4-Methylmorpholine → HCID 15951137, compound

HRID 1676957Notes

Reaction equation

HRID 1676957 reaction equation
[C:1]1([CH2:7][S:8]([NH:11][C:12]2[CH:20]=[CH:19][C:15]([C:16]([OH:18])=O)=[CH:14][CH:13]=2)(=[O:10])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)C([Cl:24])=O.[NH:27]1[CH2:31][CH2:30][CH2:29][C@H:28]1[CH2:32][N:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1.CN1CCOCC1>ClCCl.CN(C)C=O>[ClH:24].[C:1]1([CH2:7][S:8]([NH:11][C:12]2[CH:13]=[CH:14][C:15]([C:16]([N:27]3[CH2:31][CH2:30][CH2:29][C@H:28]3[CH2:32][N:33]3[CH2:37][CH2:36][CH2:35][CH2:34]3)=[O:18])=[CH:19][CH:20]=2)(=[O:9])=[O:10])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 10825CarinamideHCID 65578Oxalyl chlorideHCID 853152(S)-(+)-1-(2-Pyrrolidinylmethyl)pyrrolidine

Product 1

HCID 15951137HCID 15951137, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a stirring solution of 4-phenylmethanesulfonylamino-benzoic acid (CAS 536-95-8, available from Aldrich) (0.300 g, 1.03 mmol), in dichloromethane (10 mL) is added oxalyl chloride (0.262 g, 2.06 mmol) and 1 drop of N,N-dimethylformamide and the mixture allowed to react at ambient temperature for 1 hour. The reaction is then concentrated to dryness. The residue is dissolved in toluene (10 mL) and concentrated again. The residue is dissolved in dichloromethane (6 mL) and added to a flask containing (S)(+)-1-(2-pyrrolidinylmethyl)pyrrolidine (0.154 g, 1.0 mmol) and N-methylmorpholine (0.111 g, 1.1 mmol) and stirred for 20 min. The reaction is diluted with dichloromethane and washed successively with a saturated solution of sodium bicarbonate and water. The organic layer is separated, dried over anhydrous sodium sulfate, filtered, and concentrated to a solid. The solid is dissolved in dichloromethane (1 mL) and 2:1 diethyl ether/hexane is added. The resultant solid is filtered and dried to give the pure free base of the title compound. The free base (0.021 g, 0.049 mmol) is dissolved in dichloromethane (1 ml) and 1M anhydrous HCl in diethyl ether (0.1 ml) is added to precipitate the desired title compound as a white solid. MS (ES+) m/e 428.2 (M+1)+ (free base).

Workup

  1. customto react at ambient temperature for 1 hour
  2. concentrationThe reaction is then concentrated to dryness
  3. dissolutionThe residue is dissolved in toluene (10 mL)
  4. concentrationconcentrated again
  5. dissolutionThe residue is dissolved in dichloromethane (6 mL)
  6. additionadded to a flask
  7. washwashed successively with a saturated solution of sodium bicarbonate and water
  8. customThe organic layer is separated
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated to a solid
  12. dissolutionThe solid is dissolved in dichloromethane (1 mL)
  13. addition2:1 diethyl ether/hexane is added
  14. filtrationThe resultant solid is filtered
  15. customdried

Sources & evidence

ORD record
ord-7cf80435557b46948e8deaf2f46c3df4
Source dataset
uspto-grants-2011_08
Patent number
US08008296B2

Reaction notes

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