HCID 68282833, compound → HCID 71209106, compound

HRID 1473096Notes

Reaction equation

HRID 1473096 reaction equation
[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:14][CH2:13][N:12]([C:15]2[CH:20]=[CH:19][C:18]([NH:21][C:22]3[N:27]=[C:26]([C:28]#[C:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=4[CH2:36][C:37]([O:39][CH3:40])=[O:38])[C:25]([C:41]([F:44])([F:43])[F:42])=[CH:24][N:23]=3)=[CH:17][CH:16]=2)[CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CN(C=O)C.C(N(CC)CC)C.CO.[OH-].[OH-].[Pd+2]>[C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:10][CH2:11][N:12]([C:15]2[CH:16]=[CH:17][C:18]([NH:21][C:22]3[N:27]=[C:26]([CH2:28][CH2:29][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=4[CH2:36][C:37]([O:39][CH3:40])=[O:38])[C:25]([C:41]([F:44])([F:42])[F:43])=[CH:24][N:23]=3)=[CH:19][CH:20]=2)[CH2:13][CH2:14]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 1

HCID 68282833HCID 68282833, compound

Product 1

HCID 71209106HCID 71209106, compound

Reagents, catalysts & solvents 4

HCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of crude methyl 2-(2-((2-((4-(4-((tert-butoxycarbonyl)amino)piperidin-1-yl)phenyl)amino)-5-(trifluoromethyl)pyrimidin-4-yl)ethynyl)phenyl)acetate (I77) in DMF (10 mL) and triethylamine (1 mL) was added 20% Pd(OH)2 (0.92 g) and the resulting suspension was stirred at room temperature overnight under an atmosphere of hydrogen. The reaction mixture was filtered through celite and the filter cake washed with EtOAc (3×75 mL). The combined filtrates were evaporated to dryness to give a brown solid, which was suspended in MeOH (25 mL) and then sonicated. The resulting suspension was filtered to give the title compound (I78) (211 mg, 29%) as a tan solid; 1H NMR (400 MHz, d6-DMSO) δ 9.97 (s, 1H), 8.60 (s, 1H), 7.55 (d, J=9.0 Hz, 2H), 7.29-7.15 (m, 4H), 6.96-6.78 (m, 3H), 3.76 (s, 2H), 3.64-3.49 (m, 5H), 3.38 (s, 2H), 3.11-3.00 (m, 2H), 3.00-2.91 (m, 2H), 2.68 (t, J=12.0 Hz, 2H), 1.80 (d, J=10.7 Hz, 2H), 1.48 (ddd, J=15.0, 12.2, 3.5 Hz, 2H), 1.39 (s, 9H). LCMS Method C: rt 5.87 min; m/z 614 [M+H]+.

Workup

  1. filtrationThe reaction mixture was filtered through celite
  2. washthe filter cake washed with EtOAc (3×75 mL)
  3. customThe combined filtrates were evaporated to dryness
  4. customto give a brown solid, which
  5. customsonicated
  6. filtrationThe resulting suspension was filtered

Sources & evidence

ORD record
ord-6f58524ec54f4be090c6af6224c2f71d
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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