueous hydrochloric acid, saturated aqueous sodium chloride solution and water, and the organic phase was dried over Na2SO4 and concentrated by rotary evaporation. This gave the product (2.66 g) with a molecular weight of 221.3 g/mol (C8H15NO4S); MS (ESI): m/e=166 (M-tert-Butyl+H+).
2.66 g With dmap; triethylamine; In dichloromethane; for 16h; N-tert-Butyloxycarbonyl<strong>[154350-29-5]cyclopropanesulfonamide</strong> 1.46 g of <strong>[154350-29-5]cyclopropanesulfonamide</strong> were initially charged in a mixture of 30 ml of dichloromethane and 1.67 ml of triethylamine, and then 2.63 g of di-tert-butyl dicarbonate and 0.15 g of 4-dimethylaminopyridine were added and the mixture was stirred for 16 hours. The reaction solution was washed with 1 N aqueous hydrochloric acid, saturated aqueous sodium chloride solution and water, and the organic phase was dried over Na2SO4 and concentrated by rotary evaporation. This gave the product (2.66 g) with a molecular weight of 221.3 g/mol (C8H15NO4S); MS (EST): m/e=166 (M-tert-Butyl+H+).
2.66 g With dmap; triethylamine; In dichloromethane; for 16h; 1.46 g of <strong>[154350-29-5]cyclopropanesulfonamide</strong> were initially charged in a mixture of 30 ml of dichloromethane and 1.67 ml of triethylamine, and then 2.63 g of di-tert-butyl dicarbonate and 0.15 g of 4-dimethylaminopyridine were added and the mixture was stirred for 16 hours. The reaction solution was washed with 1 N aqueous hydrochloric acid, saturated aqueous sodium chloride solution and water, and the organic phase was dried over Na2SO4 and concentrated by rotary evaporation. This gave the product (2.66 g) with a molecular weight of 221.3 g/mol (C8H15NO4S); MS (ESI): m/e=166 (M-tert-butyl+H+).
With dmap; triethylamine; In dichloromethane; at 0 - 25℃; Step 2: Preparation of tert-butyl cyclopropylsulfonylcarbamate: To a solution of A3 (2.0 g, 16.5 mmol) in DCM (30 mL) at 0 C was added DMAP (0.1 g, 0.825 mmol), Et3N (3.52 mL, 24.7 mmol) and Boc20 (4.32 g, 19.8 mmol). The reaction mixture was allowed to warm to RT and stir overnight. After that time, the volatiles were removed under reduced pressure. To the crude residue was added water. The aqueous phase was acidified to pH= 1 with the addition of aqueous 1.0 N HC1 and the mixture was extracted with EtOAc. The combined organic layers were washed with water and brine, then dried over Na2S04, filtered and concentrated to yield compound A4. NMR (CDC13, 300 MHz): δ 7.20 (bs, 1H), 2.92 - 2.86 (m, 1H), 1.55 (s, 9H), 1.39 - 1.35 (m, 2H), 1.28 - 1.24 (m, 2H).
With dmap; triethylamine; In dichloromethane; at 0 - 20℃; for 4h; To a solution of <strong>[154350-29-5]cyclopropanesulfonamide</strong> (100 g, 82.6 mmol) in DCM (800 ml) was added triethylamine (234 ml, 165 mmol) followed by DMAP (10.28 g, 82.6 mmol) at 0 C. under nitrogen. To this reaction mixture Boc anhydride (247 ml, 107 mmol) in DCM (400 ml) was added slowly. The resulting mixture was stirred for 4 h at room temperature. The reaction mixture was diluted with water and extracted with ethyl acetate. The combine organic layer was washed with 1.5 N HCl solution and 10% NaHCO3and dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to get crude compound (143 g, 65.0%) as solid. The crude compound was directly taken for the next step.1H NMR (400 MHz, DMSO-d6): δ ppm 11.08 (s, 1H), 2.90 (m, 1H), 1.48 (s, 9H), 1.06 (m, 4H).
With dmap; triethylamine; In dichloromethane; at 0 - 20℃; for 4h;Inert atmosphere; To a solution of <strong>[154350-29-5]cyclopropanesulfonamide</strong> (100 g, 82.6 mmol) in DCM (800 ml) was added triethylamine (234 ml, 165 mmol) followed by DMAP (10.28 g, 82.6 mmol) at 0 C. under nitrogen. To this reaction mixture Boc anhydride (247 ml, 107 mmol) in DCM (400 ml) was added slowly. The resulting mixture was stirred for 4 h at room temperature. The reaction mixture was diluted with water and extracted with ethyl acetate. The combine organic layer was washed with 1.5 N HCl solution and 10% NaHCO3 and dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to get crude compound (143 g, 65%) as a solid. The crude compound was directly taken for the next step. 1H NMR (400 MHz, DMSO-d6): δ ppm 11.08 (s, 1H), 2.90 (m, 1H), 1.48 (s, 9H), 1.06 (m, 4H).
65% (143 g) With dmap; triethylamine; In dichloromethane; at 0 - 20℃; for 4h; Step 1: Preparation of tert-butyl cyclopropylsulfonylcarbamate To a solution of <strong>[154350-29-5]cyclopropanesulfonamide</strong> (100 g, 82.6 mmol) in DCM (800 ml) was added triethylamine (234 ml, 165 mmol) followed by DMAP (10.28 g, 82.6 mmol) at 0 C. under nitrogen. To this reaction mixture Boc anhydride (247 ml, 107 mmol) in DCM (400 ml) was added slowly. The resulting mixture was stirred for 4 h at room temperature. The reaction mixture was diluted with water and extracted with ethyl acetate. The combine organic layer was washed with 1.5 N HCl solution and 10% NaHCO3 and dried over anhydrous sodium sulfate, filtered and evaporated under reduced pressure to get crude compound (143 g, 65.0%) as solid. The crude compound was directly taken for the next step. 1H NMR (400 MHz, DMSO-d6): δ ppm 11.08 (s, 1H), 2.90 (m, 1H), 1.48 (s, 9H), 1.06 (m, 4H).
With dmap; triethylamine; In dichloromethane; at 0 - 20℃; for 12h; To a solution of <strong>[154350-29-5]cyclopropanesulfonamide</strong> (100 g, 825 mmol) in DCM (1 L) at 0 C was sequentially added DMAP (5.0 g, 41.3 mmol), TEA (173 mL, 1238 mmol), and Boc-anhydride (216 g, 813 mmol). The reaction mixture was allowed to warm to RT and stirred for 12 h. After the completion of reaction (monitored by TLC), it was concentrated under reduced pressure. The crude residue was taken in EtOAc (2000 mL) and washed with aqueous 1.5 _ HC1 (2 x 1000 mL). The organic layer was washed with water (1000 mL), brine (1000 mL) and dried over Na2SO4. The organic layer was concentrated under reduced pressure to afford 22a (180 g, 99%) as a transparent liquid, which was used in next step without purification. MS (ESI -ve ion) m/z: [M-1] = 220.2.1H NMR (400 MHz, chloroform-d) ^ 7.36 (s, 1H), 2.93- 2.88 (m, 1H), 1.53 (d, J = 0.6 Hz, 9H), 1.39-1.36 (m, 2H), 1.15-1.10 (m, 2H).

  • 8
  • [ 154350-29-5 ]
  • [ 914823-96-4 ]
YieldReaction ConditionsOperation in experiment
54% To a solution of EXAMPLE 11 (35 mg, 0.052 mmol) in DMF (0.3 mL) at 400C was added carbonyldiimidazole (8 mg, 0.052 mmol) and the reaction mixture was stirred for Ih. Cyclopropylsulfonamide (10 mg, 0.078 mmol) and DBU (16 mg, 0.01 mmol) were added and the reaction mixture was stirred for 1 h. Following cooling, the reaction mixture was purified on reverse phase HPLC to afford EXAMPLE 17 (22 mg, 54% yield). 1H NMR (500 MHz, CD3OD, ppm) 5 8.19 (d, J= 1.5 Hz, 1 H), 8.14 (d, J= 8.8 Hz, 1 H), 8.09 (m, 2 H), 7.98 (dd, J= 8.8, 1.5 Hz, 1 H), 7.82 (s, 1 H), 7.75 (m, 3 H), 6.01 (m, 1 H), 5.75 (ddd, J= 17.1, 10.3, 8.8 Hz, 1 H), 5.29 (dd, J= 17.1, 1.5 Hz, 1 H), 5.13 (dd, J= 10.5, 1.5 Hz, 1 H), 4.57 (dd, J= 10.7, 6.8 Hz, 1 H), 4.41 (t, J= 7.6 Hz, 1 H), 4.27 (m, 1 H), 4.12 (dd, J= 12.0, 2.9 Hz, 1 H), 3.78 (m, 1 H), 3.02-2.95 (m, 2 H), 2.83 (m, 1 H), 2.68 (dd, J= 13.9, 6.6 EPO <DP n="58"/>Hz, 1 H), 2.44 (m, 1 H), 2.20 (q, J= 8.8 Hz, 1 H), 1.90 (dd, J= 8.1, 5.4 Hz, 1 H), 1.88-1.69 (m, 5 H), 1.57 (m, 1 H), 1.42-1.32 (m, 7 H), 1.29 (m, 2 H), 1.21 (m, 1 H), 1.10 (m, 2 H), and 0.96 (m, 3 H). LRMS (M+H)+ calcd = 772.3; found = 772.4.
  • 9
  • [ 154350-29-5 ]
  • [ 1338580-58-7 ]
YieldReaction ConditionsOperation in experiment
82% Step 2:; To a solution of acid 2e2 (567 mg, 2.49 mmol), in THF (20 mL), was added GDI (515mg, 3.17 mmol). The resulting solution was stirred for 30 min, refluxed for 30 min andallowed to cool down to RT. Cyclopropylsulfonamide 2d4 (455 mg, 3.76 mmol) wasadded followed by the addition of DBU (0.75 mL, 5.02 mmol) and the reaction wasstirred 12 h. The THF was removed in vacuo and the residue was diluted with EtOAc,washed with 1 M HCI (2 X 100 ml) and brine, dried (MgSO4) and purified by flashchromatography (elution conditions: 70:30 hexane/EtOAc) to afford 682 mg (82%) ofcompound 2e3 as a white solid.
  • 10
  • [ 154350-29-5 ]
  • [ 923275-55-2 ]
YieldReaction ConditionsOperation in experiment
77% Example 5: Preparation of 4-Hydroxy-cyclopentane-l,2-dicarboxylic acid 1-[(1- cyclopropanesulfonylamino carbonyl-2-vinyl-cyclopropyl)-amide] 2-(hex-5-enyl- methyl-amide) (8).; EPO <DP n="67"/>The crude acid 7 (410 mg, 1.09 mmol) was dissolved in DMF (1.5 ml) and DCM (4.5 ml) followed by addition of EDAC (417 mg, 2.18 mmol) at room temperature. The mixture was allowed to incubate with stirring at room temperature. After 10 min, DMAP (133 mg, 1.09 mmol) was added followed by another 20 min incubation at room temperature. Subsequently, a pre-mixed solution of cyclopropanesulfonic acid amide (527 mg, 4.36 mmol) and DBU (663 mg, 4.36 mmol) in DMF (2 ml) and DCM (2 ml) was added followed by heating in the microwave to 100C for 30 min. The resulting red solution was concentrated in vacuo and re-dissolved in ethyl acetate (20 ml). The organic phase was washed with 1 M HCl (aqueous) (3x 10 ml) and brine (10 ml), dried (MgSO4) and filtered. The solvent was evaporated in vacuo to yield the crude sulfonamide which was further purified by chromatography (Silica, ethyl acetate/methanol, 97.5:2.5) to afford the target compound 8 (403 mg, 77%); LC/MS (Method A): tR= 3.31 min, >95%, m/z (ESI+)= 482(MH+).
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