HCID 71209192, compound → HCID 71208999, compound

HRID 1473159Notes

Reaction equation

HRID 1473159 reaction equation
[CH3:1][O:2][C:3](=[O:42])[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]([C:19]([F:22])([F:21])[F:20])=[CH:17][N:16]=[C:15]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([CH:30]3[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])[CH2:31]3)=[CH:26][CH:25]=2)[N:14]=1>CCO.CN(C=O)C.CN(C=O)C.CCO.[Pd]>[CH3:1][O:2][C:3](=[O:42])[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]([C:19]([F:21])([F:22])[F:20])=[CH:17][N:16]=[C:15]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([CH:30]3[CH2:34][CH2:33][N:32]([C:35]([O:37][C:38]([CH3:40])([CH3:41])[CH3:39])=[O:36])[CH2:31]3)=[CH:26][CH:25]=2)[N:14]=1

Participants

6

Reactant 1

HCID 71209192HCID 71209192, compound

Product 1

HCID 71208999HCID 71208999, compoundYield 24%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalyst2×HCID 702EthanolSolventHCID 6228DimethylformamideSolvent2×HCID 19794673N,N-dimethylformamide ethanolSolvent

Procedure

A solution of tert-butyl 3-(4-((4-((2-(2-methoxy-2-oxoethyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)pyrrolidine-1-carboxylate (I138) (0.527 g, 0.906 mmol) in EtOH (10 mL) was added to a solution of 10% Pd/C (0.500 g) in DMF (6 mL). The reaction was stirred at room temperature for 24 hours under an atmosphere of hydrogen. The reaction was filtered through a pad of celite and washed through with EtOAc (80 mL). The solvent was removed in vacuo to afford a yellow oil. This was taken up in DMF/EtOH (1:1, 10 mL) and a slurry of 10% Pd/C (0.500 g, 1 eq) in DMF was added. The reaction was stirred under an atmosphere of H2 at room temperature for an additional 24 hours. The reaction was filtered through a pad of celite and washed through with EtOAc (80 mL). The solvent removed in vacuo to afford a yellow oil which was purified by column chromatography on silica gel (0-45% EtOAc in petroleum benzine 40-60° C.) to yield the title compound (I139) (0.126 g, 24%) as a brown oil; 1H NMR (400 MHz, CDCl3) δ 8.54 (s, 1H), 7.58 (d, J=8.2 Hz, 2H), 7.39 (s, 1H), 7.30-7.17 (m, 6H), 3.91-3.72 (m, 2H), 3.75 (s, 2H), 3.68 (s, 3H), 3.66-3.52 (m, 1H), 3.47-3.21 (m, 3H), 3.17-3.04 (m, 4H), 2.23 (d, J=20.4 Hz, 1H), 1.97 (dd, J=21.1, 10.2 Hz, 1H), 1.48 (d, J=3.1 Hz, 9H). LCMS Method C: rt 6.91 min; m/z 585 [M+H], 607 [M+N]+.

Workup

  1. filtrationThe reaction was filtered through a pad of celite
  2. washwashed through with EtOAc (80 mL)
  3. customThe solvent was removed in vacuo
  4. customto afford a yellow oil
  5. stirringThe reaction was stirred under an atmosphere of H2 at room temperature for an additional 24 hours
  6. filtrationThe reaction was filtered through a pad of celite
  7. washwashed through with EtOAc (80 mL)
  8. customThe solvent removed in vacuo
  9. customto afford a yellow oil which
  10. customwas purified by column chromatography on silica gel (0-45% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-c7537da9cd4e4881bdda53984a130131
Source dataset
uspto-grants-2015_04
Patent number
US09012461B2

Reaction notes

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