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CAS No. : | 13139-28-1 | MDL No. : | MFCD00191170 |
Formula : | C13H18N2O3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | LWAHIZLDUQONHV-NSHDSACASA-N |
M.W : | 250.29 | Pubchem ID : | 10562630 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | [0197] To a stuffed solution of compound I (10 g, 39.84 mmol, 1 eq) in DMF (100 mL) was added DIPEA (19.7 mL, 119.5 mmol, 3 eq) and HATU (18.17 g, 47.8 mmol, 1.2 eq) at 0C and the resulting mixture was stuffed for 15 mm. To the mixture was added ammonium chloride (10.7 g, 199.2 mmol, 5 eq) and the resulting mixture was allowed to stir at 23C for another 16 h. The mixture was poured into ice cold water (500 mL), the organic components were extracted with EtOAc (3 x 500 mL) and the combined organic layers were washed with aqueous ammonium chloride solution and brine. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to dryness. The crude product was recrystallized from ethanol to obtain the title compound (9.8 g, 98%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) oe 7.35 (m, 6H), 7.12 (d, 1H, J = 9 Hz), 7.01 (s, 1H), 5.03 (s, 2H), 3.80 (t, 1H, J = 8 Hz), 1.95 (m, 1H), 0.85 (m, 6H). LCMS: mlz = 251.2 [M+Hj , RT = 2.81 minutes, (Program P1, Column Y). | |
93% | General procedure: To a colorless solution of 150mg (0.50mmol) of Cbz-L-Phe-OH 3a in 10mL of THF were added 67muL (0.70mmol, 1.4equiv) of ClCO2Et and 209muL (1.5mmol, 3.0equiv) of Et3N at 0C. After stirring for 30min at 0C, 0.75 ml of a 1.0M aqueous solution of NH4Cl (0.75mmol, 1.5equiv) were added at 0C to the colorless suspension. The mixture was stirred for 30min at 0C and 5mL of H2O was added to the resulted mixture. The colorless clear solution was extracted with 30mL of EtOAc and the aqueous layer was extracted with 20mL of EtOAc. The organic layers were combined, washed with 5mL of brine, and dried over anhydrous MgSO4. The crude product was chromatographed on silica gel with EtOAc to afford 129mg (86% yield) of Cbz-L-Phe-NH2 4a. 4.3.7 Cbz-l-Val-NH2 4d 117?mg (93%); >99% ee; coloress solid; mp: 172-175?C; [alpha]D25?=?+17.8 (c 0.99, DMSO); 1H NMR (400?MHz, DMSO-d6): delta 0.83 (d, J?=?6.8?Hz, 3H, CH3), 0.86 (d, J?=?6.8?Hz, 3H, CH3), 1.94 (ddd, J?=?6.7, 6.8, 6.8?Hz, 1H, CH(CH3)2), 3.80 (dd, J?=?6.7, 8.8?Hz, 1H, CHCO), 5.03 (s, 2H, OCH2C6H5), 7.03 (br, 1H, CONHA), 7.16 (d, J?=?8.8?Hz, 1H, NHCH), 7.29-7.39 (m, 6H, CONHB, C6H5); 13C NMR (100?MHz, DMSO-d6): delta 18.0, 19.3, 30.1, 60.0, 65.3, 127.6, 127.7, 128.3, 137.1, 156.1, 173.2; IR (KBr, vmax/cm-1): 3381 (CONH), 3319 (CONH), 3203 (CONH), 1654 (CON); HRMS (ESI-TOF): Calcd for C13H18N2O3Na (M+Na)+: 273.1210, found: 273.1193; The enantiomeric ratio was determined by HPLC (Chiralcel AD: hexane/2-propanol?=?90/10): Tr 11.5?min. | |
63.8% | Step 1. To a solution of 27-1 (8 g, 31.8 mmol) and Et3N (6.43 g, 63.6 mmol) in dry THF (100 mL) at -78C was added dropwise a solution of ethyl chloro formate (3.45 g, 31.8 mmol) in THF (10 mL). After the reaction was stirred at -78C for 1 h, NH3.H20 (5 mL) was added. The reaction was warmed to r.t. over 2 h. White solid was collected by filtration and dried to give 27-2 (5.1 g, 63.8%). |
53.15% | With pyridine; di-tert-butyl dicarbonate; ammonium bicarbonate; In 1,4-dioxane; at 0 - 20℃; | To a solution of (S)-2-(benzyloxycarbonylamino)-3-methylbutanoic acid (10.0 g, 39.84 mmol) in 1,4-dioxane (50 mL) was added di-tert-butyl dicarbonate (11.95 g, 51.79mmol) in portions at 0C. Then pyridine (2 mL, 25.76 mmol) was added drop-wise at 0C, followed by ammonium bicarbonate (3.94 g, 50.43 mmol) in portions. The reaction was stirred at room temperature overnight. The mixture was poured into ice water and filtered. The filter cake was washed with water and dried under vacuum. The filter cake was then re-crystallized from dioxane/water (80 mL, 9: 1, v/v) to give (S)-benzyl (1-amino-3-methyl-1-oxobutan-2-yl)carbamate(5.3 g, 53.15% yield) as a white solid. LC-MS (ESI) found: 251 [M+Hf?, ee>99%, (CHIRALPAK AS-H, 15% ethanol/ hexane) |
General procedure: The appropriate N-protected amino/peptide acid (1.0 mmol) was dissolved in THF, to which NMM (1.5 mmol) and ECF (1.5 mmol) were added at -15 C, followed by the addition of NH4HCO3 (1.5 mmol) to obtain the corresponding amide. The reaction mixture was stirred until the completion of the reaction and the progress of the reaction was checked by TLC. After the removal of THF, the product was extracted into ethyl acetate (15 mL) and the organic layer was washed with dilute HCl solution (10 mL) or citric acid solution (10 mL) in the case of the Boc-protected compounds, then with Na2CO3 solution (15 mL x 2), water (15 mL) and brine (15 mL). The organic extract was dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The amide thus formed was then treated with P2S5 (0.5 mmol) to form the thioamide under ultrasonic conditions for 2-3 hrs. The resulting thioamide in dry THF was reacted with chloroacetaldehyde (1.0 mmol) under reflux conditions for 2 hrs. N-Protected thiazoles were obtained in good yield after simple acid-base work up and purified through column chromatography using EtOAc:hexane (3:7) as an eluent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With ammonium hydroxide; In water; at 20℃; for 16h;Inert atmosphere; | General procedure: A 0.2 M solution of the corresponding methyl ester in aq NH4OH (28-30%) was stirred at r.t. for 16 h. The solvent was evaporated to affordthe amide, which was, in some cases, purified by silica gel chromatography. The known amides 3, 33 5a,34 5b, 6c 5h,35 11a,36 11b,37 11c,3611e,38 11h,4 11i,39 11j,39 13,40 14,41 20,42 and 2343 were synthesized following the general procedure described above. Compound 5e was synthesized following the literature.44 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95.2% | With 1,3,5-trichloro-2,4,6-triazine; In N,N-dimethyl-formamide; at 0 - 20℃; for 2h; | To a solution of(S)-benzyl i-amino-3-methyl-i-oxobutan-2-ylcarbamate (1.7 g,6.79 mmol) in DMF (anhydrous, 30 mL) was added 2,4,6-trichloro-i,3,5-triazine (1.75 g, 9.51mmol) at 0C. The reaction was stirred at room temperature for 2 hrs. The reaction was poured into water (300 mL), and the mixture was extracted with ethyl acetate (50 mL*3). The combined organic layers were washed with water and brine, dried over Na2SO4, filtered and concentrated to give a residue, which was purified by silica gel chromatography (petroleumether: ethyl acetate = 10: 1) to give (S)-benzyl (i-cyano-2-methylpropyl)carbamate (1.5 g,95.2% yield) as a colorless oil. LC-MS (ESI) found: 233 [M+Hf?, ee=95.97% (CHIRALPAK AS-H, 5% ethanol/hexane). |
51% | With triethylamine; ethanaminium,N-(difluoro-lambda4-sulfanylidene)-N-ethyl-,tetrafluoroborate; In ethyl acetate; at 20℃; for 1h;Inert atmosphere; | General procedure: To a solution of the aldoxime or the amide (1.0 mmol) and Et3N (1.5mmol) in EtOAc (1 mL, 1 M) at r.t. was added XtalFluor-E8 (1.1 mmol)portionwise over ca. 2 min. The resulting solution was stirred at r.t.for 1 h. The reaction mixture was quenched with sat. aq Na2CO3 and extracted with CH2Cl2 (2 × 10 mL). The combined organic layers were washed with H2O and brine, dried (MgSO4), and concentrated under vacuum to afford the crude nitrile, which was purified by flash chromatography, if required. |
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