1,2-Dichloroethane → 4-Morpholin-4-yl-4-oxo-2-benzylsulfonylmethyl-N-{-(S)-1[1-(3-phenyl-[1,2,4]oxadiazol-5-yl)-methanoyl]-propyl}-butyramide

HRID 1830169Notes

Reaction equation

HRID 1830169 reaction equation
[NH2:1][C@@H:2]([CH2:16][CH3:17])[C:3]([C:5]1[O:9][N:8]=[C:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[N:6]=1)=[O:4].[N:18]1([C:24](=[O:41])[CH2:25][CH:26]([CH2:30][S:31]([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)(=[O:33])=[O:32])[C:27](O)=[O:28])[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.[O-]S([O-])(=S)=O.[Na+].[Na+]>C(OCC)(=O)C.C([O-])(O)=O.[Na+].C(Cl)Cl>[N:18]1([C:24](=[O:41])[CH2:25][CH:26]([CH2:30][S:31]([CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)(=[O:32])=[O:33])[C:27]([NH:1][C@H:2]([C:3]([C:5]2[O:9][N:8]=[C:7]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[N:6]=2)=[O:4])[CH2:16][CH3:17])=[O:28])[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1

Participants

11

Reactant 7

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 24477Sodium ThiosulfateHCID 757711-HydroxybenzotriazoleHCID 159087TriacetoxyperiodinaneHCID 220539874-Morpholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acidHCID 58649533(S)-2-Amino-1-(3-phenyl-[1,2,4]oxadiazol-5-yl)-butan-1-one

Product 1

HCID 586495024-Morpholin-4-yl-4-oxo-2-benzylsulfonylmethyl-N-{-(S)-1[1-(3-phenyl-[1,2,4]oxadiazol-5-yl)-methanoyl]-propyl}-butyramide

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A mixture of (S)-2-amino-1-(3-phenyl-[1,2,4]oxadiazol-5-yl)-butan-1-one, prepared as in Reference 11, 4-morpholin-4-yl-4-oxo-2-benzylsulfonylmethyl-butyric acid (200 mg, 0.56 mmol), EDC (200 mg, 1.05 mmol), HOBt (200 mg, 1.30 mmol), CH2Cl2 (4 mL) and 4-methylmorpholine (0.5 mL) was stirred at ambient temperature for 2 hours. After dilution with ethyl acetate (150 mL), the solution was washed with water (30 mL), saturated aqueous NaHCO3 solution and brine, dried with MgSO4 and evaporated under vacuum. The crude product was dissolved in dry dichloromethyl (10 mL) and 1,1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3(1H)-one (Dess-Martin periodinane) (500 mg, 1.2 mmol) was added. After stirring at ambient temperatures for 1 hour, the mixture was diluted with ethyl acetate (150 mL) and treated with Na2S2O3 solution (0.26M) in saturated aqueous NaHCO3. The organic phase was washed with saturated aqueous NaHCO3 and brine, dried with MgSO4 and evaporated. The product was purified by flash chromatography on silica gel (hexane/ethyl acetate in a 1:2 to 1:4 ratio) to yield 4-Morpholin-4-yl-4-oxo-2-benzylsulfonylmethyl-N-{-(S)-1[1-(3-phenyl-[1,2,4]oxadiazol-5-yl)-methanoyl]-propyl}-butyramide (150 mg) as mixture of diastereomers; 1H NMR: (DMSO), 9.03 (d, J=5.9 Hz), 8.89 (d, J=6.4 Hz), 1H], 8.09–8.03 (m, 2H), 7.66–7.55 (m, 3H), 7.42–7.33 (m, 5H), 4.97–4.78 (m, 1H), 4.53–4.35 (m, 2H), 3.58–3.02 (m, 1H), 2.65–2.50 (m, 2H), 2.06–1.90 (m, 1H), 1.83–1.66 (m, 1H), 0.97 (t, J=7.2 Hz, 3H); MS: (M++1) 569.

Workup

  1. washAfter dilution with ethyl acetate (150 mL), the solution was washed with water (30 mL), saturated aqueous NaHCO3 solution and brine
  2. dry with materialdried with MgSO4
  3. customevaporated under vacuum
  4. dissolutionThe crude product was dissolved in dry dichloromethyl (10 mL)
  5. stirringAfter stirring at ambient temperatures for 1 hour
  6. washThe organic phase was washed with saturated aqueous NaHCO3 and brine
  7. dry with materialdried with MgSO4
  8. customevaporated
  9. customThe product was purified by flash chromatography on silica gel (hexane/ethyl acetate in a 1:2 to 1:4 ratio)

Sources & evidence

ORD record
ord-8e13ce4b83fc46ffb0098f11dc26b95d
Source dataset
uspto-grants-2006_06
Patent number
US07064123B1

Reaction notes

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