4-Methylmorpholine → HCID 22710722, compound

HRID 352971Notes

Reaction equation

HRID 352971 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][N:11]([S:14]([C:17]2[NH:18][C:19]3[C:24]([CH:25]=2)=[CH:23][C:22]([Cl:26])=[CH:21][CH:20]=3)(=[O:16])=[O:15])[CH2:10][CH:9]1[CH2:27][C:28]([N:30]1[CH2:35][CH2:34][O:33][CH2:32][CH2:31]1)=[O:29])=[O:7])(C)(C)C.Cl.C(O)C.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[CH3:62][CH:63]1[NH:68][CH2:67][C:66]2[S:69][C:70](C([O-])=O)=[N:71][C:65]=2[CH2:64]1.[Li+].CN1CCOCC1>C(O)C.C(OCC)C>[ClH:26].[Cl:26][C:22]1[CH:23]=[C:24]2[C:19](=[CH:20][CH:21]=1)[NH:18][C:17]([S:14]([N:11]1[CH2:12][CH2:13][N:8]([C:6]([C:70]3[S:69][C:66]4[CH2:67][NH:68][CH:63]([CH3:62])[CH2:64][C:65]=4[N:71]=3)=[O:7])[CH:9]([CH2:27][C:28]([N:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)=[O:29])[CH2:10]1)(=[O:16])=[O:15])=[CH:25]2

Participants

9

Reactant 6

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 21887872Ethanol hydrochlorideHCID 22711035HCID 22711035, compoundHCID 23674323Lithium 6-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate

Product 1

HCID 22710722HCID 22710722, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 3283Diethyl EtherSolvent

Conditions

Temperature
60 °C

Procedure

To an ethanol solution (50 ml) of 1-(tert-butoxycarbonyl)-4-[(5-chloroindol-2-yl)sulfonyl]-2-[[(morpholin-4-yl)carbonyl]methyl]piperazine (710 mg) was added a saturated ethanol hydrochloride solution (20 ml) at room temperature. The resulting mixture was stirred for 3 hours. After concentration of the reaction mixture under reduced pressure, diethyl ether and ethanol were added to precipitate crystals. The resulting crystals were collected by filtration, washed with ethanol and then dried under reduced pressure. The crystals were dissolved in N,N-dimethylformamide to form an N,N-dimethylformamide solution (50 ml), followed by the addition of 1-hydroxybenzotriazole (68.8 mg), 1-(3-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride (115.4 mg), lithium 6-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxylate (189.0 mg) and N-methylmorpholine (140.5 mg) at room temperature. The resulting mixture was stirred at room temperature for 19 hours. The reaction solvent was distilled off under reduced pressure. Distilled water and ethyl acetate were added to the residue and the water layer was extracted three times. The organic layers were combined, washed four times with distilled water, dried over anhydrous sodium sulfate and distilled under reduced pressure to remove the solvent. The residue was subjected to chromatography on a silica gel column (methanol : ethyl acetate=1:50). Diethyl ether and methylene chloride were added to the purified product to precipitate crystals. The resulting crystals were collected by filtration, followed by washing with diethyl ether. A 1N aqueous hydrochloric acid in ethanol (0.5 ml) and a small amount of distilled water were added. The solvent was then distilled off under reduced pressure. The residue was dried under heat at 60° C. under reduced pressure, whereby the title compound (187 mg) was obtained as a yellow amorphous solid. MS (FAB+) m/z: 607 [(M+H)+, Cl35], 609 [(M+H)+, Cl37].

Workup

  1. customto precipitate crystals
  2. filtrationThe resulting crystals were collected by filtration
  3. washwashed with ethanol
  4. customdried under reduced pressure
  5. dissolutionThe crystals were dissolved in N,N-dimethylformamide
  6. customto form an N,N-dimethylformamide solution (50 ml)
  7. customat room temperature
  8. stirringThe resulting mixture was stirred at room temperature for 19 hours
  9. distillationThe reaction solvent was distilled off under reduced pressure
  10. additionDistilled water and ethyl acetate were added to the residue
  11. extractionthe water layer was extracted three times
  12. washwashed four times with distilled water
  13. dry with materialdried over anhydrous sodium sulfate
  14. distillationdistilled under reduced pressure
  15. customto remove the solvent
  16. additionDiethyl ether and methylene chloride were added to the purified product
  17. customto precipitate crystals
  18. filtrationThe resulting crystals were collected by filtration
  19. washby washing with diethyl ether
  20. additionA 1N aqueous hydrochloric acid in ethanol (0.5 ml) and a small amount of distilled water were added
  21. distillationThe solvent was then distilled off under reduced pressure
  22. customThe residue was dried
  23. customwas obtained as a yellow amorphous solid

Sources & evidence

ORD record
ord-779f306769e245279c543e25c7b89182
Source dataset
uspto-grants-2004_06
Patent number
US06747023B1

Reaction notes

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