Sodium Bicarbonate → N-(3-{6-methyl-3-[3-(2-thienyl)propanoyl]-3-azabicyclo[3.1.0]hex-6-yl]phenyl)methanesulfonamide

HRID 428982Notes

Reaction equation

HRID 428982 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][CH2:7][C:8]([OH:10])=O.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:34][C:35]1([C:41]2[CH:42]=[C:43]([NH:47][S:48]([CH3:51])(=[O:50])=[O:49])[CH:44]=[CH:45][CH:46]=2)[CH:40]2[CH:36]1[CH2:37][NH:38][CH2:39]2.C(=O)([O-])O.[Na+]>CN(C)C=O.CO>[CH3:34][C:35]1([C:41]2[CH:42]=[C:43]([NH:47][S:48]([CH3:51])(=[O:50])=[O:49])[CH:44]=[CH:45][CH:46]=2)[CH:40]2[CH:36]1[CH2:37][N:38]([C:8](=[O:10])[CH2:7][CH2:6][C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)[CH2:39]2

Participants

8

Reactant 5

HCID 516892Sodium BicarbonateHCID 7031693-(2-Thienyl)propanoic 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 22141147N-(3-{6-methyl-3-[3-(2-thienyl)propanoyl]-3-azabicyclo[3.1.0]hex-6-yl]phenyl)methanesulfonamideYield 72.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(2-thienyl)propanoic acid (200 mg, 1.2 mmol) in N,N-dimethylformamide (25 ml) was added 1-hydroxybenzotriazole monohydrate (200 mg, 1.31 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (340 mg, 1.77 mmol). After stirring at room temperature for 10 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, 400 mg, 1.3 mmol) and sodium hydrogen carbonate (220 mg, 2.6 mmol). The reaction mixture was stirred at room temperature for 3 h before concentrating in vacuo. Water (15 ml) was added and the reaction mixture was extracted with ethyl acetate (1×30 ml and 2×15 ml). The combined organic extracts were washed with water (15 ml) and saturated brine (15 ml), dried (MgSO4), and concentrated in vacuo to give a buff solid. The crude product was sonicated in methanol (5 ml) to afford the title compound as an off-white solid (350 mg, 66%, m.p. 184.5° C.).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 3 h
  2. concentrationbefore concentrating in vacuo
  3. additionWater (15 ml) was added
  4. extractionthe reaction mixture was extracted with ethyl acetate (1×30 ml and 2×15 ml)
  5. washThe combined organic extracts were washed with water (15 ml) and saturated brine (15 ml)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customto give a buff solid

Sources & evidence

ORD record
ord-f13b541b5fd244899ba0fc8a7e818d03
Source dataset
uspto-grants-2001_11
Patent number
US06313312B1

Reaction notes

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