Sodium cyanoborohydride → (S)-5-Chloro-3-(5-(2-methyl-4-(oxetan-3-yl)piperazin-1-yl)pyridin-2-ylamino)pyridin-2(1H)-one

HRID 407743Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][NH:19][CH2:18][C@@H:17]3[CH3:22])=[CH:12][N:11]=2)[C:5](=[O:8])[NH:6][CH:7]=1.[O:23]1[CH2:26][C:25](=O)[CH2:24]1.[BH3-]C#N.[Na+]>CO.[Cl-].[Cl-].[Zn+2]>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([N:16]3[CH2:21][CH2:20][N:19]([CH:25]4[CH2:26][O:23][CH2:24]4)[CH2:18][C@@H:17]3[CH3:22])=[CH:12][N:11]=2)[C:5](=[O:8])[NH:6][CH:7]=1

Participants

Conditions

Temperature: 30 °C

Procedure

To a solution of 138b (1.0 g, 3.1 mmol) in methanol (35 mL) was added oxetan-3-one (669.6 mg, 9.3 mmol), NaBH3CN (585.9 mg, 9.3 mmol), and ZnCl2 (1.26 g, 9.3 mmol). The reaction was stirred at 30° C. for 2 h. The mixture was evaporated under reduced pressure and the residue diluted with water (20 mL). It was then extracted with dichloromethane (3×30 mL). The combined dichloromethane extract was concentrated under reduced pressure and the residue was purified by silica-gel column chromatography eluting with 40:1 ethyl acetate/methanol to afford 138c (291 mg, 25%) as a red solid. MS-ESI: [M+H]+ 376.3

Workup

customThe mixture was evaporated under reduced pressure
additionthe residue diluted with water (20 mL)
extractionIt was then extracted with dichloromethane (3×30 mL)
extractionThe combined dichloromethane extract
concentrationwas concentrated under reduced pressure
customthe residue was purified by silica-gel column chromatography
washeluting with 40:1 ethyl acetate/methanol

Sources & evidence

ORD record: ord-f894818b3a3e4bfa8626fc53060d5343
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08754077B2

Reaction notes

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