Ammonia → (2S,4R)-1-{2-[4-(4-chloro-phenyl)-piperazin-1-yl]-5-oxo-6,7-dihydro-5H-5lambda4-thieno[3,2-d]pyrimidin-4-yl}-4-hydroxy-pyrrolidine-2-carboxylic acid amide

HRID 70100Notes

Reaction equation

HRID 70100 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]3[N:15]=[C:16]([N:24]4[CH2:28][C@H:27]([OH:29])[CH2:26][C@H:25]4[C:30](O)=[O:31])[C:17]4[S:22](=[O:23])[CH2:21][CH2:20][C:18]=4[N:19]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C([N:36](C(C)C)CC)(C)C.N.O>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:9][CH2:10][N:11]([C:14]3[N:15]=[C:16]([N:24]4[CH2:28][C@H:27]([OH:29])[CH2:26][C@H:25]4[C:30]([NH2:36])=[O:31])[C:17]4[S:22](=[O:23])[CH2:21][CH2:20][C:18]=4[N:19]=3)[CH2:12][CH2:13]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 222AmmoniaHCID 962WaterHCID 81531DiisopropylethylamineHCID 59708417(2S,4R)-1-{2-[4-(4-chloro-phenyl)-piperazin-1-yl]-5-oxo-6,7-dihydro-5H-5lambda4-thieno[3,2-d]pyrimidin-4-yl}-4-hydroxy-pyrrolidine-2-carboxylic acid

Product 1

HCID 59708385(2S,4R)-1-{2-[4-(4-chloro-phenyl)-piperazin-1-yl]-5-oxo-6,7-dihydro-5H-5lambda4-thieno[3,2-d]pyrimidin-4-yl}-4-hydroxy-pyrrolidine-2-carboxylic acid amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

80 mg (2S,4R)-1-{2-[4-(4-chloro-phenyl)-piperazin-1-yl]-5-oxo-6,7-dihydro-5H-5λ4-thieno[3,2-d]pyrimidin-4-yl}-4-hydroxy-pyrrolidine-2-carboxylic acid are placed in 2.00 ml N,N-dimethylformamide and combined with 86.77 mg diisopropylethylamine and 76.20 mg O-(7-azabenzotriazol-1-yl-)-N,N,N′,N′-tetramethyluronium-hexafluorophosphate (HATU). The mixture is stirred for 0.25 hours at ambient temperature, then 334 μl ammonia solution (0.5 M in dioxane) are added. The reaction mixture is stirred for 3 hours at ambient temperature, then acidified and water is added. The diastereomers are separated by preparative HPLC (method B). 11.7 mg of Diastereomer 1 and 15.3 mg of Diastereomer 2 (Example 128) are obtained as powders. Analytical HPLC-MS (method A): Diastereomer 1, RT=1.49 min, Diastereomer 2. RT=1.49 min.

Workup

  1. stirringThe reaction mixture is stirred for 3 hours at ambient temperature
  2. customThe diastereomers are separated by preparative HPLC (method B)
  3. custom11.7 mg of Diastereomer 1 and 15.3 mg of Diastereomer 2 (Example 128) are obtained as powders

Sources & evidence

ORD record
ord-b64902e08771414299f919f516056220
Source dataset
uspto-grants-2014_09
Patent number
US08822474B2

Reaction notes

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