Trifluoroacetic acid → 4-Fluoro-2-methyl-5-(6-methylaminomethyl-pyrimidin-4-yloxy)-indole-1-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide

HRID 453204Notes

Reaction equation

HRID 453204 reaction equation
C(O[C:6](=O)[N:7]([CH2:9][C:10]1[CH:15]=[C:14]([O:16][C:17]2[C:18]([F:39])=[C:19]3[C:23](=[CH:24][CH:25]=2)[N:22]([C:26](=[O:37])[NH:27][C:28]2[CH:32]=[C:31]([C:33]([CH3:36])([CH3:35])[CH3:34])[O:30][N:29]=2)[C:21]([CH3:38])=[CH:20]3)[N:13]=[CH:12][N:11]=1)C)(C)(C)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[C:33]([C:31]1[O:30][N:29]=[C:28]([NH:27][C:26]([N:22]2[C:23]3[C:19](=[C:18]([F:39])[C:17]([O:16][C:14]4[CH:15]=[C:10]([CH2:9][NH:7][CH3:6])[N:11]=[CH:12][N:13]=4)=[CH:25][CH:24]=3)[CH:20]=[C:21]2[CH3:38])=[O:37])[CH:32]=1)([CH3:36])([CH3:35])[CH3:34]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59394696{6-[1-(5-tert-Butyl-isoxazol-3-ylcarbamoyl)-4-fluoro-2-methyl-1H-indol-5-yloxy]-pyrimidin-4-ylmethyl}-methyl-carbamic acid tert-butyl ester

Product 1

HCID 593942574-Fluoro-2-methyl-5-(6-methylaminomethyl-pyrimidin-4-yloxy)-indole-1-carboxylic acid (5-tert-butyl-isoxazol-3-yl)-amide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of {6-[1-(5-tert-Butyl-isoxazol-3-ylcarbamoyl)-4-fluoro-2-methyl-1H-indol-5-yloxy]-pyrimidin-4-ylmethyl}-methyl-carbamic acid tert-butyl ester (0.25 g, 0.452 mmol) in DCM (10 mL) is added TFA (1.5 mL). After 3 h the solvent is removed by rotary evaporation and the residue is diluted with DCM and water. Concentrated NH4OH is added to neutralize and the aqueous phase is extracted twice with DCM. The organic layers are washed with brine, dried over Na2SO4, and concentrated to give the title compound. MS (ESI) m/z 453.1 (M+1); 1H NMR (400 MHz, DMSO-d6) δ ppm 8.64 (d, J=1.01 Hz, 1 H) 7.52 (d, J=8.59 Hz, 1 H) 7.19 (s, 1H) 7.15 (dd, J=8.72, 7.71 Hz, 1H) 6.65 (s, 1 H) 6.58 (s, 1 H) 3.76 (s, 2 H) 2.56 (s, 3 H) 2.33 (s, 3 H) 1.34 (s, 9 H).

Workup

  1. customAfter 3 h the solvent is removed by rotary evaporation
  2. additionthe residue is diluted with DCM and water
  3. additionConcentrated NH4OH is added
  4. extractionthe aqueous phase is extracted twice with DCM
  5. washThe organic layers are washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-819c24b23b75473a8077a045dc4624a7
Source dataset
uspto-grants-2013_07
Patent number
US08492393B2

Reaction notes

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