반응 #2003604

반응 방정식

(5R,7R)-5-Methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol dihydrochloride

(5R,7S)-5-methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol di-hydrochloride

HATU

collidine

(S)-2-((S)-1-(tert-butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)-2-(4-chloro-2-fluorophenyl)acetic acid

→

(S)-tert-butyl 5-((S)-1-(4-chloro-2-fluorophenyl)-2-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-2-oxoethyl)-2,2-dimethylpyrrolidine-1-carboxylate

수율 59.5%

용매

DCM

반응 조건

후처리

1. 1
   기타prepared analogously to
2. 2
   기타The reaction was partitioned between water (20 mL) and DCM (50 mL)
3. 3
   기타the layers were separated
4. 4
   세척The organics were washed with water (2×10 mL)
5. 5
   추출The aqueous portion was back extracted with DCM (25 mL)
6. 6
   건조dried (MgSO4)
7. 7
   농축concentrated to an oil that
8. 8
   기타was purified by flash chromatography (5% MeOH/DCM)

실험 절차

(5R,7R)-5-Methyl-4-(piperazin-1-yl)-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-ol dihydrochloride (0.109 g, 0.356 mmol; see Example 3, Step 12), HATU (0.123 g, 0.324 mmol), and collidine (0.171 mL, 1.30 mmol) were added to a solution of (S)-2-((S)-1-(tert-butoxycarbonyl)-5,5-dimethylpyrrolidin-2-yl)-2-(4-chloro-2-fluorophenyl)acetic acid (0.125 g, 0.324 mmol; prepared analogously to that described in Example B) in DCM (25 mL). The reaction was stirred overnight at room temperature. The reaction was partitioned between water (20 mL) and DCM (50 mL), and the layers were separated. The organics were washed with water (2×10 mL). The aqueous portion was back extracted with DCM (25 mL), dried (MgSO4) and concentrated to an oil that was purified by flash chromatography (5% MeOH/DCM) to give (S)-tert-butyl 5-((S)-1-(4-chloro-2-fluorophenyl)-2-(4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazin-1-yl)-2-oxoethyl)-2,2-dimethylpyrrolidine-1-carboxylate (0.116 g, 0.193 mmol, 59.5% yield). LC/MS=3.79 minutes, (APCI+) m/z=602 [M+H]+.

출처