Water → HCID 68281611, compound

HRID 2278635Notes

Reaction equation

HRID 2278635 reaction equation
[F:1][CH:2]([F:14])[O:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][CH:7]([CH3:13])[NH:8]2.Cl.CN(C)CCCN=C=NCC.[CH3:27][N:28]1[C:33](=[O:34])[CH:32]=[C:31]([N:35]2[CH2:40][CH2:39][O:38][CH2:37][CH2:36]2)[N:30]=[C:29]1[CH2:41][C:42]([O-])=[O:43].[Na+].O>CN(C)C=O.N1C=CC=CC=1>[F:14][CH:2]([F:1])[O:3][C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][CH:7]([CH3:13])[N:8]2[C:42](=[O:43])[CH2:41][C:29]1[N:28]([CH3:27])[C:33](=[O:34])[CH:32]=[C:31]([N:35]2[CH2:40][CH2:39][O:38][CH2:37][CH2:36]2)[N:30]=1

Participants

7

Reactant 4

HCID 962WaterHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57523684Sodium [1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetateHCID 86699279HCID 86699279, compound

Product 1

HCID 68281611HCID 68281611, compoundYield 62.4%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

125 mg of 4-difluoromethoxy-2-methyl-2,3-dihydro-1H-indole [reference example 11d] and 193 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride are added to a solution of 242 mg of sodium [1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate (obtained in step 2d of example 4d) in 6 ml of N,N-dimethylformamide and 6 ml of pyridine. The reaction mixture is stirred at ambient temperature for 16 hours, and then 25 ml of water are added and the mixture is extracted with ethyl acetate. The organic phase is washed successively with a 0.1N hydrochloric acid solution, 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 (90/10: v/v), so as to give 170 mg of 2-{2-[4-(difluoromethoxy)-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one.

Workup

  1. extractionthe mixture is extracted with ethyl acetate
  2. washThe organic phase is washed successively with a 0.1N hydrochloric acid solution, 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 (90/10: v/v)

Sources & evidence

ORD record
ord-8f8bb40cf2354b8eabf7ec96d0bc44e6
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

Loading…