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

HRID 2409991노트

반응식

HRID 2409991 반응식
[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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-1dc48449d05643c18a1cb5ecc43c39af
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08815903B2

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