Water → 5-Bromo-1-methyl-3-(5-(3-(oxetan-3-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)pyridin-2-ylamino)pyridine-2(1H)-one

HRID 592694Notes

Reaction equation

[CH:1]12[N:8]([C:9]3[CH:10]=[CH:11][C:12]([NH:15][C:16]4[C:17](=[O:24])[N:18]([CH3:23])[CH:19]=[C:20]([Br:22])[CH:21]=4)=[N:13][CH:14]=3)[CH:5]([CH2:6][CH2:7]1)[CH2:4][NH:3][CH2:2]2.[O:25]1[CH2:28][C:27](=O)[CH2:26]1.[BH3-]C#N.[Na+].O>CO.[Cl-].[Zn+2].[Cl-]>[Br:22][C:20]1[CH:21]=[C:16]([NH:15][C:12]2[CH:11]=[CH:10][C:9]([N:8]3[CH:5]4[CH2:6][CH2:7][CH:1]3[CH2:2][N:3]([CH:27]3[CH2:28][O:25][CH2:26]3)[CH2:4]4)=[CH:14][N:13]=2)[C:17](=[O:24])[N:18]([CH3:23])[CH:19]=1

Participants

Conditions

Temperature: 50 °C

Procedure

A mixture of 152d (676 mg, 1.7 mmol), oxetan-3-one (251 mg, 3.5 mmol), NaBH3CN (274 mg, 4.4 mmol), and zinc chloride (592 mg, 4.4 mmol) in methanol (30 mL) was stirred at 50° C. for 5 hours. water was added and the mixture was concentrated under reduced pressure. The residue was extracted with dichloromethane three times. The combined extract was concentrated under reduced pressure to afford crude 152e as a yellow solid (650 mg, 84%), which was used in the next step without further purification. MS-ESI: [M+H]+ 446.2.

Workup

concentrationthe mixture was concentrated under reduced pressure
extractionThe residue was extracted with dichloromethane three times
extractionThe combined extract
concentrationwas concentrated under reduced pressure

Sources & evidence

ORD record: ord-ec956e354a5c46fcbcffe8f63ca1790d
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09238655B2

Reaction notes

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