Pyridine → (S)-N-[1-[[[[(5-Methyl-3-isoxazolyl)amino]sulfonyl]amino]-carbonyl]-2-oxo-3-azetidinyl]benzeneacetamide

HRID 1762392Notes

Reaction equation

HRID 1762392 reaction equation
[O:1]=[C:2]1[C@@H:5]([NH:6][C:7](=[O:15])[CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:4][NH:3]1.Cl[S:17]([N:20]=[C:21]=[O:22])(=[O:19])=[O:18].[CH3:23][C:24]1[O:28][N:27]=[C:26]([NH2:29])[CH:25]=1.C(N(CC)CC)C.N1C=CC=CC=1>C(OCC)(=O)C.O.COCCOC>[CH3:23][C:24]1[O:28][N:27]=[C:26]([NH:29][S:17]([NH:20][C:21]([N:3]2[CH2:4][C@H:5]([NH:6][C:7](=[O:15])[CH2:8][C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:2]2=[O:1])=[O:22])(=[O:19])=[O:18])[CH:25]=1

Participants

9

Reactant 5

HCID 1049PyridineHCID 8471TriethylamineHCID 661723-Amino-5-methylisoxazoleHCID 70918Chlorosulfonyl isocyanateHCID 13212049(S)-3-[[(phenylmethyl)carbonyl]amino]-2-azetidinone

Product 1

HCID 14458783(S)-N-[1-[[[[(5-Methyl-3-isoxazolyl)amino]sulfonyl]amino]-carbonyl]-2-oxo-3-azetidinyl]benzeneacetamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

A mixture of 204 mg (1 mmol) of (S)-N-(2-oxo-3-azetidinyl)benzeneacetamide and 10 mL of 1,2-dimethoxyethane was stirred and cooled. At 0°-5° C. 0.104 mL of chlorosulfonyl isocyanate was added; within 5 minutes complete solution occurred. The reaction mixture was kept at 0°-5° C. for one hour. Then, with cooling to -10° C., a mixture of 98 mg (1 mmol) of 5-methyl-3-isoxazolamine, 0.415 mL (3 mmol) of triethylamine, and 0.30 mL (3 mmol) of pyridine was added. The cold bath was removed, and stirring continue for two hours. The mixture was then concentrated under reduced pressure, the residue dissolved in methylene chloride, and the solvent evaporated to leave an amorphous residue, which was then dissolved in a mixture of ethyl acetate and water. The mixture was acidified to pH 3; the organic layer was dried (Na2SO4), treated with charcoal, filtered, and concentrated to a residue of 180 mg. Purification was accomplished by preparative layer chromatography on three 20×20 cm Merck PLC plates (Silica Gel 60 F-254) using 10% MeOH in CHCl3 as the solvent to obtain the title compound: (Me2SO-d6) δ 2.29 (s, 3H, Me), 3.25 (dd, J4α, 4β =6 Hz, J3, 4β =3 Hz, 1H, CHCHαHβ), 3.45 (s, 2H, PhCH2), 3.60 (t, J3, 4α =J4α, 4β =6 Hz, 1H, CHCHα Hβ), 4.75 (m, 1H, CHCH2), 6.13 (s, 1H, isoxazole H) 7.27 (s, 5H, Ph), 8.74 (d, J=8 Hz, 1H, NHCH), 8.97 (bs, 1H, NH); 1R (KBr) 3420, 1773, 1650, 1620, 1358, 1310, 1133 cm-1.

Workup

  1. temperaturecooled
  2. customAt 0°-5° C
  3. waitThe reaction mixture was kept at 0°-5° C. for one hour
  4. additionwas added
  5. customThe cold bath was removed
  6. stirringstirring
  7. waitcontinue for two hours
  8. concentrationThe mixture was then concentrated under reduced pressure
  9. dissolutionthe residue dissolved in methylene chloride
  10. customthe solvent evaporated
  11. customto leave an amorphous residue, which
  12. dry with materialthe organic layer was dried (Na2SO4)
  13. additiontreated with charcoal
  14. filtrationfiltered
  15. concentrationconcentrated to a residue of 180 mg
  16. customPurification

Sources & evidence

ORD record
ord-503120fb988041a587eb605160bd85d5
Source dataset
uspto-grants-1989_05
Patent number
US04831130

Reaction notes

Loading…