Sodium hydride → 1-(((5S,7S)-3-((4-bromopyridin-2-yl)methyl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile

HRID 715543Notes

Reaction equation

HRID 715543 reaction equation
[CH3:1][C@:2]1([CH2:13][N:14]2[C:18]3[CH:19]=[C:20]([C:23]#[N:24])[CH:21]=[CH:22][C:17]=3[N:16]=[CH:15]2)[CH2:12][CH2:11][CH2:10][C@:4]2([O:8][C:7](=[O:9])[NH:6][CH2:5]2)[CH2:3]1.[H-].[Na+].[Br:27][C:28]1[CH:33]=[CH:32][N:31]=[C:30]([CH2:34]Br)[CH:29]=1>CN(C)C=O.[NH4+].[Cl-]>[Br:27][C:28]1[CH:33]=[CH:32][N:31]=[C:30]([CH2:34][N:6]2[CH2:5][C@@:4]3([CH2:10][CH2:11][CH2:12][C@@:2]([CH2:13][N:14]4[C:18]5[CH:19]=[C:20]([C:23]#[N:24])[CH:21]=[CH:22][C:17]=5[N:16]=[CH:15]4)([CH3:1])[CH2:3]3)[O:8][C:7]2=[O:9])[CH:29]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 18986082HCID 18986082, compoundHCID 712269671-(((5S,7S)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile

Product 1

HCID 712276681-(((5S,7S)-3-((4-bromopyridin-2-yl)methyl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrileYield 93%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of 1-{[(5S,7S)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]dec-7-yl]methyl}-1H-benzimidazole-6-carbonitrile (1.0 g, 3.08 mmol) in N,N-Dimethylformamide (DMF) (7 mL) was added 60% sodium hydride in mineral oil (0.160 g, 4.01 mmol) and stirred for 30 minutes. To the mixture was added 4-bromo-2-(bromomethyl)pyridine (0.928 g, 3.70 mmol) and stirred overnight. The reaction was diluted with saturated NH4Cl and extracted with ethyl acetate (3×). The combined organic extracts were washed with saturated NaCl (2×), dried over Na2SO4, filtered, and concentrated. The residue was purified via silica gel chromatography (ISCO, 120 g silica, 60 mL/min, 0-10% MeOH/CH2Cl2 over 45 min) to afford 1-(((5S,7S)-3-((4-bromopyridin-2-yl)methyl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile (1.41 g, 93%). MS (m/z) 494.1 (M+).

Workup

  1. stirringstirred overnight
  2. extractionextracted with ethyl acetate (3×)
  3. washThe combined organic extracts were washed with saturated NaCl (2×)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified via silica gel chromatography (ISCO, 120 g silica, 60 mL/min, 0-10% MeOH/CH2Cl2 over 45 min)

Sources & evidence

ORD record
ord-fb6632ecf462468fb75ff3b88df4483f
Source dataset
uspto-grants-2015_11
Patent number
US09187464B2

Reaction notes

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