Water → 2-[2-(4-chloro-3,3-dimethyl-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one

HRID 2278565Notes

Reaction equation

HRID 2278565 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([CH3:12])([CH3:11])[CH2:5][NH:6]2.Cl.CN(C)CCCN=C=NCC.[CH3:25][N:26]1[C:31](=[O:32])[CH:30]=[C:29]([N:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)[N:28]=[C:27]1[CH2:39][C:40]([O-])=[O:41].[Na+].O>CN(C)C=O.N1C=CC=CC=1>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([CH3:12])([CH3:11])[CH2:5][N:6]2[C:40](=[O:41])[CH2:39][C:27]1[N:26]([CH3:25])[C:31](=[O:32])[CH:30]=[C:29]([N:33]2[CH2:38][CH2:37][O:36][CH2:35][CH2:34]2)[N:28]=1

Participants

7

Reactant 4

HCID 962WaterHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 470025134-chloro-3,3-dimethyl-2,3-dihydro-1H-indoleHCID 57523684Sodium [1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate

Product 1

HCID 574150912-[2-(4-chloro-3,3-dimethyl-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-oneYield 26.4%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

20 mg of 4-chloro-3,3-dimethyl-2,3-dihydro-1H-indole [which can be prepared according to Tet. Let. (1987) (28), 5291-5294] and 34 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride are added to a solution of 30 mg of sodium [1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate in 0.5 ml of N,N-dimethylformamide and 0.5 ml of pyridine. The reaction mixture is stirred at ambient temperature for 16 hours, and then 10 ml of water are added and the mixture is extracted with ethyl acetate. The organic phase is washed successively with water and a saturated sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica column chromatography, elution being carried out with ethyl acetate, so as to give 12 mg of 2-[2-(4-chloro-3,3-dimethyl-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one, the characteristics of which are the following:

Workup

  1. extractionthe mixture is extracted with ethyl acetate
  2. washThe organic phase is washed successively with water
  3. dry with materiala saturated sodium chloride solution, dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue is purified by silica column chromatography, elution

Sources & evidence

ORD record
ord-a930da546c314d14b4f96753157b7a69
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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