Water → (S)-5-bromo-3-(5-(2-ethyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)-1-methylpyridin-2(1H)-one
Reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][NH:20][CH2:19][C@@H:18]3[CH2:23][CH3:24])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[O:25]1[CH2:28][C:27](=O)[CH2:26]1.[BH3-]C#N.[Na+].O>CO.[Cl-].[Zn+2].[Cl-]>[Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][N:20]([CH:27]4[CH2:28][O:25][CH2:26]4)[CH2:19][C@@H:18]3[CH2:23][CH3:24])=[CH:13][N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Conditions
- Temperature
- 50 °C
Procedure
A mixture of 161d (263 mg, 0.67 mmol), oxetan-3-one (96 mg, 1.34 mmol), NaBH3CN 104 mg, 1.68 mmol), and zinc chloride (227 mg, 1.68 mmol) in methanol (10 mL) was stirred at 50° C. for 5 hours. Water (10 mL) was then added to the reaction. The resulting mixture was concentrated under reduced pressure. The residue was extracted with dichloromethane three times. The combined organic layer was concentrated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with 50:1 dichloromethane/methanol to afford 161e (203 mg, 68%). MS: [M+H]+ 448.
Workup
- concentrationThe resulting mixture was concentrated under reduced pressure
- extractionThe residue was extracted with dichloromethane three times
- concentrationThe combined organic layer was concentrated under reduced pressure
- customthe residue was purified by silica-gel column chromatography
- washeluting with 50:1 dichloromethane/methanol
Sources & evidence
- ORD record
- ord-e5407f3743cb44618dd593a5035f6a46
- Source dataset
- uspto-grants-2014_12
- Patent number
- US08921353B2
Reaction notes
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