Hydrochloric Acid → 1-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-[3-(1-hydroxyimino-ethyl)-phenyl]-urea

HRID 407485Notes

Reaction equation

HRID 407485 reaction equation
[C:1]([C:4]1[CH:5]=[C:6]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([C:22]3[N:23]([CH3:28])[N:24]=[CH:25][C:26]=3[Br:27])[CH:15]=2)=[O:12])[CH:7]=[CH:8][CH:9]=1)(=O)[CH3:2].Cl.[NH2:30][OH:31].Cl>C(O)C>[Br:27][C:26]1[CH:25]=[N:24][N:23]([CH3:28])[C:22]=1[C:16]1[CH:15]=[C:14]([NH:13][C:11]([NH:10][C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([C:1](=[N:30][OH:31])[CH3:2])[CH:5]=2)=[O:12])[CH:19]=[CH:18][C:17]=1[O:20][CH3:21]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 443297Hydroxyamine hydrochlorideHCID 111782371-(3-Acetyl-phenyl)3-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-urea

Product 1

HCID 730193591-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-[3-(1-hydroxyimino-ethyl)-phenyl]-ureaYield 16%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Compound 17 (54 mg, 0.12 mmol, see Example 1.24) was dissolved in ethanol (10 mL). Hydroxylamine hydrochloride (17 mg, 0.24 mmol) was added under Argon gas. The pH of the solution was then adjusted to pH=4 with 1N Hydrogen Chloride solution. The reaction was stirred overnight at room temperature and found to be complete by TLC and LC/MS. The ethanol was removed under reduced pressure. Then, the residue was worked up with EtOAc (2×20 mL) and Brine (20 mL). The organic layers were combined, dried over Na2SO4, filtered, and the solvent removed under reduced pressure. The residue was then purified by HPLC to afford 8.8 mg (16%) of Compound 96: LCMS m/z (%)=458 (M+H79Br, 96), 460 (M+H81Br, 100). 1H NMR (400 MHz, CDCl3) δ: 7.78 (s, 1H), 7.70 (s, 1H), 7.68 (s, 1H), 7.48 (dd, J1=12 Hz, J2=4 Hz, 1H), 7.42 (s, 1H), 7.41 (dd, J1=8 Hz, J2=4 Hz, 1H), 7.39 (d, J=4 Hz, 1H), 7.30 (t, 1H), 7.19 (d, J=8 Hz, 1H), 7.15 (s, 1H), 7.08 (dd, J1=12 Hz, J2=4 Hz, 1H), 6.88 (dd, J1=12 Hz, J2=8 Hz, 1H), 3.66 (s, 3H), 3.58 (s, 3H), 1.99 (s, 3H).

Workup

  1. customThe ethanol was removed under reduced pressure
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. customthe solvent removed under reduced pressure
  5. customThe residue was then purified by HPLC

Sources & evidence

ORD record
ord-e13d76c6ec08407dae4c845a50f5fdf3
Source dataset
uspto-grants-2014_06
Patent number
US08754238B2

Reaction notes

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