Cyclohexanecarbonyl chloride → N-[(1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)methyl]-N-{[3-(4-methylpiperazin-1-yl)-2,3,4,5-tetrahydrooxepin-3-yl]methyl}cyclohexanecarboxamide

HRID 1943015노트

반응식

HRID 1943015 반응식
[CH3:1][N:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([CH2:12][NH:13][CH2:14][C:15]2([N:22]3[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]3)[CH2:21][CH2:20][CH:19]=[CH:18][O:17][CH2:16]2)[C:3]1=[O:29].[CH:30]1([C:36](Cl)=[O:37])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1>C(Cl)Cl>[CH3:1][N:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[C:4]([CH2:12][N:13]([CH2:14][C:15]2([N:22]3[CH2:23][CH2:24][N:25]([CH3:28])[CH2:26][CH2:27]3)[CH2:21][CH2:20][CH:19]=[CH:18][O:17][CH2:16]2)[C:36]([CH:30]2[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]2)=[O:37])[C:3]1=[O:29]

참가 물질

4

반응물 2

HCID 75938Cyclohexanecarbonyl chlorideHCID 584159511-Methyl-3-[({[3-(4-methylpiperazin-1-yl)-2,3,4,5-tetrahydrooxepin-3-yl]methyl}amino)methyl]quinolin-2(1H)-one

생성물 1

HCID 58415943N-[(1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)methyl]-N-{[3-(4-methylpiperazin-1-yl)-2,3,4,5-tetrahydrooxepin-3-yl]methyl}cyclohexanecarboxamide수율 70%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

실험 절차

To a solution of 1-methyl-3-[({[3-(4-methylpiperazin-1-yl)-2,3,4,5-tetrahydrooxepin-3-yl]methyl}amino)methyl]quinolin-2(1H)-one (100 mg, 0.252 mmole) in CH2Cl2 (1.5 ml) was added TEA (0.053 ml, 0.378 mmole) then cyclohexanecarbonyl chloride (0.044 ml, 0.328 mmole). After 2 hr the mixture was concentrated. The crude material was purified by preparative reversed-phase HPLC (30×150 mm Waters Sunfire, 5-50% CH3CN/water containing 0.1% TFA over 20 min at 50 mL/min). Fractions containing the product were pooled and concentrated. The residue was taken up in MeOH then passed through Dowex 1×2-400 ion exchange resin (prewashed with 1M NaOH, H2O, MeOH) washing with MeOH. The filtrate was concentrated to give the title compound as a white solid (89 mg, 70%). 1H-NMR (CDCl3, 500 MHz) d 7.58 (t, J=8.30 Hz, 1 H), 7.52 (d, J=7.57 Hz, 1 H), 7.39 (d, J=8.30 Hz, 1 H), 7.25 (m, 1 H), 7.22 (s, 1 H), 6.21 (d, J=6.34 Hz, 1 H), 5.24 (d, J=19.77 Hz, 1 H), 4.60 (m, 2 H), 4.44 (d, J=13.19 Hz, 1 H), 4.24 (d, J=14.16 Hz, 1 H), 4.05 (d, J=13.18 Hz, 1 H), 3.78 (s, 3 H), 3.07 (d, J=14.16 Hz, 1 H), 2.74 (m, 1 H), 2.62 (m, 2 H), 2.45-2.21 (m, 6 H), 2.26 (s, 3 H), 2.16-2.05 (m, 2 H), 1.82-1.48 (m, 9 H), 1.25-1.06 (m, 3 H). HRMS (M+H)+ calculated 507.3330. found 507.3329.

후처리

  1. concentrationAfter 2 hr the mixture was concentrated
  2. customThe crude material was purified by preparative reversed-phase HPLC (30×150 mm Waters Sunfire, 5-50% CH3CN/water containing 0.1% TFA over 20 min at 50 mL/min)
  3. additionFractions containing the product
  4. concentrationconcentrated
  5. washwashing with MeOH
  6. concentrationThe filtrate was concentrated

출처 및 근거

ORD 기록
ord-09739894b86a4e9c856c842e0ea26206
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08389720B2

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