Dimethylformamide → (S)-Methyl 4-((tert-butoxycarbonyl)(5-formylthiazol-2-yl)amino)-2-((tert-butoxycarbonyl)amino)butanoate

HRID 1755490Notes

Reaction equation

HRID 1755490 reaction equation
[CH:1]([C:3]1[S:7][C:6]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[N:5][CH:4]=1)=[O:2].CN(C=O)C.[H-].[Na+].[C:23]([O:27][C:28]([NH:30][C@@H:31]([CH2:36][CH2:37]I)[C:32]([O:34][CH3:35])=[O:33])=[O:29])([CH3:26])([CH3:25])[CH3:24]>C(OCC)(=O)C>[C:11]([O:10][C:9]([N:8]([C:6]1[S:7][C:3]([CH:1]=[O:2])=[CH:4][N:5]=1)[CH2:37][CH2:36][C@H:31]([NH:30][C:28]([O:27][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:29])[C:32]([O:34][CH3:35])=[O:33])=[O:15])([CH3:12])([CH3:14])[CH3:13]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 14394150Methyl (S)-2-(Boc-amino)-4-iodobutanoateHCID 53393345tert-butyl N-(5-formyl-1,3-thiazol-2-yl)carbamate

Product 1

HCID 86700133(S)-Methyl 4-((tert-butoxycarbonyl)(5-formylthiazol-2-yl)amino)-2-((tert-butoxycarbonyl)amino)butanoateYield 91%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a dry 2-5 mL microwave vial under N2 is added tert-butyl (5-formylthiazol-2-yl)carbamate (100 mg, 0.438 mmol) and anhydrous DMF (2.5 mL). The resulting dark solution stirred at room temp for 5 min, treated with sodium hydride (22.13 mg, 0.876 mmol), flushed with N2 for 15 min, then treated with material from Example 115 (301 mg, 0.876 mmol) and securely capped. The resulting dark solution is stirred at room temp for 30 min, then heated in a microwave heating unit for 15 min at 80° C. under high power. The reaction is diluted with ethyl acetate (200 mL), washed with water (6×25 mL), brine (1×25 mL), dried over Na2SO4, filtered, the solvent removed in vacuo and the resulting residue purified by BIOTAGE® Silica gel chromatography on a 25 g Thompson Single Step silica cartridge using 100% CH2Cl2 to 75% EtOAc/CH2Cl2 over 11 column volumes to give 176.7 mg (91%) of the title compound as a thick oil, LC/MS (Condition A): ret. T=3.83 min, (M+Na) 466.

Workup

  1. customflushed with N2 for 15 min
  2. customsecurely capped
  3. stirringThe resulting dark solution is stirred at room temp for 30 min
  4. temperatureheated in a microwave
  5. temperatureheating unit for 15 min at 80° C. under high power
  6. washwashed with water (6×25 mL), brine (1×25 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customthe solvent removed in vacuo
  10. customthe resulting residue purified by BIOTAGE® Silica gel chromatography on a 25 g Thompson Single Step silica cartridge

Sources & evidence

ORD record
ord-693568b8df9f41fa9dffd639cfbfd397
Source dataset
uspto-grants-2015_10
Patent number
US09169295B2

Reaction notes

Loading…