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 428977Notes

Reaction equation

HRID 428977 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([CH2:11][C:12]([OH:14])=O)=[CH:3]1.O.ON1C2C=CC=CC=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>[NH3:2].[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:4]1[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[N:2]([CH3:1])[CH:3]=1)[CH2:44]2

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 2541662-(1-methyl-1H-indol-3-yl)acetic acidHCID 27960291-Hydroxybenzotriazole hydrateHCID 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 42.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-(1-methyl-1H-indol-3-yl)acetic acid (117 mg, 0.62 minol) 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 stirig 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 vacui. 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. concentrationbefore concentrating in vacui
  2. additionWater (10 ml) was added
  3. extractionthe reaction mixture was extracted with ethyl acetate (2×15 ml)
  4. washThe combined organic extracts were washed with water (10 ml) and saturated brine (10 ml)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a light brown oil
  9. customThe residue was purified by chromatography
  10. washeluting with dichloromethane

Sources & evidence

ORD record
ord-82dcae4067574138b557cf2a4b91191d
Source dataset
uspto-grants-2001_11
Patent number
US06313312B1

Reaction notes

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