Sodium hydride → 6-(Bis(4-methoxybenzyl)amino)-4-methylnicotinonitrile

HRID 874688

반응식

HRID 874688 반응식
[NH2:1][C:2]1[CH:9]=[C:8]([CH3:10])[C:5]([C:6]#[N:7])=[CH:4][N:3]=1.[H-].[Na+].[CH3:13][O:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19]Cl)=[CH:17][CH:16]=1>CN(C)C=O>[CH3:13][O:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][N:1]([CH2:19][C:18]2[CH:21]=[CH:22][C:15]([O:14][CH3:13])=[CH:16][CH:17]=2)[C:2]2[CH:9]=[C:8]([CH3:10])[C:5]([C:6]#[N:7])=[CH:4][N:3]=2)=[CH:17][CH:16]=1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 699934-Methyloxybenzyl chlorideHCID 99641036-Amino-4-methylnicotinonitrile

생성물 1

HCID 1176660526-(Bis(4-methoxybenzyl)amino)-4-methylnicotinonitrile수율 95%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
0 °C

실험 절차

To a stirred mixture of 6-amino-4-methylnicotinonitrile 4-2, which was prepared by using a similar method described in WO199618616 (669 mg, 5.02 mmol) and N,N-dimethylformamide (15.0 mL) at 0° C. under an atmosphere of nitrogen gas was added sodium hydride (60% dispersion in mineral oil; 605 mg, 15.1 mmol). To the mixture was added 4-methoxybenzyl chloride (1.70 mL, 12.5 mmol) at 0° C. The resulting mixture was stirred at 0° C. for 2 hours under an atmosphere of nitrogen gas. The reaction mixture was quenched with methanol (5.0 mL) and concentrated under reduced pressure. To the resulting residue was added water (50 mL) and the resulting mixture was extracted with dichloromethane (60 mL, 30 mL×2). The combined organic extracts were washed with brine (30 mL), dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by column chromatography (silica gel 30 g, step gradient eluting with 10:1, 5:1, and 2:1 hexane/ethyl acetate) to give 1.78 g (95%) of 4-3 as a pale brown solid: 1H NMR (300 MHz, CDCl3) δ 8.39 (1H, s), 7.11 (4H, m), 6.85 (4H, m), 6.32 (1H, s), 4.71 (4H, br s), 3.79 (6H, s), 2.33 (3H, s); ESI-MS m/z 374 [C23H23N3O2+H]+.

후처리

  1. customwas prepared
  2. customThe reaction mixture was quenched with methanol (5.0 mL)
  3. concentrationconcentrated under reduced pressure
  4. additionTo the resulting residue was added water (50 mL)
  5. extractionthe resulting mixture was extracted with dichloromethane (60 mL, 30 mL×2)
  6. washThe combined organic extracts were washed with brine (30 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe resulting residue was purified by column chromatography (silica gel 30 g, step gradient eluting with 10:1, 5:1, and 2:1 hexane/ethyl acetate)

출처 및 근거

ORD 기록
ord-33577ac376f74829aa55800dc4642f10
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08980916B2

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