Water → 5-Bromo-1-methyl-3-(6-(oxetan-3-yl)-5,6,7,8-tetrahydro-1,6-naphthyridin-2-ylamino)pyridin-2(1H)-one

HRID 1919014Notes

Reaction equation

HRID 1919014 reaction equation
Cl.[Br:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[CH:21]=[CH:20][C:19]3[CH2:18][NH:17][CH2:16][CH2:15][C:14]=3[N:13]=2)[C:6](=[O:10])[N:7]([CH3:9])[CH:8]=1.[O:22]1[CH2:25][C:24](=O)[CH2:23]1.[BH3-]C#N.[Na+].O>CO.[Cl-].[Zn+2].[Cl-]>[Br:2][C:3]1[CH:4]=[C:5]([NH:11][C:12]2[CH:21]=[CH:20][C:19]3[CH2:18][N:17]([CH:24]4[CH2:25][O:22][CH2:23]4)[CH2:16][CH2:15][C:14]=3[N:13]=2)[C:6](=[O:10])[N:7]([CH3:9])[CH:8]=1

Participants

7

Reactant 4

HCID 962WaterHCID 5003444Sodium cyanoborohydrideHCID 150242543-OxetanoneHCID 670165045-bromo-1-methyl-3-(5,6,7,8-tetrahydro-1,6-naphthyridin-2-ylamino)pyridine-2(1H)-one hydrochloride

Product 1

HCID 580437985-Bromo-1-methyl-3-(6-(oxetan-3-yl)-5,6,7,8-tetrahydro-1,6-naphthyridin-2-ylamino)pyridin-2(1H)-oneYield 89%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 5-bromo-1-methyl-3-(5,6,7,8-tetrahydro-1,6-naphthyridin-2-ylamino)pyridine-2(1H)-one hydrochloride 205a (800 mg, 2.16 mmol), oxetan-3-one (778 mg, 10.8 mmol), NaBH3CN (681 mg, 10.8 mmol), and zinc chloride (1.47 g, 10.8 mmol) in methanol (30 mL) was stirred for 4 hours at 50° C. The mixture was added to H2O (30 mL) and extracted with DCM (50 mL×3). The organic layers were concentrated under reduced pressure. The residue was purified by column chromatography eluting with 10:1 ethyl acetate/methanol to give 219a as a yellow solid (750 mg, 89%). MS: [M+H]+ 391.

Workup

  1. extractionextracted with DCM (50 mL×3)
  2. concentrationThe organic layers were concentrated under reduced pressure
  3. customThe residue was purified by column chromatography
  4. washeluting with 10:1 ethyl acetate/methanol

Sources & evidence

ORD record
ord-1afbe31aac324b86b9de2ba950216f73
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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