4-Methylmorpholine → HCID 22711199, compound

HRID 1061030Notes

Reaction equation

HRID 1061030 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 dropwise addition of N-methylmorpholine (170 μl) and isobutyl chloroformate (210 μl) successively at −20° C. After stirring at −20° C. for 10 minutes, 1-[(6-chloronaphthalen-2-yl)sulfonyl]piperazine hydrochloride (607 mg) dissolved in advance in dichloromethane (10 ml) was added to the reaction mixture. The reaction mixture was stirred at −20° C. for 10 minutes and then heated to room temperature. The reaction mixture was concentrated under reduced pressure. The residue was dissolved in dichloroethane. The resulting solution was washed with 1N hydrochloric acid, saturated sodium bicarbonate and saturate saline and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by chromatography on a silica gel column (hexane:ethyl acetate=4:1˜2:1), whereby the title compound (625 mg, 72%) was obtained.

Workup

  1. additionwas added to the reaction mixture
  2. stirringThe reaction mixture was stirred at −20° C. for 10 minutes
  3. temperatureheated to room temperature
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. dissolutionThe residue was dissolved in dichloroethane
  6. washThe resulting solution was washed with 1N hydrochloric acid, saturated sodium bicarbonate
  7. concentrationsaturate saline
  8. dry with materialdried over anhydrous sodium sulfate
  9. distillationThe solvent was distilled off under reduced pressure
  10. customThe residue was purified by chromatography on a silica gel column (hexane:ethyl acetate=4:1˜2:1), whereby the title compound (625 mg, 72%)
  11. customwas obtained

Sources & evidence

ORD record
ord-b099e62bfdb8496a9fe8661feef2ba22
Source dataset
uspto-grants-2003_02
Patent number
US06525042B1

Reaction notes

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