Cesium carbonate → 4-((4-((4-Hydroxy-4-methylcyclohexyl)oxy)-5-(2-methylbenzo[d]oxazol-6-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-N,3-dimethylbenzamide

HRID 529679Notes

Reaction equation

HRID 529679 reaction equation
Cl[C:2]1[N:3]=[C:4]([O:29][CH:30]2[CH2:35][CH2:34][C:33]([CH3:37])([OH:36])[CH2:32][CH2:31]2)[C:5]2[C:10]([C:11]3[CH:20]=[CH:19][C:14]4[N:15]=[C:16]([CH3:18])[O:17][C:13]=4[CH:12]=3)=[CH:9][N:8]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:6]=2[N:7]=1.[NH2:38][C:39]1[CH:48]=[CH:47][C:42]([C:43]([NH:45][CH3:46])=[O:44])=[CH:41][C:40]=1[CH3:49].C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[OH:36][C:33]1([CH3:37])[CH2:34][CH2:35][CH:30]([O:29][C:4]2[C:5]3[C:10]([C:11]4[CH:20]=[CH:19][C:14]5[N:15]=[C:16]([CH3:18])[O:17][C:13]=5[CH:12]=4)=[CH:9][N:8]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:6]=3[N:7]=[C:2]([NH:38][C:39]3[CH:48]=[CH:47][C:42]([C:43]([NH:45][CH3:46])=[O:44])=[CH:41][C:40]=3[CH3:49])[N:3]=2)[CH2:31][CH2:32]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 167716674-Amino-N,3-dimethylbenzamideHCID 867264464-((2-Chloro-5-(2-methylbenzo[d]oxazol-6-yl)-7-((2-(trimethylsilyl)ethoxy)-methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)-1-methylcyclohexanol

Product 1

HCID 867264474-((4-((4-Hydroxy-4-methylcyclohexyl)oxy)-5-(2-methylbenzo[d]oxazol-6-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-N,3-dimethylbenzamideYield 100%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a degassed mixture of 4-((2-chloro-5-(2-methylbenzo[d]oxazol-6-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy)-1-methylcyclohexanol (1 equiv), 4-amino-N,3-dimethylbenzamide (1.1 equiv) and cesium carbonate (3 equiv) in 1,4-dioxane (0.17 M) was added palladium acetate (0.1 equiv) and 2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (0.2 equiv). The reaction was stirred at 100° C. for 2 h. After the reaction was complete, the reaction mixture was cooled to room temperature and concentrated. The residue was purified by silica gel chromatography (0-2% DCM in methanol) to afford the title compound 100% yield) as a red oil. MS (ESI) m/z 671.2 [M+1]+.

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. concentrationconcentrated
  3. customThe residue was purified by silica gel chromatography (0-2% DCM in methanol)

Sources & evidence

ORD record
ord-88127abee3844c11a920e3296d98b7dc
Source dataset
uspto-grants-2016_05
Patent number
US09346812B2

Reaction notes

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