Triethylamine → N-(3-{6-methyl-3-[2-(1-methyl-1H-indol-3-yl)acetyl]-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamide

HRID 1826489Notes

Reaction equation

HRID 1826489 reaction equation
C[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]([CH2:11][C:12]([OH:14])=O)[CH:7]=[N:8]2)=[CH:4][CH:3]=1.O.ON1C2C=CC=C[C:20]=2N=N1.Cl.Cl.CN(C)CCCN=C=NCC.[CH3:39][C:40]1([C:46]2[CH:47]=[C:48]([NH:52][S:53]([CH3:56])(=[O:55])=[O:54])[CH:49]=[CH:50][CH:51]=2)[CH:45]2[CH:41]1[CH2:42][NH:43][CH2:44]2.C(N(CC)CC)C>CN(C)C=O>[NH3:8].[CH3:39][C:40]1([C:46]2[CH:47]=[C:48]([NH:52][S:53]([CH3:56])(=[O:55])=[O:54])[CH:49]=[CH:50][CH:51]=2)[CH:45]2[CH:41]1[CH2:42][N:43]([C:12](=[O:14])[CH2:11][C:6]1[C:5]3[C:9](=[CH:10][CH:2]=[CH:3][CH:4]=3)[N:8]([CH3:20])[CH:7]=1)[CH2:44]2

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 22141126HCID 22141126, compoundHCID 22141143N-[3-(6-methyl-3-azabicyclo[3.1.0]hex-6-yl)phenyl)methanesulfonamideHCID 221413011-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride hydrochloride

Product 2

HCID 222AmmoniaHCID 22141196N-(3-{6-methyl-3-[2-(1-methyl-1H-indol-3-yl)acetyl]-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamideYield 42.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(6-methyl-3H-indol-3-yl)acetic acid (117 mg, 0.62 mmol) in N,N-dimethylformamide (13 ml) was added 1-hydroxybenzotriazole monohydrate (100 mg, 0.66 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride hydrochloride (170 mg, 0.88 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 (Preparation 53, 200 mg, 0.66 mmol) and triethylamine (133 mg, 1.32 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 ammonia (300:8:1) to afford the title compound as a white foam (58 mg, 20%).

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-0eb359a373ac4d4d9397fd97519b622b
Source dataset
uspto-grants-2006_05
Patent number
US07049444B2

Reaction notes

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