1-Iodo-3-methylbutane → 6-(3-Chloro-4-fluoro-phenyl)-8-ethyl-8-methyl-5-(3-methyl-butyl)-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-carboxylic acid methyl ester

HRID 2047704

반응식

HRID 2047704 반응식
[CH3:1][O:2][C:3]([C:5]1[CH:14]=[CH:13][C:12]2[NH:11][CH:10]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[C:17]([Cl:22])[CH:16]=3)[CH2:9][C:8]([CH2:24][CH3:25])([CH3:23])[C:7]=2[N:6]=1)=[O:4].[H-].[Na+].I[CH2:29][CH2:30][CH:31]([CH3:33])[CH3:32]>CN(C)C=O>[CH3:1][O:2][C:3]([C:5]1[CH:14]=[CH:13][C:12]2[N:11]([CH2:29][CH2:30][CH:31]([CH3:33])[CH3:32])[CH:10]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[C:17]([Cl:22])[CH:16]=3)[CH2:9][C:8]([CH2:24][CH3:25])([CH3:23])[C:7]=2[N:6]=1)=[O:4]

참가 물질

5

반응물 3

HCID 109241-Iodo-3-methylbutaneHCID 24758Sodium hydrideHCID 66587522HCID 66587522, 화합물

생성물 1

HCID 665877056-(3-Chloro-4-fluoro-phenyl)-8-ethyl-8-methyl-5-(3-methyl-butyl)-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-carboxylic acid methyl ester수율 73.9%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
0 °C

실험 절차

To a 0° C. solution of 6-(3-chloro-4-fluoro-phenyl)-8-ethyl-8-methyl-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-carboxylic acid methyl ester (200 mg, 0.5 mmol) in N,N-dimethylformamide (5 mL) was added a 60% dispersion of sodium hydride in mineral oil (44 mg, 1.1 mmol) portionwise. The mixture was stirred at 0° C. for 30 min and then 1-iodo-3-methyl-butane (327 mg, 1.6 mmol) was added to above mixture dropwise at 0° C. The mixture was stirred at 0° C. for 3 hours and then extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The yellowish residue was purified by ISCO combi-flash chromatography (gradient elution, 0-5% ethyl acetate/hexane) to afford 6-(3-chloro-4-fluoro-phenyl)-8-ethyl-8-methyl-5-(3-methyl-butyl)-5,6,7,8-tetrahydro-[1,5]naphthyridine-2-carboxylic acid methyl ester (160 mg, 67.5%) as a yellow oil. MS (ESI+) [(M+H)+] 433.1.

후처리

  1. stirringThe mixture was stirred at 0° C. for 3 hours
  2. extractionextracted with ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe yellowish residue was purified by ISCO combi-flash chromatography (gradient elution, 0-5% ethyl acetate/hexane)

출처 및 근거

ORD 기록
ord-94d32a24d5124111b84cf2d5c19ac397
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08592594B2

연결된 노트

불러오는 중…