4-Amino-N-methylbenzamide → 4-(4-chloro-5-(trifluoromethyl)pyrimidin-2-ylamino)-N-methylbenzamide

HRID 886988Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.[NH2:13][C:14]1[CH:23]=[CH:22][C:17]([C:18]([NH:20][CH3:21])=[O:19])=[CH:16][CH:15]=1>[Zn+2].[Br-].[Br-].CC(O)(C)C.ClCCCl>[Cl:8][C:6]1[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=[C:2]([NH:13][C:14]2[CH:15]=[CH:16][C:17]([C:18]([NH:20][CH3:21])=[O:19])=[CH:22][CH:23]=2)[N:7]=1

Participants

Conditions

Temperature: 5 °C

Procedure

A solution of 2,4-dichloro-5-trifluoromethyl-pyrimidine (8.63 mmol) in 1:1 t-BuOH/DCE (10 mL) was cooled to 5° C., treated with solid ZnBr2 (22.5 mmol), and stirred at 5° C. for 30 minutes. The resultant solution was maintained at 5° C. and treated first with solid 4-amino-N-methyl-benzamide (7.5 mmol) followed by TEA (16.5 mmol). The resultant white mixture was allowed to warm 25° C., and it was mixed at 25° C. for 20 hours. The mixture was adsorbed onto silica gel, and the fraction eluting 0-10% methanol/DCM was collected and concentrated. The resultant residue was triturated with water and filtered to provide B20. Yield: 3.0 mmol, 40%. LCMS 2.3 min, MZ+=331.1 1H NMR (500 MHz, d6-DMSO) δ ppm 10.89 (s, 1H), 8.87 (s, 1H), 8.34 (d, J=4.67 Hz, 1H), 7.73-7.89 (m, 3H), 2.78 (d, J=4.67 Hz, 3H).

Workup

temperatureto warm 25° C.
additionit was mixed at 25° C. for 20 hours
washthe fraction eluting 0-10% methanol/DCM
customwas collected
concentrationconcentrated
customThe resultant residue was triturated with water
filtrationfiltered
customto provide B20

Sources & evidence

ORD record: ord-8f8725f725a542a49443dc6fa8f60bcf
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08247411B2

Reaction notes

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