1-Hydroxybenzotriazole → N-(5-chloropyridin-2-yl)-3-hydroxy-2-{[4-(1-methyl-4-oxo-1,4-dihydropyridin-3-yl)benzoyl]amino}benzamide hydrochloride

HRID 910621노트

반응식

HRID 910621 반응식
Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[NH2:23][C:24]1[C:39]([OH:40])=[CH:38][CH:37]=[CH:36][C:25]=1[C:26]([NH:28][C:29]1[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][N:30]=1)=[O:27].[CH3:41][N:42]1[CH:47]=[CH:46][C:45](=[O:48])[C:44]([C:49]2[CH:57]=[CH:56][C:52]([C:53](O)=[O:54])=[CH:51][CH:50]=2)=[CH:43]1>O.CN(C)C=O.C(N(CC)CC)C>[ClH:35].[Cl:35][C:32]1[CH:33]=[CH:34][C:29]([NH:28][C:26](=[O:27])[C:25]2[CH:36]=[CH:37][CH:38]=[C:39]([OH:40])[C:24]=2[NH:23][C:53](=[O:54])[C:52]2[CH:51]=[CH:50][C:49]([C:44]3[C:45](=[O:48])[CH:46]=[CH:47][N:42]([CH3:41])[CH:43]=3)=[CH:57][CH:56]=2)=[N:30][CH:31]=1

참가 물질

8

반응물 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 180011272-amino-N-(5-chloro-2-pyridinyl)-3-hydroxybenzamideHCID 575840694-(1-Methyl-4-oxo-1,4-dihydropyridin-3-yl)benzoic acid

생성물 1

HCID 67392177N-(5-chloropyridin-2-yl)-3-hydroxy-2-{[4-(1-methyl-4-oxo-1,4-dihydropyridin-3-yl)benzoyl]amino}benzamide hydrochloride수율 104.8%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8471Triethylamine용매

실험 절차

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (72 mg), 1-hydroxybenzotriazole (62 mg), triethylamine (64 μl) and 2-amino-N-(5-chloro-2-pyridinyl)-3-hydroxybenzamide (121 mg) were added to an N,N-dimethylformamide solution (3 ml) of 4-(1-methyl-4-oxo-1,4-dihydropyridin-3-yl)benzoic acid (88 mg), followed by stirring at room temperature for 14 hours. After this, water (30 ml) was added to the reaction solution, and the precipitated insoluble solid was collected by filtration. The resulting solid was dried at 60° C. under reduced pressure, then tetrahydrofuran (5 ml), N,N-dimethylformamide (1 ml) and acetic acid (104 μl) were added to the solid, followed by stirring under heating at 60° C. for 2 days. After this, the reaction solution was concentrated under reduced pressure, an aqueous saturated sodium hydrogencarbonate solution (30 ml) was added to the residue, followed by extraction with ethyl acetate. The organic layer was washed with an aqueous saturated sodium hydrogencarbonate solution and saturated brine, dried with magnesium sulfate, and concentrated under reduced pressure. The residue was purified by NH-silica gel column chromatography (chloroform:methanol=97:3). The purified product was suspended in ethanol, 1 M hydrochloric acid (324 μl) was added, followed by concentration under reduced pressure. The residue was recrystallized from ethanol to obtain N-(5-chloropyridin-2-yl)-3-hydroxy-2-{[4-(1-methyl-4-oxo-1,4-dihydropyridin-3-yl)benzoyl]amino}benzamide hydrochloride (123 mg).

후처리

  1. filtrationthe precipitated insoluble solid was collected by filtration
  2. customThe resulting solid was dried at 60° C. under reduced pressure
  3. additiontetrahydrofuran (5 ml), N,N-dimethylformamide (1 ml) and acetic acid (104 μl) were added to the solid
  4. stirringby stirring
  5. temperatureunder heating at 60° C. for 2 days
  6. concentrationAfter this, the reaction solution was concentrated under reduced pressure
  7. additionan aqueous saturated sodium hydrogencarbonate solution (30 ml) was added to the residue
  8. extractionfollowed by extraction with ethyl acetate
  9. washThe organic layer was washed with an aqueous saturated sodium hydrogencarbonate solution and saturated brine
  10. dry with materialdried with magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by NH-silica gel column chromatography (chloroform:methanol=97:3)
  13. addition1 M hydrochloric acid (324 μl) was added
  14. concentrationfollowed by concentration under reduced pressure
  15. customThe residue was recrystallized from ethanol

출처 및 근거

ORD 기록
ord-133b185c8fb344a99f002d741e8f4d25
출처 데이터셋
uspto-grants-2011_09
특허 번호
US08022208B2

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