Diisopropylethylamine → ethyl 2-[(3S)-3-aminopyrrolidin-1-yl]-4-methyl-1,3-thiazole-5-carboxylate

HRID 43926Notes

Reaction equation

HRID 43926 reaction equation
[NH2:1][C@H:2]1[CH2:6][CH2:5][NH:4][CH2:3]1.Br[C:8]1[S:9][C:10]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:11]([CH3:13])[N:12]=1.C(N(C(C)C)CC)(C)C>CN(C=O)C.C(OCC)(=O)C>[NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:8]2[S:9][C:10]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[C:11]([CH3:13])[N:12]=2)[CH2:3]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 1519351(3S)-(-)-3-AminopyrrolidineHCID 2824057Ethyl 2-bromo-4-methyl-1,3-thiazole-5-carboxylate

Product 1

HCID 67548886ethyl 2-[(3S)-3-aminopyrrolidin-1-yl]-4-methyl-1,3-thiazole-5-carboxylateYield 84%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (3S)-3-aminopyrrolidine (0.16 mL, 1.80 mmol), ethyl 2-bromo-4-methylthiazole-5-carboxylate (300 mg, 1.20 mmol) and diisopropylethylamine (0.42 mL, 2.40 mmol) in DMF (12 mL) was stirred at 90° C. for 75 minutes. The reaction solution was diluted with ethyl acetate, and then the mixture was washed with saturated aqueous sodium bicarbonate solution, and dried over anhydrous magnesium sulfate. Following filtration, the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (elution solvent: dichloromethane/methanol=5/1) to obtain 257 mg of the title compound as a pale yellow solid (84%).

Workup

  1. washthe mixture was washed with saturated aqueous sodium bicarbonate solution
  2. dry with materialdried over anhydrous magnesium sulfate
  3. filtrationfiltration
  4. customthe solvent was evaporated under reduced pressure
  5. customThe resulting residue was purified by silica gel column chromatography (elution solvent: dichloromethane/methanol=5/1)

Sources & evidence

ORD record
ord-b3b12c02fc1942e1b97cac6c69807882
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Reaction notes

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