Triethylamine → 2-fluoro-N-(thiazolo[4,5-c]pyridin-2-yl)-5-(trifluoromethyl)benzamide
Reaction equation
[S:1]1[C:9]2[CH:8]=[CH:7][N:6]=[CH:5][C:4]=2[N:3]=[C:2]1[NH2:10].[F:11][C:12]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][C:13]=1[C:14](O)=[O:15].C(N(CC)CC)C.CCCP1(OP(CCC)(=O)OP(CCC)(=O)O1)=O>C1COCC1.CCOC(C)=O>[F:11][C:12]1[CH:20]=[CH:19][C:18]([C:21]([F:22])([F:23])[F:24])=[CH:17][C:13]=1[C:14]([NH:10][C:2]1[S:1][C:9]2[CH:8]=[CH:7][N:6]=[CH:5][C:4]=2[N:3]=1)=[O:15]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
A mixture of thiazolo[4,5-c]pyridin-2-amine (Milestone Pharm Tech USA Inc.) (1.35 g, 8.93 mmol), 2-fluoro-5-(trifluoromethyl)benzoic acid (2.23 g, 10.72 mmol) and triethylamine (2.71 g, 26.8 mmol) in THF (30 mL) was treated dropwise with 1-propanephosphonic acid cyclic anhydride (50% in ethyl acetate) (6.82 g, 10.72 mmol). The mixture was stirred at room temperature for 12 hrs. The reaction mixture was diluted with EtOAc, and washed with saturated NaHCO3. The organic layer was dried (Na2SO4), filtered, and concentrated. The residue was triturated with Et2O and hexane to afford the title compound (2.2 g, 72%) as a brown solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 7.66 (t, J=9.46 Hz, 1H) 8.07 (m, 1H) 8.12 (d, J=4.88 Hz, 1H) 8.26 (dd, J=6.10, 2.14 Hz, 1H) 8.44 (d, J=5.49 Hz, 1H) 9.07 (s, 1H); MS (DCI/NH3) m/z 342 (M+H)+.
Workup
- washwashed with saturated NaHCO3
- dry with materialThe organic layer was dried (Na2SO4)
- filtrationfiltered
- concentrationconcentrated
- customThe residue was triturated with Et2O and hexane
Sources & evidence
- ORD record
- ord-4a7eaaa2c12842b89cb4bd1db0ad06e4
- Source dataset
- uspto-grants-2014_11
- Patent number
- US08895592B2
Reaction notes
Loading…