Water → HCID 136378692, compound

HRID 2278634Notes

Reaction equation

HRID 2278634 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.[N:27]1([C:33]2[N:34]=[C:35]([CH2:40][C:41]([O-])=[O:42])[NH:36][C:37](=[O:39])[CH:38]=2)[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1.[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:41](=[O:42])[CH2:40][C:35]1[NH:36][C:37](=[O:39])[CH:38]=[C:33]([N:27]2[CH2:28][CH2:29][O:30][CH2:31][CH2:32]2)[N:34]=1

Participants

7

Reactant 4

HCID 962WaterHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86699279HCID 86699279, compoundHCID 136041844Sodium (4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetate

Product 1

HCID 136378692HCID 136378692, compoundYield 83.4%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

125 mg of 4-difluoromethoxy-2-methyl-2,3-dihydro-1H-indole (reference example 11d) and 192.7 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride are added to a solution of 196.8 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate (obtained in step 2d of example 1d) 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 (95/05: v/v), so as to give 220 mg of 2-{2-[4-(difluoromethoxy)-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-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 (95/05: v/v)

Sources & evidence

ORD record
ord-ebe56ab44c7e45b79d07071e7f680b86
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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