Cesium carbonate → 4-((4-(Cyclopentyloxy)-5-(2-methylbenzo[d]oxazol-6-yl)-7H-pyrrolo[2,3-d]pyrimidine-2-yl)amino)-3-methoxy-N-(oxetan-3-yl)benzamide

HRID 529680Notes

Reaction equation

HRID 529680 reaction equation
[CH:1]1([O:6][C:7]2[C:8]3[C:31]([C:32]4[CH:41]=[CH:40][C:35]5[N:36]=[C:37]([CH3:39])[O:38][C:34]=5[CH:33]=4)=[CH:30][N:29](COCC[Si](C)(C)C)[C:9]=3[N:10]=[C:11]([NH:13][C:14]3[CH:26]=[CH:25][C:17]([C:18]([NH:20][CH:21]4[CH2:24][O:23][CH2:22]4)=[O:19])=[CH:16][C:15]=3[O:27][CH3:28])[N:12]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.ClC1N=C(OC2CCCC2)C2C(C3C=CC4N=C(C)OC=4C=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:6][C:7]2[C:8]3[C:31]([C:32]4[CH:41]=[CH:40][C:35]5[N:36]=[C:37]([CH3:39])[O:38][C:34]=5[CH:33]=4)=[CH:30][NH:29][C:9]=3[N:10]=[C:11]([NH:13][C:14]3[CH:26]=[CH:25][C:17]([C:18]([NH:20][CH:21]4[CH2:22][O:23][CH2:24]4)=[O:19])=[CH:16][C:15]=3[O:27][CH3:28])[N:12]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 867264206-(2-Chloro-4-(cyclopentyloxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylbenzo[d]oxazoleHCID 867264484-Amino-3-methoxy-N-(oxetan-3-yl)benzamideHCID 867264494-((4-(Cyclopentyloxy)-5-(2-methylbenzo[d]oxazol-6-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxy-N-(oxetan-3-yl)benzamide

Product 1

HCID 902931954-((4-(Cyclopentyloxy)-5-(2-methylbenzo[d]oxazol-6-yl)-7H-pyrrolo[2,3-d]pyrimidine-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-(Cyclopentyloxy)-5-(2-methylbenzo[d]oxazol-6-yl)-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 6-(2-chloro-4-(cyclopentyloxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylbenzo[d]oxazole (1 equiv), 4-amino-3-methoxy-N-(oxetan-3-yl)benzamide (1.2 equiv) and cesium carbonate (3 equiv) in 1,4-dioxane (0.1 M) was added palladium acetate (0.2 equiv) and 2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (0.2 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 686.1 [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-2739c02a322f472598fcd59e6f05afe2
Source dataset
uspto-grants-2016_05
Patent number
US09346812B2

Reaction notes

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