Cesium carbonate → 4-((4-Cyclobutoxy-5-(4-(methylcarbamoyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxy-N-(oxetan-3-yl)benzamide

HRID 529683Notes

Reaction equation

HRID 529683 reaction equation
[CH:1]1([O:5][C:6]2[C:7]3[C:30]([C:31]4[CH:36]=[CH:35][C:34]([C:37](=[O:40])[NH:38][CH3:39])=[CH:33][CH:32]=4)=[CH:29][N:28](COCC[Si](C)(C)C)[C:8]=3[N:9]=[C:10]([NH:12][C:13]3[CH:25]=[CH:24][C:16]([C:17]([NH:19][CH:20]4[CH2:23][O:22][CH2:21]4)=[O:18])=[CH:15][C:14]=3[O:26][CH3:27])[N:11]=2)[CH2:4][CH2:3][CH2:2]1.ClC1N=C(OC2CCC2)C2C(C3C=CC(C(NC)=O)=CC=3)=CN(COCC[Si](C)(C)C)C=2N=1.NC1C=CC(C(NC2COC2)=O)=CC=1OC.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>[CH:1]1([O:5][C:6]2[C:7]3[C:30]([C:31]4[CH:32]=[CH:33][C:34]([C:37](=[O:40])[NH:38][CH3:39])=[CH:35][CH:36]=4)=[CH:29][NH:28][C:8]=3[N:9]=[C:10]([NH:12][C:13]3[CH:25]=[CH:24][C:16]([C:17]([NH:19][CH:20]4[CH2:23][O:22][CH2:21]4)=[O:18])=[CH:15][C:14]=3[O:26][CH3:27])[N:11]=2)[CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 867264484-Amino-3-methoxy-N-(oxetan-3-yl)benzamideHCID 867264544-(2-Chloro-4-cyclobutoxy-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylbenzamideHCID 867264554-((4-Cyclobutoxy-5-(4-(methylcarbamoyl)phenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxy-N-(oxetan-3-yl)benzamide

Product 1

HCID 902847794-((4-Cyclobutoxy-5-(4-(methylcarbamoyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxy-N-(oxetan-3-yl)benzamide

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

4-((4-Cyclobutoxy-5-(4-(methylcarbamoyl)phenyl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxy-N-(oxetan-3-yl)benzamide. To a degassed mixture of 4-(2-chloro-4-cyclobutoxy-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylbenzamide (1 equiv), 4-amino-3-methoxy-N-(oxetan-3-yl)benzamide (1.1 equiv) and cesium carbonate (3 equiv) in 1,4-dioxane (0.09 M) was added palladium acetate (0.1 equiv) and 2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (0.3 equiv). The reaction was stirred at 100° C. for 2 h. The reaction mixture was cooled to room temperature, and concentrated. The residue was purified by silica gel chromatography (0-5% DCM in methanol) to afford the title compound (crude) as a yellow solid which was used in the next step without further purification. MS (ESI) m/z 673.1 [M+1]+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated
  3. customThe residue was purified by silica gel chromatography (0-5% DCM in methanol)

Sources & evidence

ORD record
ord-3fcea9ecb2584fcb99bc7883a832b970
Source dataset
uspto-grants-2016_05
Patent number
US09346812B2

Reaction notes

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