4-Piperidinol, 1-methyl- → 2-(4-Chlorophenyl)-6-{3-[(1-methylpiperidin-4-yl)oxy]benzyl}thieno[2,3-d]pyridazin-7(6H)-one, acetate salt

HRID 2239331Notes

Reaction equation

HRID 2239331 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:25][C:11]3[C:12](=[O:24])[N:13]([CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([OH:23])[CH:18]=4)[N:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1.[CH3:26][N:27]1[CH2:32][CH2:31][CH:30]([OH:33])[CH2:29][CH2:28]1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[C:19]([OH:23])(=[O:33])[CH3:20].[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:25][C:11]3[C:12](=[O:24])[N:13]([CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH:30]5[CH2:31][CH2:32][N:27]([CH3:26])[CH2:28][CH2:29]5)[CH:18]=4)[N:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 660484-Piperidinol, 1-methyl-HCID 5462977Diethyl azodicarboxylateHCID 593044042-(4-Chlorophenyl)-6-(3-hydroxybenzyl)thieno[2,3-d]pyridazin-7(6H)-one

Product 1

HCID 1317281322-(4-Chlorophenyl)-6-{3-[(1-methylpiperidin-4-yl)oxy]benzyl}thieno[2,3-d]pyridazin-7(6H)-one, acetate saltYield 32.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-(4-Chlorophenyl)-6-(3-hydroxybenzyl)thieno[2,3-d]pyridazin-7(6H)-one (0.082 g, 0.22 mmol), 1-methylpiperidin-4-ol (0.050 g, 0.43 mmol) and TPP (0.107 g, 0.41 mmol) were stirred in THF (3 mL) at 0° C. DEAD (0.2 mL, 40% in toluene, 0.44 mmol) was added and the resulting mixture was allowed to attain room temperature and the stirring was continued over night. Concentration and purification on C8-HPLC (0.1% HOAc, gradient 30→40% CH3CN) gave 0.019 g (16%) of the title compound. 1H NMR (400 MHz, CDCl3/MeOH-d4 1:1, internal standard: MeOH-d4) δ 8.30 (s, 1H), 7.66 (d, 2H, J=8.5 Hz), 7.59 (s, 1H), 7.43 (d, 2H, J=8.5 Hz), 7.22 (t, 1H, J=7.9 Hz), 7.03 (m, 2H), 6.83 (d, 1H, J=7.7 Hz), 5.39 (s, 2H), 4.53 (br, 1H), 3.07-2.86 (m, 4H), 2.59 (s, 3H), 2.16-1.94 (m, 4H), 1.97 (s, 3H). 13C NMR (100 MHz, CDCl3/MeOH-d4 1:1, internal standard: MeOH-d4) δ 177.1, 157.9, 157.5, 153.2, 141.2, 138.8, 136.5, 136.3, 134.7, 131.6, 130.4, 130.1, 128.6, 122.1, 119.9, 116.8, 115.8, 69.1, 51.1, 44.4, 28.8, 22.3. MS (ESI+) 466.1 (M+1H+).

Workup

  1. customto attain room temperature
  2. waitthe stirring was continued over night
  3. concentrationConcentration and purification on C8-HPLC (0.1% HOAc, gradient 30→40% CH3CN)

Sources & evidence

ORD record
ord-b7241d683af741c3a0fa0636c85cdced
Source dataset
uspto-grants-2010_05
Patent number
US07723331B2

Reaction notes

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