Sulfuric Acid → 4-{[2-(4-Bromo-3-methylphenylcarbamoyl)thiophen-3-ylamino]methyl}pyridine-2-carboxylic acid methylamide

HRID 641791

反応式

HRID 641791 の反応式
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[S:12][CH:13]=[CH:14][C:15]=2[NH2:16])=[O:10])=[CH:4][C:3]=1[CH3:17].BrC1C=CC(N)=CC=1C.[CH3:27][NH:28][C:29]([C:31]1[CH:36]=[C:35]([CH:37]=O)[CH:34]=[CH:33][N:32]=1)=[O:30].OS(O)(=O)=O.[BH4-].[Na+].[OH-].[Na+]>C1COCC1.O>[CH3:27][NH:28][C:29]([C:31]1[CH:36]=[C:35]([CH2:37][NH:16][C:15]2[CH:14]=[CH:13][S:12][C:11]=2[C:9](=[O:10])[NH:8][C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[C:3]([CH3:17])[CH:4]=2)[CH:34]=[CH:33][N:32]=1)=[O:30]

参加物

9

反応物 6

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 233594-Bromo-3-methylanilineHCID 4311764Sodium borohydrideHCID 219638894-formyl-N-methylpicolinamideHCID 61091031N-(4-bromo-3-methylphenyl)3-aminothiophene-2-carboxamide

生成物 1

HCID 100043674-{[2-(4-Bromo-3-methylphenylcarbamoyl)thiophen-3-ylamino]methyl}pyridine-2-carboxylic acid methylamide

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

To a stirred solution of N-(4-bromo-3-methylphenyl)3-aminothiophene-2-carboxamide (1 equiv, prepared as described above for EXAMPLE 1, part 1, using 4-bromo-3-methylaniline instead of 4-trifluoromethoxyaniline) in THF at 0° C. in an open flask, was added 2-(N-methylcarbamoyl)pyridine-4-carboxaldehyde (prepared as described in International Patent Publication No. WO 01/23375) (1.1 equiv) in THF and 4M H2SO4 (0.1 equiv) and the mixture was stirred for 30 min at 0° C. Sodium borohydride (1 equiv) was added portionwise and the mixture was allowed to warm to RT and stirred for 2 h. Water was then added, the mixture was basified to pH 12 with 2M sodium hydroxide solution, and the resulting product was extracted into ethyl acetate. The combined extracts were washed with water followed by brine, dried (MgSO4), filtered and concentrated in vacuo to afford a yellow semisolid, which was purified by column chromatography eluting with a 95:5 mixture of hexane:ethyl acetate increasing gradually to a 50:50 mixture. MS (ES+): 459, 461 [MH+]

後処理

  1. customat 0° C.
  2. temperatureto warm to RT
  3. stirringstirred for 2 h
  4. extractionthe resulting product was extracted into ethyl acetate
  5. washThe combined extracts were washed with water
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford a yellow semisolid, which
  10. customwas purified by column chromatography
  11. washeluting with a 95:5 mixture of hexane

出典と根拠

ORDレコード
ord-1cdab2a2b05c416290bd1e76b24adbcc
出典データセット
uspto-grants-2010_04
特許番号
US07696225B2

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