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

HRID 2239330ノート

反応式

HRID 2239330 の反応式
[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

参加物

10

反応物 5

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

生成物 1

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

試薬・触媒・溶媒 4

HCID 176Acetic Acid溶媒HCID 887Methanol溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

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+).

後処理

  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)

出典と根拠

ORDレコード
ord-15a21db0a8ae4f1e9b7af55b44f7aef7
出典データセット
uspto-grants-2010_05
特許番号
US07723331B2

反応ノート

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