Methanesulfonic Acid → HCID 178505258, compound

HRID 49201Notes

Reaction equation

HRID 49201 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]1[CH2:18][C:17]2[N:16]=[CH:15][CH:14]=[C:13]([CH3:19])[C:12]=2[C:11](=[N:20][NH:21][C:22]([NH2:24])=[NH:23])[CH2:10]1.[CH3:25][S:26]([OH:29])(=[O:28])=[O:27]>C(O)C>[CH3:25][S:26]([OH:29])(=[O:28])=[O:27].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]1[CH2:18][C:17]2[N:16]=[CH:15][CH:14]=[C:13]([CH3:19])[C:12]=2[C:11](=[N:20][NH:21][C:22]([NH2:24])=[NH:23])[CH2:10]1

Participants

4

Reactant 2

HCID 6395Methanesulfonic AcidHCID 178428132HCID 178428132, compound

Product 1

HCID 178505258HCID 178505258, compoundYield 105.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mother liquor and washings which had been resolved with L-pyroglutamic acid were combined with a 28% solution of sodium methoxide in methanol (2.6 g), concentrated and washed with water to obtain a (−)-isomer-rich crystal (3.7 g). This was dissolved in ethanol (30 ml) and combined with a solution of D-pyroglutamic acid (1.4 g) in ethanol (10 ml) at 80° C. The solution was allowed to warm to room temperature gradually, and the mixture was stirred at room temperature for 14 hours. The precipitated crystal was recovered by a filtration, washed with ethanol to obtain (−)-7-(2-chloro-5-fluorophenyl)-5-guanidinoimino-4-methyl-5,6,7,8-tetrahydroquinoline D-pyroglutamate (4.0 g). This crystal was suspended in methanol (40 ml) and combined with a 28% solution of sodium methoxide in methanol (1.6 g) and the solvent was distilled off under reduced pressure. The residue was washed with water and dried to obtain (−)-7-(2-chloro-5-fluorophenyl)-5-guanidinoimino-4-methyl-5,6,7,8-tetrahydroquinoline (2.9 g). (−)-7-(2-Chloro-5-fluorophenyl)-5-guanidinoimino-4-methyl-5,6,7,8-tetrahydroquinoline (1.7 g) was dissolved in ethanol (30 ml) and combined with methanesulfonic acid (0.97 g). The solvent was distilled off under reduced pressure and the resultant crystal was recrystallized from ethanol to obtain (−)-7-(2-chloro-5-fluorophenyl)-5-guanidinoimino-4-methyl-5,6,7,8-tetrahydroquinoline methanesulfonate (Compound I) (2.3 g, 99.5% ee).

Workup

  1. distillationThe solvent was distilled off under reduced pressure
  2. customthe resultant crystal was recrystallized from ethanol

Sources & evidence

ORD record
ord-055142009e36497cb3919986b472e4df
Source dataset
uspto-grants-2004_03
Patent number
US06706732B1

Reaction notes

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