Hydrochloric Acid → (+/-)-cis-N1-[(5-Chloroindol-2-yl) sulfonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclohexanediamine hydrochloride

HRID 459554Notes

Reaction equation

HRID 459554 reaction equation
FC(F)(F)C(O)=O.[CH3:8][N:9]1[CH2:14][CH2:13][C:12]2[N:15]=[C:16]([C:18]([NH:20][C@@H:21]3[CH2:26][CH2:25][CH2:24][CH2:23][C@@H:22]3[NH2:27])=[O:19])[S:17][C:11]=2[CH2:10]1.[Cl:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[N:34](S(C1C=CC=CC=1)(=O)=O)[C:33]([S:47](Cl)(=[O:49])=[O:48])=[CH:32]2.[OH-].[Na+].Cl>ClCCl.O1CCCC1.CO.O.C(N(CC)CC)C>[ClH:28].[Cl:28][C:29]1[CH:30]=[C:31]2[C:35](=[CH:36][CH:37]=1)[NH:34][C:33]([S:47]([NH:27][C@@H:22]1[CH2:23][CH2:24][CH2:25][CH2:26][C@@H:21]1[NH:20][C:18]([C:16]1[S:17][C:11]3[CH2:10][N:9]([CH3:8])[CH2:14][CH2:13][C:12]=3[N:15]=1)=[O:19])(=[O:48])=[O:49])=[CH:32]2

Participants

10

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 18442855(+/-)-cis-N-[(5-methyl-4,5,6,7-tetrahydrothiazolo-[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclohexanediamine trifluoroacetateHCID 235137375-Chloro-1-phenylsulfonylindole-2-sulfonyl chloride

Product 1

HCID 68912573(+/-)-cis-N1-[(5-Chloroindol-2-yl) sulfonyl]-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclohexanediamine hydrochloride

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent

Procedure

(±)-cis-N-[(5-methyl-4,5,6,7-tetrahydrothiazolo-[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclohexanediamine trifluoroacetate (400 mg) was suspended in dichloromethane (10 ml), triethylamine (0.514 ml) and 5-chloro-1-phenylsulfonylindole-2-sulfonyl chloride (Japanese Patent Application Laid-Open No. 2000-119253) (319 mg) were added, and the mixture was stirred at room temperature for 15 minutes. After water was added to the reaction mixture to conduct liquid separation, the resultant organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by column chromatography on silica gel (dichloromethane:methanol=100:3) to obtain a pale yellow foamy substance. This substance was dissolved in tetrahydrofuran (3 ml), and methanol (2 ml) and a 1N aqueous solution (1.5 ml) of sodium hydroxide were added to heat the mixture under reflux for 2 hours. The reaction mixture was concentrated under reduced pressure, and dichloromethane and 1N hydrochloric acid were added to the residue to conduct liquid separation. After the resultant organic layer was dried over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure, and the residue was purified by column chromatography on silica gel (dichloromethane:methanol=100:3) to obtain a pale yellow foamy substance. This substance was added to 1N hydrochloric acid (1 ml), and the mixture was concentrated under reduced pressure to obtain the title compound (108 mg) as a pale yellow foamy substance.

Workup

  1. addition2000-119253) (319 mg) were added
  2. customliquid separation
  3. dry with materialthe resultant organic layer was dried over anhydrous sodium sulfate
  4. distillationThe solvent was distilled off under reduced pressure
  5. customthe residue was purified by column chromatography on silica gel (dichloromethane:methanol=100:3)
  6. customto obtain a pale yellow foamy substance
  7. temperatureto heat the mixture
  8. temperatureunder reflux for 2 hours
  9. concentrationThe reaction mixture was concentrated under reduced pressure, and dichloromethane and 1N hydrochloric acid
  10. additionwere added to the residue
  11. customliquid separation
  12. dry with materialAfter the resultant organic layer was dried over anhydrous sodium sulfate
  13. distillationthe solvent was distilled off under reduced pressure
  14. customthe residue was purified by column chromatography on silica gel (dichloromethane:methanol=100:3)
  15. customto obtain a pale yellow foamy substance
  16. concentrationthe mixture was concentrated under reduced pressure

Sources & evidence

ORD record
ord-90bd1f0749484e2f9980ba5965080306
Source dataset
uspto-grants-2007_03
Patent number
US07192968B2

Reaction notes

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