Triethylamine → HCID 45381814, compound

HRID 906591Notes

Reaction equation

HRID 906591 reaction equation
CO[C:3](=[O:21])[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]([CH2:18][F:19])=[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>[F:19][CH2:18][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]([CH:15]([CH3:16])[CH3:17])[N:12]=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 269268MethanesulfonohydrazideHCID 59164455HCID 59164455, compound

Product 1

HCID 45381814HCID 45381814, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-amino-4-fluoromethyl-5-(2-isopropyl-2H-pyrazol-3-yl)-benzoic acid methyl ester (243 mg, 0.834 mmol) in DCM (15 mL) were added Et3N (0.35 mL, 3 equiv) and then (CCl3O)2CO (177 mg, 0.7 equiv). The resulting mixture was stirred at r.t. for 1 h. The solvent was removed in vacuo and the crude solubilised in THF. CH3SO2NHNH2 (101 mg, 1.1 equiv) was added and the mixture was stirred at r.t. for 1 h. Then, aq NaOH (1N, 0.92 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 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. This solid was dissolved into 10 mL of DCM and then 10 ml of hexanes was added. The mixture was sonicated for 1 min. The resulting solid was filtered off, washed with hexanes and high-vacuum dried to afford the title compound (227 mg, 69%) as an off-white solid. (ES-MS: m/z 396.4 [M+H]+, rt 4.39 min) 1H-NMR (DMSO-d6, 400 MHz) 11.07 (bs, 1H); 7.76 (d, 1H, J=1.07 Hz); 7.55 (d, 1H, J=1.58 Hz); 7.40 (s, 1H); 6.30 (d, 1H, J=1.77 Hz); 5.30 (d, 2H, J=46.55 Hz); 4.14 (m, 1H); 3.16 (s, 1H); 1.31 (d, 6H, J=6.51 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 for 30 min
  4. customThe solvent was removed in vacuo and water
  5. additionwas added
  6. additionThe pH was adjusted to 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 mixture was sonicated for 1 min
  13. filtrationThe resulting solid was filtered off
  14. washwashed with hexanes and high-vacuum
  15. customdried

Sources & evidence

ORD record
ord-b9fac79460f64a67b44efd68ab701d9b
Source dataset
uspto-grants-2011_09
Patent number
US08012988B2

Reaction notes

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