1,2-Dichloroethane → Morpholine-4-carboxylic acid[1-(3-benzenesulfonylamino-2-oxo-propylcarbamoyl)-2-phenylmethanesulfonyl-ethyl]-amide

HRID 460409Notes

Reaction equation

HRID 460409 reaction equation
[N:1]1([C:7]([NH:9][CH:10]([CH2:14][S:15]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)(=[O:17])=[O:16])[C:11]([OH:13])=O)=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.OC(C(F)(F)F)=O.[NH2:32][CH2:33][CH:34]([OH:46])[CH2:35][NH:36][S:37]([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)(=[O:39])=[O:38].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>CN(C=O)C>[C:40]1([S:37]([NH:36][CH2:35][C:34](=[O:46])[CH2:33][NH:32][C:11]([CH:10]([NH:9][C:7]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)=[O:8])[CH2:14][S:15]([CH2:18][C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)(=[O:16])=[O:17])=[O:13])(=[O:39])=[O:38])[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 112797342-[(Morpholine-4-carbonyl)-amino]-3-phenylmethanesulfonyl-propionic acidHCID 86612923N-(3-amino-2-hydroxy-propyl)-benzenesulfonamide TFA salt

Product 1

HCID 10120571Morpholine-4-carboxylic acid[1-(3-benzenesulfonylamino-2-oxo-propylcarbamoyl)-2-phenylmethanesulfonyl-ethyl]-amideYield 19.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-[(Morpholine-4-carbonyl)-amino]-3-phenylmethanesulfonyl-propionic acid (50 mg, 0. 14 mmol), N-(3-amino-2-hydroxy-propyl)-benzenesulfonamide TFA salt (60 mg, 0.17 mmol), EDC (100 mg, 0.52 mmol), and HOBt (100 mg, 0.64 mmol) were combined. DMF (3 mL) was added and then 4-methylmorpholine (0.3 mL). The mixture was stirred at ambient temperature for 3 hours. After dilution with ethyl acetate (100 mL) the solution was washed with 1N HCl, saturated aqueous NaHCO3 and brine, dried with MgSO4 and evaporated under vacuum. The residue was dissolved in acetone (5 mL). Jones reagent was added until the orange color persisted. The mixture was stirred for 2 hours, quenched with isopropanol, and diluted with ethyl acetate (100 mL). The solution was washed with water, saturated aqueous NaHCO3 and brine, dried with MgSO4 and evaporated under vacuum. The crude product was recrystallized from ethyl acetate/diethyl ether to give morpholine-4-carboxylic acid [1-(3-benzenesulfonylamino-2-oxo-propylcarbamoyl)-2-phenylmethanesulfonyl-ethyl]-amide as white solid (19 mg); 1H NMR: (DMSO) 8.17 (t, J=5.7 Hz, 1H), 7.93 (t, J=5.9 Hz, 1H), 7.76–7.48 (m, 5H), 7.36–7.29 (m, 5H), 7.05 (d, J=8.1 Hz, 1H), 4.68–4.59 (m, 1H), 4.45 (s, 2H), 3.89 (d, J=5.7 Hz, 2H), 3.79–3,75 (m, 2H), 3.56–3.22 (m, 10H); MS: (M+H)+ 567.

Workup

  1. washAfter dilution with ethyl acetate (100 mL) the solution was washed with 1N HCl, saturated aqueous NaHCO3 and brine
  2. dry with materialdried with MgSO4
  3. customevaporated under vacuum
  4. dissolutionThe residue was dissolved in acetone (5 mL)
  5. additionJones reagent was added until the orange color
  6. stirringThe mixture was stirred for 2 hours
  7. customquenched with isopropanol
  8. additiondiluted with ethyl acetate (100 mL)
  9. washThe solution was washed with water, saturated aqueous NaHCO3 and brine
  10. dry with materialdried with MgSO4
  11. customevaporated under vacuum
  12. customThe crude product was recrystallized from ethyl acetate/diethyl ether

Sources & evidence

ORD record
ord-6a9f034b73c14dcf9a88164f0d173113
Source dataset
uspto-grants-2007_03
Patent number
US07196099B2

Reaction notes

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