Citric Acid → HCID 59279494, compound

HRID 1098156Notes

Reaction equation

[H-].[Na+].[OH:3][C@@H:4]([CH2:9][O:10][C@H:11]([CH3:15])[CH2:12][O:13][CH3:14])[C:5]([O:7][CH3:8])=[O:6].Cl[C:17]1[N:22]=[CH:21][N:20]=[C:19]2[N:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[Cl:32])[N:24]=[CH:25][C:18]=12.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C1COCC1.C(OCC)(=O)C>[Cl:32][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][C:26]=1[N:23]1[C:19]2=[N:20][CH:21]=[N:22][C:17]([O:3][C@@H:4]([CH2:9][O:10][C@H:11]([CH3:15])[CH2:12][O:13][CH3:14])[C:5]([O:7][CH3:8])=[O:6])=[C:18]2[CH:25]=[N:24]1

Participants

Conditions

Temperature: 0 °C

Procedure

Sodium hydride (94 mg, 2.34 mmol) was added to (S)-methyl 2-hydroxy-3-((R)-1-methoxypropan-2-yloxy)propanoate (Intermediate Y6) (300 mg, 1.56 mmol) in anhydrous THF (5 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 10 minutes and then 4-chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine (Intermediate B1) (538 mg, 2.03 mmol) was added. The reaction mixture was allowed to warm up to room temperature and stirred for 30 minutes. The reaction mixture was neutralized with 1M citric acid, diluted with ethyl acetate (20 mL), and washed sequentially with water (10 mL) and saturated brine (5 mL). The organic layer was dried (MgSO4) and evaporated. The crude product was purified by flash silica chromatography, eluting with 0-100% ethyl acetate in isohexane to afford the product (358 mg, 54.5%).

Workup

temperatureto warm up to room temperature
stirringstirred for 30 minutes
washwashed sequentially with water (10 mL) and saturated brine (5 mL)
dry with materialThe organic layer was dried (MgSO4)
customevaporated
customThe crude product was purified by flash silica chromatography
washeluting with 0-100% ethyl acetate in isohexane

Sources & evidence

ORD record: ord-53d775fa015b4437980e11ccf1190a94
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08143263B2

Reaction notes

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