Реакция #91953

Уравнение реакции

(R)-6-bromomethyl-4-(2-chloro-4-fluoro-phenyl)-2-thiazol-2-yl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester

(S)-4,4-difluoro-pyrrolidine-2-carboxylic acid

DIPEA

→

(R)-6-((S)-2-carboxy-4,4-difluoro-pyrrolidin-1-ylmethyl)-4-(2-chloro-4-fluoro-phenyl)-2-thiazol-2-yl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester

Растворители

1,2-dichloroethane

EtOAc

Условия реакции

Обработка

1. 1
   Промывкаwashed successively with saturated aqueous NH4Cl solution and brine
2. 2
   ДругоеThe organic layer was separated
3. 3
   Сушкаdried over Na2SO4
4. 4
   КонцентрированиеThe solvent was concentrated in vacuo
5. 5
   Другоеthe crude product was purified by prep-HPLC

Методика

To a stirred solution of (R)-6-bromomethyl-4-(2-chloro-4-fluoro-phenyl)-2-thiazol-2-yl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester (0.049 g, 0.11 mmol) and (S)-4,4-difluoro-pyrrolidine-2-carboxylic acid (0.044 g, 0.17 mmol) in 1,2-dichloroethane (5 mL) was added dropwise DIPEA (0.078 mL, 0.45 mmol). The reaction mixture was stirred at room temperature until the disappearance of starting material which was checked by LC/MS. The mixture was diluted with EtOAc (50 mL) and washed successively with saturated aqueous NH4Cl solution and brine. The organic layer was separated and dried over Na2SO4. The solvent was concentrated in vacuo and the crude product was purified by prep-HPLC to give (R)-6-((S)-2-carboxy-4,4-difluoro-pyrrolidin-1-ylmethyl)-4-(2-chloro-4-fluoro-phenyl)-2-thiazol-2-yl-1,4-dihydro-pyrimidine-5-carboxylic acid methyl ester (Example 2) as a light yellow solid.

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