Water → METHYL (2S,4R)-1-{2-[4-(4-CHLORO-PHENYL)-PIPERAZIN-1-YL]-5-OXO-6,7-DIHYDRO-5H-5lambda4-THIENO [3,2-D]PYRIMIDIN-4-YL}-4-HYDROXY-PYRROLIDINE-2-CARBOXYLATE

HRID 70098

반응식

HRID 70098 반응식
Cl[C:2]1[C:3]2[S:23](=[O:24])[CH2:22][CH2:21][C:4]=2[N:5]=[C:6]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[CH2:10][CH2:9]2)[N:7]=1.[OH:25][C@H:26]1[CH2:30][NH:29][C@H:28]([C:31]([O:33][CH3:34])=[O:32])[CH2:27]1.C(N(C(C)C)CC)(C)C.O>O1CCOCC1.ClCCl>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([N:11]2[CH2:12][CH2:13][N:8]([C:6]3[N:7]=[C:2]([N:29]4[CH2:30][C@H:26]([OH:25])[CH2:27][C@H:28]4[C:31]([O:33][CH3:34])=[O:32])[C:3]4[S:23](=[O:24])[CH2:22][CH2:21][C:4]=4[N:5]=3)[CH2:9][CH2:10]2)=[CH:15][CH:16]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 7015125(4R)-4-Hydroxy-L-proline methyl esterHCID 594758954-Chloro-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-6,7-dihydro-thieno[3,2-d]pyrimidine 5-oxide

생성물 1

HCID 59708424METHYL (2S,4R)-1-{2-[4-(4-CHLORO-PHENYL)-PIPERAZIN-1-YL]-5-OXO-6,7-DIHYDRO-5H-5lambda4-THIENO [3,2-D]PYRIMIDIN-4-YL}-4-HYDROXY-PYRROLIDINE-2-CARBOXYLATE

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매

반응 조건

온도
120 °C

실험 절차

500 mg 4-chloro-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-6,7-dihydro-thieno[3,2-d]pyrimidine 5-oxide (cf Example 124), 284.19 mg methyl (2S,4R)-4-hydroxy-pyrrolidine-2-carboxylate and 691.65 μl diisopropylethylamine are placed in 8 ml dioxane, heated to 120° C. in the microwave for 0.3 hours. Then the reaction mixture is combined with water and dichloromethane and extracted. The organic phase is separated off using a phase separation cartridge and evaporated to dryness. The diastereomers are separated by preparative HPLC (method B). 200 mg of Diastereomer I (Example 125) and 160 mg of a Diastereomer 2 (Example 126) are obtained as powders. Analytical HPLC-MS (method A): Diastereomer 1, RT=2.51 min, Diastereomer 2, RT=2.57 min.

후처리

  1. extractionextracted
  2. customThe organic phase is separated off
  3. customa phase separation cartridge
  4. customevaporated to dryness
  5. customThe diastereomers are separated by preparative HPLC (method B)
  6. custom200 mg of Diastereomer I (Example 125) and 160 mg of a Diastereomer 2 (Example 126) are obtained as powders

출처 및 근거

ORD 기록
ord-0985aff65b9b4c70a322c66845821bed
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822474B2

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