Potassium Carbonate → 7-(2,5-Dichloropyrimidin-4-ylamino)-4-(4-isopropylpiperazin-1-yl)-2-methyl-2,3-dihydroisoindol-1-one

HRID 604271Notes

Reaction equation

HRID 604271 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([N:13]2[CH2:18][CH2:17][N:16]([CH:19]([CH3:21])[CH3:20])[CH2:15][CH2:14]2)=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH3:12])[CH2:7]2.C(=O)([O-])[O-].[K+].[K+].[Cl:28][C:29]1[N:34]=[C:33](Cl)[C:32]([Cl:36])=[CH:31][N:30]=1>CS(C)=O>[Cl:28][C:29]1[N:34]=[C:33]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([N:13]3[CH2:14][CH2:15][N:16]([CH:19]([CH3:21])[CH3:20])[CH2:17][CH2:18]3)=[C:6]3[C:10]=2[C:9](=[O:11])[N:8]([CH3:12])[CH2:7]3)[C:32]([Cl:36])=[CH:31][N:30]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 2372592,4,5-Trichloropyrimidine2×HCID 598492047-amino-2-methyl-4-(4-propan-2-ylpiperazin-1-yl)-3H-isoindol-1-one

Product 1

HCID 598492227-(2,5-Dichloropyrimidin-4-ylamino)-4-(4-isopropylpiperazin-1-yl)-2-methyl-2,3-dihydroisoindol-1-oneYield 80%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
70 °C

Procedure

To a suspension of 7-amino-4-(4-isopropyl-piperazin-1-yl)-2-methyl-2,3-dihydro-isoindol-1-one (1.62 g, 5.6 mmol) and potassium carbonate (2.55 g, 8.7 mmol) in dimethylsulfoxide (30 mL), 2, 4, 5-trichloropyrimidine (970 μL, 8.4 mmol) is added and stirred at 70° C. for 4 hours. To the mixture is added 2,4,5-trichloropyrimidine (650 μL, 5.6 mmol) and the mixture is stirred at 70° C. for 6 hours. The mixture is cooled and then extracted twice with dichloromethane. The organic layer is successively washed with water and brine, dried over magnesium sulfate, and evaporated in vacuo. The residue is purified by silica gel column chromatography to afford 7-(2,5-dichloro-pyrimidin-4-ylamino)-4-(4-isopropyl-piperazin-1-yl)-2-methyl-2,3-dihydro-isoindol-1-one (1.95 g) as yellow solids in 80% yield. Rf=0.26 (MeOH/AcOEt=1/4). 1H-NMR (400 MHz, CDCl3, δ, ppm): 1.13 (s, 3H), 1.14 (s, 3H), 2.87-2.69 (m, 5H), 3.18-3.08 (m, 4H), 3.22 (s, 3H), 4.40 (s, 2H), 7.20 (d, 1H), 8.20 (s, 1H), 8.66 (d, 1H), 11.0 (s, 1H).

Workup

  1. additionis added
  2. stirringthe mixture is stirred at 70° C. for 6 hours
  3. temperatureThe mixture is cooled
  4. extractionextracted twice with dichloromethane
  5. washThe organic layer is successively washed with water and brine
  6. dry with materialdried over magnesium sulfate
  7. customevaporated in vacuo
  8. customThe residue is purified by silica gel column chromatography

Sources & evidence

ORD record
ord-7c27da38d3784899964578233a33b549
Source dataset
uspto-grants-2011_03
Patent number
US07910585B2

Reaction notes

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