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

HRID 718770Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 718770
[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

Komponenten

5

Edukt 3

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 80711,2-DimethoxyethaneLösungsmittel

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-01f44aef68d04fbb98e4fe0282189a5e
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09193744B2

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