반응 #91953

반응 방정식

(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

용매

1,2-dichloroethane

EtOAc

반응 조건

후처리

1. 1
   세척washed successively with saturated aqueous NH4Cl solution and brine
2. 2
   기타The organic layer was separated
3. 3
   건조dried over Na2SO4
4. 4
   농축The solvent was concentrated in vacuo
5. 5
   기타the crude product was purified by prep-HPLC

실험 절차

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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