Trifluoroacetic acid → 2-[(6-chloro-2-methylpyrimidin-4-yl)amino]-N-(2-chloro-6-methylphenyl)-1,3-thiazole-5-carboxamide
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[N:9](CC1C=CC(OC)=CC=1)[C:10]([C:12]1[S:16][C:15]([NH:17][C:18]2[CH:23]=[C:22]([Cl:24])[N:21]=[C:20]([CH3:25])[N:19]=2)=[N:14][CH:13]=1)=[O:11].FC(F)(F)S(O)(=O)=O.FC(F)(F)C(O)=O>ClCCl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[NH:9][C:10]([C:12]1[S:16][C:15]([NH:17][C:18]2[CH:23]=[C:22]([Cl:24])[N:21]=[C:20]([CH3:25])[N:19]=2)=[N:14][CH:13]=1)=[O:11]Participants
Procedure
The first step of the process involves reacting 2-chlorothiazole with 2-chloro-6-methylphenylisocyanate in the presence of n-butyl lithium in tetrahydrofuran to obtain 2-chloro-N-(2-chloro-6-methylphenyl)-1,3-thiazole-5-carboxamide. The second step involves reacting 2-chloro-N-(2-chloro-6-methylphenyl)-1,3-thiazole-5-carboxamide with 4-methoxybenzylchloride in the presence of sodium hydride in tetrahydrofuran to obtain 2-chloro-N-(2-chloro-6-methylphenyl)-N-(4-methoxybenzyl)-1,3-thiazole-5-carboxamide. The third step involves reacting 2-chloro-N-(2-chloro-6-methylphenyl)-N-(4-methoxybenzyl)-1,3-thiazole-5-carboxamide with 4-amino-6-chloro-2-methylpyrimidine in the presence of sodium hydride in tetrahydrofuran at reflux temperature to obtain N-(2-chloro-6-methylphenyl)-2-[(6-chloro-2-methylpyrimidin-4-yl)amino]-N-(4-methoxybenzyl)-1,3-thiazole-5-carboxamide. The fourth step involves reacting N-(2-chloro-6-methylphenyl)-2-[(6-chloro-2-methylpyrimidin-4-yl)amino]-N-(4-methoxybenzyl)-1,3-thiazole-5-carboxamide with trifluoromethanesulfonic acid and trifluoroacetic acid in dichloromethane to obtain N-(2-chloro-6-methylphenyl)-2-[(6-chloro-2-methylpyrimidin-4-yl)amino]-1,3-thiazole-5-carboxamide (Formula 1d).
Sources & evidence
- ORD record
- ord-d71e3e76ac1d4a9994d4b47ad10537f0
- Source dataset
- uspto-grants-2016_06
- Patent number
- US09365526B2
Reaction notes
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