Water → 2-{2-[4-bromo-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-5-fluoro-6-(morpholin-4-yl)pyrimidin-4(3H)-one

HRID 2278492Notes

Reaction equation

HRID 2278492 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH:5]([CH3:11])[NH:6]2.Cl.CN(C)CCCN=C=NCC.[F:24][C:25]1[C:30](=[O:31])[NH:29][C:28]([CH2:32][C:33]([O-])=[O:34])=[N:27][C:26]=1[N:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1.[Na+].O>CN(C)C=O.N1C=CC=CC=1>[Br:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][CH:5]([CH3:11])[N:6]2[C:33](=[O:34])[CH2:32][C:28]1[NH:29][C:30](=[O:31])[C:25]([F:24])=[C:26]([N:36]2[CH2:41][CH2:40][O:39][CH2:38][CH2:37]2)[N:27]=1

Participants

7

Reactant 4

HCID 962WaterHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 107272374-bromo-2-methyl-2,3-dihydro-1H-indoleHCID 136069585Sodium (5-fluoro-4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetate

Product 1

HCID 1363786662-{2-[4-bromo-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-5-fluoro-6-(morpholin-4-yl)pyrimidin-4(3H)-oneYield 51.1%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

150 mg of 4-bromo-2-methyl-2,3-dihydro-1H-indole [reference example 4a] and 197 mg of N-[3-(dimethylamino)propyl]-N′-ethylcarbodiimide hydrochloride are added to a solution of 217 mg of sodium (5-fluoro-4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetate (obtained in step 2a of example 6a) in 7 ml of N,N-dimethylformamide and 7 ml of pyridine. The reaction mixture is stirred at ambient temperature for 72 hours, then 50 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 triturated from dichloromethane, filtered and washed with diethyl ether so as to give 163 mg of 2-{2-[4-bromo-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-5-fluoro-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 triturated from dichloromethane
  7. filtrationfiltered
  8. washwashed with diethyl ether so as

Sources & evidence

ORD record
ord-32817725490a4f019ab8ccd75f536500
Source dataset
uspto-grants-2015_09
Patent number
US09133168B2

Reaction notes

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