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

반응식

HRID 70102 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.[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

참가 물질

7

반응물 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

생성물 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

시약·촉매·용매 2

HCID 679Dimethyl Sulfoxide용매HCID 312751,4-Dioxane용매

반응 조건

온도
120 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-b85e78a599bd45b0b555cdc6586ca07e
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08822474B2

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