Water → 6-(morpholin-4-yl)-2-{2-oxo-2-[4-(trifluoromethyl)-2,3-dihydro-1H-indol-1-yl]ethyl}pyrimidin-4(3H)-one

HRID 2278615Notes

Reaction equation

HRID 2278615 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH2:5][CH2:6][NH:7]2.Cl.CN(C)CCCN=C=NCC.[N:26]1([C:32]2[N:33]=[C:34]([CH2:39][C:40]([O-])=[O:41])[NH:35][C:36](=[O:38])[CH:37]=2)[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.[Na+].O>CN(C)C=O.N1C=CC=CC=1>[N:26]1([C:32]2[N:33]=[C:34]([CH2:39][C:40](=[O:41])[N:7]3[C:8]4[C:4](=[C:3]([C:2]([F:1])([F:12])[F:13])[CH:11]=[CH:10][CH:9]=4)[CH2:5][CH2:6]3)[NH:35][C:36](=[O:38])[CH:37]=2)[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1

Participants

7

Reactant 4

HCID 962WaterHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 162444454-(Trifluoromethyl)indolineHCID 136041844Sodium (4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetate

Product 1

HCID 1360696056-(morpholin-4-yl)-2-{2-oxo-2-[4-(trifluoromethyl)-2,3-dihydro-1H-indol-1-yl]ethyl}pyrimidin-4(3H)-oneYield 14.4%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

700 mg of 4-trifluoromethyl-2,3-dihydro-1H-indole and 1.15 g of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride are added to a solution of 977 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate (obtained in step 2d of example 1d) in 25 ml of N,N-dimethylformamide and 25 ml of pyridine. The reaction mixture is stirred at ambient temperature for 16 hours, and then water is 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 a mixture of dichloromethane and methanol (95/05: v/v), so as to give 220 mg of 6-(morpholin-4-yl)-2-{2-oxo-2-[4-(trifluoromethyl)-2,3-dihydro-1H-indol-1-yl]ethyl}pyrimidin-4(3H)-one in the form of a white solid, 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
  7. additionbeing carried out with a mixture of dichloromethane and methanol (95/05: v/v)

Sources & evidence

ORD record
ord-1c297b81518642a08f4edd3b3e85fe51
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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