HCID 86712674, compound → HCID 86712675, compound

HRID 1779024Notes

Reaction equation

HRID 1779024 reaction equation
[CH3:1][O:2][C:3](=[O:47])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][C:6]=1[C:15]#[C:16][C:17]1[C:22]([C:23]([F:26])([F:25])[F:24])=[CH:21][N:20]=[C:19]([NH:27][C:28]2[CH:33]=[CH:32][C:31]([CH:34]3[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:36][CH2:35]3)=[CH:30][CH:29]=2)[N:18]=1>CN(C=O)C.CCN(CC)CC.[Pd]>[CH3:1][O:2][C:3](=[O:47])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]([F:12])([F:13])[F:14])=[CH:7][C:6]=1[CH2:15][CH2:16][C:17]1[C:22]([C:23]([F:25])([F:26])[F:24])=[CH:21][N:20]=[C:19]([NH:27][C:28]2[CH:29]=[CH:30][C:31]([CH:34]3[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:36][CH2:35]3)=[CH:32][CH:33]=2)[N:18]=1

Participants

5

Reactant 1

HCID 86712674HCID 86712674, compound

Product 1

HCID 86712675HCID 86712675, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A suspension of 10% Pd/C (0.050 g) and tert-butyl 4-(4-((4-((2-(2-methoxy-2-oxoethyl)-5-(trifluoromethyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (A60) (0.200 g, 0.302 mmol) in DMF (10 mL) and Et3N (1 mL) was stirred at room temperature for 16 hours under an atmosphere of hydrogen. The resulting mixture was filtered through Celite, washing with MeOH. The volatiles were removed under reduced pressure then the residue was adsorbed onto silica gel and purified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.; repeated twice) to give the title compound A61 (170 mg, 84%); 1H NMR (400 MHz, CDCl3) δ 8.54 (s, 1H), 7.55 (d, J=8.6 Hz, 2H), 7.49 (s, 1H), 7.47-7.45 (m, 1H), 7.41 (s, 1H), 7.37 (d, J=8.0 Hz, 1H), 7.20 (d, J=8.5 Hz, 2H), 4.37-4.17 (m, 2H), 3.79 (s, 2H), 3.69 (s, 3H), 3.24-3.14 (m, 2H), 3.21-3.06 (m, 2H), 2.92-2.72 (m, 2H), 2.71-2.52 (m, 1H), 1.90-1.74 (m, 2H), 1.68-1.60 (m, 2H), 1.48 (s, 9H). LCMS-A: rt 7.149 min; m/z 667 [M+H]+.

Workup

  1. filtrationThe resulting mixture was filtered through Celite
  2. washwashing with MeOH
  3. customThe volatiles were removed under reduced pressure
  4. custompurified by column chromatography (Biotage Isolera, SiO2 cartridge, 0-100% EtOAc in petroleum benzine 40-60° C.

Sources & evidence

ORD record
ord-be371520dc75427a81765e4068727e5b
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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