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

HRID 2278614Notes

Reaction equation

HRID 2278614 reaction equation
N1C=CC=CC=1.[F:7][C:8]([F:19])([F:18])[C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[CH2:11][CH2:12][NH:13]2.Cl.CN(C)CCCN=C=NCC.[CH3:32][N:33]1[C:38](=[O:39])[CH:37]=[C:36]([N:40]2[CH2:45][CH2:44][O:43][CH2:42][CH2:41]2)[N:35]=[C:34]1[CH2:46][C:47]([O-])=[O:48].[Na+]>CN(C)C=O.C(OCC)(=O)C.O>[CH3:32][N:33]1[C:38](=[O:39])[CH:37]=[C:36]([N:40]2[CH2:45][CH2:44][O:43][CH2:42][CH2:41]2)[N:35]=[C:34]1[CH2:46][C:47](=[O:48])[N:13]1[C:14]2[C:10](=[C:9]([C:8]([F:7])([F:18])[F:19])[CH:17]=[CH:16][CH:15]=2)[CH2:11][CH2:12]1

Participants

8

Reactant 4

HCID 1049PyridineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 162444454-(Trifluoromethyl)indolineHCID 57523684Sodium [1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate

Product 1

HCID 573895513-methyl-6-(morpholin-4-yl)-2-{2-oxo-2-[4-(trifluoromethyl)-2,3-dihydro-1H-indol-1-yl]ethyl}pyrimidin-4(3H)-oneYield 30.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

3 ml of pyridine, 94 mg of 4-trifluoromethyl-2,3-dihydro-1H-indole and 153 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride are successively added to a solution of 138 mg of sodium [1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetate in 3 ml of N,N-dimethylformamide. The reaction mixture is stirred at ambient temperature for 16 hours. After the addition of 50 ml of water and extraction with ethyl acetate (3×15 ml), the organic phases are combined and then washed with water (2×15 ml), and a saturated aqueous sodium chloride solution (15 ml), and then dried over magnesium sulfate, filtered through sintered glass, and concentrated under reduced pressure. The solid obtained is washed with diethyl ether (5 ml) and then dried, so as to give 64 mg of 3-methyl-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 pink solid, the characteristics of which are the following:

Workup

  1. washwashed with water (2×15 ml)
  2. dry with materiala saturated aqueous sodium chloride solution (15 ml), and then dried over magnesium sulfate
  3. filtrationfiltered through sintered glass
  4. concentrationconcentrated under reduced pressure
  5. customThe solid obtained
  6. washis washed with diethyl ether (5 ml)
  7. customdried

Sources & evidence

ORD record
ord-c7d7c19ed6c04fbb8066f0b74fc57d62
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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