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

HRID 1424791노트

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HRID 1424791 반응식
[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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 6344Dichloromethane용매2회HCID 516892Sodium Bicarbonate용매HCID 21584188Chloroform methanol용매

실험 절차

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+).

후처리

  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)

출처 및 근거

ORD 기록
ord-a9ceb824724e4a53b5341b693d9751fa
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08927593B2

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