1,2-Dichloroethane → 2-(4-((2-Cyclopentyl-6-(trifluoromethyl)pyrimidin-4-yl)methyl)phenyl)acetamide

HRID 1508942Notes

Reaction equation

[CH:1]1([C:6]2[N:11]=[C:10]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([CH2:19][C:20](O)=[O:21])=[CH:15][CH:14]=3)[CH:9]=[C:8]([C:23]([F:26])([F:25])[F:24])[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)CCl.C1C=CC2N(O)N=[N:37]C=2C=1.N.CO>CN(C=O)C.C(OCC)(=O)C>[CH:1]1([C:6]2[N:11]=[C:10]([CH2:12][C:13]3[CH:14]=[CH:15][C:16]([CH2:19][C:20]([NH2:37])=[O:21])=[CH:17][CH:18]=3)[CH:9]=[C:8]([C:23]([F:26])([F:24])[F:25])[N:7]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

Conditions

Temperature: 85 °C

Procedure

To a solution of 2-(4-((2-cyclopentyl-6-(trifluoromethyl)pyrimidin-4-yl)methyl)phenyl)acetic acid (0.045 g, 0.12 mmol) in DMF (2 mL) was added EDC (0.047 g, 0.24 mmol), HOBT (0.033 g, 0.24 mmol) and 7N ammonia in methanol (0.17 mL, 1.2 mmol). The mixture was sealed and stirred at 85° C. for 3 h. After this time, the mixture was diluted with ethyl acetate and then washed with water. The organic layer were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by column chromatography (silica, hexanes/ethyl acetate) to afford the title compound (0.034 g, 79%) as a white solid. MW=363.38. 1H NMR (DMSO-d6, 500 MHz) δ 7.71 (s, 1H), 7.41 (s, 1H), 7.26 (d, J=8.0 Hz, 2H), 7.20 (d, J=8.0 Hz, 2H), 6.83 (s, 1H), 4.16 (s, 2H), 3.41-3.33 (m, 1H), 3.33 (s, 2H), 2.09-1.99 (m, 2H), 1.89-1.61 (m, 6H); APCI MS m/z 364 [M+H]+.

Workup

customThe mixture was sealed
washwashed with water
dry with materialThe organic layer were dried over anhydrous sodium sulfate
filtrationfiltered
concentrationthe filtrate was concentrated
customThe residue was purified by column chromatography (silica, hexanes/ethyl acetate)

Sources & evidence

ORD record: ord-908b4a71b04e4adab5da7bec79def457
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09221843B2

Reaction notes

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