Water → (R)-2-{2-[4-(4-chloro-phenyl)-piperazin-1-yl]-5-oxo-6,7-dihydro-5H-5lambda4-thieno[3,2-d]pyrimidin-4-ylamino}-2-phenyl-ethanol

HRID 70102

Reaktionsgleichung

Reaktionsgleichung von HRID 70102
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.[C:25]1([C@H:31]([CH2:33][OH:34])[NH2:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(N(C(C)C)CC)(C)C.O>O1CCOCC1.CS(C)=O>[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]([NH:32][C@H:31]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[CH2:33][OH:34])[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 2724025(R)-beta-aminophenethyl alcoholHCID 594758954-Chloro-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-6,7-dihydro-thieno[3,2-d]pyrimidine 5-oxide

Produkt 1

HCID 59708479(R)-2-{2-[4-(4-chloro-phenyl)-piperazin-1-yl]-5-oxo-6,7-dihydro-5H-5lambda4-thieno[3,2-d]pyrimidin-4-ylamino}-2-phenyl-ethanol

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

220 mg 4-chloro-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-6,7-dihydro-thieno[3,2-d]pyrimidine 5-oxide (cf Example 124), 157.48 mg (R)-(−)-2-phenylglycinol and 197.52 μl diisopropylethylamine are placed in 4 ml dioxane, heated to 120° C. in the microwave for 0.3 hours. Then the reaction mixture is mixed with water, the precipitate formed is suction filtered, washed and dried. The diastereomers are separated by preparative HPLC (method B). 52.8 mg of Diastereomer 1 (Example 49) and 42.0 mg of Diastereomer 2 (Example 56) are obtained as a powder. 1H NMR (400 MHz, DMSO): Diastereomer 1: 7.41-7.35 (m, 2H), 7.35-7.28 (m, 2H), 7.28-7.19 (m, 3H), 6.99-6.92 (m, 2H); Diastereomer 2: 7.42-7.35 (m, 2H), 7.33-7.15 (m, 5H), 6.99-6.92 (m, 2H).

Aufarbeitung

  1. customthe precipitate formed
  2. filtrationfiltered
  3. washwashed
  4. customdried
  5. customThe diastereomers are separated by preparative HPLC (method B)
  6. custom52.8 mg of Diastereomer 1 (Example 49) and 42.0 mg of Diastereomer 2 (Example 56) are obtained as a powder

Quellen und Nachweise

ORD-Eintrag
ord-b85e78a599bd45b0b555cdc6586ca07e
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822474B2

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