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

HRID 2239330노트

반응식

HRID 2239330 반응식
[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

참가 물질

10

반응물 5

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

생성물 1

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

시약·촉매·용매 4

HCID 176Acetic Acid용매HCID 887Methanol용매HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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+).

후처리

  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)

출처 및 근거

ORD 기록
ord-15a21db0a8ae4f1e9b7af55b44f7aef7
출처 데이터셋
uspto-grants-2010_05
특허 번호
US07723331B2

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