Potassium Carbonate → 3-(3-(cyclopropanecarboxamido)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-ylamino)-4-methyl-N-(3-(trifluoromethyl)phenyl)benzamide

HRID 876895Notes

Reaction equation

HRID 876895 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([C:6]([NH:19][C:20]([CH:22]3[CH2:24][CH2:23]3)=[O:21])=[N:7][N:8]2[CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[CH:4][CH:3]=1.[NH2:25][C:26]1[CH:27]=[C:28]([CH:42]=[CH:43][C:44]=1[CH3:45])[C:29]([NH:31][C:32]1[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[CH:33]=1)=[O:30].C([O-])([O-])=O.[K+].[K+]>CC(O)(C)C>[CH:22]1([C:20]([NH:19][C:6]2[C:5]3[C:9](=[CH:10][C:2]([NH:25][C:26]4[CH:27]=[C:28]([CH:42]=[CH:43][C:44]=4[CH3:45])[C:29]([NH:31][C:32]4[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:39])([F:40])[F:41])[CH:33]=4)=[O:30])=[CH:3][CH:4]=3)[N:8]([CH2:11][O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])[N:7]=2)=[O:21])[CH2:24][CH2:23]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 201196943-amino-4-methyl-N-(3-(trifluoromethyl)phenyl)benzamideHCID 67387411N-(6-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-3-yl)cyclo-propanecarboxamide

Product 1

HCID 674006613-(3-(cyclopropanecarboxamido)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-6-ylamino)-4-methyl-N-(3-(trifluoromethyl)phenyl)benzamideYield 40.1%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of N-(6-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazol-3-yl)cyclo-propanecarboxamide (41 mg, 0.1 mmol) in t-BuOH (1.5 mL) were added 3-amino-4-methyl-N-(3-(trifluoromethyl)-phenyl)benzamide (29 mg, 0.1 mmol) and K2CO3 (42 mg, 0.3 mmol). The reaction mixture was degassed for 10 minutes. To a mixture were added Pd2(dba)3 (6.0 mg) and t-Bu-X-phos (4 mg). The reaction mixture was heated at 100° C. until it was complete as monitored by LC-MS. Then the resulting mixture was filtered through a pad of celite and eluted with dichloromethane. The to solvent was removed by rotavapor and the crude residue was purified by flash chromatography with methylene chloride-methanol to afford the title product (25 mg, 40%), MS (ESI) m/z 624 (M+H)+.

Workup

  1. customThe reaction mixture was degassed for 10 minutes
  2. additionTo a mixture were added Pd2(dba)3 (6.0 mg) and t-Bu-X-phos (4 mg)
  3. filtrationThen the resulting mixture was filtered through a pad of celite
  4. washeluted with dichloromethane
  5. customThe to solvent was removed by rotavapor
  6. customthe crude residue was purified by flash chromatography with methylene chloride-methanol

Sources & evidence

ORD record
ord-ed4f487a71224f4dac58558c4688a971
Source dataset
uspto-grants-2015_03
Patent number
US08987275B2

Reaction notes

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