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

HRID 906597Notes

Reaction equation

HRID 906597 reaction equation
CO[C:3](=[O:22])[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]([CH:18]([F:20])[F:19])=[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>[F:20][CH:18]([F:19])[C:7]1[CH:6]=[C:5]2[C:4]([C:3](=[O:22])[N:25]([NH:34][S:31]([CH3:30])(=[O:33])=[O:32])[C:28](=[O:36])[NH:21]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 591644772-Amino-4-difluoromethyl-5-(2-isopropyl-2H-pyrazol-3-yl)-benzoic acid methyl ester

Product 1

HCID 45381994N-[7-difluoromethyl-6-(2-isopropyl-2H-pyrazol-3-yl)-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl]-methanesulfonamideYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-amino-4-difluoromethyl-5-(2-isopropyl-2H-pyrazol-3-yl)-benzoic acid methyl ester (380 mg, 1.23 mmol) in DCM (15 mL) were added Et3N (0.52 mL, 3 equiv) and then (CCl3O)2CO (261 mg, 0.7 equiv). The resulting mixture was stirred at r.t. for 1 h. The solvent was removed in vacuo and the residue was solubilized in THF. CH3SO2NHNH2 (149 mg, 1.1 equiv) was added and the mixture was stirred at r.t. for 1 h. Then, aq NaOH (1N, 1.4 mL) was added and the mixture was stirred at r.t. 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 (2×). The organic phases were combined, washed with brine, dried (Na2SO4) and concentrated in vacuo to afford a crude solid. This solid was dissolved in DCM (10 mL) and hexanes (10 mL) was added. The mixture was sonicated for 1 min. The resulting solid was filtered off, washed with hexanes and dried to afford the title compound as an off-white solid (305 mg, 60%). ES-MS: m/z 414.4 [M+H]+, rt 4.52 min. 1H-NMR (DMSO-d6, 400 MHz) 11.23 (bs, 1H); 7.83 (s, 1H); 7.57 (d, 1H, J=1.64 Hz); 7.55 (s, 1H); 6.80 (t, 1H, J=54.1 Hz); 6.32 (d, 1H, J=1.71 Hz); 4.12 (m, 1H); 3.16 (s, 1H); 1.31 (d, 6H, J=6.38 Hz).

Workup

  1. customThe solvent was removed in vacuo
  2. stirringthe mixture was stirred at r.t. for 1 h
  3. stirringthe mixture was stirred at r.t. 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 (2×)
  8. washwashed with brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. customto afford a crude solid
  12. customThe mixture was sonicated for 1 min
  13. filtrationThe resulting solid was filtered off
  14. washwashed with hexanes
  15. customdried

Sources & evidence

ORD record
ord-667f00e5cfa640fe98d245d2459cc47a
Source dataset
uspto-grants-2011_09
Patent number
US08012988B2

Reaction notes

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