Triethylamine → N-[6-(2-isopropyl-2H-pyrazol-3-yl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamide

HRID 1894080Notes

Reaction equation

HRID 1894080 reaction equation
CO[C:3](=[O:23])[C:4]1[CH:9]=[C:8]([C:10]2[N:11]([CH:15]([CH3:17])[CH3:16])[N:12]=[CH:13][CH:14]=2)[C:7]([C:18]([F:21])([F:20])[F:19])=[CH:6][C:5]=1[NH2:22].CC[N:26]([CH2:29]C)CC.[CH3:31][S:32]([NH:35]N)(=[O:34])=[O:33].[OH-:37].[Na+]>C(Cl)Cl>[F:20][C:18]([F:19])([F:21])[C:7]1[CH:6]=[C:5]2[C:4]([C:3](=[O:23])[N:26]([NH:35][S:32]([CH3:31])(=[O:34])=[O:33])[C:29](=[O:37])[NH:22]2)=[CH:9][C:8]=1[C:10]1[N:11]([CH:15]([CH3:16])[CH3:17])[N:12]=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 269268MethanesulfonohydrazideHCID 119657792-Amino-4-trifluoromethyl-5-(2-isopropyl-2H-pyrazol-3-yl)-benzoic acid methyl ester

Product 1

HCID 52932007N-[6-(2-isopropyl-2H-pyrazol-3-yl)-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamideYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-amino-4-trifluoromethyl-5-(2-isopropyl-2H-pyrazol-3-yl)-benzoic acid methyl ester (510 mg, 1.56 mmol) in DCM (20 mL) were added Et3N (0.88 mL, 4 equiv) and then (CCl3O)2CO (377 mg, 0.8 equiv). The resulting mixture was stirred at r.t. for 3 h. The solvent was removed in vacuo and the crude intermediate was solubilized in THF. CH3SO2NHNH2 (116 mg, 1.0 equiv) was added and the mixture was stirred at r.t. for 1 h. Then, aq NaOH (1N, 1.56 mL) was added and the mixture was stirred for 30 min. The solvent was removed in vacuo and water was added. The pH was adjusted to pH 3-4 by addition of 1N aq HCl. The aqueous phase was extracted with AcOEt twice. The organic phases were combined, washed with brine, dried (Na2SO4) and concentrated in vacuo to afford a crude solid. The crude product was purified by flash chromatography (silica gel, EtOAc/hexanes (25:75 to 100:0)) to furnish a white solid (285 mg, 42%). (ES-MS: m/z 432.4 [M+H]+, rt 4.61 min) 1H-NMR (DMSO-d6, 400 MHz) 12.05 (bs, 1H); 10.4 (bs, 1H); 7.88 (s, 1H); 7.66 (s, 1H); 7.55 (s, 1H); 6.27 (s, 1H); 4.08 (m, 1H); 3.16 (s, 1H); 1.31 (bd, 6H).

Workup

  1. customThe solvent was removed in vacuo
  2. stirringthe mixture was stirred at r.t. for 1 h
  3. stirringthe mixture was stirred for 30 min
  4. customThe solvent was removed in vacuo and water
  5. additionwas added
  6. additionThe pH was adjusted to pH 3-4 by addition of 1N aq HCl
  7. extractionThe aqueous phase was extracted with AcOEt twice
  8. washwashed with brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. customto afford a crude solid
  12. customThe crude product was purified by flash chromatography (silica gel, EtOAc/hexanes (25:75 to 100:0))

Sources & evidence

ORD record
ord-e11125cb275847cdadb4991d9e61dfb7
Source dataset
uspto-grants-2013_08
Patent number
US08513268B2

Reaction notes

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