Potassium Carbonate → Ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropanecarbonyl)-4-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-4-oxobutanoate

HRID 1056260노트

반응식

HRID 1056260 반응식
Br[CH2:2][C:3]([C:5]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:6]=1[N:7]=[C:8]([NH:16][CH2:17][C:18]([F:21])([F:20])[F:19])[C:9]([CH3:15])=[N:10]2)=[O:4].[C:22]([O:26][C:27]([NH:29][C:30]1([C:33](=[O:40])[CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:32][CH2:31]1)=[O:28])([CH3:25])([CH3:24])[CH3:23].C([O-])([O-])=O.[K+].[K+].[NH4+].[Cl-]>CN(C=O)C.CCOC(C)=O>[C:22]([O:26][C:27]([NH:29][C:30]1([C:33]([CH:34]([CH2:2][C:3]([C:5]2[CH:14]=[CH:13][CH:12]=[C:11]3[C:6]=2[N:7]=[C:8]([NH:16][CH2:17][C:18]([F:21])([F:20])[F:19])[C:9]([CH3:15])=[N:10]3)=[O:4])[C:35]([O:37][CH2:38][CH3:39])=[O:36])=[O:40])[CH2:32][CH2:31]1)=[O:28])([CH3:25])([CH3:24])[CH3:23]

참가 물질

7

반응물 4

HCID 11430Potassium CarbonateHCID 25517Ammonium ChlorideHCID 89781999Ethyl 3-(1-{[(tert-butoxy)carbonyl]amino}cyclopropyl)-3-oxopropanoateHCID 897820082-Bromo-1-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)ethanone

생성물 1

HCID 89782129Ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropanecarbonyl)-4-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-4-oxobutanoate수율 83.5%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of 2-bromo-1-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)ethanone (616) (700 mg, 1.93 mmol), ethyl 3-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-3-oxopropanoate (604, 629 mg, 2.32 mmol) and K2CO3 (668 mg, 4.83 mmol) in DMF (7.0 mL) was stirred at RT for 45 min. The reaction mixture was treated with a saturated solution of NH4Cl (aq.) and EtOAc was added and the layers were separated. The organic layer was washed with brine (25 mL), and dried over anhydrous MgSO4, filtered and concentrated. The crude material was purified by chromatography on an ISCO Combiflash RF (40 g SingleStep column, eluted using a gradient of 0-90% EtOAc in hexanes) affording ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropanecarbonyl)-4-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-4-oxobutanoate (890 mg, 1.611 mmol, 83% yield) as a light orange viscous oil. m/z (ESI, +ve ion) 553.3 (M+H)+. The light orange viscous oil was added to a sealed tube with EtOH (4 mL). AcOH (2 mL) and NH4OAc (1192 mg, 15.46 mmol) were added and the mixture was stirred at 60° C. for 12 h. The reaction mixture was concentrated. The residue was treated with EtOAc and water. The layers were separated and the organic layer was washed with brine. The organic layer was dried over anhydrous MgSO4, filtered and concentrated. The crude material was purified by chromatography on an ISCO Combiflash RF (40 g Thomson SingleStep column, eluting with a gradient of 0-70% EtOAc in hexanes) to provide the title compound (970 mg, 1.81 mmol, 94% yield) as yellow crystalline solid. 19F NMR (376 MHz, CDCl3) δ ppm −71.24 (3F, s). m/z (ESI, +ve ion) 534.2 (M+H)+.

후처리

  1. additionwas added
  2. customthe layers were separated
  3. washThe organic layer was washed with brine (25 mL)
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by chromatography on an ISCO Combiflash RF (40 g SingleStep column
  8. washeluted

출처 및 근거

ORD 기록
ord-d78eec2ffd5d4543b0caf5bc30e3dc8b
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394297B2

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