Ammonia → 2-(4-((2-(Cyclopentyloxy)-6-(trifluoromethyl)pyrimidin-4-yl)methyl)phenyl)acetamide

HRID 1508905Notes

Reaction equation

[CH:1]1([O:6][C:7]2[N:12]=[C:11]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([CH2:20][C:21]([O:23]C)=O)=[CH:16][CH:15]=3)[CH:10]=[C:9]([C:25]([F:28])([F:27])[F:26])[N:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH3:29]>CO>[CH:1]1([O:6][C:7]2[N:12]=[C:11]([CH2:13][C:14]3[CH:15]=[CH:16][C:17]([CH2:20][C:21]([NH2:29])=[O:23])=[CH:18][CH:19]=3)[CH:10]=[C:9]([C:25]([F:28])([F:27])[F:26])[N:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

Conditions

Temperature: 100 °C

Procedure

A 20-mL vial was charged with methyl 2-(4-((2-(cyclopentyloxy)-6-(trifluoromethyl)pyrimidin-4-yl)methyl)phenyl)acetate (0.150 g, 0.38 mmol) in methanol (2 mL). To this mixture was added NH3 (10.8 mL, 7N in methanol, 76.0 mmol). The vial was sealed and the resulting mixture was stirred at 100° C. for 23 h. The crude reaction solution concentrated under reduced pressure. The residue was purified by chromatography on silica using hexanes/ethyl acetate (10:0 to 0:10) as eluent followed by chromatography on silica using dichloromethane/methanol (10:0 to 96:4) as eluent to afford the title compound (0.066 g, 46%) as a white solid. MW=379.38. M.p. 130-132° C. 1H NMR (DMSO-d6, 500 MHz) δ 7.51 (s, 1H), 7.41 (br s, 1H), 7.26 (d, J=8.0 Hz, 2H), 7.20 (d, J=8.0 Hz, 2H), 6.83 (br s, 1H), 5.35 (septet, J=3.0 Hz, 1H), 4.10 (s, 2H), 3.33 (s, 2H), 2.00-1.90 (m, 2H), 1.77-1.66 (m, 4H), 1.65-1.55 (m, 2H); ESI MS m/z 380 [M+H]+.

Workup

customThe vial was sealed
customThe crude reaction solution
concentrationconcentrated under reduced pressure
customThe residue was purified by chromatography on silica

Sources & evidence

ORD record: ord-7bcfb17f112e45dda7087cb31d3e2910
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09221843B2

Reaction notes

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