Sodium cyanoborohydride → 5-Bromo-1-methyl-3-(2-(oxetan-3-yl)-1,2,3,4-tetrahydroisoquinolin-6-ylamino)pyrazin-2(1H)-one

HRID 1919019Notes

Reaction equation

HRID 1919019 reaction equation
[Br:1][C:2]1[N:3]=[C:4]([NH:10][C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][CH:20]=2)[CH2:17][NH:16][CH2:15][CH2:14]3)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1.[O:21]1[CH2:24][C:23](=O)[CH2:22]1.[BH3-]C#N.[Na+]>CO.[Cl-].[Zn+2].[Cl-]>[Br:1][C:2]1[N:3]=[C:4]([NH:10][C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][CH:20]=2)[CH2:17][N:16]([CH:23]2[CH2:24][O:21][CH2:22]2)[CH2:15][CH2:14]3)[C:5](=[O:9])[N:6]([CH3:8])[CH:7]=1

Participants

6

Reactant 3

HCID 5003444Sodium cyanoborohydrideHCID 150242543-OxetanoneHCID 580437085-Bromo-1-methyl-3-(1,2,3,4-tetrahydroisoquinolin-6-ylamino)pyrazin-2(1H)-one

Product 1

HCID 580442615-Bromo-1-methyl-3-(2-(oxetan-3-yl)-1,2,3,4-tetrahydroisoquinolin-6-ylamino)pyrazin-2(1H)-one

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent

Procedure

A mixture of 5-bromo-1-methyl-3-(1,2,3,4-tetrahydroisoquinolin-6-ylamino)pyrazin-2(1H)-one 221a (2.75 g, 7.5 mmol), oxetan-3-one (2.5 g, 37.5 mmol), NaBH3CN (4.75 g, 22.5 mmol) and zinc chloride (5 g, 37.5 mmol) in methanol (125 ml) was stirred for 4 hours at room temperature. The mixture was filtered and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography eluting with 20:1 DCM/methanol to 222a (0.76 g, 25.9%). LC/MS: m/z 392 (M+H)+

Workup

  1. filtrationThe mixture was filtered
  2. concentrationthe filtrate was concentrated under reduced pressure
  3. customThe residue was purified by column chromatography
  4. washeluting with 20:1 DCM/methanol to 222a (0.76 g, 25.9%)

Sources & evidence

ORD record
ord-89c8471ea8724a4b87bd3b86ee3b3e75
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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