Acetic Acid → 4-{[(6-Phenoxypyridin-3-yl)methyl]amino}-1H-imidazole-5-carboxamide

HRID 912717노트

반응식

HRID 912717 반응식
C(N(CC)CC)C.Cl.[NH2:9][C:10]1[NH:14][CH:13]=[N:12][C:11]=1[C:15]([NH2:17])=[O:16].[O:18]([C:25]1[CH:32]=[CH:31][C:28]([CH:29]=O)=[CH:27][N:26]=1)[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.C(O)(=O)C.C([BH3-])#N.[Na+].[BH4-].[Na+].C([O-])(O)=O.[Na+]>CO.CN1C(=O)CCC1>[O:18]([C:25]1[N:26]=[CH:27][C:28]([CH2:29][NH:9][C:10]2[N:14]=[CH:13][NH:12][C:11]=2[C:15]([NH2:17])=[O:16])=[CH:31][CH:32]=1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1

참가 물질

10

반응물 7

HCID 176Acetic AcidHCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 27765006-PhenoxynicotinaldehydeHCID 4311764Sodium borohydride2회HCID 5003444Sodium cyanoborohydride3회HCID 178479549HCID 178479549, 화합물

생성물 1

HCID 674149314-{[(6-Phenoxypyridin-3-yl)methyl]amino}-1H-imidazole-5-carboxamide

시약·촉매·용매 2

HCID 887Methanol용매HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
50 °C

실험 절차

Triethylamine (0.47 mL, 3.38 mmol) was added to 5-aminoimidazole-4-carboxamide hydrochloride (0.50 g, 3.1 mmol) in anhydrous methanol (12 mL). The reaction mixture was stirred for 10 min and 6-phenoxynicotinaldehyde (0.74 g, 3.7 mmol) and acetic acid (0.09 mL, 1.57 mmol) were added. The dark solution was stirred over night and sodium cyanoborohydride (0.23 g, 3.7 mmol) was added. More sodium cyanoborohydride (0.15 g, 2.4 mmol) was added after 40 min and the mixture was stirred for another 3 h. The reaction mixture was heated at 50° C. for 3 h, sodium cyanoborohydride (0.15 g, 2.4 mmol) was added and the mixture was heated at 50° C. over night. Sodium borohydride (0.12 g, 3.2 mmol) was added and the mixture was heated at 50° C. for 1 h, more sodium borohydride (0.15 g, 4.0 mmol) and NMP (1.0 mL) were added and the mixture was heated at 60° C. for 3.5 h. After cooling, NaHCO3 (sat., 20 mL) was added and some of the methanol was removed in vacuo. The mixture was extracted with EtOAc, the organic phase was extracted with 1N HCl (2×30 mL) and the acidic phase was made basic with 2N NaOH and was extracted with DCM. The organic phase was dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography on silica (0 to 10% MeOH in DCM+NH3) to yield 0.25 g (0.81 mmol, 26%) of a slightly green syrup.

후처리

  1. stirringThe dark solution was stirred over night
  2. stirringthe mixture was stirred for another 3 h
  3. temperaturethe mixture was heated at 50° C. over night
  4. temperaturethe mixture was heated at 50° C. for 1 h
  5. temperaturethe mixture was heated at 60° C. for 3.5 h
  6. temperatureAfter cooling
  7. customsome of the methanol was removed in vacuo
  8. extractionThe mixture was extracted with EtOAc
  9. extractionthe organic phase was extracted with 1N HCl (2×30 mL)
  10. extractionwas extracted with DCM
  11. dry with materialThe organic phase was dried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe crude product was purified by column chromatography on silica (0 to 10% MeOH in DCM+NH3)
  15. customto yield 0.25 g (0.81 mmol, 26%) of a slightly green syrup

출처 및 근거

ORD 기록
ord-b498cf7ce1b84a598d7fb6ee44900a82
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08026244B2

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