Cesium carbonate → HCID 89457119, compound

HRID 1915851Notes

Reaction equation

HRID 1915851 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]([F:48])=[C:6]([C:8]2[S:9][C:10]([NH:40][C:41](=[O:47])[O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[C:11]([C:13](=[O:39])[NH:14][C:15]3[CH:16]=[N:17][N:18]([CH3:38])[C:19]=3[N:20]3[CH2:26][CH2:25][CH2:24][CH:23]([NH:27][C:28]([O:30][CH2:31][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)=[O:29])[CH2:22][CH2:21]3)[N:12]=2)[CH:7]=1.[CH:49]1([B-](F)(F)F)[CH2:51][CH2:50]1.[K+].C(P(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2)CCC.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:49]1([C:2]2[CH:3]=[CH:4][C:5]([F:48])=[C:6]([C:8]3[S:9][C:10]([NH:40][C:41](=[O:47])[O:42][C:43]([CH3:44])([CH3:45])[CH3:46])=[C:11]([C:13](=[O:39])[NH:14][C:15]4[CH:16]=[N:17][N:18]([CH3:38])[C:19]=4[N:20]4[CH2:26][CH2:25][CH2:24][CH:23]([NH:27][C:28]([O:30][CH2:31][C:32]5[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=5)=[O:29])[CH2:22][CH2:21]4)[N:12]=3)[CH:7]=2)[CH2:51][CH2:50]1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneHCID 23697338Potassium cyclopropyltrifluoroborateHCID 89456437HCID 89456437, compound

Product 1

HCID 89457119HCID 89457119, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
105 °C

Procedure

tert-butyl 2-(5-chloro-2-fluorophenyl)-4-(1-methyl-5-(4-(benzyloxycarbonylamino)azepan-1-yl)-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate (309 mg, 0.44 mmol), potassium cyclopropyltrifluoroborate (98 mg, 0.66 mmol), palladium acetate (20.0 mg, 0.088 mmol), butyl-di-1-adamantylphosphine (50.1 mg, 0.133 mmol) and cesium carbonate (437 mg, 1.33 mmol) were charged in a 40 mL reaction vial and vacuum purged with nitrogen three times. Toluene (10.8 mL) and water (1.2 mL) were added and the mixture was heated at 105° C. for four days, monitoring with LCMS. The reaction was filtered through Celite and washed thoroughly with methanol. The filtrate was concentrated under reduced pressure and the residue was purified via flash chromatography, eluted with 0 to 100% ethyl acetate in heptane to give tert-butyl 2-(5-cyclopropyl-2-fluorophenyl)-4-(1-methyl-5-(4-(benzyloxycarbonylamino)azepan-1-yl)-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate (192 mg, 62%).

Workup

  1. customvacuum purged with nitrogen three times
  2. additionToluene (10.8 mL) and water (1.2 mL) were added
  3. filtrationThe reaction was filtered through Celite
  4. washwashed thoroughly with methanol
  5. concentrationThe filtrate was concentrated under reduced pressure
  6. customthe residue was purified via flash chromatography
  7. washeluted with 0 to 100% ethyl acetate in heptane

Sources & evidence

ORD record
ord-f4999f4da15e4a36a279afa2240c5d3f
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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