Cyclobutanone → 4-(4-(1-Cyanocyclobutylamino)-2-fluorophenyl)-N-methylbutanamide

HRID 1192869Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][C:11]([NH:13][CH3:14])=[O:12])=[C:4]([F:15])[CH:3]=1.[C:16]1(=O)[CH2:19][CH2:18][CH2:17]1.C[Si]([C:25]#[N:26])(C)C>C(OCC)(=O)C>[C:25]([C:16]1([NH:1][C:2]2[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][C:11]([NH:13][CH3:14])=[O:12])=[C:4]([F:15])[CH:3]=2)[CH2:19][CH2:18][CH2:17]1)#[N:26]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 4-(4-Amino-2-fluorophenyl)-N-methylbutanamide (80) (8 mg, 0.04 mmol), cyclobutanone (5 mg, 0.08 mmol) and trimethylsilyl cyanide (TMSCN, 8 mg, 0.08 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-(1-Cyanocyclobutylamino)-2-fluorophenyl)-N-methylbutanamide (79) (10 mg, 92%).

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-905785bdb8064407ab9b80d3547520c0
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08680291B2

Reaction notes

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