Acetic Acid → HCID 86710675, compound

HRID 1027263Notes

Reaction equation

HRID 1027263 reaction equation
CO[C:3]1C=C2C(CCC2=O)=C[C:4]=1[C:13]1[N:14]=[N:15][C:16]([N:19]([CH3:30])[CH:20]2[CH2:25][C:24]([CH3:27])([CH3:26])[NH:23][C:22]([CH3:29])([CH3:28])[CH2:21]2)=[CH:17][CH:18]=1.[CH:31]([O:33][CH2:34][CH3:35])=O.[H-].[Na+].C(O)(=O)C.O.[NH2:43][NH2:44].[C:45]1([CH3:51])[CH:50]=[CH:49][CH:48]=[CH:47]C=1>C(O)C>[CH3:31][O:33][C:34]1[CH:35]=[C:49]2[C:48]([CH2:47][C:45]3[CH:51]=[N:44][NH:43][C:50]=32)=[CH:3][C:4]=1[C:13]1[N:14]=[N:15][C:16]([N:19]([CH3:30])[CH:20]2[CH2:25][C:24]([CH3:26])([CH3:27])[NH:23][C:22]([CH3:29])([CH3:28])[CH2:21]2)=[CH:17][CH:18]=1

Participants

8

Reactant 6

HCID 176Acetic AcidHCID 1140TolueneHCID 8025Ethyl formateHCID 24654Hydrazine hydrate (1:1)HCID 24758Sodium hydrideHCID 86710623HCID 86710623, compound2×

Product 1

HCID 86710675HCID 86710675, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a 100 mL round bottom flask containing toluene (1.0 mL) was added 6-methoxy-5-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-2,3-dihydro-1H-inden-1-one (Intermediate 7-1, 330 mg, 0.81 mmol), ethyl formate (0.13 mL, 1.62 mmol), and sodium hydride (97 mg, 2.42 mmol). The reaction mixture was stirred at RT for 16 h then concentrated in vacuo. Ethanol (5.0 mL), acetic acid (0.51 mL, 8.89 mmol) and hydrazine hydrate (0.53 mL, 10.50 mmol) were added. The mixture was refluxed at 80° C. for 3 h and concentrated in vacuo. The crude material was adjusted to pH 3 using 1 M HCl aqueous solution and loaded onto an SCX column. The crude material was washed with methanol then eluted with 2 N ammonia in methanol. The product-containing fractions were concentrated to afford 6-(7-methoxy-1,4-dihydroindeno[1,2-c]pyrazol-6-yl)-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine (75 mg) MS [M+H+]=433.5.

Workup

  1. concentrationthen concentrated in vacuo
  2. temperatureThe mixture was refluxed at 80° C. for 3 h
  3. concentrationconcentrated in vacuo
  4. washThe crude material was washed with methanol
  5. washthen eluted with 2 N ammonia in methanol
  6. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-fb889d3483e04f72b639b980037bd4d4
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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