天堂网亚洲,天天操天天搞,91视频高清,菠萝蜜视频在线观看入口,美女视频性感美女视频,95丝袜美女视频国产,超高清美女视频图片

Home Cart 0 Sign in  

[ CAS No. 171178-45-3 ] {[proInfo.proName]}

,{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]}
Chemical Structure| 171178-45-3
Chemical Structure| 171178-45-3
Structure of 171178-45-3 * Storage: {[proInfo.prStorage]}

Please Login or Create an Account to: See VIP prices and availability

Cart0 Add to My Favorites Add to My Favorites Bulk Inquiry Inquiry Add To Cart

Search after Editing

* Storage: {[proInfo.prStorage]}

* Shipping: {[proInfo.prShipping]}

Quality Control of [ 171178-45-3 ]

Related Doc. of [ 171178-45-3 ]

Alternatived Products of [ 171178-45-3 ]
Product Citations

Product Details of [ 171178-45-3 ]

CAS No. :171178-45-3 MDL No. :MFCD08062421
Formula : C10H13ClN2O2 Boiling Point : No data available
Linear Structure Formula :- InChI Key :IRHNQVINMHHEIO-UHFFFAOYSA-N
M.W : 228.68 Pubchem ID :7330593
Synonyms :

Calculated chemistry of [ 171178-45-3 ]      Expand+

Physicochemical Properties

Num. heavy atoms : 15
Num. arom. heavy atoms : 6
Fraction Csp3 : 0.4
Num. rotatable bonds : 4
Num. H-bond acceptors : 3.0
Num. H-bond donors : 1.0
Molar Refractivity : 59.49
TPSA : 51.22 ?2

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : Yes
CYP2C9 inhibitor : No
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.01 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.42
Log Po/w (XLOGP3) : 2.38
Log Po/w (WLOGP) : 2.89
Log Po/w (MLOGP) : 1.4
Log Po/w (SILICOS-IT) : 1.78
Consensus Log Po/w : 2.17

Druglikeness

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

Water Solubility

Log S (ESOL) : -2.79
Solubility : 0.372 mg/ml ; 0.00162 mol/l
Class : Soluble
Log S (Ali) : -3.1
Solubility : 0.183 mg/ml ; 0.000801 mol/l
Class : Soluble
Log S (SILICOS-IT) : -3.6
Solubility : 0.0574 mg/ml ; 0.000251 mol/l
Class : Soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 1.0 alert
Leadlikeness : 1.0
Synthetic accessibility : 2.46

Safety of [ 171178-45-3 ]

Signal Word:Warning Class:
Precautionary Statements:P261-P280-P305+P351+P338 UN#:
Hazard Statements:H302+H312+H332-H315-H319-H335 Packing Group:
GHS Pictogram:

Application In Synthesis of [ 171178-45-3 ]

* 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 [ 171178-45-3 ]

[ 171178-45-3 ] Synthesis Path-Downstream   1~8

  • 1
  • [ 124-38-9 ]
  • [ 171178-45-3 ]
  • [ 171178-46-4 ]
YieldReaction ConditionsOperation in experiment
87% To a 500 ml. oven dried 3 necked round bottom flask, tert- butyl (6-chloropyridin-3- yl)carbamate (Intermediate A) (5 g, 21 .82 mmol, 1 equiv.) was dissolved in anhydrous diethyl ether (200 ml.) giving a yellow solution. TMEDA 0.1 M (1 1 .7 ml_, 76 mmol, 3.5 equiv.) were added and the mixture was cooled to -78C. A solution of n-butyl lithium 2.5 M in hexanes (30.5 ml_, 76 mmol, 3.5 equiv) was dropwise added (the reaction mixture turned brown-red colour). When the addition of the reagent was completed, the reaction mixture was permitted to reach to -10C and stirred at this temperature for 3 h. The reaction mixture was then re-cooled to -78C and a carbon dioxide gas bag (1 gal) was fitted under Ar atmosphere. The system was evacuated and flushed with carbon dioxide for three times. The reaction mixture was stirred at -78C under carbon dioxide atmosphere at atmospheric pressure for 4 h. The reaction was permitted to warm up to 22C and stirred for 18 h. Water was added to the reaction mixture until complete solution of solid materials (300 ml_). The phases were separated and the aqueous phase was washed with diethyl ether (2 x 100 ml_). After that, the pH-value of the aqueous phase was adjusted to 6.32 with HCI 2.7M and extracted with diethyl ether (4 x 200 mL) and EtOAc (5 x 200 ml_). The combined organic phases were dried over anhyd. Na2S04 and concentrated under reduced pressure giving 5 -((tert- butoxycarbonyl)amino)-2-chloroisonicotinic acid as a pale yellow solid, (5.13 g, 87% yield). Purity: 99.1% (UPLC-A); 1H-NMR (DMSO-de), 5(ppm): 10.01 (s, 1 H), 9.12 (s, 1 H), 7.75 (s, 1 H), 1.48 (s, 9H); LR-MS (ESI+): m/z= 273.0 Da [M+H]+, calcd. for C11H13CIN2O4: 272.7.
69.3% Step (c): 5-TERT-BUTOXYCARBONYLAMINO-2-CHLORO-ISONICOTINIC acid A suspension of (6-CHLORO-PYRIDIN-3-YL)-CARBAMIC acid tert-butyl ester in 800mL of ether was treated with TMEDA, and the mixture cooled TO-75C. To this was added 1.6M BuLi in hexanes dropwise while keeping the temperature BELOW-65C. After the addition was complete, the reaction mixture was allowed to warm to-15C TO-10C, and stirred in this temperature range for 2 hours. The reaction mixture was again cooled TO-75C, and dry carbon dioxide was bubbled into the mixture for 3 hours before allowing the reaction to warm to room temperature overnight with continued bubbling of carbon dioxide. The reaction mixture was carefully quenched with 20% aqueous ammonium hydroxide solution (1.8L), the aqueous portion extracted with ether, then acidified to pH 5 using 50% aqueous HCI. The resulting solid was collected by filtration, washed with water, and dried to give 33.07g (69. 3% yield) of 5-tert- butoxycarbonylamino-2-chloro-isonicotinic acid as a light yellow solid. 1H NMR (400 MHz, DMSO-D6) d ppm 1.5 (s, 9H), 7.7 (s, 1H), 9.1 (s, 1H), 10.0 (s, 1H) MS (APCI) M+1 = 273.1
60% Step (c): 5-TERT-BUTOXYCARBONYLAMINO-2-CHLORO-ISONICOTINIC acid The reaction was run under Argon. A 20 L jacketed reactor was charged with (6-chloro-pyridin-3-yl)-carbamic acid tert-butyl ester (200 g, 0. 875 moles), THF (5 L), and TMEDA (304 ML, 2.3 equivalents, 2 wt% water), and the mixture was cooled to BETWEEN-70C AND-75C. nBuLi (805 ML, 2.5 M in hexanes, 2.3 mole equivalents) was added via dropping funnel at a rate that kept the reaction temperature BETWEEN-70C AND-75C. The resulting brown solution was warmed to-15C and stirred for 1 hour. The reaction mixture was then cooled back to- 35C, and a lecture bottle of C02 was bubbled through. The reaction mixture was allowed to warm to 20C over 2 hours, during which time the solution became an orange slurry. The reaction mixture was stirred at room temperature overnight. The reaction was quenched by the addition of 1.5 L of water. During the quench a precipitate formed in the aqueous layer. The layers were separated, taking the precipitated solid with the aqueous layer. The organic layer was washed once with 1 N NaOH. The aqueous portions were combined, and the pH adjusted to pH 2 with 6 N HC1. The solid was collected by filtration, washed twice with water and dried overnight in the vacuum oven at 45C. The reaction yielded 143 g (60% total yield) of 5-tert-Butoxycarbonylamino-2-chloro-isonicotinic acid as a tan solid that was sufficiently pure by NMR to use in the next reaction. ON (DMSO) 10.06 (1 H, s), 9.07 (1 H, s), 7.71 (1 H, d), 1.42 (9 H, s) MS [M+H] + 273
[00479] To a stirred solution of (6-chloro-pyridin-3-yl)-carbamic acid tert-butyl ester (5.6 g, 24.6 mmol) in THF (100 mL) was added n-BuLi (29 mL, 74.0 mmol) dropwise at -78 C. The mixture was stirred at this temperature for 1 hors. Then the vessel was charged with carbon dioxide to a pressure of 0.7 Mbar and stirred at - 40 C for 10 min. After warmed to room temperature, the mixture was poured into the ice water and the pH value was adjusted to pH = 3. The aqueous phase was extracted with EA (100 mL x2). The combined organic layers were washed with brine (30 mL x2), dried over anhydrous Na2S04 and filtered. The filtrate was evaporated in vacuum to give the product (crude, 8.0 g) of 5-tert- butoxycarbonylamino-2-chloro-isonicotinic acid as red oil.
(c) 5-(tert-Butoxycarbonyl)-2-chloroisonicotinic acid. To a solution of tert-butyl 6-chloropyridin-3-ylcarbamate (1O g, 0.045 mol) and N, N, N', N'-tetramethyleethylenediamine (20 mL) in dry Et2O (200 mL) was added n- BuLi (2.5 M solution in hexanes, 84 mL) dropwise with stirring at -78C. After the addition, the reaction mixture was warmed to -15C and stirred at the same temperature for 2 hours. The mixture was cooled to -78C and CO2 gas was bubbled into the reaction solution at -78C for 1 hour. The reaction mixture was then stirred at room temperature overnight, cooled to 0C and quenched with <n="115"/>water. The pH of the aqueous phase was adjusted to pH=3 with IN hydrochloric acid. The organic layer was separated, and the aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over anhydrous MgSO4, and filtered. The filtrate was evaporated under reduced pressure, and the residue was dried in vacuo to give the title compound.
(c) 5-(tert-Butoxycarbonyl)-2-chloroisonicotinic acid. To a solution of tert-butyl 6-chloropyridin-3-ylcarbamate (10 g, 0.045 mol) and N, N, N',N'-tetramethylethylenediamine (20 mL) in dry diethyl ether (200 mL) was added n-BuLi (2.5 M solution in hexanes, 84 mL) dropwise with stirring at - 78C. After the addition, the reaction mixture was warmed to -15C, and the reaction was stirred at this temperature for 2 hours. The mixture was cooled to - 78C and CO2 gas was bubbled into the reaction solution at -78C for 1 hour. The reaction mixture was then stirred at room temperature overnight, cooled to 0C, and quenched with water. The pH of the aqueous phase was adjusted to pH=3 with IN HCl. The organic layer was separated, and the aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over anhydrous MgSO4, and filtered. The filtrate was evaporated under reduced pressure, and the residue was dried in vacuo to give the title compound.
Step 2: Preparation of 5- tert-butoxycarbonylamino-2-chloro- isonicotinic acid; A solution of ( 6-chloro-pyridin-3-yl) -carbamic acid tert- <n="406"/>butyl ester (4.19 g) in diethyl ether (150 mL) was cooled to -78C and N,N,N' ,N'-tetramethylethylendiamine (6.60 g) was added. After slow addition of n-butyl lithium solution (1.32 M in hexane, 41.6 mL) over a time period of 10 minutes, the mixture was allowed to warm up to -100C, stirred at this temperature for 2 hours and then was re- cooled to -78C. The mixture was poured slowly into a stirred mixture of crushed dry ice in THF and stirred for 30 minutes. The mixture was concentrated on a rotary evaporator and water was added to the residue. The aqueous layer was washed 2x with MTB-ether and acidified with 6N hydrochloric acid to pH ~ 3. The formed precipitate was filtered off, washed with water, ethyl acetate and dried in vacuum to afford 2.46 g of the title compound of the formulaas beige solid.1H-NMR (DMSO-D6) delta (ppm) : 1.48 (9H, s), 7.77 (IH, s), 9.13 (IH, s) , 10.13 (IH, s) .

  • 2
  • [ 171178-45-3 ]
  • [ 400777-00-6 ]
YieldReaction ConditionsOperation in experiment
33% Step b: tert-Butyl 6-chloro-4-iodopyridin-3-ylcarbamate To a solution of TMEDA (25.4 g, 219.3 mmol) in dry THF (300 mL) was added dropwise n-BuLi (87.7 mL, 219.3 mmol) at -78 C., the mixture was stirred for 0.5 h at this temperature. A solution of tert-butyl 6-chloropyridin-3-yl-carbamate (20 g, 87.7 mmol) in THF (170 mL) was added dropwise to the reaction mixture at -78 C. and the resulting mixture was continued to stir for 1 h at -78 C. Then a solution of I2 (26.7 g, 105.3 mmol) in dry THF (170 mL) was added dropwise at -78 C. After 1 h, the reaction was quenched with sat. aqueous NH4Cl (300 mL). The organic layer was separated and the aqueous phase was extracted with EtOAc (150 mL*3). The combined organic layers were dried over anhydrous Na2SO4 and concentrated under reduced pressure to yield a residue that was purified by column chromatography on silica gel (petroleum ether/ethyl acetate, 10/1) to give tert-butyl 6-chloro-4-iodopyridin-3-ylcarbamate (10.0 g, 33%). 1H-NMR (CDCl3, 400 MHz) delta 8.95 (s, 1H), 7.73 (s, 1H), 6.64 (br s, 1H), 1.53 (s, 9H).
32.3% Step 2 To the solution of tert-butyl (6-chloropyridin-3-yl)carbamate (160 g, 0.7 mol) in 1 L of anhydrous THF was added n-BuLi (600 mL, 1.5 mol) at -78 C. under N2 atmosphere. After the addition was finished, the solution was stirred at -78 C. for 30 min, and the solution of I2 (177.68 g, 0.7 mol) in 800 mL of anhydrous THF was added. Then the solution was stirred at -78 C. for 4 hrs. TLC indicated the reaction was over. Water was added for quench, and EtOAc was added to extract twice. The combined organic phases were washed with brine, dried over Na2SO4, filtered and purified by flash chromatography to afford 80 g of tert-butyl (6-chloro-4-iodopyridin-3-yl)carbamate as a yellow solid (32.3%).
32.3% Step 2: (0190) To the solution of tert-butyl(6-chloropyridin-3-yl)carbamate (160 g, 0.7 mol) in 1 L of anhydrous THF was added n-BuLi (600 mL, 1.5 mol) at -78 C. under N2 atmosphere. After the addition was finished, the solution was stirred at -78 C. for 30 min, and the solution of I2 (177.68 g, 0.7 mol) in 800 mL of anhydrous THF was added. Then the solution was stirred at -78 C. for 4 hrs. TLC indicated the reaction was over. Water was added for quench, and EtOAc was added to extract twice. The combined organic phases were washed with brine, dried over Na2SO4, filtered and purified by flash chromatography to afford 80 g of tert-butyl(6-chloro-4-iodopyridin-3-yl)carbamate as a yellow solid (32.3%).
32.3% To the solution of tert-butyl (6-chloropyridin-3-yl)carbamate (160 g, 0.7 mol) in 1 L of anhydrous THF was added n-BuLi (600 mL, 1.5 mol) at -78 C. under N2atmosphere. After the addition was finished, the solution was stirred at -78 C. for 30 min, and the solution of I2(177.68 g, 0.7 mol) in 800 mL of anhydrous THF was added. Then the solution was stirred at -78 C. for 4 hrs. TLC indicated the reaction was over. Water was added for quench, and EtOAc was added to extract twice. The combined organic phases were washed with brine, dried over Na2SO4, filtered and purified by flash chromatography to afford 80 g of tert-butyl (6-chloro-4-iodopyridin-3-yl)carbamate as a yellow solid (32.3%).
Preparation 7 : (6-Chloro-4-iodopyridin-3-yl)carbamic acid tert-butyl ester The title compound was prepared according to the method described in US 2002/0022624 Al from the compound of Preparation 6. 5H(CDC13): 1.54 (9H, s), 6.62 (IH, s), 7.72 (IH, s), 8.93 (IH, s).
Step B: tert-Butyl (6-chloro-4-iodopyridin-3-yl)carbamateteri-Butyllithium (1.3 M in heptanes, 1 11 mL, 144 mmol) was added dropwise to a solution of t-butyl (6-chloropyridin-3-yl)carbamate (15.0 g, 65.6 mmol) in anhydrous THF (300 mL) at -78 C over 30 min under 2 atmosphere. The resulting mixture was stirred at -78 C for 1 h, then at -10 C for 1 h. The reaction mixture was cooled to -78 C and a solution of I2 (36.6 g, 144 mmol) in anhydrous THF (100 mL) was added. The resulting mixture was warmed to ambient temperature and stirred for 18 h. Excess ?-butyllithium and I2 were quenched with saturated aqueous NH4C1 solution (150 mL) and saturated aqueous a2S203 solution (500 mL), respectively, and the resulting mixture was stirred for 30 min. The organic layer was separated and the aqueous layer was extracted with EtOAc (250 mL x 2). The combined organic layers were washed with brine (250 mL), dried over Na2S04 and concentrated. The residue was purified by column chromatography on silica gel (EtOAc:PE:Et3N = 2 : 98 : 1, then 2.5 : 97.5 : 1) to afford the title compound. MS: m/z = 355 (M + 1). XH NMR (400 MHz, CDC13) delta 8.93 (s, 1H), 7.72 (s, 1H), 6.64 (s, 1H), 1.53 (s, 9H).
2.59 g Under argon gas atmosphere, to diethyl ether (120mL)solution of (6-chloropyridin-3-yl) carbamic acid tert- butyl (5.0 g) and N, N,N ', N'- tetramethyl ethane-1,2-diamine (7.7 g), at -78 n-butyl lithium solution (2.65mol / L tetrahydrofuran solution, 25mL) was addeddropwise. after stirring the mixture for 2 hours at -10 , diethyl ether (40mL) solution of iodine (11.4g) wasdropped at -78 , and the mixture was stirred one day at roomtemperature. To the reaction mixture, a saturated aqueous ammonium chloridesolution was added, and extracted with diethyl ether. The organic layer was washed with 10%aqueous solution of sodium pyrosulfite and saturated brine, dried overanhydrous magnesium sulfate, and evaporated under reduced pressure. Theresulting crude product was purified by silica gel column chromatography (eluting solvent: n- hexane / ethyl acetate = 100 / 0 ~60 / 40) to give the title compound (2.59 g).
2.59 g To a solution of (6-chloropyridin-3-yl)carbamic acid tert-butyl ester(5.0 g) at -78 C and N, N, N ', N'-tetramethylethane-1,2-diamine (7.7 g) of diethyl ether (120 mL) after the drop of the solution was stirred at 10 C for 2 hours, iodine (11.4 g) was added dropwise at -78 C, of diethyl ether (40 mL) solution. The mixture was stirred at room temperature for one day. To the reaction mixture was added a saturated aqueous ammonium chloride solution, and extracted with diethyl ether. The organic layer was washed with 10% aqueous sodium metabisulfite solution, after washing with saturated saline, and then dried over anhydrous magnesium sulfate, and distilled off under reduced pressure. The obtained crude product was purified by silica gel column chromatography (elution solvent; n-hexane-ethyl acetate) to give the title compound (2.59 g).
2.59 g Reference Example 4 (0080) (6-Chloro-4-iodopyridin-3-yl)cathamic acid tert-butyl ester (0081) To a solution of (6-chloropyridin-3-yl)cathamic acid tert-butyl ester (5.0 g) and N,N,N?,N-tetramethylethane-1,2-diamine (7.7 g) in diethyl ether (120 mL) was added dropwise n-buthyllithium (2.65 mol/L n-hexane solution, 25 mL) at -78 C. under an argon gas atmosphere. After the mixture was stirred at -10 C. for 2 hours, a solution of iodine (11.4 g) in diethyl ether (40 mL) was added dropwise at -78 C. The resulting mixture was stirred at room temperature for 1 day. To the reaction mixture was added a saturated aqueous ammonium chloride solution, and the resulting mixture was extracted with diethyl ether. The organic layer was washed with 10% aqueous sodium pyrosulfite and brine, and dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The obtained crude product was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate) to give the title compound (2.59 g).

  • 3
  • [ 171178-45-3 ]
  • [ 171178-47-5 ]
  • 5
  • [ 171178-45-3 ]
  • [ 171178-46-4 ]
YieldReaction ConditionsOperation in experiment
57% With n-butyllithium; N,N,N,N,-tetramethylethylenediamine; In diethyl ether; 5-[N-(tert -Butoxycarbonyl)amino]-2-chloropyridine-4-carboxylic acid. A solution of 5-[N-(tert-butoxycarbonyl)amino]-2-chloropyridine (22.87 g, 0.1 mol) and TMEDA (47 mL, 0.31 mol) in dry Et2 O (600 mL) is cooled to -78 C., and n-BuLi (10M in hexanes, 30 mL, 0.3 mol) is added dropwise. The solution is allowed to warm to -10 C. and is then kept at that temperature for 2 h, before being recooled to -78 C. Dry CO2 is then bubbled in, and the resulting mixture is allowed to warm to 20 C., before being quenched with water (300 mL) containing a small amount of NH4 OH. The resulting aqueous layer is washed with EtOAc, then acidified slowly with dilute HCl to precipitate 5-[N-(tert-butoxycarbonyl)amino]-2-chloropyridine-4-carboxylic acid (15.5 g, 57%). 1 H NMR (DMSO) delta 10.00 (1H, s), 9.13 (1H, s), 7.74 (1H, s), 1.47 (9H, s).
With n-butyllithium; In tetramethylethylenediamine; diethyl ether; hexane; at -78 - 0℃; To 13 g of (6-chloro-pyridin-3-yl)-carbamic acid, tert-butyl ester in 24 ML of tetramethylethylenediamine and 300 ML of ether at -78 C. under an inert atmosphere was added slowly 68 ML of 2.5 M n-butyllithium/hexanes (3 eq).. After the addition was complete, the reaction was allowed to warm to -15 C. for two hours then recooled to -78 C. Dry ice was allowed to sublime in a separate flask and the vapor was passed over the rapidly stirred reaction mixture while the cooling bath was removed and the reaction allowed to warm to 0 C. Sufficient water was added to dissolve the precipitated product and the resultant aqueous phase was washed twice with ether before acidifying with concentrated HCl. The precipitate was filtered, washed with water, and dried in vacuo to give 10.9 g of 5-tert-butoxycarbonylamino-2-chloro-isonicotinic acid, which was used as is for the next step: melting point 250 C. and higher (slowly decomposed); mass spectrum (negative mode, m/e): M-H 271.1.
  • 6
  • [ 110-18-9 ]
  • [ 171178-45-3 ]
  • [ 171178-46-4 ]
YieldReaction ConditionsOperation in experiment
With n-butyllithium; In diethyl ether; at -78 - -15℃; for 2h; To 13 g of (6-chloro-pyridin-3-yl)-carbamic acid, tert-butyl ester in 24 mL of tetramethylethylenediamine and 300 mL of ether at -78C under an inert atmosphere was added slowly 68 mL of 2.5 M n-butyllithium/hexanes (3 eq). After the addition was complete, the reaction was allowed to warm to -15C for two hours then recooled to -78C. Dry ice was allowed to sublime in a separate flask and the vapor was passed over the rapidly stirred reaction mixture while the cooling bath was removed and the reaction allowed to warm to 0C. Sufficient water was added to dissolve the precipitated product and the resultant aqueous phase was washed twice with ether before acidifying with concentrated HCl. The precipitate was filtered, washed with water, and dried in vacuo to give 10.9 g of 5-tert-butoxycarbonylamino-2-chloro-isonicotinic acid, which was used as is for the next step: melting point 250C and higher (slowly decomposed); mass spectrum (negative mode, m/e): M-H 271.1.
  • 7
  • [ 60-29-7 ]
  • [ 171178-45-3 ]
  • [ 171178-46-4 ]
YieldReaction ConditionsOperation in experiment
35% With n-butyllithium; N,N,N,N,-tetramethylethylenediamine; at -78 - 0℃; for 2h; A stirred solution of (6-chloro-pyridin-3-yl)-carbamic acid tert-butyl ester (3.28 g, 14.3 mmol) and TMEDA (6.7 mL, 44.4 mmol) in Et2O (100 mL) at -78 C. was treated with n-BuLi (4.3 mL, 10 M, 43 mmol). After stirring the mixture at -78 C. for 2 hours CO2 was bubbled into the reaction and the solution was warmed to 0 C. Water was added and the mixture was extracted with EtOAc. The aqueous layer was acidified and extracted with Et2O. The Et2O layer was washed with brine, dried (MgSO4) and the solvent was removed in vacuo. The residual solid was triturated with Hexane/Et2O to give 25A (1.38 g, 35%) HPLC Rt=2.98 min.
  • 8
  • [ 109-72-8 ]
  • ammonium chloride [ No CAS ]
  • [ 171178-45-3 ]
  • [ 400777-00-6 ]
YieldReaction ConditionsOperation in experiment
55% With N,N,N,N,-tetramethylethylenediamine; iodine; 1,1-Dimethylethyl (6-Chloro-4-iodo-3-pyridinyl)carbamate n-Butyllithium (1.6M in hexanes, 22 mL, 35 mmol) was added dropwise to a stirred, cooled (-78 C.) solution of 1,1-dimethylethyl (6-chloro-3-pyridinyl)carbamate (Description 6, 2.68 g, 11.7 mmol) and N,N,N',N'-tetramethylethylenediamine (5.3 mL, 4.1 g, 35 mmol) in ether (60 mL). The mixture was allowed to warm to -10 C. and stirred for 2 h. The mixture was cooled to -78 C. and a cooled (-10 C.) solution of iodine (6.0 g, 24 mmol) in ether (20 mL) was added dropwise. The mixture was allowed to warm to room temperature and stirred for 18 h. Saturated aqueous ammonium chloride was added and the mixture was extracted with ether. The combined organic fractions were washed with aqueous sodium metabisulfite (10%), dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was triturated with hexane and the solid was collected and dried in vacuo to give the title compound as a brown solid (2.3 g, 55%). 1H NMR (400 MHz, CDCl3) delta 8.94 (1H, s), 7.73 (1H, s), 6.64 (1H, br s), and 1.54 (9H, s).
Recommend Products
Same Skeleton Products

Technical Information

Historical Records

Related Functional Groups of
[ 171178-45-3 ]

Chlorides

Chemical Structure| 1227958-32-8

[ 1227958-32-8 ]

tert-Butyl (2-bromo-6-chloropyridin-3-yl)carbamate

Similarity: 0.86

Chemical Structure| 1640995-60-3

[ 1640995-60-3 ]

tert-Butyl ((6-chloropyridin-2-yl)methyl)carbamate

Similarity: 0.83

Chemical Structure| 400777-00-6

[ 400777-00-6 ]

tert-Butyl (6-chloro-4-iodopyridin-3-yl)carbamate

Similarity: 0.82

Chemical Structure| 501907-61-5

[ 501907-61-5 ]

tert-Butyl (2,6-dichloropyridin-4-yl)carbamate

Similarity: 0.81

Chemical Structure| 159603-71-1

[ 159603-71-1 ]

tert-Butyl (6-chloropyridin-2-yl)carbamate

Similarity: 0.76

Amides

Chemical Structure| 1227958-32-8

[ 1227958-32-8 ]

tert-Butyl (2-bromo-6-chloropyridin-3-yl)carbamate

Similarity: 0.86

Chemical Structure| 56700-70-0

[ 56700-70-0 ]

tert-Butyl pyridin-3-ylcarbamate

Similarity: 0.85

Chemical Structure| 1640995-60-3

[ 1640995-60-3 ]

tert-Butyl ((6-chloropyridin-2-yl)methyl)carbamate

Similarity: 0.83

Chemical Structure| 400777-00-6

[ 400777-00-6 ]

tert-Butyl (6-chloro-4-iodopyridin-3-yl)carbamate

Similarity: 0.82

Chemical Structure| 501907-61-5

[ 501907-61-5 ]

tert-Butyl (2,6-dichloropyridin-4-yl)carbamate

Similarity: 0.81

Amines

Chemical Structure| 1227958-32-8

[ 1227958-32-8 ]

tert-Butyl (2-bromo-6-chloropyridin-3-yl)carbamate

Similarity: 0.86

Chemical Structure| 56700-70-0

[ 56700-70-0 ]

tert-Butyl pyridin-3-ylcarbamate

Similarity: 0.85

Chemical Structure| 1640995-60-3

[ 1640995-60-3 ]

tert-Butyl ((6-chloropyridin-2-yl)methyl)carbamate

Similarity: 0.83

Chemical Structure| 400777-00-6

[ 400777-00-6 ]

tert-Butyl (6-chloro-4-iodopyridin-3-yl)carbamate

Similarity: 0.82

Chemical Structure| 501907-61-5

[ 501907-61-5 ]

tert-Butyl (2,6-dichloropyridin-4-yl)carbamate

Similarity: 0.81

Related Parent Nucleus of
[ 171178-45-3 ]

Pyridines

Chemical Structure| 1227958-32-8

[ 1227958-32-8 ]

tert-Butyl (2-bromo-6-chloropyridin-3-yl)carbamate

Similarity: 0.86

Chemical Structure| 56700-70-0

[ 56700-70-0 ]

tert-Butyl pyridin-3-ylcarbamate

Similarity: 0.85

Chemical Structure| 1640995-60-3

[ 1640995-60-3 ]

tert-Butyl ((6-chloropyridin-2-yl)methyl)carbamate

Similarity: 0.83

Chemical Structure| 400777-00-6

[ 400777-00-6 ]

tert-Butyl (6-chloro-4-iodopyridin-3-yl)carbamate

Similarity: 0.82

Chemical Structure| 501907-61-5

[ 501907-61-5 ]

tert-Butyl (2,6-dichloropyridin-4-yl)carbamate

Similarity: 0.81

; ;