Ammonia → 2-(4-((2-(3-Chlorophenyl)-6-(trifluoromethyl)pyridin-4-yl)amino)phenyl)acetamide

HRID 1508816Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22](OCC)=[O:23])=[CH:17][CH:16]=3)[CH:11]=[C:10]([C:27]([F:30])([F:29])[F:28])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[Cl-].[NH4+:32].N>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([NH:14][C:15]3[CH:16]=[CH:17][C:18]([CH2:21][C:22]([NH2:32])=[O:23])=[CH:19][CH:20]=3)[CH:11]=[C:10]([C:27]([F:28])([F:30])[F:29])[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A 10-mL vial was charged with ethyl 2-(4-((2-(3-chlorophenyl)-6-(trifluoromethyl)pyridin-4-yl)amino)phenyl)acetate (0.064 g, 0.15 mmol) and ammonium chloride (0.024 g, 0.44 mmol) in methanol (2 mL). To this mixture was added NH3 (4.2 mL, 7N in methanol, 29.4 mmol). The vial was sealed and the resulting mixture was stirred at 100° C. for 42 h. After this time, the crude reaction solution concentrated under reduced pressure. The residue absorbed on silica (2 g) then purified by chromatography on silica using dichloromethane/methanol (10:0 to 9:1) as eluent to afford the title compound (0.027 g, 46%) as a light brown solid. MW=405.80. M.p. 97-99° C. 1H NMR (DMSO-d6, 500 MHz) δ 9.39 (s, 1H), 7.99-7.97 (m, 1H), 7.91-7.86 (m, 1H), 7.57-7.51 (m, 3H), 7.46 (br s, 1H), 7.33-7.29 (m, 2H), 7.27-7.23 (m, 2H), 7.19 (d, J=2.0 Hz, 1H), 6.88 (br s, 1H), 3.37 (s, 2H); APCI MS m/z 406 [M+H]+.

Workup

customThe vial was sealed
customAfter this time, the crude reaction solution
concentrationconcentrated under reduced pressure
customThe residue absorbed on silica (2 g)
customthen purified by chromatography on silica

Sources & evidence

ORD record: ord-43d5eb96b9dc482b8ab43abc75aba80a
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09221843B2

Reaction notes

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