3-({[2-amino-5-(trifluoromethyl)phenyl]carbamoyl}methyl)-N-methoxy-N-methylcyclobutane-1-carboxamide → HCID 178502665, compound

HRID 2040660Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[NH:12][C:13]([CH2:15][CH:16]1[CH2:19][CH:18]([C:20]([N:22]([O:24][CH3:25])[CH3:23])=[O:21])[CH2:17]1)=O>CC(O)=O>[CH3:25][O:24][N:22]([CH3:23])[C:20]([CH:18]1[CH2:19][CH:16]([CH2:15][C:13]2[NH:1][C:2]3[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=3[N:12]=2)[CH2:17]1)=[O:21]

Participants

Conditions

Temperature: 125 °C

Procedure

A solution of the 3-({[2-amino-5-(trifluoromethyl)phenyl]carbamoyl}methyl)-N-methoxy-N-methylcyclobutane-1-carboxamide (0.82 g, 2.29 mmol) in AcOH (10 ml) was heated to reflux (˜125° C.) whilst stirring for 2.5 h. The reaction was monitored by LC MS. The reaction mixture was allowed to cool to RT and then evaporated in vacuo. The residue was dissolved in DCM (30 ml) and washed with sat. NaHCO3 (50 ml), dried over Na2SO4, filtered and evaporated. The crude was purified by silica gel column chromatography, eluting with MeOH:DCM (2:98-5:95) to give a yellow-brown oil (0.75 g, 94%); MS (ESI+) for C16H18F3N3O2 m/z 342.10[M+H]+; HPLC purity 97% (ret. time, 1.40 min); 1H NMR (500 MHz, MeOD) δH ppm 1.96-2.17 (2 H, m), 2.27-2.55 (2 H, m), 2.66-2.92 (1 H, m), 2.97-3.15 (2 H, m), 3.15-3.22 (3 H, m), 3.32-3.62 (1 H, m), 3.63-3.73 (3 H, m), 7.37-7.53 (1 H, m), 7.53-8.00 (2 H, m).

Workup

temperatureto cool to RT
customevaporated in vacuo
dissolutionThe residue was dissolved in DCM (30 ml)
washwashed with sat. NaHCO3 (50 ml)
dry with materialdried over Na2SO4
filtrationfiltered
customevaporated
customThe crude was purified by silica gel column chromatography
washeluting with MeOH:DCM (2:98-5:95)

Sources & evidence

ORD record: ord-3e4f10b5142a4622acaa20e07b4f0b8f
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08580762B2

Reaction notes

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