N-[3-(3-aminopropoxy)phenyl]acetamide → N-(3-{3-[(2-Oxo-2,3,7,8-Tetrahydro-1H-6,9-Dioxa-1,3-Diaza-Cyclopenta[a]Naphthalen-8-Ylmethyl)-Amino]-Propoxy}-Phenyl)-Acetamide

HRID 982680Notes

Reaction equation

HRID 982680 reaction equation
CC1C=CC(S(O[CH2:12][C@@H:13]2[O:26][C:17]3[C:18]4[NH:22][C:21](=[O:23])[NH:20][C:19]=4[CH:24]=[CH:25][C:16]=3[O:15][CH2:14]2)(=O)=O)=CC=1.[NH2:27][CH2:28][CH2:29][CH2:30][O:31][C:32]1[CH:33]=[C:34]([NH:38][C:39](=[O:41])[CH3:40])[CH:35]=[CH:36][CH:37]=1>CS(C)=O.C(OCC)(=O)C>[O:23]=[C:21]1[NH:22][C:18]2=[C:17]3[C:16](=[CH:25][CH:24]=[C:19]2[NH:20]1)[O:15][CH2:14][CH:13]([CH2:12][NH:27][CH2:28][CH2:29][CH2:30][O:31][C:32]1[CH:33]=[C:34]([NH:38][C:39](=[O:41])[CH3:40])[CH:35]=[CH:36][CH:37]=1)[O:26]3

Participants

5

Reactant 2

HCID 2735413N-[3-(3-aminopropoxy)phenyl]acetamideHCID 11428826(8R)-1,3,7,8-tetrahydro-8-[[[(4-methylphenyl)sulfonyl]oxy]methyl]-2H-[1,4]dioxino[2,3-e]benzimidazol-2-one

Product 1

HCID 10136384N-(3-{3-[(2-Oxo-2,3,7,8-Tetrahydro-1H-6,9-Dioxa-1,3-Diaza-Cyclopenta[a]Naphthalen-8-Ylmethyl)-Amino]-Propoxy}-Phenyl)-Acetamide

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 0.60 g (1.6 mmole) of (8R)-1,3,7,8-tetrahydro-8-[[[(4-methylphenyl)sulfonyl]oxy]methyl]-2H-[1,4]dioxino[2,3-e]benzimidazol-2-one and 1.6 g (8.0 mmole) of N-[3-(3-amino-propoxy)phenyl]-acetamide in 30 mL of DMSO was heated at 90-100° C. under nitrogen for 6 hours. The reaction was allowed to come to room temperature, diluted to 500 mL with ethyl acetate, washed with 500 mL portions of saturated aqueous sodium bicarbonate and water, dried over sodium sulfate, filtered and evaporated in vacuum. The residue was column chromatographed on silica gel with 2% methanol in chloroform as eluant and the product fractions evaporated to give the free base of the title compound. This was recrystallized from ethanol with the addition of fumaric acid to give 0.19 g of the (S)-enantiomer of the title compound as a white solid fumarate, three-quarter hydrate, m.p. 125° C. (d).

Workup

  1. customto come to room temperature
  2. washwashed with 500 mL portions of saturated aqueous sodium bicarbonate and water
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuum
  6. customchromatographed on silica gel with 2% methanol in chloroform as eluant
  7. customthe product fractions evaporated

Sources & evidence

ORD record
ord-569cfcc7a233497da708854ec7d52c5e
Source dataset
uspto-grants-2005_03
Patent number
US06861434B2

Reaction notes

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