Carbon Dioxide → 2-((2-Chloro-5-(trifluoromethyl)pyrimidin-4-yl)amino)-N-methylbenzamide

HRID 1947856Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.[NH2:13][C:14]1[CH:23]=[CH:22][CH:21]=[CH:20][C:15]=1[C:16]([NH:18][CH3:19])=[O:17].C(=O)=O.[OH-].[K+]>CC#N>[Cl:1][C:2]1[N:7]=[C:6]([NH:13][C:14]2[CH:23]=[CH:22][CH:21]=[CH:20][C:15]=2[C:16]([NH:18][CH3:19])=[O:17])[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1

Participants

Conditions

Temperature: -30 °C

Procedure

To a solution of 2,4-dichloro-5-trifluoromethylpyrimidine (500 mg, 2.3 mmol) in dry CH3CN (40 mL) was added 2-amino-N-methylbenzamide (350 mg, 2.3 mmol) at room temperature. The reaction mixture was cooled to −30° C. using dry ice. Powdered KOH (1.0 g, 17.8 mmol) was added and the reaction mixture was stirred at −30° C. for 1 h, and then warmed to −10° C. to −5° C. and stirred for another 2 h, then quenched with water (200 mL). The mixture was extracted with EtOAc (3×100 mL), the combined organic layer was dried over MgSO4, concentrated, and residue was purified by column chromatography to give 213 mg of the title compound (yield: 28%). 1H NMR (DMSO, 400 MHz): δ=2.75 (d, J=4.4 Hz, 3H), 7.20-7.24 (m, 1H), 7.53-7.58 (m, 1H), 7.74 (dd, J=2.0, 8.0 Hz, 1H), 8.33 (dd, J=1.2, 8.4 Hz, 1H), 8.85 (s, br, 1H), 12.0 (s, br, 1H).

Workup

temperaturewarmed to −10° C. to −5° C.
stirringstirred for another 2 h
customquenched with water (200 mL)
extractionThe mixture was extracted with EtOAc (3×100 mL)
dry with materialthe combined organic layer was dried over MgSO4
concentrationconcentrated
customresidue was purified by column chromatography

Sources & evidence

ORD record: ord-c44182e2fe6d44369a9089a3fa3dd129
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399433B2

Reaction notes

Loading…