Acetic Acid → 2-(4-Chlorophenyl)-6-({6-[(1-methylpiperidin-4-yl)oxy]pyridin-2-yl}methyl)thieno[2,3-d]pyridazin-7(6H)-one

HRID 2239365Notes

Reaction equation

HRID 2239365 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:31][C:11]3[C:12](=[O:30])[N:13]([CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH:24]5[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]5)[N:18]=4)[N:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1.C=O.[C:34](O)(=O)C>C(Cl)Cl.CO.C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:31][C:11]3[C:12](=[O:30])[N:13]([CH2:16][C:17]4[CH:22]=[CH:21][CH:20]=[C:19]([O:23][CH:24]5[CH2:25][CH2:26][N:27]([CH3:34])[CH2:28][CH2:29]5)[N:18]=4)[N:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 712Formaldehyde2×HCID 687073382-(4-Chlorophenyl)-6-{[6-(piperidin-4-yloxy)pyridin-2-yl]methyl}thieno[2,3-d]pyridazin-7(6H)-one

Product 1

HCID 247822462-(4-Chlorophenyl)-6-({6-[(1-methylpiperidin-4-yl)oxy]pyridin-2-yl}methyl)thieno[2,3-d]pyridazin-7(6H)-one

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 21226129Dichloromethane methanolSolvent

Procedure

To a solution of 2-(4-chlorophenyl)-6-{[6-(piperidin-4-yloxy)pyridin-2-yl]methyl}thieno[2,3-d]pyridazin-7(6H)-one (0.16 g, 0.34 mmol) in DCM/MeOH (1:1, 10 mL) was added (polystyrylmethyl)trimethylammonium cyanoborohydride (0.25 g, 1.03 mmol), 36% aq. formaldehyde (0.05 mL, 0.69 mmol) and acetic acid (one drop). After 3 hours of stirring one additional amount of (polystyrylmethyl)trimethylammonium cyanoborohydride, formaldehyde and acetic acid added to the reaction mixture and stirred for two hours. The reaction mixture was filtrated, concentrated in vacuo and purified by flash chromatography using a gradient with EtOAc:MeOH:TEA (1:0.1:0.05) in n-heptane, which gave the product. Yield: 0.084 g (52%). 1H NMR (400 MHz, CDCl3) δ 8.19 (s, 1H), 7.57-7.64 (m, 2H), 7.30-7.49 (m, 4H), 6.71 (d, 1H, J=7.31 Hz), 6.52 (d, 1H, J=8.16 Hz), 5.47 (s, 2H), 4.69-4.79 (m, 1H), 2.49-2.58 (m, 2H), 2.13 (s, 3H), 1.87-1.99 (m, 2H), 1.75-1.84 (m, 2H), 1.58-1.69 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 163.0, 157.4, 153.5, 152.3, 140.3, 139.3, 136.4, 136.0, 133.1, 131.3, 129.8, 128.1, 113.8, 110.1, 70.5, 55.6, 53.3, 46.4, 31.0 MS (ESI+) 467.08 (M+1H+).

Workup

  1. additionadded to the reaction mixture
  2. filtrationThe reaction mixture was filtrated
  3. concentrationconcentrated in vacuo
  4. custompurified by flash chromatography
  5. customgave the product

Sources & evidence

ORD record
ord-c7454408ec4d4d719b0e9e66b112f662
Source dataset
uspto-grants-2010_05
Patent number
US07723331B2

Reaction notes

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