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

HRID 919504Notes

Reaction equation

HRID 919504 reaction equation
[CH3:1]NN.[Cl:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[C:17]([C:22]3[N:23](C)[N:24]=[CH:25][CH:26]=3)[CH:16]=2)=[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:20]=[CH:19][C:18]([OH:21])=[C:17]([C:22]3[CH:26]=[CH:25][N:24]([CH3:1])[N:23]=3)[CH:16]=2)=[O:13])=[CH:7][CH:6]=1

Participants

4

Reactant 2

HCID 6061MethylhydrazineHCID 1356979361-(4-Chloro-phenyl)-3-[4-hydroxy-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-urea

Product 1

HCID 1356979391-(4-Chloro-phenyl)-3-[4-hydroxy-3-(1-methyl-1H-pyrazol-3-yl)-phenyl]-ureaYield 12%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent2×

Procedure

To a cooled and stirred solution of methyl hydrazine (1.46 g, 31.6 mmol) in pyridine was added slurry of Compound 119 (2.5 g, 7.9 mmol) in pyridine over a period of 10 mins. The reaction mixture was left at this temperature for another 2 hrs and then warmed to room temperature slowly. After 6 hrs the reaction mixture turned clear. The reaction was stirred at this temperature for 18 hrs. Then pyridine was evaporated. The dark colored residue was dissolved in DMSO and purified using Varian Preparative HPLC system at a flow rate of 60 mL/Min. and λ=240. The regio isomers were separated. The fractions containing Compound 154 were dried in vacuo to produce an off-white solid 1-(4-Chloro-phenyl)-3-[4-hydroxy-3-(1-methyl-1H-pyrazol-3-yl)-phenyl]urea (0.3 g, 12%). LCMS m/z (%)=343 (M+H, 35Cl 100), 345 (M+H, 37Cl, 32.5). 1H NMR (400 MHz, DMSO-d6) δ: 10.26 (bs, 1H), 8.73 (bs, 1H), 8.46 (bs, 1H), 7.82 (d, J=2.32 Hz, 1H), 7.77 (d, J=3.62 Hz, 1H), 7.44-7.49 (m, 2H), 7.16-7.19 (dd, J=8.74, 2.62 Hz, 1H), 6.83-6.85 (d, J=8.72 Hz, 1H), 6.71-6.72 (d, J=2.36 Hz, 1H), 3.91 (s, 3H).

Workup

  1. temperatureTo a cooled
  2. waitAfter 6 hrs the reaction mixture turned clear
  3. customThen pyridine was evaporated
  4. dissolutionThe dark colored residue was dissolved in DMSO
  5. custompurified
  6. customThe regio isomers were separated
  7. additionThe fractions containing Compound 154
  8. customwere dried in vacuo

Sources & evidence

ORD record
ord-e7015f6d433d47138ef76b017b13431c
Source dataset
uspto-grants-2016_03
Patent number
US09273035B2

Reaction notes

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