Hydrogen Bromide → methyl 2-bromo-3-chloro-5-{N-[5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-6-yl]methanesulfonamido}benzoate

HRID 2272336노트

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HRID 2272336 반응식
N([O-])=O.[Na+].N[C:6]1[C:15]([Cl:16])=[CH:14][C:13]([N:17]([C:22]2[C:41]([CH:42]3[CH2:44][CH2:43]3)=[CH:40][C:25]3[C:26]([C:36](=[O:39])[NH:37][CH3:38])=[C:27]([C:29]4[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=4)[O:28][C:24]=3[CH:23]=2)[S:18]([CH3:21])(=[O:20])=[O:19])=[CH:12][C:7]=1[C:8]([O:10][CH3:11])=[O:9].[BrH:45]>C(#N)C.CCOC(C)=O.O.[Cu]Br>[Br:45][C:6]1[C:15]([Cl:16])=[CH:14][C:13]([N:17]([C:22]2[C:41]([CH:42]3[CH2:44][CH2:43]3)=[CH:40][C:25]3[C:26]([C:36](=[O:39])[NH:37][CH3:38])=[C:27]([C:29]4[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=4)[O:28][C:24]=3[CH:23]=2)[S:18]([CH3:21])(=[O:20])=[O:19])=[CH:12][C:7]=1[C:8]([O:10][CH3:11])=[O:9]

참가 물질

8

반응물 3

HCID 260Hydrogen BromideHCID 23668193Sodium NitriteHCID 122643072HCID 122643072, 화합물

생성물 1

HCID 122643076methyl 2-bromo-3-chloro-5-{N-[5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)-1-benzofuran-6-yl]methanesulfonamido}benzoate수율 86%

시약·촉매·용매 4

HCID 24593copper(I) bromide촉매HCID 962Water용매HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

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온도
0 °C

실험 절차

Sodium nitrite (0.17 g, 2.42 mmol) was added to a 0° C. solution of methyl 2-amino-3-chloro-5-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)benzoate (1.29 g, 2.20 mmol) in acetonitrile (7.3 ml) and 48% aqueous HBr (7.3 ml) at 0° C. and the reaction mixture was stirred at 0° C. for 30 mins, Copper(I) bromide (0.38 g, 2.64 mmol) was added and the solution was heated at 50° C. for 30 mins. The reaction mixture was cooled to RT, diluted with EtOAc and water. The organic layer was washed with brine, dried (Na2SO4), filtered, evaporated and purified by silica gel chromatography (0-50% EtOAc/hexanes) to afford the title compound (1.24 g, 86%) as a white foam. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.86-7.93 (m, 2H), 7.50-7.63 (m, 4H), 7.17-7.25 (m, 2H), 5.79 (br. s., 1H), 3.92 (s, 3H), 3.28 (s, 3H), 3.01 (d, J=4.88 Hz, 3H), 1.94-2.04 (m, 1H), 0.76-1.09 (m, 3H), 0.55 (br. s., 1H).

후처리

  1. temperaturethe solution was heated at 50° C. for 30 mins
  2. temperatureThe reaction mixture was cooled to RT
  3. washThe organic layer was washed with brine
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. custompurified by silica gel chromatography (0-50% EtOAc/hexanes)

출처 및 근거

ORD 기록
ord-d195688fdd9740c79a9db7fb9ce0b10f
출처 데이터셋
uspto-grants-2015_09
특허 번호
US09119868B2

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