HCID 67430729, compound → HCID 67432108, compound

HRID 410521Notes

Reaction equation

HRID 410521 reaction equation
[Si:1]([O:8][C:9]1([C:13]2[S:14][C:15]([C:18]3[CH:19]=[C:20]([N:27]([C:35]4[N:40]=[C:39]([C:41]([F:44])([F:43])[F:42])[CH:38]=[CH:37][N:36]=4)[C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31])[CH:21]=[C:22]([N+:24]([O-])=O)[CH:23]=3)=[CH:16][N:17]=2)[CH2:12][CH2:11][CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]>C(OCC)(=O)C.[Pd]>[NH2:24][C:22]1[CH:21]=[C:20]([N:27]([C:35]2[N:40]=[C:39]([C:41]([F:42])([F:43])[F:44])[CH:38]=[CH:37][N:36]=2)[C:28](=[O:34])[O:29][C:30]([CH3:32])([CH3:33])[CH3:31])[CH:19]=[C:18]([C:15]2[S:14][C:13]([C:9]3([O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:2])[CH3:3])[CH2:10][CH2:11][CH2:12]3)=[N:17][CH:16]=2)[CH:23]=1

Participants

4

Reactant 1

HCID 67430729HCID 67430729, compound

Product 1

HCID 67432108HCID 67432108, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of the product of Step 1 (200 mg, 0.307 mmol) in ethyl acetate (1.5 mL) was added 10% Pd/C (65 mg, 0.061 mmol), and the vessel headspace was evacuated and purged with H2. The mixture was stirred under an atmosphere of H2 (balloon) for 3 hours, at which point LCMS analysis indicated incomplete reaction. The headspace was evacuated and purged with N2, then 100 mg additional catalyst was added and the headspace evacuated again and purged with H2. The catalyst was deactivated by adding dichloromethane, then the mixture was filtered through a pre-packed Celite cartridge (ethyl acetate rinse) and concentrated in vacuo. Purification by chromatography on silica gel (80:20 to 0:100, hexanes:ethyl acetate) provided 112 mg (0.180 mmol, 59%) of tert-butyl {3-amino-5-[2-(1-{[tert-butyl(dimethyl)silyl]oxy}cyclobutyl)-1,3-thiazol-5-yl]phenyl}[4-(trifluoromethyl)pyrimidin-2-yl]carbamate as a colorless oil.

Workup

  1. customthe vessel headspace was evacuated
  2. custompurged with H2
  3. customreaction
  4. customThe headspace was evacuated
  5. custompurged with N2
  6. addition100 mg additional catalyst was added
  7. customthe headspace evacuated again
  8. custompurged with H2
  9. additionby adding dichloromethane
  10. filtrationthe mixture was filtered through a pre-packed Celite cartridge (ethyl acetate rinse)
  11. concentrationconcentrated in vacuo
  12. customPurification by chromatography on silica gel (80:20 to 0:100, hexanes:ethyl acetate)

Sources & evidence

ORD record
ord-b4e39caf21094e08b50d0d3b9991f1f5
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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