Methylhydrazine → 1-(4-Chloro-phenyl)-3-[4-hydroxy-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-urea

HRID 1626167Notes

Reaction equation

HRID 1626167 reaction equation
[CH3:1][NH:2][NH2:3].[Cl:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([NH:14][C:15]2[CH:16]=[C:17]3[C:22](=[CH:23][CH:24]=2)[O:21][CH:20]=[CH:19][C:18]3=O)=[O:13])=[CH:7][CH:6]=1>N1C=CC=CC=1>[Cl:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([NH:14][C:15]2[CH:24]=[CH:23][C:22]([OH:21])=[C:17]([C:18]3[N:2]([CH3:1])[N:3]=[CH:20][CH:19]=3)[CH:16]=2)=[O:13])=[CH:7][CH:6]=1

Participants

4

Reactant 2

HCID 6061MethylhydrazineHCID 231394541-(4-chloro-phenyl)-3-(4-oxo-4H-chromen-6-yl)-urea

Product 1

HCID 1356979361-(4-Chloro-phenyl)-3-[4-hydroxy-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-urea

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

To a stirred and ice-cooled solution of methyl hydrazine (1.46 g, 31.6 mmol) in pyridine was added a slurry of 1-(4-chloro-phenyl)-3-(4-oxo-4H-chromen-6-yl)-urea (2.5 g, 7.9 mmol) in pyridine over a period of 10 mins. The reaction mixture was stirred further at this temperature for 2 hours and then allowed to warm slowly to ambient temperature. After 6 hrs the reaction mixture turned clear. The reaction was stirred at this temperature for 18 hours. Pyridine was evaporated and the resulting dark colored residue was dissolved in DMSO and purified using a Varian Prep. HPLC system (20 mL/min., λ=240, 0.1% TFA/H2O:0.1% TFA/CH3CN). The two regio-isomers were separated. The fractions containing the product were concentrated and dried in vacuo to produce (1.78 g, 47%) as a colorless powder. LCMS m/z (%)=343 (M+H35Cl, 100), 345 (M+H37Cl, 32.5). 1H NMR (400 MHz, DMSO-d6) δ: 9.59 (bs, 1H), 8.72 (bs, 1H), 8.48 (bs, 1H), 7.43 (dd, J=6.8, 2.07 Hz, 2H), 7.41 (d, J=1.83 Hz, 1H), 7.28 (dd, J=7.13, 2.09 Hz, 2H), 7.26 (d, J=2.72 Hz, 1H), 6.89 (d, J=9.36 Hz, 1H), 6.21 (d, J=1.84 Hz, 1H), 3.67 (s, 3H).

Workup

  1. stirringThe reaction mixture was stirred further at this temperature for 2 hours
  2. stirringThe reaction was stirred at this temperature for 18 hours
  3. customPyridine was evaporated
  4. dissolutionthe resulting dark colored residue was dissolved in DMSO
  5. custompurified
  6. customThe two regio-isomers were separated
  7. additionThe fractions containing the product
  8. concentrationwere concentrated
  9. customdried in vacuo
  10. customto produce (1.78 g, 47%) as a colorless powder

Sources & evidence

ORD record
ord-ea4bdbd087db4d7884ea9ef0eb872b4f
Source dataset
uspto-grants-2014_07
Patent number
US08785441B2

Reaction notes

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