Triethylamine → HCID 59164460, compound

HRID 1441571Notes

Reaction equation

HRID 1441571 reaction equation
CO[C:3](=[O:29])[C:4]1[CH:9]=[C:8]([C:10]2[N:11]([CH2:16][CH2:17][O:18][CH2:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[N:12]=[C:13]([CH3:15])[CH:14]=2)[C:7]([C:24]([F:27])([F:26])[F:25])=[CH:6][C:5]=1[NH2:28].CC[N:32]([CH2:35]C)CC.[CH3:37][S:38]([NH:41]N)(=[O:40])=[O:39].[OH-:43].[Na+]>C(Cl)Cl.O>[CH3:15][C:13]1[CH:14]=[C:10]([C:8]2[CH:9]=[C:4]3[C:5](=[CH:6][C:7]=2[C:24]([F:26])([F:25])[F:27])[NH:28][C:35](=[O:43])[N:32]([NH:41][S:38]([CH3:37])(=[O:40])=[O:39])[C:3]3=[O:29])[N:11]([CH2:16][CH2:17][O:18][CH2:19][Si:20]([CH3:22])([CH3:23])[CH3:21])[N:12]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 269268MethanesulfonohydrazideHCID 59164500HCID 59164500, compound

Product 1

HCID 59164460HCID 59164460, compoundYield 26%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-amino-5-[5-methyl-2-(2-trimethylsilanylmethoxy-ethyl)-2H-pyrazol-3-yl]-4-trifluoromethyl-benzoic acid methyl ester (426 mg, 0.99 mmol) in DCM (10 mL) containing Et3N (0.55 mL, 4 equiv) was added (CCl3O)2CO (147 mg, 0.5 equiv) portionwise. The mixture was stirred at r.t. for 2 h and then concentrated in vacuo to dryness. The resulting paste was dissolved in THF (10 mL) and CH3SO2NHNH2 (109 mg, 1 equiv) was added. After stirring the mixture at r.t. for 1 h, an aqueous solution of NaOH (1N, 1 mL, 1 equiv) was added. The mixture was stirred for 2 h at r.t. Then, the mixture was poured into water and the aqueous phase was extracted with AcOEt (3 times). The organic phases were combined, dried (Na2SO4) and concentrated in vacuo to afford a crude solid. The crude product was purified by flash chromatography (hexanes to EtOAc/hexanes (3:1)) to provide N-{6-[5-methyl-2-(2-trimethylsilanylmethoxy-ethyl)-2H-pyrazol-3-yl]-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl}-methanesulfonamide (140 mg, 26%) as a yellow paste. (ESI-MS: m/z 534.6 [M+H]+, rt 5.69 min).

Workup

  1. concentrationconcentrated in vacuo to dryness
  2. dissolutionThe resulting paste was dissolved in THF (10 mL)
  3. stirringAfter stirring the mixture at r.t. for 1 h
  4. stirringThe mixture was stirred for 2 h at r.t
  5. extractionthe aqueous phase was extracted with AcOEt (3 times)
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customto afford a crude solid
  9. customThe crude product was purified by flash chromatography (hexanes to EtOAc/hexanes (3:1))

Sources & evidence

ORD record
ord-cf1601561ae1467d807206eb080f78ec
Source dataset
uspto-grants-2010_02
Patent number
US07655666B2

Reaction notes

Loading…