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}-4-METHYL-PENTAN-1-OL

HRID 1641347Notes

Reaction equation

HRID 1641347 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]([CH2:31][OH:32])[CH2:27][CH:28]([CH3:30])[CH3:29].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]([CH2:27][CH:28]([CH3:30])[CH3:29])[CH2:31][OH: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

Participants

6

Reactant 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 2724002D(-)-LeucinolHCID 594758954-Chloro-2-[4-(4-chloro-phenyl)-piperazin-1-yl]-6,7-dihydro-thieno[3,2-d]pyrimidine 5-oxide

Product 1

HCID 59708497(R)-2-{2-[4-(4-CHLORO-PHENYL)-PIPERAZIN-1-YL]-5-OXO-6,7-DIHYDRO-5H-5lambda4-THIENO [3,2-D]PYRIMIDIN-4-YLAMINO}-4-METHYL-PENTAN-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), 134.53 mg D-leucinol 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). 43.9 mg of Diastereomer 1 (Example 53) and 46.9 mg of Diastereomer 2 (Example 69) are obtained as an oil. Analytical HPLC-MS (method B): Diastereomer 1, RT=1.86 min, Diastereomer 2, RT=1.90 min.

Workup

  1. customthe precipitate formed
  2. filtrationfiltered
  3. washwashed
  4. customdried
  5. customThe diastereomers are separated by preparative HPLC (method B)
  6. custom43.9 mg of Diastereomer 1 (Example 53) and 46.9 mg of Diastereomer 2 (Example 69) are obtained as an oil

Sources & evidence

ORD record
ord-53585b0d55a74c5b9c29aa3de8595fc5
Source dataset
uspto-grants-2012_02
Patent number
US08114878B2

Reaction notes

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