Water → 4-[7-(2,5-Dichloro-pyrimidin-4-ylamino)-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl]-piperazine-1-carboxylic acid tert-butyl ester

HRID 604270Notes

Reaction equation

HRID 604270 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:22]=[CH:21][C:20]([NH2:23])=[C:19]3[C:15]=2[CH2:16][N:17]([CH3:25])[C:18]3=[O:24])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].[Cl:32][C:33]1[N:38]=[C:37](Cl)[C:36]([Cl:40])=[CH:35][N:34]=1.O>CS(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][N:11]([C:14]2[CH:22]=[CH:21][C:20]([NH:23][C:35]3[C:36]([Cl:40])=[CH:37][N:38]=[C:33]([Cl:32])[N:34]=3)=[C:19]3[C:15]=2[CH2:16][N:17]([CH3:25])[C:18]3=[O:24])[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 2372592,4,5-Trichloropyrimidine3×HCID 598491864-(7-Amino-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester

Product 1

HCID 598492014-[7-(2,5-Dichloro-pyrimidin-4-ylamino)-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl]-piperazine-1-carboxylic acid tert-butyl esterYield 60%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
60 °C

Procedure

To a suspension of 4-(7-Amino-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (6.14 g, 18 mmol) and potassium carbonate (3.86 g, 4.76 mmol) in dimethylsulfoxide (60 mL), 2,4,5-trichloropyrimidine (3.1 mL, 27 mmol) is added and the mixture is stirred at 60° C. for 2 hours. To the mixture, 2,4,5-trichloro pyrimidine (1.0 mL, 9 mmol) is added. After stirring at 60° C. for 2 hours, 2,4,5-trichloropyrimidine (1.0 mL, 9 mmol) is added and the mixture is further allowed to stir at 60° C. for 10 hours. The mixture is cooled and then poured into iced water. The resulting brown solids are collected by filtration and washed with MeOH, and dried in vacuo at 50° C. to afford 4-[7-(2,5-Dichloro-pyrimidin-4-ylamino)-2-methyl-1-oxo-2,3-dihydro-1H-isoindol-4-yl]-piperazine-1-carboxylic acid tert-butyl ester as brown solids (5.29 g) in 60% yield. Rf=0.28 (Hexane/AcOEt=111). 1H-NMR (400 MHz, CDCl3, δ, ppm): 1.50 (s, 9H), 2.99 (t, 4H), 3.23 (s, 3H), 3.59 (t, 4H), 4.40 (s, 2H), 7.18 (d, 1H), 8.21 (s, 1H), 8.67 (d, 1H), 11.0 (s, 1H).

Workup

  1. additionis added
  2. stirringAfter stirring at 60° C. for 2 hours
  3. stirringto stir at 60° C. for 10 hours
  4. temperatureThe mixture is cooled
  5. filtrationThe resulting brown solids are collected by filtration
  6. washwashed with MeOH
  7. customdried in vacuo at 50° C.

Sources & evidence

ORD record
ord-2b062a4d14d842a68df98f5fd3a5ad38
Source dataset
uspto-grants-2011_03
Patent number
US07910585B2

Reaction notes

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