Sodium hydride → (8S)-2-chloro-9-[2-(6-methylpyrid-3-yl)-2-oxoethyl]-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one

HRID 633748

반응식

HRID 633748 반응식
[Cl:1][C:2]1[N:3]=[C:4]2[NH:12][C@H:11]([C:13]([F:16])([F:15])[F:14])[CH2:10][CH2:9][N:5]2[C:6](=[O:8])[CH:7]=1.[H-].[Na+].Br.Br[CH2:21][C:22]([C:24]1[CH:25]=[N:26][C:27]([CH3:30])=[CH:28][CH:29]=1)=[O:23]>CN(C=O)C>[Cl:1][C:2]1[N:3]=[C:4]2[N:12]([CH2:21][C:22]([C:24]3[CH:25]=[N:26][C:27]([CH3:30])=[CH:28][CH:29]=3)=[O:23])[C@H:11]([C:13]([F:14])([F:15])[F:16])[CH2:10][CH2:9][N:5]2[C:6](=[O:8])[CH:7]=1

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 454805112-Bromo-1-(6-methylpyridin-3-yl)ethanone hydrobromideHCID 136238740(S)-8-chloro-2-(trifluoromethyl)-3,4-dihydro-1H-pyrimido[1,2-a]pyrimidin-6(2H)-one

생성물 1

HCID 118194335(8S)-2-chloro-9-[2-(6-methylpyrid-3-yl)-2-oxoethyl]-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

실험 절차

1 g (3.94 mmol) of (8S)-2-chloro-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one is added to a suspension of 394.27 mg (9.86 mmol) of sodium hydride in 40 mL of DMF. The reaction mixture is placed under magnetic stirring at room temperature for 15 minutes. A solution of 1.16 g (3.94 mmol) of 2-bromo-1-(6-methylpyrid-3-yl)ethanone hydrobromide in 10 mL of DMF is added dropwise to the reaction medium at 0° C. The reaction is stirred at room temperature overnight. The reaction medium is evaporated to dryness. The crude product is taken up in water and extracted with ethyl acetate. The organic phase is dried over magnesium sulfate and evaporated to dryness. After purification by chromatography on silica gel (eluent A/B: heptane/EtOAc, gradient A/B: t 0 min 30% B, t 35 min 60% B, t 40 min 60% B), 480 mg of (8S)-2-chloro-9-[2-(6-methylpyrid-3-yl)-2-oxoethyl]-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one were obtained, corresponding to the following characteristics:

후처리

  1. stirringThe reaction is stirred at room temperature overnight
  2. customThe reaction medium is evaporated to dryness
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic phase is dried over magnesium sulfate
  5. customevaporated to dryness
  6. customAfter purification by chromatography on silica gel (eluent A/B: heptane/EtOAc, gradient A/B: t 0 min 30% B, t 35 min 60% B, t 40 min 60% B), 480 mg of (8S)-2-chloro-9-[2-(6-methylpyrid-3-yl)-2-oxoethyl]-8-trifluoromethyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one
  7. customwere obtained, corresponding to the following characteristics

출처 및 근거

ORD 기록
ord-05edf66e4562436892f128b576a48f75
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09321790B2

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