1H-Indole-3-propanoic acid → HCID 22141354, compound

HRID 428981Notes

Reaction equation

HRID 428981 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH2:11][C:12]([OH:14])=O)=[CH:2]1.O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:38][C:39]1([C:45]2[CH:46]=[C:47]([NH:51][S:52]([CH3:55])(=[O:54])=[O:53])[CH:48]=[CH:49][CH:50]=2)[CH:44]2[CH:40]1[CH2:41][NH:42][CH2:43]2.C(=O)([O-])O.[Na+]>CN(C)C=O>[NH3:1].[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH2:11][C:12]([N:42]2[CH2:43][CH:44]3[CH:40]([C:39]3([C:45]3[CH:46]=[C:47]([NH:51][S:52]([CH3:55])(=[O:54])=[O:53])[CH:48]=[CH:49][CH:50]=3)[CH3:38])[CH2:41]2)=[O:14])=[CH:2]1

Participants

8

Reactant 5

HCID 37441H-Indole-3-propanoic acidHCID 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)methanesulfonamide

Product 2

HCID 222AmmoniaHCID 22141354HCID 22141354, compoundYield 89.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(1H-indol-3-yl)propanoic acid (235 mg, 1.2 mmol) in N,N-dimethylformamide (13 ml) was added 1-hydroxybenzotriazole monohydrate (200 mg, 1.31 mmol) and 1-(3-dimethylarninopropyl)-3-ethylcarbodiimide hydrochloride (340 mg, 1.77 numol). 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, 400 mg, 1.3 mmol) and sodium hydrogen carbonate (220 mg, 2.6 mmol). The reaction mixture was stirred at room temperature for 72 h before concentrating in vacua. Water (20 ml) was added and the reaction mixture was extracted with ethyl acetate (2×30 ml). The combined organic extracts were washed with water (20 ml) and saturated brine (20 ml), dried (MgSO4), filtered and concentrated in vacuo to give a pale yellow solid. The crude product was purified by shaking with dichloromethane (10 ml) and after filtration the filtrate was concentrated in vacuo to afford a pale yellow solid which was further purified by chromatography using a Sep-Pak™ cartridge packed with silica gel (10 g) eluting with dichoromethane:ethanol:0.88 ammonia (300:8:1) to afford the title compound as a white solid (235 mg, 43%).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 72 h
  2. concentrationbefore concentrating in vacua
  3. additionWater (20 ml) was added
  4. extractionthe reaction mixture was extracted with ethyl acetate (2×30 ml)
  5. washThe combined organic extracts were washed with water (20 ml) and saturated brine (20 ml)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a pale yellow solid
  10. customThe crude product was purified
  11. stirringby shaking with dichloromethane (10 ml)
  12. filtrationafter filtration the filtrate
  13. concentrationwas concentrated in vacuo
  14. customto afford a pale yellow solid which
  15. customwas further purified by chromatography
  16. washeluting with dichoromethane

Sources & evidence

ORD record
ord-6d3e8725140c408695b82fbf3933c493
Source dataset
uspto-grants-2001_11
Patent number
US06313312B1

Reaction notes

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