1,4-Dioxane → 4-((4-Cyclobutoxy-5-(4-(methylcarbamoyl)phenyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxy-N-(oxetan-3-yl)benzamide

HRID 529682Notes

Reaction equation

HRID 529682 reaction equation
Cl[C:2]1[N:3]=[C:4]([O:29][CH:30]2[CH2:33][CH2:32][CH2:31]2)[C:5]2[C:10]([C:11]3[CH:20]=[CH:19][C:14]([C:15]([NH:17][CH3:18])=[O:16])=[CH:13][CH:12]=3)=[CH:9][N:8](COCC[Si](C)(C)C)[C:6]=2[N:7]=1.ClC1N=[C:37]([O:53][CH:54]2CCC2)[C:38]2[C:43](I)=[CH:42][N:41]([CH2:45]OCC[Si](C)(C)C)C=2N=1.C[NH:59][C:60](=O)[C:61]1[CH:66]=CC(B2OC(C)(C)C(C)(C)O2)=CC=1.[OH2:77].O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[O:88]1[CH2:93]COC[CH2:89]1>O>[CH:30]1([O:29][C:4]2[C:5]3[C:10]([C:11]4[CH:20]=[CH:19][C:14]([C:15](=[O:16])[NH:17][CH3:18])=[CH:13][CH:12]=4)=[CH:9][NH:8][C:6]=3[N:7]=[C:2]([NH:59][C:60]3[CH:61]=[CH:66][C:43]([C:42]([NH:41][CH:45]4[CH2:93][O:88][CH2:89]4)=[O:77])=[CH:38][C:37]=3[O:53][CH3:54])[N:3]=2)[CH2:33][CH2:32][CH2:31]1

Participants

7

Reactant 5

HCID 312751,4-DioxaneHCID 17750267N-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 18407952Tripotassium phosphate trihydrateHCID 867264532-Chloro-4-cyclobutoxy-5-iodo-7-((2-(trimethylsilyl)ethoxy)-methyl)-7H-pyrrolo[2,3-d]pyrimidineHCID 867264544-(2-Chloro-4-cyclobutoxy-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylbenzamide

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)benzamideYield 67%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

4-(2-Chloro-4-cyclobutoxy-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylbenzamide. To a degassed mixture of 2-chloro-4-cyclobutoxy-5-iodo-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (1 equiv), N-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (1.2 equiv) and tripotassium phosphate trihydrate (3 equiv) in a 9:1 mixture of 1,4-dioxane and water (0.1 M) was added palladium 1,1-bis(diphenylphosphino)ferrocene dichloride (0.1 equiv). The reaction mixture was stirred at 80° C. for 2 h. After the reaction was completed, the reaction mixture was cooled to room temperature and concentrated. The residue was purified by silica gel chromatography (0-30% ethyl acetate in petroleum ether) to afford the title compound (67% yield) as a yellow solid. MS (ESI) m/z 487.2 [M+1]+.

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. concentrationconcentrated
  3. customThe residue was purified by silica gel chromatography (0-30% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-2925408c5be2417680af8f6b27f175a8
Source dataset
uspto-grants-2016_05
Patent number
US09346812B2

Reaction notes

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