Trifluoroacetic acid → HCID 86699775, compound

HRID 1777397Notes

Reaction equation

HRID 1777397 reaction equation
C([O:3][CH:4](OCC)[CH2:5][N:6]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][N:12]=2)=[N:7]1)C.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C:8]2[CH:9]=[CH:10][N:6]([CH2:5][CH:4]=[O:3])[N:7]=2)=[N:12][CH:13]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acid2×HCID 516892Sodium BicarbonateHCID 86699776HCID 86699776, compound

Product 1

HCID 86699775HCID 86699775, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
35 °C

Procedure

To a solution of 2-[1-(2,2-diethoxyethyl)-1H-pyrazol-3-yl]-5-fluoropyridine obtained in Reference Example 12 (4.0 g, 14.3 mmol) in CHCl3 (72 mL), TFA (6.4 mL, 85.9 mmol) was added, and the resulting mixture was stirred for 6 hours at 35° C. TFA (6.4 mL, 85.9 mmol) was further added thereto, and the mixture was stirred for 3 hours at 35° C. The reaction mixture was allowed to cool to room temperature, then an aqueous solution of NaHCO3 was added to the reaction mixture, followed by extraction with CHCl3. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over MgSO4, and then the drying agent was filtered off. The solvent was distilled off under reduced pressure to obtain [3-(5-fluoropyridin-2-yl)-1H-pyrazol-1-yl]acetaldehyde (colorless oil). To a solution of [3-(5-fluoropyridin-2-yl)-1H-pyrazol-1-yl]acetaldehyde in CHCl3 (36 mL), activated molecular sieve 4 A (29 g) and 2-aminoethanol (1.1 mL, 14.3 mmol) were added, and the resulting mixture was stirred for 48 hours at room temperature. The molecular sieve 4 A was filtered off through Celite®, and then the solvent was distilled off under reduced pressure to obtain a colorless oil. To a solution of the obtained colorless oil (0.10 g, 0.40 mmol) and 2-(2H-1,2,3-triazol-2-yl)benzoic acid (76 mg, 0.40 mmol) in DMF (0.4 mL), DIPEA (0.21 mL, 1.2 mmol) and HATU (0.16 g, 0.48 mmol) were added, and the resulting mixture was stirred for 48 hours at room temperature. The reaction mixture was purified by HPLC to obtain the title compound (40.8 mg) (colorless solid).

Workup

  1. additionwas added
  2. stirringthe mixture was stirred for 3 hours at 35° C
  3. temperatureto cool to room temperature
  4. extractionfollowed by extraction with CHCl3
  5. washThe organic layer was washed with a saturated aqueous solution of sodium chloride
  6. dry with materialdried over MgSO4
  7. filtrationthe drying agent was filtered off
  8. distillationThe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-72d37126958642ac94f12543611b51d2
Source dataset
uspto-grants-2016_02
Patent number
US09266870B2

Reaction notes

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