Dichloromethane → HCID 45381906, compound

HRID 1894101Notes

Reaction equation

HRID 1894101 reaction equation
CO[C:3](=[O:20])[C:4]1[CH:9]=[C:8]([C:10]2[N:11]([CH3:15])[N:12]=[CH:13][CH:14]=2)[C:7]([CH:16]([F:18])[F:17])=[CH:6][C:5]=1[NH2:19].[CH3:21][S:22]([NH:25][NH2:26])(=[O:24])=[O:23].[OH-:27].[Na+].[CH2:29](Cl)Cl>>[F:18][CH:16]([F:17])[C:7]1[CH:6]=[C:5]2[C:4]([C:3](=[O:20])[N:26]([NH:25][S:22]([CH3:21])(=[O:24])=[O:23])[C:29](=[O:27])[NH:19]2)=[CH:9][C:8]=1[C:10]1[N:11]([CH3:15])[N:12]=[CH:13][CH:14]=1

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 269268MethanesulfonohydrazideHCID 591644782-Amino-4-difluoromethyl-5-(2-methyl-2H-pyrazol-3-yl)-benzoic acid methyl ester

Product 1

HCID 45381906HCID 45381906, compoundYield 55%

Procedure

To a solution of 2-amino-4-difluoromethyl-5-(2-methyl-2H-pyrazol-3-yl)-benzoic acid methyl ester (200 mg, 0.71 mmol) in DCM (15 mL), was added (CCl3O)2CO (151 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 (86 mg, 1.1 equiv) was added and, after stirring at r.t. for 1 h, the mixture was treated with aq NaOH (1N, 0.78 mL) 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 (2×). The organic phases were combined, washed with brine, dried (Na2SO4) and concentrated in vacuo to afford a crude solid. This solid was triturated in 15 mL of DCM/hexanes (1/1). The resulting solid was filtered off, washed with hexanes and dried to afford the title compound as an off-white solid (150 mg, 55%). ES-MS: m/z 386.3 [M+H]+, rt 4.16 min. 1H-NMR (DMSO-d6, 400 MHz) 12.04 (s, 1H), 10.34 (s, 1H); 7.93 (s, 1H); 7.55 (s, 1H); 7.52 (s, 1H); 6.83 (t, 1H, J=54 Hz), 6.34 (s, 1H). 3.62 (s, 3H); 3.17 (s, 1H)

Workup

  1. customThe solvent was removed in vacuo
  2. stirringafter stirring at r.t. for 1 h
  3. customThe solvent was removed in vacuo and water
  4. additionwas added
  5. additionThe pH was adjusted to 3-4 by addition of 1N aq HCl
  6. extractionThe aqueous phase was extracted with AcOEt (2×)
  7. washwashed with brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customto afford a crude solid
  11. customThis solid was triturated in 15 mL of DCM/hexanes (1/1)
  12. filtrationThe resulting solid was filtered off
  13. washwashed with hexanes
  14. customdried

Sources & evidence

ORD record
ord-b10a972c9e40470593d9e7396367cc2b
Source dataset
uspto-grants-2013_08
Patent number
US08513268B2

Reaction notes

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