Tolvaptan → HCID 66733251, 화합물

HRID 1184645

반응식

HRID 1184645 반응식
[CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:7]=1[C:8]([NH:10][C:11]1[CH:12]=[CH:13][C:14]([C:18]([N:20]2[C:26]3[CH:27]=[CH:28][C:29]([Cl:31])=[CH:30][C:25]=3[CH:24]([OH:32])[CH2:23][CH2:22][CH2:21]2)=[O:19])=[C:15]([CH3:17])[CH:16]=1)=[O:9].Cl.[CH3:34][N:35]([CH3:42])[CH2:36][CH2:37][CH2:38][C:39](O)=[O:40].Cl.CN(C)CCCN=C=NCC.C(=O)([O-])O.[Na+]>CN(C)C1C=CN=CC=1.ClCCl.C(N(CC)CC)C>[ClH:31].[CH3:34][N:35]([CH3:42])[CH2:36][CH2:37][CH2:38][C:39]([O:32][CH:24]1[CH2:23][CH2:22][CH2:21][N:20]([C:18](=[O:19])[C:14]2[CH:13]=[CH:12][C:11]([NH:10][C:8](=[O:9])[C:7]3[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=3[CH3:1])=[CH:16][C:15]=2[CH3:17])[C:26]2[CH:27]=[CH:28][C:29]([Cl:31])=[CH:30][C:25]1=2)=[O:40]

참가 물질

8

반응물 4

HCID 216237TolvaptanHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 126916404-(Dimethylamino)butyric acid hydrochloride

생성물 1

HCID 66733251HCID 66733251, 화합물수율 138.2%

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매HCID 8471Triethylamine용매

실험 절차

Tolvaptan (1.0 g, 2.2 mmol), 4-dimethylamino-butyric acid hydrochloride (0.48 g, 2.9 mmol), and 4-dimethylaminopyridine (27 mg, 0.22 mmol) were suspended in dichloromethane (5 ml). Triethylamine (0.4 ml) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (WSC) (0.55 g, 2.9 mmol) were added thereto, and the mixture was stirred at room temperature for 12 hours. An aqueous saturated sodium hydrogen carbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with an aqueous saturated sodium chloride solution, dried over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was purified by silica gel flash chromatography (n-hexane:ethyl acetate=50:50→0:100). The purified product was concentrated under reduced pressure. The residue was then dissolved in ethyl acetate, a 4N hydrogen chloride ethyl acetate solution was added thereto, and the resultant mixture was concentrated under reduced pressure. To the residue was added water (10 ml). After filteration, the filtrate was freeze-dried to obtain 0.91 g of 7-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl 4-dimethylaminobutyrate hydrochloride as white amorphous solid.

후처리

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with an aqueous saturated sodium chloride solution
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationAfter filtration and concentration under reduced pressure
  5. customthe residue was purified by silica gel flash chromatography (n-hexane:ethyl acetate=50:50→0:100)
  6. concentrationThe purified product was concentrated under reduced pressure
  7. dissolutionThe residue was then dissolved in ethyl acetate
  8. additiona 4N hydrogen chloride ethyl acetate solution was added
  9. concentrationthe resultant mixture was concentrated under reduced pressure
  10. additionTo the residue was added water (10 ml)
  11. customAfter filteration, the filtrate was freeze-dried

출처 및 근거

ORD 기록
ord-a321a6aa93664227ac09a582f8845467
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08669229B2

연결된 노트

불러오는 중…