Tolvaptan → HCID 66733251、化合物

HRID 1184645

反応式

HRID 1184645 の反応式
[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]

参加物

8

反応物 4

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

生成物 1

HCID 66733251HCID 66733251、化合物収率 138.2%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒HCID 8471Triethylamine溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-a321a6aa93664227ac09a582f8845467
出典データセット
uspto-grants-2014_03
特許番号
US08669229B2

関連ノート

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