Isopropylamine → Indecainide

HRID 1277474Notes

Reaction equation

HRID 1277474 reaction equation
[NH2:1][C:2]([C:4]1([CH2:17][CH2:18][C:19]#[N:20])[C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2)=[O:3].[CH:21](N)([CH3:23])[CH3:22].[H][H]>[Pd]>[CH:21]([NH:20][CH2:19][CH2:18][CH2:17][C:4]1([C:2]([NH2:1])=[O:3])[C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:10]2[C:5]1=[CH:6][CH:7]=[CH:8][CH:9]=2)([CH3:23])[CH3:22]

Participants

5

Reactant 3

HCID 6363IsopropylamineHCID 30188199-(2-Cyanoethyl)-9H-fluorene-9-carboxamideHCID 178418361HCID 178418361, compound

Product 1

HCID 52195IndecainideYield 60%

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Conditions

Temperature
100 °C

Procedure

A mixture of 500 g. of 9-aminocarbonyl-9-(2-cyanoethyl)fluorene, 1500 ml. of isopropylamine and 100 g. of 5% palladium on carbon was placed in a onegallon high pressure hydrogenation bomb. The bomb was pressurized with hydrogen to a pressure of 1500 psi, and the reaction mixture was then stirred at 100° C. for ten hours, and for an additional eight hoursat room temperature. The reaction mixture was filtered to remove the hydrogenation catalyst, and the solvent was removed from the filtrate by evaporation under reduced pressure. The residue was dissolved in ethyl acetate, and the solution was extracted several times with 1 N hydrochloric acid. The acidic extracts were combined, made alkaline by theaddition of sodium hydroxide, and the alkaline mixture was extracted with fresh ethyl acetate. The organic layer was separated, washed with water and dried. Removal of the solvent by evaporation under reduced pressure provided 9-(3-isopropylaminopropyl)-9-aminocarbonylfluorene as a solid residue. The solid was dissolved in methanol and treated with anhydrous hydrogen chloride. The crystalline product which formed was recrystallizedfrom chloroform to afford 391 g. of 9-(3-isopropylaminopropyl)-9-aminocarbonylfluorene hydrochloride. Yield 60%. m.p. 216.5°-217° C.

Workup

  1. additionA mixture of 500 g
  2. customfor an additional eight hoursat room temperature
  3. filtrationThe reaction mixture was filtered
  4. customto remove the hydrogenation catalyst
  5. customthe solvent was removed from the filtrate by evaporation under reduced pressure
  6. dissolutionThe residue was dissolved in ethyl acetate
  7. extractionthe solution was extracted several times with 1 N hydrochloric acid
  8. extractionthe alkaline mixture was extracted with fresh ethyl acetate
  9. customThe organic layer was separated
  10. washwashed with water
  11. customdried
  12. customRemoval of the solvent
  13. customby evaporation under reduced pressure

Sources & evidence

ORD record
ord-096ed4bcaa654588b4c96a819d5ea7be
Source dataset
uspto-grants-1981_07
Patent number
US04277495

Reaction notes

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