Triethylamine → n-[6-(2,5-Dimethyl-2h-pyrazol-3-yl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2h-quinazolin-3-yl]-methanesulfonamide

HRID 906550Notes

Reaction equation

HRID 906550 reaction equation
CO[C:3](=[O:22])[C:4]1[CH:9]=[C:8]([C:10]2[N:11]([CH3:16])[N:12]=[C:13]([CH3:15])[CH:14]=2)[C:7]([C:17]([F:20])([F:19])[F:18])=[CH:6][C:5]=1[NH2:21].CC[N:25]([CH2:28]C)CC.[CH3:30][S:31]([NH:34]N)(=[O:33])=[O:32].[OH-:36].[Na+]>C(Cl)Cl.O>[CH3:16][N:11]1[C:10]([C:8]2[CH:9]=[C:4]3[C:5](=[CH:6][C:7]=2[C:17]([F:18])([F:19])[F:20])[NH:21][C:28](=[O:36])[N:25]([NH:34][S:31]([CH3:30])(=[O:33])=[O:32])[C:3]3=[O:22])=[CH:14][C:13]([CH3:15])=[N:12]1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 269268MethanesulfonohydrazideHCID 119655392-amino-5-(2,5-dimethyl-2H-pyrazol-3-yl)-4-trifluoromethyl-benzoic acid methyl ester

Product 1

HCID 11965538n-[6-(2,5-Dimethyl-2h-pyrazol-3-yl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2h-quinazolin-3-yl]-methanesulfonamideYield 26%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-amino-5-(2,5-dimethyl-2H-pyrazol-3-yl)-4-trifluoromethyl-benzoic acid methyl ester (610 mg, 1.95 mmol) in DCM (20 mL) containing Et3N (1.1 mL, 4 equiv) was added (CCl3O)2CO (294 mg, 0.5 equiv) portionwise. The mixture was stirred at r.t. for 2 h and was the solvent was removed in vacuo. The resulting paste was dissolved in THF (20 mL) and CH3SO2NHNH2 (214 mg, 1 equiv) was added. The mixture was stirred at r.t. for 1 h and an aqueous solution of NaOH (1N, 1.95 mL, 1 equiv) was added. The mixture was stirred at r.t. for 2 h. The mixture was then poured into water and the aqueous phase was extracted with AcOEt. The aqueous layer was acidified to pH 3 by addition of 2N aq HCl and then extracted with AcOEt. The organic phases were combined, dried (Na2SO4) and concentrated in vacuo to afford a brown syrup. The crude product was purified by flash chromatography (EtOAc/hexanes (25:75) to EtOAc) to furnish N-[6-(2,5-dimethyl-2H-pyrazol-3-yl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide (213 mg, 26%) as a white powder. (ESI-MS: m/z 418.4 [M+H]+, rt 4.30 min) 1H-NMR (DMSO-d6, 400 MHz) 12.1 (s, 1H), 10.38 (s, 1H), 7.91 (s, 1H), 7.64 (s, 1H), 6.08 (s, 1H), 3.47 (s, 3H), 3.16 (s, 3H), 2.17 (s, 3H).

Workup

  1. customwas removed in vacuo
  2. dissolutionThe resulting paste was dissolved in THF (20 mL)
  3. stirringThe mixture was stirred at r.t. for 1 h
  4. stirringThe mixture was stirred at r.t. for 2 h
  5. extractionthe aqueous phase was extracted with AcOEt
  6. additionThe aqueous layer was acidified to pH 3 by addition of 2N aq HCl
  7. extractionextracted with AcOEt
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customto afford a brown syrup
  11. customThe crude product was purified by flash chromatography (EtOAc/hexanes (25:75) to EtOAc)

Sources & evidence

ORD record
ord-17d51674a60a4fcba0ba448d83e1a53f
Source dataset
uspto-grants-2011_09
Patent number
US08012988B2

Reaction notes

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