1,4-Dioxane → 4-(2-Chloro-4-cyclobutoxy-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-N-methylbenzamide

HRID 1487650Notes

Reaction equation

[Cl:1][C:2]1[N:3]=[C:4]([O:20][CH:21]2[CH2:24][CH2:23][CH2:22]2)[C:5]2[C:10](I)=[CH:9][N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:6]=2[N:7]=1.[CH3:25][NH:26][C:27](=[O:43])[C:28]1[CH:33]=[CH:32][C:31](B2OC(C)(C)C(C)(C)O2)=[CH:30][CH:29]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>O>[Cl:1][C:2]1[N:3]=[C:4]([O:20][CH:21]2[CH2:24][CH2:23][CH2:22]2)[C:5]2[C:10]([C:31]3[CH:32]=[CH:33][C:28]([C:27]([NH:26][CH3:25])=[O:43])=[CH:29][CH:30]=3)=[CH:9][N:8]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[C:6]=2[N:7]=1

Participants

Conditions

Temperature: 80 °C

Procedure

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 (1.1 equiv) and tripotassium phosphate trihydrorate (3.0 equiv) in a 9:1 mixture of 1,4-dioxane and water (0.125 M) was added palladium 1,1-bis(diphenylphosphion)ferrocene dicholoride (0.1 equiv). The reaction mixture was stirred at 80° C. for 4 h. After the reaction was completed, the reaction mixture was cooled to room temperature and concentrated. The residue was purified by silica gel chromatography (1% MeOH in DCM) to afford the desired product (65.7% yield) as a yellow solid. MS (ESI) m/z 487.2 [M+H]+.

Workup

temperaturethe reaction mixture was cooled to room temperature
concentrationconcentrated
customThe residue was purified by silica gel chromatography (1% MeOH in DCM)

Sources & evidence

ORD record: ord-978619aaec4f4a9ca706cf32f046112c
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09428509B2

Reaction notes

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