Triethylamine → N-(4-bromo-3-methyl-5-isoxazolyl)-2-[N-(3-carboxyphenyl)aminocarbonyl]thiophene-3-sulfonamide

HRID 234409

Reaction equation

HRID 234409 reaction equation
CCN(CC)CC.[NH2:8][C:9]1[CH:10]=[C:11]([CH:17]=[CH:18][CH:19]=1)[C:12]([O:14]CC)=[O:13].N1P(Cl)(Cl)=NP(Cl)(Cl)=NP=1(Cl)Cl.[Br:32][C:33]1[C:34]([CH3:51])=[N:35][O:36][C:37]=1[NH:38][S:39]([C:42]1[CH:46]=[CH:45][S:44][C:43]=1[C:47](OC)=[O:48])(=[O:41])=[O:40]>C1COCC1.O>[Br:32][C:33]1[C:34]([CH3:51])=[N:35][O:36][C:37]=1[NH:38][S:39]([C:42]1[CH:46]=[CH:45][S:44][C:43]=1[C:47]([NH:8][C:9]1[CH:19]=[CH:18][CH:17]=[C:11]([C:12]([OH:14])=[O:13])[CH:10]=1)=[O:48])(=[O:40])=[O:41]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 11400Ethyl 3-aminobenzoateHCID 220225HexachlorocyclotriphosphazeneHCID 10833686N-(4-Bromo-3-methyl-5-isoxazolyl)-2-(carbomethoxy)thiophene-3-sulfonamide

Product 1

HCID 10576889N-(4-bromo-3-methyl-5-isoxazolyl)-2-[N-(3-carboxyphenyl)aminocarbonyl]thiophene-3-sulfonamideYield 13.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Et3N (2.27 ml. 16. mmol), ethyl 3-aminobenzoate (836 ml, 5.44 mmol) and phosphonitrilic chloride trimer (1.89 g, 5.44 mmol) were sequentially added to a solution of N-(4-bromo-3-methyl-5-isoxazolyl)-2-(carbonyl)thiophene-3-sulfonamide (Example 17) (1 g, 2.27 mmol) in dry THF (20 ml). The reaction was stirred at room temperature for 1 hour and cooled. Water (5 ml) was added to quench the reaction. The resulting solution was concentrated on a rotavap. The residue was diluted with EtOAc and washed with 2N HCl (2×150 ml). The organic layer was dried (MgSO4). The solid was filtered off and the filtrate was concentrated. The residue was treated with 1N NaOH (200 ml) and stirred at 0° C. for 15 minutes. The mixture was then acidified with conc. HCl to pH ~1. The resulting yellow precipitate was filtered off and recrystalized from CH3CN/H2O to give N-(4-bromo-3-methyl-5-isoxazolyl)-2-[N-(3-carboxyphenyl)aminocarbonyl]thiophene-3-sulfonamide (153 mg., 11.6%) as a yellowish powder, m.p. 183°-185° C.

Workup

  1. temperaturecooled
  2. customto quench
  3. customthe reaction
  4. concentrationThe resulting solution was concentrated on a rotavap
  5. additionThe residue was diluted with EtOAc
  6. washwashed with 2N HCl (2×150 ml)
  7. dry with materialThe organic layer was dried (MgSO4)
  8. filtrationThe solid was filtered off
  9. concentrationthe filtrate was concentrated
  10. additionThe residue was treated with 1N NaOH (200 ml)
  11. stirringstirred at 0° C. for 15 minutes
  12. filtrationThe resulting yellow precipitate was filtered off
  13. customrecrystalized from CH3CN/H2O

Sources & evidence

ORD record
ord-b0869138e75d47fe91948b619d7f759b
Source dataset
uspto-grants-1997_01
Patent number
US05594021

Linked notes

Loading…