Nitrogen → 2-(4-Chlorophenyl)-6-(3-hydroxybenzyl)thieno[2,3-d]pyridazin-7(6H)-one

HRID 2239330Notes

Reaction equation

HRID 2239330 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:17][C:11]3[C:12](=[O:16])[NH:13][N:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1.N#N.[H-].[Na+].CS(O[CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([O:34]S(C)(=O)=O)[CH:29]=1)(=O)=O.[OH-].[K+]>CN(C=O)C.CC(O)=O.CO.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:17][C:11]3[C:12](=[O:16])[N:13]([CH2:27][C:28]4[CH:33]=[CH:32][CH:31]=[C:30]([OH:34])[CH:29]=4)[N:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:6][CH:7]=1

Participants

10

Reactant 5

HCID 947NitrogenHCID 14797Potassium HydroxideHCID 24758Sodium hydrideHCID 115798042-(4-Chlorophenyl)thieno[2,3-d]pyridazin-7(6H)-oneHCID 593044053-[(Methylsulfonyl)oxy]benzyl methanesulfonate

Product 1

HCID 593044042-(4-Chlorophenyl)-6-(3-hydroxybenzyl)thieno[2,3-d]pyridazin-7(6H)-oneYield 65%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred slurry of 2-(4-chlorophenyl)thieno[2,3-d]pyridazin-7(6H)-one (0.192 g, 0.73 mmol) in DMF (5 mL), under an atm of N2, was added NaH (60%, 0.040 g, 1.0 mmol) and the resulting mixture stirred for 5 min. 3-[(Methylsulfonyl)oxy]benzyl methanesulfonate (0.246 g, 0.88 mmol) was added, and the resulting mixture stirred for 2 hours at room temperature. H2O was added and the mixture concentrated. Residual DMF was removed by evaporation from toluene. MeOH (20 mL) and KOH (1.0 g, 18 mmol) were added and the resulting mixture was stirred over night. The mixture was neutralised with HOAc, concentrated and purified on C8-HPLC (0.1% HOAc, gradient 5→100% CH3CN) to give 0.175 g (65%) of the title compound. 1H NMR (400 MHz, DMSO-d6) δ 9.38 (s, 1H), 8.47 (s, 1H), 7.98 (s, 1H), 7.88 (d, 2H, J=8.5 Hz), 7.59 (d, 2H, J=8.5 Hz), 7.12 (dd, 1H, J=8.0, 7.7 Hz), 6.74 (d, 1H, J=7.7 Hz), 6.70 (s, 1H), 6.66 (d, 1H, J=8.0 Hz). MS (ESI+) 369 (M+1H+), MS (ESI−) 367(M-1H+).

Workup

  1. stirringthe resulting mixture stirred for 2 hours at room temperature
  2. concentrationthe mixture concentrated
  3. customResidual DMF was removed by evaporation from toluene
  4. stirringthe resulting mixture was stirred over night
  5. concentrationconcentrated
  6. custompurified on C8-HPLC (0.1% HOAc, gradient 5→100% CH3CN)

Sources & evidence

ORD record
ord-15a21db0a8ae4f1e9b7af55b44f7aef7
Source dataset
uspto-grants-2010_05
Patent number
US07723331B2

Reaction notes

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