2-(2-Aminoethyl)-1-methylpyrrolidine → 2-(cyclohexylmethyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

HRID 1624928Notes

Reaction equation

HRID 1624928 reaction equation
F[C:2](F)(F)[C:3]([N:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][C:9]([S:15](Cl)(=[O:17])=[O:16])=[CH:10][CH:11]=2)[CH2:6]1)=O.[NH2:21][CH2:22][CH2:23][CH:24]1[CH2:28][CH2:27][CH2:26][N:25]1[CH3:29]>CO.Cl>[CH:2]1([CH2:3][N:5]2[CH2:14][CH2:13][C:12]3[C:7](=[CH:8][C:9]([S:15]([NH:21][CH2:22][CH2:23][C@@H:24]4[CH2:28][CH2:27][CH2:26][N:25]4[CH3:29])(=[O:17])=[O:16])=[CH:10][CH:11]=3)[CH2:6]2)[CH2:11][CH2:12][CH2:7][CH2:8][CH2:9]1

Participants

5

Reactant 2

HCID 983882-(2-Aminoethyl)-1-methylpyrrolidineHCID 113249022-(Trifluoroacetyl)-1,2,3,4-tetrahydroisoquinoline-7-sulfonyl chloride

Product 1

HCID 115026452-(cyclohexylmethyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Procedure

WO2005/118547 describes a general method of synthesis which is difficult to transpose to the industrial scale for production in large quantities. This method of synthesis entails reacting 2-(2,2,2-trifluoroacetyl)-1,2,3,4-tetrahydro-isoquinoline-7-sulfonyl chloride with (+/−)-2-(2-aminoethyl)-1-methylpyrrolidine, which product is deprotected in methanol and hydrochloric acid. The enantiomers are next separated by chiral chromatography. The resulting N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide undergoes reductive amination with cyclohexanecarboxaldehyde in the presence of a palladium catalyst. 2-(Cyclohexylmethyl)-N-{2-[(2S)-1-methylpyrrolidin-2-yl]ethyl}-1,2,3,4-tetrahydroisoquinoline-7-sulfonamide is isolated as the free base and converted to a salt.

Workup

  1. customa general method of synthesis which
  2. customThis method of synthesis
  3. customThe enantiomers are next separated by chiral chromatography

Sources & evidence

ORD record
ord-8ffc578a4ae74a5ab14c443fbec9c4cf
Source dataset
uspto-grants-2014_07
Patent number
US08779145B2

Reaction notes

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