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

HRID 2272336ノート

反応式

HRID 2272336 の反応式
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]

参加物

8

反応物 3

HCID 260Hydrogen BromideHCID 23668193Sodium NitriteHCID 122643072HCID 122643072、化合物

生成物 1

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

試薬・触媒・溶媒 4

HCID 24593copper(I) bromide触媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-d195688fdd9740c79a9db7fb9ce0b10f
出典データセット
uspto-grants-2015_09
特許番号
US09119868B2

反応ノート

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