Cesium carbonate → 4-((4-(Cyclopentyloxy)-5-(2-methylbenzo[d]oxazol-6-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-N-(2-hydroxyethyl)-3-methoxybenzamide

HRID 1487597Notes

Reaction equation

HRID 1487597 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.[NH2:35][C:36]1[CH:47]=[CH:46][C:39]([C:40]([NH:42][CH2:43][CH2:44][OH:45])=[O:41])=[CH:38][C:37]=1[O:48][CH3:49].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>[CH:30]1([O:29][C:4]2[C:5]3[C:10]([C:11]4[CH:20]=[CH:19][C:14]5[N:15]=[C:16]([CH3:18])[O:17][C:13]=5[CH:12]=4)=[CH:9][N:8]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:6]=3[N:7]=[C:2]([NH:35][C:36]3[CH:47]=[CH:46][C:39]([C:40]([NH:42][CH2:43][CH2:44][OH:45])=[O:41])=[CH:38][C:37]=3[O:48][CH3:49])[N:3]=2)[CH2:34][CH2:33][CH2:32][CH2:31]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 537410594-amino-N-(2-hydroxyethyl)-3-methoxybenzamideHCID 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 867264324-((4-(Cyclopentyloxy)-5-(2-methylbenzo[d]oxazol-6-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-N-(2-hydroxyethyl)-3-methoxybenzamideYield 30%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °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), 4-amino-N-(2-hydroxyethyl)-3-methoxybenzamide (1.2 equiv) and cesium carbonate (5 equiv) in 1,4-dioxane (0.14 M) were added palladium acetate (0.1 equiv) and 2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl (0.2 equiv). The mixture was stirred at 120° C. overnight. The reaction was cooled to room temperature and filtered. The filtrate was concentrated and the residue obtained was purified by preparative thin layer chromatography (8% MeOH in DCM) to afford the title compound (30% yield). MS (ESI) m/z 673.1 [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 (8% MeOH in DCM)

Sources & evidence

ORD record
ord-a9728ab536e242638d09c27ef9bc8082
Source dataset
uspto-grants-2016_08
Patent number
US09428509B2

Reaction notes

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