Triethylamine → 2-fluoro-N-(thiazolo[4,5-c]pyridin-2-yl)-5-(trifluoromethyl)benzamide

HRID 43291Notes

Reaction equation

HRID 43291 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

7

Reactant 4

HCID 8471TriethylamineHCID 111923Propylphosphonic anhydrideHCID 6882922-Fluoro-5-(trifluoromethyl)benzoic acidHCID 14252938(1,3)Thiazolo(4,5-c)pyridin-2-amine

Product 1

HCID 866445402-fluoro-N-(thiazolo[4,5-c]pyridin-2-yl)-5-(trifluoromethyl)benzamideYield 72.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

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 drop wise 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+1)+.

Workup

  1. washwashed with saturated NaHCO3
  2. dry with materialThe organic layer was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was triturated with Et2O and hexane

Sources & evidence

ORD record
ord-bdacc40749ed429aad131aa32c656c68
Source dataset
uspto-grants-2013_09
Patent number
US08536336B2

Reaction notes

Loading…