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 2278492ノート

反応式

HRID 2278492 の反応式
[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

参加物

7

反応物 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

生成物 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)-one収率 51.1%

試薬・触媒・溶媒 2

HCID 1049Pyridine溶媒HCID 6228Dimethylformamide溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-32817725490a4f019ab8ccd75f536500
出典データセット
uspto-grants-2015_09
特許番号
US09133168B2

反応ノート

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