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

HRID 2211950

반응식

HRID 2211950 반응식
[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]

참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
0 °C

실험 절차

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+]

후처리

  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

출처 및 근거

ORD 기록
ord-4a87829b6f7b4c64a1c0ddb5a837466d
출처 데이터셋
uspto-grants-2006_09
특허 번호
US07101893B2

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