Trifluoroacetic acid → 6-Fluoro-3-(R)-pyrrolidin-3-yl-[1,2,4]triazolo[4,3-a]pyridine

HRID 2282582Notes

Reaction equation

HRID 2282582 reaction equation
C(OC([N:8]1[CH2:12][CH2:11][C@@H:10]([C:13]2[N:17]3[CH:18]=[C:19]([F:22])[CH:20]=[CH:21][C:16]3=[N:15][N:14]=2)[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:22][C:19]1[CH:20]=[CH:21][C:16]2[N:17]([C:13]([C@@H:10]3[CH2:11][CH2:12][NH:8][CH2:9]3)=[N:14][N:15]=2)[CH:18]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 86687137(R)-3-(6-Fluoro-[1,2,4]triazolo[4,3-a]pyridin-3-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 866871396-Fluoro-3-(R)-pyrrolidin-3-yl-[1,2,4]triazolo[4,3-a]pyridine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of Intermediate 90b (335 mg, 1.09 mmol) and TFA (0.812 mL, 10.9 mmol) in DCM (5 mL) was stirred at reflux for 45 min. The cooled solution was concentrated in vacuo, redissolved in MeOH (2 mL), applied to an SCX-2 cartridge (10 g) and washed with MeOH (50 mL). The product was eluted with 2M NH3 in MeOH; concentration in vacuo left the title compound as a pale yellow solid (225 mg, >99%). LCMS (Method 3): Rt 0.44 min, m/z 207 [MH+].

Workup

  1. temperatureat reflux for 45 min
  2. concentrationThe cooled solution was concentrated in vacuo
  3. dissolutionredissolved in MeOH (2 mL)
  4. washwashed with MeOH (50 mL)
  5. washThe product was eluted with 2M NH3 in MeOH
  6. concentrationconcentration in vacuo
  7. waitleft the title compound as a pale yellow solid (225 mg, >99%)

Sources & evidence

ORD record
ord-b2b5e389585d4d45b9b12c685cea0c3d
Source dataset
uspto-grants-2015_09
Patent number
US09139584B2

Reaction notes

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