Sodium hydride → 2-(1-(4-fluorophenyl)-7,8-dihydro-1H-benzo[f]indazol-5(6H)-ylidene)acetonitrile

HRID 718770노트

반응식

HRID 718770 반응식
[H-].[Na+].[C:3]([CH2:5]P(=O)(OCC)OCC)#[N:4].[F:14][C:15]1[CH:20]=[CH:19][C:18]([N:21]2[C:29]3[C:24](=[CH:25][C:26]4[C:33](=O)[CH2:32][CH2:31][CH2:30][C:27]=4[CH:28]=3)[CH:23]=[N:22]2)=[CH:17][CH:16]=1>COCCOC>[F:14][C:15]1[CH:16]=[CH:17][C:18]([N:21]2[C:29]3[C:24](=[CH:25][C:26]4[C:33](=[CH:5][C:3]#[N:4])[CH2:32][CH2:31][CH2:30][C:27]=4[CH:28]=3)[CH:23]=[N:22]2)=[CH:19][CH:20]=1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 75676Diethyl (cyanomethyl)phosphonateHCID 867223541-(4-fluorophenyl)-7,8-dihydro-1H-benzo[f]indazol-5(6H)-one

생성물 1

HCID 867223532-(1-(4-fluorophenyl)-7,8-dihydro-1H-benzo[f]indazol-5(6H)-ylidene)acetonitrile

시약·촉매·용매 1

HCID 80711,2-Dimethoxyethane용매

실험 절차

To a stirred suspension of sodium hydride (60% in oil, 12.0 g, 300 mmol) in DME (600 mL) was added diethyl (cyanomethyl)phosphonate (53.1 g, 300 mmol) at a dropwise rate under nitrogen. After gas evolution ceases (about 30 min), 1-(4-fluorophenyl)-7,8-dihydro-1H-benzo[f]indazol-5(6H)-one (4, R1=4-Fluorophenyl) (42.0 g, 150 mmol) was added in portions. The reaction was stirred at rt for about 3 h, then the reaction was concentrated under reduced pressure and the residue was dissolved with EtOAc (1000 mL) and sat. aq. NH4Cl (500 mL). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified on silica gel (330 g) using a gradient of 70-100% DCM in heptane. Product fractions were combined and concentrated under reduced pressure to yield 2-(1-(4-fluorophenyl)-7,8-dihydro-1H-benzo[f]indazol-5(6H)-ylidene)acetonitrile (27, R1=4-Fluorophenyl) as a 2:1 mixture of isomers (42.9 g, 94%); LC/MS, method 3, Rt=2.57 min, MS m/z 304 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.60 (bs, 0.33H), 8.50 (d, J=0.9 Hz, 0.33H), 8.42 (bs, 0.67H), 8.40 (d, J=0.9 Hz, 0.67H), 7.88-7.76 (m, 2H), 7.67 (bs, 0.33H), 7.64 (bs, 0.67H), 7.52-7.36 (m, 2H), 6.32 (t, J=1.6 Hz, 0.67H), 5.73 (t, J=1.5 Hz, 0.33H), 3.03-2.95 (m, 2H), 2.90-2.83 (m, 1H), 2.71-2.64 (m, 1H), 1.93-1.81 (m, 2H).

후처리

  1. concentrationthe reaction was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved with EtOAc (1000 mL) and sat. aq. NH4Cl (500 mL)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified on silica gel (330 g)
  7. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-01f44aef68d04fbb98e4fe0282189a5e
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09193744B2

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