Dimethylformamide → N-[(Z)-N-hydroxy-C-methylcarbonimidoyl]-5-methoxy-2-[(5-methyl-2-phenylpyrazol-3-yl)amino]benzamide

HRID 915599Notes

Reaction equation

HRID 915599 reaction equation
[CH3:1][C:2]1[CH:6]=[C:5]([NH:7][C:8]2[CH:16]=[CH:15][CH:14]=[CH:13][C:9]=2[C:10]([OH:12])=O)[N:4]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:3]=1.C1C=[N:27][C:26]2[N:29]([OH:32])N=N[C:25]=2C=1.CCN=C=NCCCN(C)C.C(N(CC)CC)C.ONC(=N)C.CN([CH:59]=[O:60])C>>[OH:32]/[N:29]=[C:26](\[NH:27][C:10](=[O:12])[C:9]1[CH:13]=[C:14]([O:60][CH3:59])[CH:15]=[CH:16][C:8]=1[NH:7][C:5]1[N:4]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:3]=[C:2]([CH3:1])[CH:6]=1)/[CH3:25]

Participants

7

Reactant 6

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 181649HOAtHCID 2727736HCID 2727736, compoundHCID 178465666HCID 178465666, compound

Product 1

HCID 136043039N-[(Z)-N-hydroxy-C-methylcarbonimidoyl]-5-methoxy-2-[(5-methyl-2-phenylpyrazol-3-yl)amino]benzamide

Procedure

To a mixture of 2-[(3-methyl-1-phenyl-1H-pyrazol-5-yl)amino]benzoic acid (400 mg, 1.04 mmol) (prepared by the sequence of Buchwald-type coupling and hydrolysis, similar to Examples 108 and 109), HOAT (186 mg, 1.39 mmol), and EDCI (263 mg, 1.39 mmol) in DMF (7 mL) at −20° C. was added triethylamine (0.45 mL, 3.25 mmol). After stirring at that temperature for 15 min, N-hydroxy-acetamidine (305 mg, 2.78 mmol) was added, and the temperature was slowly raised to rt. Stirring was continued for 16 h, the solvent was evaporated in vacuo and the residue was partitioned between water and EtOAc. The layers were separated, and the aqueous layer was extracted with EtOAc. The combined organic layers were washed successively with 5% citric acid, saturated aqueous Na2CO3 solution and brine, dried (MgSO4), filtered, and concentrated to give 147 mg of a crude solid. This solid was used in the next step with no further purification. ES-MS m/z 380.1 (MH+); HPLC RT (min) 2.53.

Workup

  1. stirringStirring
  2. waitwas continued for 16 h
  3. customthe solvent was evaporated in vacuo
  4. customthe residue was partitioned between water and EtOAc
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with EtOAc
  7. washThe combined organic layers were washed successively with 5% citric acid, saturated aqueous Na2CO3 solution and brine
  8. dry with materialdried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-0e6f11303d2743ee9975abcea53f83e4
Source dataset
uspto-grants-2007_09
Patent number
US07265144B2

Reaction notes

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