1,4-Dioxane → n-[6-(3-Cyano-phenyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2h-quinazolin-3-yl]-methanesulfonamide

HRID 1441586Notes

Reaction equation

HRID 1441586 reaction equation
CO[C:3]([C:5]1[CH:6]=[C:7]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([C:22]#[N:23])[CH:17]=2)[C:8]([C:12]([F:15])([F:14])[F:13])=[CH:9][C:10]=1[NH2:11])=[O:4].CCN(C(C)C)C(C)C.[CH3:33][S:34]([NH:37][NH2:38])(=[O:36])=[O:35].[O:39]1CCOC[CH2:40]1>>[C:22]([C:18]1[CH:17]=[C:16]([C:7]2[CH:6]=[C:5]3[C:10](=[CH:9][C:8]=2[C:12]([F:15])([F:13])[F:14])[NH:11][C:40](=[O:39])[N:38]([NH:37][S:34]([CH3:33])(=[O:36])=[O:35])[C:3]3=[O:4])[CH:21]=[CH:20][CH:19]=1)#[N:23]

Participants

5

Reactant 4

HCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 269268MethanesulfonohydrazideHCID 119656184-Amino-3'-cyano-6-trifluoromethyl-biphenyl-3-carboxylic acid methyl ester

Product 1

HCID 11965619n-[6-(3-Cyano-phenyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2h-quinazolin-3-yl]-methanesulfonamideYield 84%

Conditions

Temperature
60 °C

Procedure

A solution of 4-amino-3′-cyano-6-trifluoromethyl-biphenyl-3-carboxylic acid methyl ester (0.7 g, 2.19 mmol) in dioxane (15 mL) was treated with i-Pr2NEt (0.5 mL, 2.92 mmol) and (CCl3O)2CO (0.655 g, 2.19 mmol) and the mixture was stirred at 60° C. for 1 h under nitrogen. To this solution was added CH3SO2NHNH2 (0.24 g, 2.19 mmol) and stirring was continued for 1 h at 60° C. and for 16 h at r.t. The mixture was concentrated in vacuo, diluted with water and extracted three times with 25 mL each of EtOAc. The combined organic layers were washed twice with water and dried (Na2SO4), filtered and the solvent evaporated. The product was recrystallized from MeOH/DCM 3:1 to give N-[6-(3-cyano-phenyl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide (0.78 g, 1.84 mmol, 84%), m.p. 291-292° C., ESI-MS: m/z 425 [M+H]+.

Workup

  1. stirringstirring
  2. waitwas continued for 1 h at 60° C. and for 16 h at r.t
  3. concentrationThe mixture was concentrated in vacuo
  4. additiondiluted with water
  5. extractionextracted three times with 25 mL each of EtOAc
  6. washThe combined organic layers were washed twice with water
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customthe solvent evaporated
  10. customThe product was recrystallized from MeOH/DCM 3:1

Sources & evidence

ORD record
ord-9663077be98c4b528632c097c76a3634
Source dataset
uspto-grants-2010_02
Patent number
US07655666B2

Reaction notes

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