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}-3-METHYL-BUTAN-1-OL

HRID 70101

反応式

HRID 70101 の反応式
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.[NH2:25][C@H:26]([CH:29]([CH3:31])[CH3:30])[CH2:27][OH:28].C(N(C(C)C)CC)(C)C.O>O1CCOCC1>[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:25][C@H:26]([CH:29]([CH3:31])[CH3:30])[CH2:27][OH:28])[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

参加物

6

反応物 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 6950587D-ValinolHCID 594758954-Chloro-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-6,7-dihydro-thieno[3,2-d]pyrimidine 5-oxide

生成物 1

HCID 59475912(R)-2-{2-[4-(4-CHLORO-PHENYL)-PIPERAZIN-1-YL]-5-OXO-6,7-DIHYDRO-5H-5lambda4-THIENO-[3,2-D]PYRIMIDIN-4-YLAMINO}-3-METHYL-BUTAN-1-OL

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
120 °C

実験手順

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), 118.43 mg (R)-(−)-2-amino-3-methyl-butan-1-ol and 197.52 μl diisopropylethylamine are placed in 4 ml dioxane, and the mixture is 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). 25.5 mg of Diastereomer 1 (Example 54) and 40.5 mg of Diastereomer 2 (Example 57) are obtained as a powder. Analytical HPLC (method A): Diastereomer I: RT=3.61 min; Diastereomer 2, RT=3.71 min.

後処理

  1. customthe precipitate formed
  2. filtrationfiltered
  3. washwashed
  4. customdried
  5. customThe diastereomers are separated by preparative HPLC (method B)
  6. custom25.5 mg of Diastereomer 1 (Example 54) and 40.5 mg of Diastereomer 2 (Example 57) are obtained as a powder

出典と根拠

ORDレコード
ord-1e7cedad7cd441eabe301eec4eeae6c0
出典データセット
uspto-grants-2014_09
特許番号
US08822474B2

関連ノート

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