Methylamine → 5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-(methylsulfonamido)benzofuran-3-carboxamide

HRID 1424791ノート

反応式

HRID 1424791 の反応式
[CH:1]1([C:4]2[C:5]([NH:23][S:24]([CH3:27])(=[O:26])=[O:25])=[CH:6][C:7]3[O:11][C:10]([C:12]4[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=4)=[C:9]([C:19]([OH:21])=O)[C:8]=3[CH:22]=2)[CH2:3][CH2:2]1.[CH3:28][N:29](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.CN>ClCCl.C(=O)(O)[O-].[Na+].CO.C(Cl)(Cl)Cl>[CH:1]1([C:4]2[C:5]([NH:23][S:24]([CH3:27])(=[O:26])=[O:25])=[CH:6][C:7]3[O:11][C:10]([C:12]4[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=4)=[C:9]([C:19]([NH:29][CH3:28])=[O:21])[C:8]=3[CH:22]=2)[CH2:3][CH2:2]1

参加物

8

反応物 4

HCID 6329MethylamineHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 673529905-Cyclopropyl-2-(4-fluorophenyl)-6-((methylsulfonyl)amino)-3-benzofurancarboxylic acid

生成物 1

HCID 160735125-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-(methylsulfonamido)benzofuran-3-carboxamide

試薬・触媒・溶媒 3

HCID 6344Dichloromethane溶媒2 回HCID 516892Sodium Bicarbonate溶媒HCID 21584188Chloroform methanol溶媒

実験手順

A solution of 5-cyclopropyl-2-(4-fluorophenyl)-6-[(methylsulfonyl)amino]-1-benzofuran-3-carboxylic acid (2.52 g, 6.47 mmol), HATU (2.95 g, 7.77 mmol) and triethylamine (1.984 mL, 14.24 mmol) in dry dichloromethane (100 mL) was stirred at room temperature for 1 hour, then treated with methylamine (16.18 mL, 32.4 mmol). The solution was stirred at room temperature under nitrogen for 4 hours, during which time a precipitate formed. The reaction was diluted with dichloromethane (300 mL) and sodium bicarbonate solution (200 mL) and stirred for 10 minutes. The layers were separated and the aqueous layer extracted with further dichloromethane (150 mL). The combined organics were washed with brine (200 mL), dried using a hydrophobic frit and evaporated to dryness to give an off-white solid. The crude product was purified by flash chromatography (eluting with 0-100% ethyl acetate/cyclohexane followed by 10% methanol/dichloromethane) to give a white solid. The solid was dissolved in hot methanol-chloroform (10% v/v), preabsorped onto silica gel and purified by flash chromatography (0-10% methanol/dichloromethane) to give the 5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-[(methylsulfonyl)amino]-1-benzofuran-3-carboxamide. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.30 (br s, 1H) 8.42 (q, 1H) 7.88-7.98 (m, 2H) 7.60 (s, 1H) 7.37 (t, 2H) 7.16 (s, 1H) 3.06 (s, 3H) 2.83 (d, 3H) 2.23-2.36 (m, 1H) 0.93-1.05 (m, 2H) 0.65-0.74 (m, 2H). LCMS (m/z, ES+)=403 (M+H+).

後処理

  1. customformed
  2. stirringstirred for 10 minutes
  3. customThe layers were separated
  4. extractionthe aqueous layer extracted with further dichloromethane (150 mL)
  5. washThe combined organics were washed with brine (200 mL)
  6. customdried
  7. customevaporated to dryness
  8. customto give an off-white solid
  9. customThe crude product was purified by flash chromatography (eluting with 0-100% ethyl acetate/cyclohexane followed by 10% methanol/dichloromethane)
  10. customto give a white solid
  11. custompurified by flash chromatography (0-10% methanol/dichloromethane)

出典と根拠

ORDレコード
ord-a9ceb824724e4a53b5341b693d9751fa
出典データセット
uspto-grants-2015_01
特許番号
US08927593B2

反応ノート

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