Triethylamine → HCID 11965461, compound

HRID 1894044Notes

Reaction equation

HRID 1894044 reaction equation
CO[C:3](=[O:21])[C:4]1[CH:9]=[C:8]([C:10]2[N:11]([CH3:15])[N:12]=[CH:13][CH:14]=2)[C:7]([C:16]([F:19])([F:18])[F:17])=[CH:6][C:5]=1[NH2:20].CC[N:24]([CH2:27]C)CC.[CH3:29][S:30]([NH:33]N)(=[O:32])=[O:31].[OH-:35].[Na+]>C(Cl)Cl.C1COCC1.O>[F:17][C:16]([F:18])([F:19])[C:7]1[CH:6]=[C:5]2[C:4]([C:3](=[O:21])[N:24]([NH:33][S:30]([CH3:29])(=[O:32])=[O:31])[C:27](=[O:35])[NH:20]2)=[CH:9][C:8]=1[C:10]1[N:11]([CH3:15])[N:12]=[CH:13][CH:14]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 269268MethanesulfonohydrazideHCID 11965460HCID 11965460, compound

Product 1

HCID 11965461HCID 11965461, compoundYield 48%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

2-Amino-4-trifluoromethyl-5-(2-methyl-2H-pyrazol-3-yl)-benzoic acid methyl ester (4.6 g, 15.4 mmol) in DCM (60 mL) and Et3N (10.7 mL, 5 equiv), (CCl3O)2CO (3.9 g, 0.85 equiv) was added portionwise. The mixture was stirred at r.t. for 2 h before concentration in vacuo to dryness. The resulting paste was dissolved in THF (60 mL) and CH3SO2NHNH2 (2.02 g, 1.2 equiv) was added. The mixture was stirred at r.t. for 1 h. An aqueous NaOH solution (1N, 15.4 mL, 1 equiv) was added and the mixture was stirred for 1 h at r.t. 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 crude solid (7 g). The crude product was purified by flash chromatography (EtOAc/hexanes (1:9) to EtOAc). The fractions containing the final compound were concentrated in vacuo in order to afford an off-white solid. This solid was sonicated in DCM and the resulting precipitate was filtered off and dried in vacuo to afford the title compound (3.0 g, 48%) as an off-white solid. (ESI-MS: m/z 404.3 [M+H]+, rt 4.20 min) 1H-NMR (DMSO-d6, 400 MHz) 11.7 (s, 1H), 10.45 (s, 1H), 8.0 (s, 1H), 7.70 (s, 1H), 7.55 (s, 1H), 6.35 (s, 1H), 3.60 (s, 3H), 3.20 (s, 3H).

Workup

  1. stirringThe mixture was stirred at r.t. for 1 h
  2. stirringthe mixture was stirred for 1 h at r.t
  3. extractionthe aqueous phase was extracted with AcOEt
  4. additionThe aqueous layer was acidified to pH 3 by addition of 2N aq HCl
  5. extractionextracted with AcOEt
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customto afford a crude solid (7 g)
  9. customThe crude product was purified by flash chromatography (EtOAc/hexanes (1:9) to EtOAc)
  10. additionThe fractions containing the final compound
  11. concentrationwere concentrated in vacuo in order
  12. customto afford an off-white solid
  13. filtrationthe resulting precipitate was filtered off
  14. customdried in vacuo

Sources & evidence

ORD record
ord-a9daed4ca9f44429ab1ab59189148b3d
Source dataset
uspto-grants-2013_08
Patent number
US08513268B2

Reaction notes

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