Cesium carbonate → N-(5-Chloro-1-isopropyl-1H-pyrazol-4-yl)-4-(cyclopentyloxy)-5-(2-methylbenzo[d]oxazol-6-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine

HRID 1487669Notes

Reaction equation

HRID 1487669 reaction equation
Cl[C:2]1[N:3]=[C:4]([O:29][CH:30]2[CH2:34][CH2:33][CH2:32][CH2:31]2)[C:5]2[C:10]([C:11]3[CH:20]=[CH:19][C:14]4[N:15]=[C:16]([CH3:18])[O:17][C:13]=4[CH:12]=3)=[CH:9][N:8]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:6]=2[N:7]=1.[Cl:35][C:36]1[N:40]([CH:41]([CH3:43])[CH3:42])[N:39]=[CH:38][C:37]=1[NH2:44].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>[Cl:35][C:36]1[N:40]([CH:41]([CH3:43])[CH3:42])[N:39]=[CH:38][C:37]=1[NH:44][C:2]1[N:3]=[C:4]([O:29][CH:30]2[CH2:31][CH2:32][CH2:33][CH2:34]2)[C:5]2[C:10]([C:11]3[CH:20]=[CH:19][C:14]4[N:15]=[C:16]([CH3:18])[O:17][C:13]=4[CH:12]=3)=[CH:9][N:8]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:26])([CH3:28])[CH3:27])[C:6]=2[N:7]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 679699165-Chloro-1-isopropyl-1H-pyrazol-4-amineHCID 867264206-(2-Chloro-4-(cyclopentyloxy)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylbenzo[d]oxazole

Product 1

HCID 86726498N-(5-Chloro-1-isopropyl-1H-pyrazol-4-yl)-4-(cyclopentyloxy)-5-(2-methylbenzo[d]oxazol-6-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-amine

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

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), 5-chloro-1-isopropyl-1H-pyrazol-4-amine (1.3 equiv) and cesium carbonate (3 equiv) in 1,4-dioxane (0.06 M) was added palladium acetate (0.1 equiv) and 2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (0.3 equiv). The reaction was stirred at 100° C. for 2 h. Upon completion, the reaction mixture was cooled to room temperature, and concentrated. The residue was purified by silica gel chromatography (1-2% MeOH in DCM) to afford the desired product as a yellow solid, which was used in next step without further purification. MS (ESI) m/z 622.2 [M+H]+.

Workup

  1. temperatureUpon completion, the reaction mixture was cooled to room temperature
  2. concentrationconcentrated
  3. customThe residue was purified by silica gel chromatography (1-2% MeOH in DCM)

Sources & evidence

ORD record
ord-dee94b57630940af951ba422a26fa2c2
Source dataset
uspto-grants-2016_08
Patent number
US09428509B2

Reaction notes

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