Trifluoroacetic acid → HCID 58404779, compound

HRID 1253556Notes

Reaction equation

HRID 1253556 reaction equation
[CH3:1][O:2][C:3]1[C:4]2[N:5]([N:15]=[CH:16][C:17]=2[C:18]#[C:19][CH:20]2[CH2:23][N:22](C(OC(C)(C)C)=O)[CH2:21]2)[CH:6]=[C:7]([C:9]2[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=2)[CH:8]=1.[F:31][C:32]([F:37])([F:36])[C:33](O)=[O:34].C(OCC)(=[O:40])C>ClCCl>[CH3:1][O:2][C:3]1[C:4]2[N:5]([N:15]=[CH:16][C:17]=2[C:18](=[O:40])[CH2:19][CH:20]2[CH2:23][N:22]([C:33](=[O:34])[C:32]([F:37])([F:36])[F:31])[CH2:21]2)[CH:6]=[C:7]([C:9]2[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=2)[CH:8]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 8857Ethyl AcetateHCID 58404885HCID 58404885, compound

Product 1

HCID 58404779HCID 58404779, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 3-{[4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-3-yl]ethynyl}azetidine-1-carboxylate (24 mg, 0.059 mmol) in dichloromethane (0.5 ml), was added trifluoroacetic acid (0.50 ml, 6.49 mmol) at 0° C. The reaction mixture was warmed to room temperature and stirred for 30 mins. The reaction was diluted with ethyl acetate, and washed with saturated aqueous sodium bicarbonate. The organic layer was separated, and the aqueous layer was back extracted two times with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel (methanol/dichloromethane gradient) to afford 1-[4-methoxy-6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyridin-3-yl]-2-[1-(trifluoroacetyl)azetidin-3-yl]ethanone. 1H NMR (500 MHz, CDCl3) δ 8.35 (s, 1H), 8.32 (s, 1H), 7.77 (s, 1H), 7.67 (s, 1H), 6.81 (s, 1H), 4.68 (app t, 1H), 4.39 (app t, 1H), 4.10-4.16 (m, 1H), 4.06 (s, 3H), 3.98 (s, 3H), 3.85-3.91 (m, 1H), 3.36-3.53 (m, 2H), 3.23-3.33 (m, 1H). LRMS (ESI) calculated for C19H19F3N5O3 [M+H]+, 422.1; found 422.0.

Workup

  1. washwashed with saturated aqueous sodium bicarbonate
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was back extracted two times with ethyl acetate
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography on silica gel (methanol/dichloromethane gradient)

Sources & evidence

ORD record
ord-18df91ac0949440aaf1ab758e04b5dc3
Source dataset
uspto-grants-2013_06
Patent number
US08455477B2

Reaction notes

Loading…