Hydrochloric Acid → HCID 15887032, compound

HRID 382470Notes

Reaction equation

HRID 382470 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([CH2:17][C@H:18]([N:20]([CH2:28][CH2:29][O:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=2[O:37][CH2:38][CH3:39])C(=O)OC(C)(C)C)[CH3:19])[CH:7]=[C:8]2[C:12]=1[N:11]([CH2:13][CH2:14][CH2:15][OH:16])[CH:10]=[CH:9]2)(=[O:3])[NH2:2].Cl.C(=O)(O)[O-].[Na+]>C(O)(C)C>[CH2:38]([O:37][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=1[O:30][CH2:29][CH2:28][NH:20][C@H:18]([CH3:19])[CH2:17][C:6]1[CH:7]=[C:8]2[C:12](=[C:4]([C:1]([NH2:2])=[O:3])[CH:5]=1)[N:11]([CH2:13][CH2:14][CH2:15][OH:16])[CH:10]=[CH:9]2)[CH3:39]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 15887031HCID 15887031, compound

Product 1

HCID 15887032HCID 15887032, compoundYield 35%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

tert-Butyl (R)-N-[2-[7-carbamoyl-1-(3-hydroxy-propyl)-1H-indol-5-yl]-1-methylethyl]-N-[2-(2-ethoxyphenoxy)ethyl]carbamate (4.45 g) was dissolved in isopropanol (50 ml), and concentrated hydrochloric acid (25 ml) was added portionwise to the solution under ice-cooling with stirring. After the mixture was stirred for 3 hours at room temperature, a saturated aqueous sodium bicarbonate solution was added to the reaction mixture under ice-cooling and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was purified by column chromatography on aminopropyl silica gel (eluent: methylene chloride/methanol=20/1) to give white amorphous (R)-5-[2-[[2-(2-ethoxyphenoxy)ethyl]amino]-propyl]-1-(3-hydroxypropyl)-1H-indole-7-carboxamide (1.27 g). Unpurified mixture was further purified by column chromatography on aminopropyl silica gel (eluent:ethyl acetate/ethanol=7/1) and the purified product was combined with the previously purified product to give white amorphous (R)-5-[2-[[2-(2-ethoxyphenoxy)ethyl]amino]propyl]-1-(3-hydroxypropyl)-1H-indole-7-carboxamide (2.39 g).

Workup

  1. temperaturecooling
  2. stirringAfter the mixture was stirred for 3 hours at room temperature
  3. temperaturecooling
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe ethyl acetate layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was removed in vacuo
  8. customthe residue was purified by column chromatography on aminopropyl silica gel (eluent: methylene chloride/methanol=20/1)

Sources & evidence

ORD record
ord-3764b44dfb81459ab4a91afc530ebfe3
Source dataset
uspto-grants-2001_10
Patent number
US06310086B1

Reaction notes

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