Sodium Bicarbonate → N-(3-{3-[3-(5-fluoro-3-methyl-1H-indol-2-yl)propanoyl]-6-methyl-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamide

HRID 1826497Notes

Reaction equation

HRID 1826497 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([CH2:11][CH2:12][C:13]([OH:15])=O)=[C:5]2[CH3:16].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:40][C:41]1([C:47]2[CH:48]=[C:49]([NH:53][S:54]([CH3:57])(=[O:56])=[O:55])[CH:50]=[CH:51][CH:52]=2)[CH:46]2[CH:42]1[CH2:43][NH:44][CH2:45]2.C(=O)([O-])O.[Na+]>CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([CH2:11][CH2:12][C:13]([N:44]1[CH2:45][CH:46]3[CH:42]([C:41]3([C:47]3[CH:48]=[C:49]([NH:53][S:54]([CH3:57])(=[O:56])=[O:55])[CH:50]=[CH:51][CH:52]=3)[CH3:40])[CH2:43]1)=[O:15])=[C:5]2[CH3:16]

Participants

7

Reactant 5

HCID 516892Sodium BicarbonateHCID 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)methanesulfonamideHCID 221411665-fluoro-3-methyl-1H-indole-2-propanoic acid

Product 1

HCID 22141190N-(3-{3-[3-(5-fluoro-3-methyl-1H-indol-2-yl)propanoyl]-6-methyl-3-azabicyclo[3.1.0]hex-6-yl}phenyl)methanesulfonamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(5-fluoro-3-methyl-1H-indol-2-yl)propanoic acid (prepared according to the method described in EP 510398 A2, 200 mg, 0.90 mmol) in N,N-dimethylformamide (20 ml) was added 1-hydroxybenzotriazole monohydrate (154 mg, 1.00 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (262 mg, 1.36 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, 308 mg, 0.90 mmol) and sodium hydrogen carbonate (150 mg, 1.80 mmol). The reaction mixture was stirred at room temperature overnight before concentrating in vacuo. Water (15 ml) was added and the reaction mixture was extracted with ethyl acetate (2×20 ml). The combined organic extracts were washed with water (15 ml), dried (MgSO4), and concentrated in vacuo to afford 350 mg of a brown viscous oil which was not purified further.

Workup

  1. stirringThe reaction mixture was stirred at room temperature overnight
  2. concentrationbefore concentrating in vacuo
  3. additionWater (15 ml) was added
  4. extractionthe reaction mixture was extracted with ethyl acetate (2×20 ml)
  5. washThe combined organic extracts were washed with water (15 ml)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-bd42ab16a868462481fb2d552d8416f2
Source dataset
uspto-grants-2006_05
Patent number
US07049444B2

Reaction notes

Loading…