Cesium carbonate → N2-(4-(2-(Pyrrolidin-1-yl)ethoxy)phenyl)-5-methyl-N4-(7-methyl-1H-indol-4-yl)pyrimidine-2,4-diamine

HRID 1095037

Reaction equation

HRID 1095037 reaction equation
[CH3:1][C:2]1[C:3]([NH2:23])=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][N:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)=[CH:11][CH:10]=2)=[N:6][CH:7]=1.Br[C:25]1[CH:33]=[CH:32][C:31]([CH3:34])=[C:30]2[C:26]=1[CH:27]=[CH:28][NH:29]2.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:18]1([CH2:17][CH2:16][O:15][C:12]2[CH:11]=[CH:10][C:9]([NH:8][C:5]3[N:4]=[C:3]([NH:23][C:25]4[CH:33]=[CH:32][C:31]([CH3:34])=[C:30]5[C:26]=4[CH:27]=[CH:28][NH:29]5)[C:2]([CH3:1])=[CH:7][N:6]=3)=[CH:14][CH:13]=2)[CH2:22][CH2:21][CH2:20][CH2:19]1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 247292794-Bromo-7-methyl-1H-indoleHCID 576750855-Methyl-N2-(4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)pyrimidine-2,4-diamine

Product 1

HCID 57675002N2-(4-(2-(Pyrrolidin-1-yl)ethoxy)phenyl)-5-methyl-N4-(7-methyl-1H-indol-4-yl)pyrimidine-2,4-diamineYield 16%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of intermediate 38 (410 mg, 1.3 mmol), 4-bromo-7-methyl-1H-indole (275 mg, 1.3 mmol), Pd2(dba)3 (92 mg, 0.1 mmol), Xantphos (180 mg, 0.3 mmol) and cesium carbonate (1.3 g, 4 mmol) was suspended in dioxane (50 mL) and heated at reflux under the argon atmosphere for 20 h. The mixture was filtered and the filtrate concentrated in vacuo. The residue was purified by HPLC to afford the title compound (92 mg of HCl salt, 15%) as a white solid.

Workup

  1. temperatureheated
  2. temperatureat reflux under the argon atmosphere for 20 h
  3. filtrationThe mixture was filtered
  4. concentrationthe filtrate concentrated in vacuo
  5. customThe residue was purified by HPLC

Sources & evidence

ORD record
ord-a63d1d05a49840a49d21b79c6304c135
Source dataset
uspto-grants-2012_03
Patent number
US08133900B2

Linked notes

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