Water → N-[(4-chlorophenyl)methyl]-6-[(4-fluoro-3,6-dihydro-2H-pyridin-1-yl)methyl]-1-methyl-4-oxo-quinoline-3-carboxamide

HRID 1067996노트

반응식

HRID 1067996 반응식
[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([CH2:21]Cl)[CH:17]=3)[N:12]([CH3:23])[CH:11]=2)=[O:9])=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.Cl.[F:36][C:37]1[CH2:38][CH2:39][NH:40][CH2:41][CH:42]=1.O>CN1CCCC1=O>[Cl:1][C:2]1[CH:25]=[CH:24][C:5]([CH2:6][NH:7][C:8]([C:10]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([CH2:21][N:40]4[CH2:39][CH:38]=[C:37]([F:36])[CH2:42][CH2:41]4)[CH:17]=3)[N:12]([CH3:23])[CH:11]=2)=[O:9])=[CH:4][CH:3]=1

참가 물질

6

반응물 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 211925684-Fluoro-1,2,3,6-tetrahydropyridine hydrochlorideHCID 21192571N-(4-Chlorobenzyl)-6-(chloromethyl)-1-methyl-4-oxo-1,4-dihydro-3-quinolinecarboxamide

생성물 1

HCID 16073869N-[(4-chlorophenyl)methyl]-6-[(4-fluoro-3,6-dihydro-2H-pyridin-1-yl)methyl]-1-methyl-4-oxo-quinoline-3-carboxamide수율 46%

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

실험 절차

To a solution of N-(4-chlorobenzyl)-6-(chloromethyl)-1-methyl-4-oxo-1,4-dihydro-3-quinolinecarboxamide from Preparation No. 35 (60 mg) in 1-methyl-2-pyrrolidinone (3 mL) is added N,N-diisopropylethylamine (0.075 mL) and 4-fluoro-1,2,3,6-tetrahydropyridine hydrochloride from Preparation No. 38 (119 mg). The reaction mixture is stirred at room temperature overnight and then heated at 60° C. for 4 hrs. The mixture is cooled to room temperature and poured into water to precipitate the product. The crude solid is adsorbed onto silica and purified by chromatography (eluent 100% CH2Cl2 (1 L), 0.25% MeOH in CH2Cl2 (1 L), 0.5% MeOH in CH2Cl2 (1 L), 0.75% MeOH in CH2Cl2 (1 L), 1% MeOH in CH2Cl2 (1 L), 1.25% MeOH in CH2Cl2 (1 L), 1.5% MeOH in CH2Cl2 (2 L)). Fractions homogenous by TLC are combined and concentrated to afford 32.2 mg (46%) of the desired product as a white solid.

후처리

  1. customfrom Preparation No
  2. temperatureheated at 60° C. for 4 hrs
  3. temperatureThe mixture is cooled to room temperature
  4. customto precipitate the product
  5. custompurified by chromatography (eluent 100% CH2Cl2 (1 L), 0.25% MeOH in CH2Cl2 (1 L), 0.5% MeOH in CH2Cl2 (1 L), 0.75% MeOH in CH2Cl2 (1 L), 1% MeOH in CH2Cl2 (1 L), 1.25% MeOH in CH2Cl2 (1 L), 1.5% MeOH in CH2Cl2 (2 L))
  6. concentrationconcentrated

출처 및 근거

ORD 기록
ord-e20fc72c516747b68f581b5dd2c8ca99
출처 데이터셋
uspto-grants-2001_06
특허 번호
US06248739B1

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