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

Reaction equation

HRID 70101 reaction equation
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

Participants

6

Reactant 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

Product 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

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-1e7cedad7cd441eabe301eec4eeae6c0
Source dataset
uspto-grants-2014_09
Patent number
US08822474B2

Linked notes

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