1,4-Dioxane hydrochloride → HCID 53740475, compound

HRID 344372Notes

Reaction equation

HRID 344372 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]([CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH:23]=2)=[O:21])[CH2:11]1)=[O:7])(C)(C)C.[ClH:38].O1[CH2:44][CH2:43][O:42][CH2:41]C1>>[NH2:24][C:25]1[C:26]([Cl:38])=[CH:27][C:44]([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]([CH2:31][C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)[CH:23]=3)=[O:21])[CH2:11]2)=[O:7])=[C:43]([O:42][CH3:41])[CH:30]=1

Participants

3

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 53886366HCID 53886366, compound

Product 1

HCID 53740475HCID 53740475, compound

Conditions

Temperature
0 °C

Procedure

N-(4-((3R)-3-tert-Butoxycarbonylaminomethylpyrrolidin-1-yl)-butyl)-1-benzyl-1 H-indole-3-carboxamide (1.35 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 (0.74 ml). 4-Amino-5-chloro-2-methoxybenzoic acid (0.54 g) and 1-hydroxybenzotriazole (0.40 g) were added thereto, and the mixture was stirred at 0° C. for 15 min. Then, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.56 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 1.03 g of N-(4-((3R)-3-(4-amino-5-chloro-2-methoxybenzoylaminomethyl)pyrrolidin-1-yl)butyl)-l-benzyl-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 (0.54 g) and 1-hydroxybenzotriazole (0.40 g) were added
  4. additionThen, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.56 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-ad92511a25574e2c8b600959bbcbe6dd
Source dataset
uspto-grants-1999_01
Patent number
US05864039

Reaction notes

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