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

HRID 1425395Notes

Reaction equation

HRID 1425395 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-251fe6acf41845829135b3ed13a73376
Source dataset
uspto-grants-2015_01
Patent number
US08927588B2

Reaction notes

Loading…