Cyclobutanone → N,N-Dimethyl 4-[4-(1-cyanocyclobutylamino)phenyl]butanamide

HRID 245035Notes

Reaction equation

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

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of N,N-Dimethyl 4-(4-aminophenyl)butanamide (Formula 47) (74 mg, 0.36 mmol), cyclobutanone (54 mg, 0.78 mmol) and TMSCN (77 mg, 0.78 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 N,N-Dimethyl 4-[4-(1-cyanocyclobutylamino)phenyl]butanamide (Formula 48) (58 mg, 57%) as a white solid. 1H NMR δ 7.07 (d, 2H, J=8.5 Hz), 6.59 (d, 2H, J=8.5 Hz), 3.94 (br s, 1H), 2.94 (s, 3H), 2.93 (s, 3H), 2.75-2.83 (m, 2H), 2.60 (t, 2H, J=7.6 Hz), 2.33-2.42 (m, 2H), 2.30 (t, 2H, J=7.6 Hz), 2.11-2.28 (m, 2H), 1.93 (p, 2H, J=7.6 Hz).

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-c8637d1c00034a32afc0349b5319356b
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658681B2

Reaction notes

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