HCID 67257900, compound → HCID 67433232, compound

HRID 410519Notes

Reaction equation

HRID 410519 reaction equation
[C:1]([Si:5]([CH3:37])([CH3:36])[O:6][C:7]1([C:11]2[S:12][C:13]([C:16]3[CH:17]=[C:18]([NH:25][C:26]4[N:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[CH:28][N:27]=4)[CH:19]=[C:20]([N+:22]([O-])=O)[CH:21]=3)=[CH:14][N:15]=2)[CH2:10][CH2:9][CH2:8]1)([CH3:4])([CH3:3])[CH3:2]>C(OCC)(=O)C.[Pd]>[Si:5]([O:6][C:7]1([C:11]2[S:12][C:13]([C:16]3[CH:21]=[C:20]([NH2:22])[CH:19]=[C:18]([NH:25][C:26]4[N:31]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:29]=[CH:28][N:27]=4)[CH:17]=3)=[CH:14][N:15]=2)[CH2:10][CH2:9][CH2:8]1)([C:1]([CH3:2])([CH3:3])[CH3:4])([CH3:36])[CH3:37]

Participants

4

Reactant 1

HCID 67257900HCID 67257900, compound

Product 1

HCID 67433232HCID 67433232, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the product of Step 1 (252 mg, 0.457 mmol) in ethyl acetate (5 mL) was added 10% Pd/C (97 mg, 0.091 mmol), then the vessel headspace was purged with H2(g) and the mixture was stirred under an atmosphere of H2 (g) (1 atm) for 2 hours. Due to incomplete reaction (as evidenced by LCMS analysis), the headspace was purged with N2, additional catalyst (˜100 mg) was added and the vessel was again purged with H2 and stirred under H2 balloon overnight. The catalyst was deactivated by addition of dichloromethane, then the mixture was filtered through Celite (ethyl acetate rinse) and concentrated in vacuo to provide 219 mg (0.420 mmol, 92%) of 5-[2-(1-{[tert-butyl(dimethyl)silyl]oxy}cyclobutyl)-1,3-thiazol-5-yl]-N-[4-(trifluoromethyl)pyrimidin-2-yl]benzene-1,3-diamine as a brown foam.

Workup

  1. customthe vessel headspace was purged with H2(g)
  2. customDue to incomplete reaction (as evidenced by LCMS analysis)
  3. customthe headspace was purged with N2, additional catalyst (˜100 mg)
  4. additionwas added
  5. customthe vessel was again purged with H2
  6. stirringstirred under H2 balloon overnight
  7. additionThe catalyst was deactivated by addition of dichloromethane
  8. filtrationthe mixture was filtered through Celite (ethyl acetate rinse)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0dc7f5f8252348bb9316439441b8fc42
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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