1,4-Dioxane hydrochloride → HCID 54557691, compound

HRID 344371Notes

Reaction equation

HRID 344371 reaction equation
C(O[C:6]([NH:8][CH2:9][C@H:10]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]([C:22]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[N:24]([CH:31]([CH3:33])[CH3:32])[CH:23]=2)=[O:21])[CH2:11]1)=[O:7])(C)(C)C.[ClH:34].O1[CH2:40][CH2:39][O:38][CH2:37]C1>>[NH2:24][C:25]1[C:26]([Cl:34])=[CH:27][C:40]([C:6]([NH:8][CH2:9][C@H:10]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]([C:22]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[N:24]([CH:31]([CH3:33])[CH3:32])[CH:23]=3)=[O:21])[CH2:11]2)=[O:7])=[C:39]([O:38][CH3:37])[CH:30]=1

Participants

3

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 54300511HCID 54300511, compound

Product 1

HCID 54557691HCID 54557691, compound

Procedure

N-(4-((3R)-3-tert-Butoxycarbonylaminomethylpyrrolidin-1-yl)-butyl)-1-isopropyl-1 H-indole-3-carboxamide (1.34 g) was dissolved in 4N hydrochloric acid-dioxane solution (30 ml) and the mixture was stood at room temperature for 60 min. The reaction mixture was concentrated under reduced pressure. Dimethylformamide (30 ml) was added to the residue and the mixture was neutralized with triethylamine (0.81 ml). 4-Amino-5-chloro-2-methoxybenzoic acid (0.59 g) and 1-hydroxybenzotriazole (0.44 g) were added thereto, and the mixture was stirred at 0C for 15 min. Then, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.62 g) was added, and the mixture was stirred at room temperature for 8 hr. The reaction mixture was concentrated under reduced pressure. Aqueous potassium carbonate solution was added to the residue and the mixture was extracted with ethyl acetate. The extract was dried over magnesium sulfate and concentrated under reduced pressure. The obtained residue was purified by silica gel chromatography to give 0.62 g of N-(4-((3R)-3-(4-amino-5-chloro-2-methoxybenzoylaminomethyl)pyrrolidin-1-yl)butyl)-1-isopropyl-1 H-indole-3-carboxamide.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. additionDimethylformamide (30 ml) was added to the residue
  3. addition4-Amino-5-chloro-2-methoxybenzoic acid (0.59 g) and 1-hydroxybenzotriazole (0.44 g) were added
  4. additionThen, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.62 g) was added
  5. stirringthe mixture was stirred at room temperature for 8 hr
  6. concentrationThe reaction mixture was concentrated under reduced pressure
  7. additionAqueous potassium carbonate solution was added to the residue
  8. extractionthe mixture was extracted with ethyl acetate
  9. dry with materialThe extract was dried over magnesium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe obtained residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-5863c3d2457c46b8b8f9d9fabbe4a78e
Source dataset
uspto-grants-1999_01
Patent number
US05864039

Reaction notes

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