Methanol → HCID 68281711, compound

HRID 2278626Notes

Reaction equation

HRID 2278626 reaction equation
[CH:1]1([N:4]2[C:9](=[O:10])[CH:8]=[C:7]([N:11]3[CH2:16][CH2:15][O:14][CH2:13][CH2:12]3)[N:6]=[C:5]2[CH2:17][C:18]([O:20]CC)=O)[CH2:3][CH2:2]1.C[Al](C)C.[Cl:27][C:28]1[CH:36]=[CH:35][CH:34]=[C:33]2[C:29]=1[CH2:30][CH2:31][NH:32]2.CO>C1(C)C=CC=CC=1.O1CCCC1>[Cl:27][C:28]1[CH:36]=[CH:35][CH:34]=[C:33]2[C:29]=1[CH2:30][CH2:31][N:32]2[C:18](=[O:20])[CH2:17][C:5]1[N:4]([CH:1]2[CH2:3][CH2:2]2)[C:9](=[O:10])[CH:8]=[C:7]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[N:6]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 30163064-ChloroindolineHCID 16682925TrimethylaluminumHCID 86699278HCID 86699278, compound

Product 1

HCID 68281711HCID 68281711, compoundYield 32.1%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

2 ml of toluene, 90 mg of ethyl (1-cyclopropyl-4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetate and, finally, dropwise, 0.55 ml of a 2M solution of trimethylaluminum in toluene are successively added to a solution of 113 mg of 4-chloroindoline in 4 ml of tetrahydrofuran. The reaction mixture is heated at 90° C. for 4 hours, and then cooled to ambient temperature, and 5 ml of methanol are added. After the addition of 10 g of silica, the reaction mixture is concentrated under reduced pressure. After purification by silica column chromatography (solid deposit), elution being carried out with a mixture of dichloromethane and methanol (100/0 then 98/02 V/V), 39 mg of 2-[2-(4-chloro-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-3-cyclopropyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one are obtained in the form of a white solid, the characteristics of which are the following:

Workup

  1. temperaturecooled to ambient temperature
  2. additionAfter the addition of 10 g of silica
  3. concentrationthe reaction mixture is concentrated under reduced pressure
  4. customAfter purification
  5. washby silica column chromatography (solid deposit), elution
  6. additionbeing carried out with a mixture of dichloromethane and methanol (100/0

Sources & evidence

ORD record
ord-6b1cb4a00f8a450a89b2d81b9c00e056
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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