4-Methylmorpholine → HCID 22711199, compound

HRID 352845Notes

Reaction equation

HRID 352845 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[S:14][C:15]([CH2:17][CH2:18][C:19]([OH:21])=O)=[CH:16][C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.Cl.[Cl:38][C:39]1[CH:40]=[C:41]2[C:46](=[CH:47][CH:48]=1)[CH:45]=[C:44]([S:49]([N:52]1[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1)(=[O:51])=[O:50])[CH:43]=[CH:42]2>O1CCCC1.ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[S:14][C:15]([CH2:17][CH2:18][C:19]([N:55]3[CH2:54][CH2:53][N:52]([S:49]([C:44]4[CH:43]=[CH:42][C:41]5[C:46](=[CH:47][CH:48]=[C:39]([Cl:38])[CH:40]=5)[CH:45]=4)(=[O:51])=[O:50])[CH2:57][CH2:56]3)=[O:21])=[CH:16][C:10]=2[CH2:9]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 227097661-(6-Chloronaphth-2-ylsulphonyl)piperazine hydrochlorideHCID 22709810HCID 22709810, compound

Product 1

HCID 22711199HCID 22711199, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

In tetrahydrofuran (10 ml), 3-(5-tert-butoxycarbonyl -4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)propionic acid (445 mg) was dissolved, followed by the successive dropwise addition of N-methylmorpholine (170 μl) and isobutyl chloroformate (210 μl) at −20° C. After stirring at −20° C. for 10 minutes, a solution of 1-[(6-chloronaphthalen-2-yl)sulfonyl]piperazine hydrochloride (607 mg) which had been dissolved in dichloromethane (10 ml) was added. After stirring at −20° C. for 10 minutes, the reaction mixture was warmed up to room temperature. The reaction mixture was concentrated under reduced pressure. The residue was then dissolved in dichloroethane. The resulting solution was washed with 1N hydrochloric acid, a saturated aqueous solution of sodium bicarbonate and saturated aqueous NaCl solution, dried over anhydrous sodium sulfate and then distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column (hexane:ethyl acetate=4:1 to 2:1), whereby the title compound (625 mg, 72%) was obtained.

Workup

  1. additionwas added
  2. stirringAfter stirring at −20° C. for 10 minutes
  3. temperaturethe reaction mixture was warmed up to room temperature
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. dissolutionThe residue was then dissolved in dichloroethane
  6. washThe resulting solution was washed with 1N hydrochloric acid
  7. dry with materiala saturated aqueous solution of sodium bicarbonate and saturated aqueous NaCl solution, dried over anhydrous sodium sulfate
  8. distillationdistilled under reduced pressure
  9. customto remove the solvent
  10. customThe residue was purified by chromatography on a silica gel column (hexane:ethyl acetate=4:1 to 2:1), whereby the title compound (625 mg, 72%)
  11. customwas obtained

Sources & evidence

ORD record
ord-3d41e5723c0e45499396b6b1c7368174
Source dataset
uspto-grants-2004_06
Patent number
US06747023B1

Reaction notes

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