Triethylamine → N-(3-{3-[3-(3,4-dichlorophenyl)propanoyl]-6-methyl-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamide

HRID 428979Notes

Reaction equation

HRID 428979 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][C:11]([OH:13])=O)[CH:5]=[CH:6][C:7]=1[Cl:8].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:37][C:38]1([C:44]2[CH:45]=[C:46]([NH:50][S:51]([CH3:54])(=[O:53])=[O:52])[CH:47]=[CH:48][CH:49]=2)[CH:43]2[CH:39]1[CH2:40][NH:41][CH2:42]2.C(N(CC)CC)C>>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][C:11]([N:41]2[CH2:42][CH:43]3[CH:39]([C:38]3([C:44]3[CH:45]=[C:46]([NH:50][S:51]([CH3:54])(=[O:53])=[O:52])[CH:47]=[CH:48][CH:49]=3)[CH3:37])[CH2:40]2)=[O:13])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

6

Reactant 5

HCID 8471TriethylamineHCID 1411813-(3,4-Dichlorophenyl)propionic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 22141143N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl)methanesulfonamide

Product 1

HCID 22141281N-(3-{3-[3-(3,4-dichlorophenyl)propanoyl]-6-methyl-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamideYield 51%

Procedure

To a solution of 3(3,4-dichlorophenyl)propanoic acid (35 mg, 0.16 mmol) in N,N-dimethylfonnarnide (4 ml) was added 1-hydroxybenzotriazole monohydrate (26 mg, 0.17 mmol) and 1-(3dimethylaminopropyl)-3ethylcarbodiimide hydrochloride (44 mg, 0.23 mmol). After stirring at room temperature for 5 min the mixture was treated with the hydrochloride salt of N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl)methanesulfonamide (Peparation 53, 52 mg, 0.17 mmol) and triethylarnine (33 mg, 0.33 mmol). The reaction mixture was stirred at room temperature for 72 h before concentrating in vacuo. Water (10 ml) was added and the reaction mixture was extracted with ethyl acetate (2×15 ml). The combined organic extracts were washed with water (10 ml) and saturated brine (10 ml), dried (Na2SO4), filtered and concentrated in vacuo to give a light brown oil. The residue was purified by chromatography using a Sep-Pak™ cartridge packed with silica gel (10 g) eluting with dichloromethane:ethanol:0.88 amnionia (300:8:1) to afford the title compound as a white foam (38 mg, 51%).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 72 h
  2. concentrationbefore concentrating in vacuo
  3. additionWater (10 ml) was added
  4. extractionthe reaction mixture was extracted with ethyl acetate (2×15 ml)
  5. washThe combined organic extracts were washed with water (10 ml) and saturated brine (10 ml)
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a light brown oil
  10. customThe residue was purified by chromatography
  11. washeluting with dichloromethane

Sources & evidence

ORD record
ord-ade63e38ced44537821b48632c424662
Source dataset
uspto-grants-2001_11
Patent number
US06313312B1

Reaction notes

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