Sodium Hydroxide → 5-HT3 antagonist 1

HRID 374101Notes

Reaction equation

HRID 374101 reaction equation
[C:1]([NH:4][CH:5]1[CH2:11][N:10]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[CH:14]=2)[CH2:9][CH2:8][N:7]([CH3:20])[CH2:6]1)(=[O:3])[CH3:2].[OH-].[Na+].[NH:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)C(C(O)=O)=[N:24]1.Cl.C(N=C=NCCCN(C)C)C>Cl.ClCCl>[CH3:19][C:15]1[CH:14]=[C:13]([CH:18]=[CH:17][CH:16]=1)[CH2:12][N:10]1[CH2:11][CH:5]([NH:4][C:1]([C:2]2[C:26]3[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=3)[NH:23][N:24]=2)=[O:3])[CH2:6][N:7]([CH3:20])[CH2:8][CH2:9]1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 78250Indazole-3-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 149989916-acetylamino-1-(3-methylbenzyl)-4-methylhexahydro-1H-1,4-diazepine

Product 1

HCID 104072565-HT3 antagonist 1Yield 32.4%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 6-acetylamino-1-(3-methylbenzyl)-4-methyl-hexahydro-1H-1,4-diazepine (0.9 g) in 10% hydrochloric acid (20 ml) is refluxed with stirring for 2 hours. After cooling, the reaction mixture is basified with 48% aqueous sodium hydroxide solution and extracted with chloroform. The organic layer is washed with water and dried over magnesium sulfate. The solvent is evaporated under reduced pressure to give an oil. A mixture of this oil, 1H-indazole-3-carboxylic acid (530 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (630 mg) and dichloromethane (20 ml) is stirred at 25° C. for 2 hours. The reaction mixture is washed successively with water and 10% aqueous sodium hydroxide solution, dried over magnesium sulfate, and evaporated under reduced pressure. The residue is chromatographed on silica gel with elution of acetone. Fractions containing the title compound are pooled and evaporated under reduced pressure to give the title compound (0.4 g) as an oil.

Workup

  1. temperatureAfter cooling
  2. extractionextracted with chloroform
  3. washThe organic layer is washed with water
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent is evaporated under reduced pressure
  6. customto give an oil
  7. stirringis stirred at 25° C. for 2 hours
  8. washThe reaction mixture is washed successively with water and 10% aqueous sodium hydroxide solution
  9. dry with materialdried over magnesium sulfate
  10. customevaporated under reduced pressure
  11. customThe residue is chromatographed on silica gel with elution of acetone
  12. additionFractions containing the title compound
  13. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-74f6d78a7c7f40ab8d1342a521befe3b
Source dataset
uspto-grants-1992_11
Patent number
US05166341

Reaction notes

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