5-(1H-pyrazol-1-yl)-2-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)phenol → 2-(6-Piperidin-4-yl-pyridazin-3-yl)-5-pyrazol-1-yl-phenol

HRID 1027197Notes

Reaction equation

HRID 1027197 reaction equation
[N:1]1([C:6]2[CH:7]=[CH:8][C:9]([C:13]3[N:14]=[N:15][C:16]([C:19]4[CH2:20][CH2:21][NH:22][CH2:23][CH:24]=4)=[CH:17][CH:18]=3)=[C:10]([OH:12])[CH:11]=2)[CH:5]=[CH:4][CH:3]=[N:2]1>CO.[Pd]>[NH:22]1[CH2:21][CH2:20][CH:19]([C:16]2[N:15]=[N:14][C:13]([C:9]3[CH:8]=[CH:7][C:6]([N:1]4[CH:5]=[CH:4][CH:3]=[N:2]4)=[CH:11][C:10]=3[OH:12])=[CH:18][CH:17]=2)[CH2:24][CH2:23]1

Participants

4

Reactant 1

HCID 1363771455-(1H-pyrazol-1-yl)-2-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)phenol

Product 1

HCID 1363771462-(6-Piperidin-4-yl-pyridazin-3-yl)-5-pyrazol-1-yl-phenolYield 11.5%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

To a round-bottomed flask containing 10% Pd/C (27.7 mg, 0.026 mmol), was added 5-pyrazol-1-yl-2-[6-(1,2,3,6-tetrahydro-pyridin-4-yl)-pyridazin-3-yl]-phenol (Example 19-1) (166 mg, 0.52 mmol) in MeOH (2.5 mL). H2 was bubbled through the solution for 5 min, then the reaction was stirred under H2 at 55 psi at RT. After 18 hr, the reaction mixture was filtered through celite and washed with MeOH. The solvent was removed in vacuo and the resulting oil was dissolved in MeOH then adsorbed onto a MeOH conditioned SCX column. The column was washed several times (5-7 column volume) with MeOH then eluted with 2 N NH3 in MeOH to provide the desired product, 2-(6-(piperidin-4-yl)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol (19.8 mg, 0.06 mmol, 11% yield). LCMS Rt=0.48 min, M+1=322.6 (LCMS method Q). 1H NMR (DMSO-d6) δ 8.63 (d, J=2.5 Hz, 1H), 8.50 (d, J=9.3 Hz, 1H), 8.15 (d, J=8.5 Hz, 1H), 7.76-7.92 (m, 2H), 7.47-7.56 (m, 2H), 6.59 (dd, J=2.5, 1.8 Hz, 1H), 3.24 (s, 2H), 3.07-3.19 (m, 1H), 2.84 (td, J=12.2, 2.4 Hz, 2H), 2.00 (s, 2H), 1.77-1.92 (m, 2H).

Workup

  1. customH2 was bubbled through the solution for 5 min
  2. filtrationthe reaction mixture was filtered through celite
  3. washwashed with MeOH
  4. customThe solvent was removed in vacuo
  5. dissolutionthe resulting oil was dissolved in MeOH
  6. washThe column was washed several times (5-7 column volume) with MeOH
  7. washthen eluted with 2 N NH3 in MeOH

Sources & evidence

ORD record
ord-ef1c809c40c645b387361eab8e6e514b
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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