Cyclobutanone → 4-(4-(2-Cyanopropan-2-ylamino)-2-fluorophenyl)-N,N-dimethylbutanamide

HRID 1192873Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][C:11]([N:13]([CH3:15])[CH3:14])=[O:12])=[C:4]([F:16])[CH:3]=1.[C:17]1(=O)[CH2:20][CH2:19]C1.C[Si]([C:26]#[N:27])(C)C>C(OCC)(=O)C>[C:26]([C:20]([NH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][C:11]([N:13]([CH3:15])[CH3:14])=[O:12])=[C:4]([F:16])[CH:3]=1)([CH3:19])[CH3:17])#[N:27]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 4-(4-Amino-2-fluorophenyl)-N,N-dimethylbutanamide (76) (10 mg, 0.05 mmol), cyclobutanone (6 mg, 0.09 mmol) and trimethylsilyl cyanide (TMSCN, 9 mg, 0.09 mmol) was heated to 80° C. and stirred for 15 h. To the medium was added ethyl acetate (2×20 mL) and then washed with water (2×20 mL). The organic layer was dried over MgSO4 and concentrated and the residue was purified with silica gel column chromatography (dichloromethane:acetone, 9:1) to give 4-(4-(2-Cyanopropan-2-ylamino)-2-fluorophenyl)-N,N-dimethylbutanamide (75) (12 mg, 89%): 1H NMR δ 7.04 (dd, 1H, J=8.0, 7.8 Hz), 6.36 (dd, 1H, J=8.0, 2.3 Hz), 6.32 (dd, 1H, J=11.6, 2.3 Hz), 4.08 (br s, 1H), 2.96 (s, 3H), 2.93 (s, 3H), 2.77-2.81 (m, 2H), 2.61 (t, 2H, J=7.4 Hz) 2.35-2.38 (m, 2H), 2.31 (t, 2H, J=7.6 Hz), 2.10-2.37 (m, 2H), 1.87-1.95 (m, 2H).

Workup

washwashed with water (2×20 mL)
dry with materialThe organic layer was dried over MgSO4
concentrationconcentrated
customthe residue was purified with silica gel column chromatography (dichloromethane:acetone, 9:1)

Sources & evidence

ORD record: ord-cb91ff5e4e80450da72fa9fb369bc1d4
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680291B2

Reaction notes

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