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

HRID 2278619Notes

Reaction equation

HRID 2278619 reaction equation
N1(C2N=C(CC(=O)N3C4C(=C([C:24]([F:27])(F)[F:25])C=CC=4)CC3)NC(=O)C=2)CCOCC1.Cl.CN(C)[CH2:33][CH2:34][CH2:35][N:36]=[C:37]=NCC.[N:42]1([C:48]2[N:49]=[C:50]([CH2:55][C:56]([O-:58])=O)[NH:51][C:52](=[O:54])[CH:53]=2)[CH2:47][CH2:46][O:45][CH2:44][CH2:43]1.[Na+].[OH2:60].N1C=[CH:65][CH:64]=[CH:63][CH:62]=1>CN(C)C=O>[F:25][CH:24]([F:27])[O:60][C:64]1[CH:65]=[CH:33][CH:34]=[C:35]2[C:63]=1[CH2:62][CH2:37][N:36]2[C:56](=[O:58])[CH2:55][C:50]1[NH:51][C:52](=[O:54])[CH:53]=[C:48]([N:42]2[CH2:43][CH2:44][O:45][CH2:46][CH2:47]2)[N:49]=1

Participants

7

Reactant 5

HCID 962WaterHCID 1049PyridineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 136041844Sodium (4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetateHCID 1360696056-(morpholin-4-yl)-2-{2-oxo-2-[4-(trifluoromethyl)-2,3-dihydro-1H-indol-1-yl]ethyl}pyrimidin-4(3H)-one

Product 1

HCID 1360696082-{2-[4-(difluoromethoxy)-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

220 mg of 4-difluoromethoxy-2,3-dihydro-1H-indole (reference example 5d) and 364 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride are added to a solution of 327 mg of sodium [4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate (obtained in step 2d of example 1d) in 7 ml of N,N-dimethylformamide and 7 ml of pyridine. The reaction mixture is stirred at ambient temperature for 16 hours, and then 15 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 a mixture of dichloromethane and methanol (95/05: v/v), so as to give 24 mg of 2-{2-[4-(difluoromethoxy)-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-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
  7. additionbeing carried out with a mixture of dichloromethane and methanol (95/05: v/v)

Sources & evidence

ORD record
ord-39c99674320e4db3aacea58c25c09cd2
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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