tert-butyl 3-{[3-(3,5-dichlorophenoxy)-2-oxo-4-(trifluoromethyl)pyridin-1(2H)-yl]methyl}-1H-pyrazolo[3,4-b]pyridine-1-carboxylate → HCID 178516861, compound

HRID 1952374Notes

Reaction equation

HRID 1952374 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:34]=[C:35]([Cl:37])[CH:36]=1)[O:5][C:6]1[C:7](=[O:33])[N:8]([CH2:16][C:17]2[C:25]3[C:20](=[N:21][CH:22]=[CH:23][CH:24]=3)[N:19](C(OC(C)(C)C)=O)[N:18]=2)[CH:9]=[CH:10][C:11]=1[C:12]([F:15])([F:14])[F:13]>C(O)(C(F)(F)F)=O>[Cl:37][C:35]1[CH:34]=[C:4]([CH:3]=[C:2]([Cl:1])[CH:36]=1)[O:5][C:6]1[C:7](=[O:33])[N:8]([CH2:16][C:17]2[C:25]3[C:20](=[N:21][CH:22]=[CH:23][CH:24]=3)[NH:19][N:18]=2)[CH:9]=[CH:10][C:11]=1[C:12]([F:13])([F:14])[F:15]

Participants

3

Reactant 1

HCID 68513204tert-butyl 3-{[3-(3,5-dichlorophenoxy)-2-oxo-4-(trifluoromethyl)pyridin-1(2H)-yl]methyl}-1H-pyrazolo[3,4-b]pyridine-1-carboxylate

Product 1

HCID 178516861HCID 178516861, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

To tert-butyl 3-{[3-(3,5-dichlorophenoxy)-2-oxo-4-(trifluoromethyl)pyridin-1(2H)-yl]methyl}-1H-pyrazolo[3,4-b]pyridine-1-carboxylate (0.625 g, 1.13 mmol) in a flask was added TFA (10 mL). This solution under an atmosphere of N2 was placed in an oil bath at 75° C. After 4 hours, the reaction mixture was concentrated under reduced pressure, diluted with ethyl acetate (100 mL) and washed with 50% aqueous sodium carbonate (50 mL). The aqueous layer was back extracted with ethyl acetate (100 mL) and the combined organic extracts were dried (MgSO4), filtered and the solvent evaporated under reduced pressure. The resulting solid was adsorbed onto silica gel and purified by column chromatography on a pre-packed silica gel Redi Sep 40 gram column, eluting with 0-5% methanol in CH2Cl2 to afford the title compound. 1H NMR (DMSO-d6) δ 13.65 (s, 1H), 8.54-8.52 (m, 1H), 8.16 (d, J=8.0 Hz, 1H), 8.04 (d, J=7.3 Hz, 1H), 7.32-7.30 (m, 1H), 7.18 (dd, J=8.0 Hz, J=4.4 Hz, 1H), 7.06-7.04 (m, 2H), 6.63 (d, J=7.3 Hz, 1H), 5.54 (s, 2H). HRMS (M+1)=455.0289.

Workup

  1. customThis solution under an atmosphere of N2 was placed in an oil bath at 75° C
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. additiondiluted with ethyl acetate (100 mL)
  4. washwashed with 50% aqueous sodium carbonate (50 mL)
  5. extractionThe aqueous layer was back extracted with ethyl acetate (100 mL)
  6. dry with materialthe combined organic extracts were dried (MgSO4)
  7. filtrationfiltered
  8. customthe solvent evaporated under reduced pressure
  9. custompurified by column chromatography on a pre-packed silica gel Redi Sep 40 gram column
  10. washeluting with 0-5% methanol in CH2Cl2

Sources & evidence

ORD record
ord-98fc0e92967243b498a18069ff4ef81b
Source dataset
uspto-grants-2013_03
Patent number
US08404856B2

Reaction notes

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