Diethyl Ether → HCID 22711190, compound

HRID 352970Notes

Reaction equation

HRID 352970 reaction equation
C(OC([CH:8]1[NH:13][CH2:12][C:11]2[S:14][C:15]([C:17]([N:19]3[CH2:24][CH2:23][N:22]([S:25]([C:28]4[NH:29][C:30]5[C:35]([CH:36]=4)=[CH:34][C:33]([Cl:37])=[CH:32][CH:31]=5)(=[O:27])=[O:26])[CH2:21][CH:20]3[CH2:38][C:39]([N:41]3[CH2:46][CH2:45][O:44][CH2:43][CH2:42]3)=[O:40])=[O:18])=[N:16][C:10]=2[CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+].CCOCC>C(Cl)Cl>[Cl:37][C:33]1[CH:34]=[C:35]2[C:30](=[CH:31][CH:32]=1)[NH:29][C:28]([S:25]([N:22]1[CH2:23][CH2:24][N:19]([C:17]([C:15]3[S:14][C:11]4[CH2:12][NH:13][CH:8]([S:25]([CH3:28])(=[O:27])=[O:26])[CH2:9][C:10]=4[N:16]=3)=[O:18])[CH:20]([CH2:38][C:39]([N:41]3[CH2:42][CH2:43][O:44][CH2:45][CH2:46]3)=[O:40])[CH2:21]1)(=[O:26])=[O:27])=[CH:36]2

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 22710421HCID 22710421, compound

Product 1

HCID 22711190HCID 22711190, compoundYield 12.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

In methylene chloride (5 ml) was dissolved 1-[(6-tert-butoxycarbonyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-4-[(5-chloroindol-2-yl)sulfonyl]-2-[[(morpholin-4-yl)carbonyl]methyl]piperazine (585 mg), followed by the addition of trifluoroacetic acid (2 ml). The resulting mixture was stirred at room temperature for 30 minutes. A saturated aqueous solution of sodium bicarbonate was added and the resulting mixture was extracted with methylene chloride (to which N,N-dimethylformamide was added in a small amount). The organic layer was dried over anhydrous sodium sulfate and distilled under reduced pressure to remove the solvent. To the residue was added a 1N aqueous hydrochloride in ethanol (1 ml) and the solvent was distilled off under reduced pressure, whereby the hydrochloride (585 mg, containing two molecules of N,N-dimethylformamide). A 100 mg portion of the resulting hydrochloride was added to methylene chloride (3 ml), followed by the addition of triethylamine (0.5 ml) and methanesulfonyl chloride (20 mg). The resulting mixture was stirred at room temperature for 2 hours. A saturated aqueous solution of sodium bicarbonate was added to the reaction mixture. The resulting mixture was extracted with methylene chloride. The extract was dried over anhydrous sodium sulfate and distilled under reduced pressure to remove the solvent. The residue was purified by preparative thin-layer chromatography (methylene chloride:methanol=9:1). The solid thus obtained was dissolved in methylene chloride, followed by the addition of ether for crystallization, whereby the title compound (34.2 mg) was obtained as a white solid.

Workup

  1. extractionthe resulting mixture was extracted with methylene chloride (to which N,N-dimethylformamide
  2. additionwas added in a small amount)
  3. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  4. distillationdistilled under reduced pressure
  5. customto remove the solvent
  6. additionTo the residue was added a 1N aqueous hydrochloride in ethanol (1 ml)
  7. distillationthe solvent was distilled off under reduced pressure, whereby the hydrochloride (585 mg, containing two molecules of N,N-dimethylformamide)
  8. additionA 100 mg portion of the resulting hydrochloride was added to methylene chloride (3 ml)
  9. additionfollowed by the addition of triethylamine (0.5 ml) and methanesulfonyl chloride (20 mg)
  10. stirringThe resulting mixture was stirred at room temperature for 2 hours
  11. additionA saturated aqueous solution of sodium bicarbonate was added to the reaction mixture
  12. extractionThe resulting mixture was extracted with methylene chloride
  13. dry with materialThe extract was dried over anhydrous sodium sulfate
  14. distillationdistilled under reduced pressure
  15. customto remove the solvent
  16. customThe residue was purified by preparative thin-layer chromatography (methylene chloride:methanol=9:1)
  17. customThe solid thus obtained

Sources & evidence

ORD record
ord-1b0085cccb994099ad41504896b0c43a
Source dataset
uspto-grants-2004_06
Patent number
US06747023B1

Reaction notes

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