Trifluoroacetic acid → HCID 54596615, compound

HRID 1046034Notes

Reaction equation

HRID 1046034 reaction equation
CC(C)(OC([N:7](C(OC(C)(C)C)=O)[C:8]1[C:13]([C:14]2[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=2)=[C:12]([O:20][C:21]2[C:26]([F:27])=[CH:25][C:24]([NH:28][C:29]([C:31]3[C:36](=[O:37])[C:35]([C:38]4[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=4)=[CH:34][N:33]([CH3:45])[CH:32]=3)=[O:30])=[C:23]([F:46])[CH:22]=2)[CH:11]=[CH:10][N:9]=1)=O)C.C(O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:7][C:8]1[C:13]([C:14]2[CH:15]=[N:16][N:17]([CH3:19])[CH:18]=2)=[C:12]([O:20][C:21]2[C:26]([F:27])=[CH:25][C:24]([NH:28][C:29]([C:31]3[C:36](=[O:37])[C:35]([C:38]4[CH:39]=[CH:40][C:41]([F:44])=[CH:42][CH:43]=4)=[CH:34][N:33]([CH3:45])[CH:32]=3)=[O:30])=[C:23]([F:46])[CH:22]=2)[CH:11]=[CH:10][N:9]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 68009336HCID 68009336, compound

Product 1

HCID 54596615HCID 54596615, compoundYield 100%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of N-(4-(2-[bis[(1,1-dimethylethoxy)carbonyl]amino]-3-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)-2,5-difluorophenyl)-5-(4-fluorophenyl)-1-methyl-4-oxo-1,4-dihydropyridine-3-carboxamide (0.115 g, 0.15 mmol) in CH2Cl2 (5 mL) was treated with TFA (0.35 mL, 4.62 mmol) and the solution was stirred at RT for 3 h. The solvent was removed in vacuo and the residue was partitioned between satd NaHCO3 solution (30 mL) and EtOAc (30 mLl). The aqueous layer was extracted with EtOAc (25 mL) and the combined organics were washed with brine, dried (Na2SO4) and concentrated in vacuo to afford N-(4-(2-amino-3-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yloxy)-2,5-difluorophenyl)-5-(4-fluorophenyl)-1-methyl-4-oxo-1,4-dihydropyridine-3-carboxamide as off-white solid (82 mg, 97% yield). 1H NMR (400 MHz, DMSO-d6): δ 13.43 (s, 1H), 8.70 (d, J=2.4 Hz, 1H), 8.49 (dd, J=12.6 Hz, 7.3 Hz, 1H), 8.15 (d, J=2.3 Hz, 1H), 7.88 (s, 1H), 7.75 (d, J=5.8 Hz, 1H), 7.69 (m, 2H), 7.59 (d, J=0.8 Hz, 1H), 7.41 (dd, J=11.2 Hz, 7.4 Hz, 1H), 7.27 (t, J=8.9 Hz, 2H), 6.00 (d, J=5.8 Hz, 1H), 5.69 (s, 2H), 3.91 (s, 3H), 3.85 (s, 3H); MS (ESI) m/z: 547.1 (M+H+).

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was partitioned between satd NaHCO3 solution (30 mL) and EtOAc (30 mLl)
  3. extractionThe aqueous layer was extracted with EtOAc (25 mL)
  4. washthe combined organics were washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a8754cfc3c474285870b6a6c36cae5f6
Source dataset
uspto-grants-2013_10
Patent number
US08569319B2

Reaction notes

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