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

Reaktionsgleichung

Reaktionsgleichung von HRID 70098
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

Komponenten

7

Edukt 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

Produkt 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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-0985aff65b9b4c70a322c66845821bed
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822474B2

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