Cesium carbonate → N,N,3-trimethyl-4-((5-(1-methyl-1H-pyrazol-4-yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)benzamide

HRID 529660Notes

Reaction equation

HRID 529660 reaction equation
Cl[C:2]1[N:3]=[C:4]([O:25][CH:26]2[CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[C:5]2[C:10]([C:11]3[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=3)=[CH:9][N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:6]=2[N:7]=1.[NH2:32][C:33]1[CH:43]=[CH:42][C:36]([C:37]([N:39]([CH3:41])[CH3:40])=[O:38])=[CH:35][C:34]=1[CH3:44].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>[CH3:41][N:39]([CH3:40])[C:37](=[O:38])[C:36]1[CH:42]=[CH:43][C:33]([NH:32][C:2]2[N:3]=[C:4]([O:25][CH:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)[C:5]3[C:10]([C:11]4[CH:12]=[N:13][N:14]([CH3:16])[CH:15]=4)=[CH:9][N:8]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:6]=3[N:7]=2)=[C:34]([CH3:44])[CH:35]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 167817704-amino-N,N,3-trimethylbenzamideHCID 867264342-Chloro-5-(1-methyl-1H-pyrazol-4-yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 86726435N,N,3-trimethyl-4-((5-(1-methyl-1H-pyrazol-4-yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)benzamideYield 76%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

To a degassed mixture of 2-chloro-5-(1-methyl-1H-pyrazol-4-yl)-4-((tetrahydro-2H-pyran-4-yl)oxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (1 equiv), 4-amino-N,N,3-trimethylbenzamide (1 equiv) and cesium carbonate (3 equiv) in 1.4-dioxane (0.086 M) were added palladium acetate (0.3 equiv) and 2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (0.6 equiv). The mixture was stirred at 110° C. for 2 h. The reaction was cooled to room temperature and filtered. The filtrate was concentrated and the residue obtained was purified by preparative thin layer chromatography (3.3% methanol in DCM) to afford the title compound (76% yield). MS (ESI) m/z 606.1 [M+1]+.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. filtrationfiltered
  3. concentrationThe filtrate was concentrated
  4. customthe residue obtained
  5. customwas purified by preparative thin layer chromatography (3.3% methanol in DCM)

Sources & evidence

ORD record
ord-4a9360c17cd34bb8991e6d39b53c2bbc
Source dataset
uspto-grants-2016_05
Patent number
US09346812B2

Reaction notes

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