Cesium carbonate → 3-Methoxy-4-((5-(2-methoxypyridin-4-yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-N-methylbenzamide

HRID 529673Notes

Reaction equation

HRID 529673 reaction equation
Cl[C:2]1[N:3]=[C:4]([O:27][CH:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[C:5]2[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([O:17][CH3:18])[CH:12]=3)=[CH:9][N:8]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:26])([CH3:25])[CH3:24])[C:6]=2[N:7]=1.[NH2:34][C:35]1[CH:44]=[CH:43][C:38]([C:39]([NH:41][CH3:42])=[O:40])=[CH:37][C:36]=1[O:45][CH3:46].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>[CH3:46][O:45][C:36]1[CH:37]=[C:38]([CH:43]=[CH:44][C:35]=1[NH:34][C:2]1[N:3]=[C:4]([O:27][CH:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[C:5]2[C:10]([C:11]3[CH:16]=[CH:15][N:14]=[C:13]([O:17][CH3:18])[CH:12]=3)=[CH:9][N:8]([CH2:19][O:20][CH2:21][CH2:22][Si:23]([CH3:25])([CH3:24])[CH3:26])[C:6]=2[N:7]=1)[C:39]([NH:41][CH3:42])=[O:40]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 204444344-Amino-3-methoxy-N-methylbenzamideHCID 867264432-Chloro-5-(2-methoxypyridin-4-yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 867264443-Methoxy-4-((5-(2-methoxypyridin-4-yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-N-methylbenzamideYield 95%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

To a degassed mixture of 2-chloro-5-(2-methoxypyridin-4- yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (1 equiv), 4-amino-3-methoxy-N-methylbenzamide (1.1 equiv) and cesium carbonate (3 equiv) in 1,4-dioxane (0.175 M) was added palladium acetate (0.3 equiv) and 2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (0.6 equiv). The reaction was stirred at 100° C. for 2 h. After the reaction was complete, the reaction mixture was cooled to room temperature, filtered and concentrated to afford the crude product (95% yield, crude) as a brown solid which was used in the next step without further purification . MS (ESI) m/z 635.3 [M+1]+.

Workup

  1. temperaturethe reaction mixture was cooled to room temperature
  2. filtrationfiltered
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-a2181a4ba365481782c0512781dfcc96
Source dataset
uspto-grants-2016_05
Patent number
US09346812B2

Reaction notes

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