Sodium cyanoborohydride → 5-bromo-1-methyl-3-(5-(oxetan-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridin-2(1H)-one

HRID 1919055Notes

Reaction equation

HRID 1919055 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:19]=[C:14]3[CH2:15][NH:16][CH2:17][CH2:18][N:13]3[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[O:20]1[CH2:23][C:22](=O)[CH2:21]1.C([BH3-])#N.[Na+].C(Cl)Cl.C(OCC)C.CO>CO.[Cl-].[Zn+2].[Cl-]>[Br:1][C:2]1[CH:3]=[C:4]([NH:10][C:11]2[CH:19]=[C:14]3[CH2:15][N:16]([CH:22]4[CH2:23][O:20][CH2:21]4)[CH2:17][CH2:18][N:13]3[N:12]=2)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1

Participants

7

Reactant 4

HCID 5003444Sodium cyanoborohydrideHCID 150242543-OxetanoneHCID 22565053DCM ether MeOHHCID 580437855-Bromo-1-methyl-3-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridin-2(1H)-one

Product 1

HCID 580441695-bromo-1-methyl-3-(5-(oxetan-3-yl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridin-2(1H)-oneYield 34%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent2×

Conditions

Temperature
48 °C

Procedure

Following Example 214b, 5-bromo-1-methyl-3-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazin-2-ylamino)pyridin-2(1H)-one 126a (250 mg, 0.78 mmol), oxetan-3-one (600 mg, 8.3 mmol) were dissolved in methanol (8 mL). Sodium cyanoborohydride (148 mg, 3 mmol) and zinc chloride (165 mg, 1.5 mmol) in methanol (8 mL) was added, and the reaction was heated at 48° C. for 12 hours. Work-up and flash column chromatography (silica, 60:35:5 methylene chloride/diethyl ether/methanol) afford a 34% yield (100 mg) of 252a as a light green solid: MS (ESI+) m/z 382.1 (M+H).

Sources & evidence

ORD record
ord-cb2ae82d474042a1b0e9165845abd697
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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