Trifluoroacetic acid → 4-(4-bromo-2-fluorophenylamino)-1H-indazole-5-carboxylic acid
Reaction equation
C(OC([N:8]1[C:16]2[C:11](=[C:12]([NH:24][C:25]3[CH:30]=[CH:29][C:28]([Br:31])=[CH:27][C:26]=3[F:32])[C:13]([C:17]([O:19]C(C)(C)C)=[O:18])=[CH:14][CH:15]=2)[CH:10]=[N:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Br:31][C:28]1[CH:29]=[CH:30][C:25]([NH:24][C:12]2[C:13]([C:17]([OH:19])=[O:18])=[CH:14][CH:15]=[C:16]3[C:11]=2[CH:10]=[N:9][NH:8]3)=[C:26]([F:32])[CH:27]=1Participants
Procedure
To a solution of 4-(4-bromo-2-fluorophenylamino)-indazole-1,5-dicarboxylic acid di-tert-butyl ester (420 mg, 0.83 mmol) in DCM (5 ml) was added TFA (1.2 mL, 16.2 mmol). The reaction mixture was stirred at room temperature for 16 hours before being concentrated in vacuo. The resultant residue was dissolved in ethyl acetate (10 mL), washed with aqueous saturated sodium bicarbonate solution (10 mL) and the aqueous fraction extracted with ethyl acetate (2×10 mL). The combined organic extracts were washed with brine (20 mL), dried with MgSO4 and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si—PPC, gradient 0-100% ethyl acetate in cyclohexane) to yield the title compound as an off-white solid (232 mg, 80%). LCMS (Method B): RT=3.22 min, [M+H]+=350/352.
Workup
- concentrationbefore being concentrated in vacuo
- dissolutionThe resultant residue was dissolved in ethyl acetate (10 mL)
- washwashed with aqueous saturated sodium bicarbonate solution (10 mL)
- extractionthe aqueous fraction extracted with ethyl acetate (2×10 mL)
- washThe combined organic extracts were washed with brine (20 mL)
- dry with materialdried with MgSO4
- concentrationconcentrated in vacuo
Sources & evidence
- ORD record
- ord-c64e35c0315749d79c1bd1abaf1a4a06
- Source dataset
- uspto-grants-2014_09
- Patent number
- US08841462B2
Reaction notes
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