Sodium hydride → tert-Butyl {2-[1-(6-cyanopyridin-2-ylmethyl)-2-(1-methylcyclopropyl)-2-oxoethyl]-5-methoxyphenyl}carbamate

HRID 2409991Notes

Reaction equation

HRID 2409991 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:17][C:18]([C:20]2([CH3:23])[CH2:22][CH2:21]2)=[O:19])=[C:7]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[CH:8]=1.[H-].[Na+].Cl[CH2:27][C:28]1[N:33]=[C:32]([C:34]#[N:35])[CH:31]=[CH:30][CH:29]=1.[Cl-].[NH4+]>CN(C)C=O.O>[C:34]([C:32]1[N:33]=[C:28]([CH2:27][CH:17]([C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][C:7]=2[NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:13])[CH3:14])[C:18]([C:20]2([CH3:23])[CH2:22][CH2:21]2)=[O:19])[CH:29]=[CH:30][CH:31]=1)#[N:35]

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 103518756-Chloromethyl-2-cyanopyridineHCID 86703301tert-Butyl {5-methoxy-2-[2-(1-methylcyclopropyl)-2-oxoethyl]phenyl}carbamate

Product 1

HCID 86703308tert-Butyl {2-[1-(6-cyanopyridin-2-ylmethyl)-2-(1-methylcyclopropyl)-2-oxoethyl]-5-methoxyphenyl}carbamateYield 66.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Under an argon atmosphere, to a solution of tert-butyl {5-methoxy-2-[2-(1-methylcyclopropyl)-2-oxoethyl]phenyl}carbamate (300 mg) in N,N-dimethylformamide (3.1 mL) was added sodium hydride (50-72% in oil, 50 mg) under ice-cooling, and the mixture was stirred for 1 hour. 6-(Chloromethyl)pyridine-2-carbonitrile (158 mg) was added thereto in one portion, and the mixture was gradually warmed to room temperature. 13 Hours later, to the reaction mixture were added a saturated aqueous ammonium chloride solution and water, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine successively, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane) to obtain the title compound (271 mg). 1H-NMR (CDCl3) δ ppm: 0.62-0.73 (2H, m), 1.22-1.30 (5H, m), 1.57 (9H, s), 3.21 (1H, dd, J=8.2, 15.7 Hz), 3.54 (1H, dd, J=6.7, 15.7 Hz), 3.78 (3H, s), 4.68-4.78 (1H, m), 6.54-6.61 (1H, m), 6.95 (1H, d, J=8.5 Hz), 7.18-7.25 (1H, m), 7.33-7.40 (1H, m), 7.48-7.55 (1H, m), 7.64 (1H, t, J=7.8 Hz), 7.82 (1H, br s).

Workup

  1. temperaturecooling
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with water and saturated brine successively
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (eluting solvent: ethyl acetate-hexane)

Sources & evidence

ORD record
ord-1dc48449d05643c18a1cb5ecc43c39af
Source dataset
uspto-grants-2014_08
Patent number
US08815903B2

Reaction notes

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