2-Hydrazinoethanol → 3-[1-(2-Hydroxyethyl)-1H-pyrazol-5-yl]-1-(4-morpholin-4-ylphenyl)pyridazin-4(1H)-one

HRID 1407338Notes

Reaction equation

HRID 1407338 reaction equation
CN(C)[CH:3]=[CH:4][C:5]([C:7]1[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[CH:16][CH:15]=2)[N:8]=1)=O.[OH:27][CH2:28][CH2:29][NH:30][NH2:31]>CO>[OH:27][CH2:28][CH2:29][N:30]1[C:5]([C:7]2[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]3[CH:15]=[CH:16][C:17]([N:20]4[CH2:21][CH2:22][O:23][CH2:24][CH2:25]4)=[CH:18][CH:19]=3)[N:8]=2)=[CH:4][CH:3]=[N:31]1

Participants

4

Reactant 2

HCID 80172-HydrazinoethanolHCID 667107903-[3-(dimethylamino)prop-2-enoyl]-1-(4-morpholin-4-ylphenyl)pyridazin-4(1H)-one

Product 1

HCID 580722053-[1-(2-Hydroxyethyl)-1H-pyrazol-5-yl]-1-(4-morpholin-4-ylphenyl)pyridazin-4(1H)-oneYield 7.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 3-[3-(dimethylamino)prop-2-enoyl]-1-(4-morpholin-4-ylphenyl)pyridazin-4(1H)-one (476 mg, 1.34 mmol) in 20 mL of methanol, 2-hydroxyethylhydrazine (414 mg, 5.36 mmol) was added, the resulting mixture was refluxed for 4 hours, and then concentrated. The residue was dissolved in dichloromethane (20 mL), washed with 1 M acetic acid aqueous solution and brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The residue was purified by prep-HPLC to give the title compound (36 mg, 7.3% yield) as a yellow solid: 1H NMR (400 MHz, CDCl3): δ 3.20-3.22 (4H, m), 3.87-3.89 (4H, m), 4.03-4.05 (2H, m), 4.33-4.36 (2H, m), 6.69 (1H, d, J=7.6 Hz), 6.98 (2H, dd, J=6.8, 2.0 Hz), 7.34 (1H, d, J=2.4 Hz), 7.51-7.53 (3H, m), 8.14 (1H, d, J=7.6 Hz); LCMS (mobile phase: from 95% water and 5% CH3CN to 5% water and 95% CH3CN in 6 min, finally under these conditions for 0.5 min.) purity is >95%, Rt=2.770 min; MS Calcd.: 367, MS Found: 368 [M+H]+.

Workup

  1. temperaturethe resulting mixture was refluxed for 4 hours
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in dichloromethane (20 mL)
  4. washwashed with 1 M acetic acid aqueous solution and brine
  5. dry with materialdried over anhydrous Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-2c45aa9c54504cc8960891e30216375a
Source dataset
uspto-grants-2014_12
Patent number
US08916566B2

Reaction notes

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