HCID 86712729, compound → HCID 86712730, compound

HRID 1779097Notes

Reaction equation

HRID 1779097 reaction equation
[CH3:1][O:2][C:3](=[O:39])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]#[C:12][C:13]1[C:18]([CH3:19])=[CH:17][N:16]=[C:15]([NH:20][C:21]2[CH:22]=[N:23][N:24]([CH:26]3[CH2:31][CH2:30][N:29]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:28][CH2:27]3)[CH:25]=2)[N:14]=1>CN(C=O)C.CCN(CC)CC.[Pd]>[CH3:1][O:2][C:3](=[O:39])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH2:11][CH2:12][C:13]1[C:18]([CH3:19])=[CH:17][N:16]=[C:15]([NH:20][C:21]2[CH:22]=[N:23][N:24]([CH:26]3[CH2:27][CH2:28][N:29]([C:32]([O:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[O:33])[CH2:30][CH2:31]3)[CH:25]=2)[N:14]=1

Participants

5

Reactant 1

HCID 86712729HCID 86712729, compound

Product 1

HCID 86712730HCID 86712730, compound

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A suspension of 10% Pd/C (53% water; 0.020 g) and tert-butyl 4-(4-((4-((2-(2-methoxy-2-oxoethyl)phenyl)ethynyl)-5-methylpyrimidin-2-yl)amino)-1H-pyrazol-1-yl)piperidine-1-carboxylate (A125) (0.092 g, 0.17 mmol) in DMF (5 mL) and Et3N (0.5 mL) was stirred at room temperature for 18 hours under a hydrogen atmosphere. The resulting mixture was filtered through Celite, and the filter cake washed with EtOAc (250 mL). The combined filtrates were washed with water (3×100 mL) and brine (3×100 mL). The organic layer was dried (Na2SO4), filtered and concentrated under reduced pressure. The resulting oil was purified by silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in hexanes) to give the title compound A126 as a pale brown oil (80 mg, 86%); 1H NMR (400 MHz, CDCl3) δ 8.06 (s, 1H), 7.89 (s, 1H), 7.51 (d, J=0.4 Hz, 1H), 7.25-7.15 (m, 4H), 6.92 (s, 1H), 4.31-4.15 (m, 3H), 3.70 (s, 2H), 3.66 (s, 3H), 3.08 (dd, J=9.4, 6.3 Hz, 2H), 2.90 (dd, J=9.5, 6.3 Hz, 4H), 2.15-2.07 (m, 2H), 2.05 (s, 3H), 2.00-1.85 (m, 2H), 1.46 (s, 9H). LCMS-A: rt 6.195 min; m/z 535.3 [M+H]+.

Workup

  1. filtrationThe resulting mixture was filtered through Celite
  2. washthe filter cake washed with EtOAc (250 mL)
  3. washThe combined filtrates were washed with water (3×100 mL) and brine (3×100 mL)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting oil was purified by silica gel column chromatography (Biotage Isolera, 40 g SiO2 cartridge, 0-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-81f22ce8053e49a09025fa7301ebf7da
Source dataset
uspto-grants-2016_02
Patent number
US09266864B2

Reaction notes

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