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

HRID 540601Notes

Reaction equation

HRID 540601 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, H2=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-e116d4c38b9b4ce59542bba7153ab1da
Source dataset
uspto-grants-2014_10
Patent number
US08871797B2

Reaction notes

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