Thiophenol → 2-(6-(piperidin-4-yloxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol

HRID 1027186Notes

Reaction equation

HRID 1027186 reaction equation
C1(S)C=CC=CC=1.C[O:9][C:10]1[CH:15]=[C:14]([N:16]2[CH:20]=[CH:19][CH:18]=[N:17]2)[CH:13]=[CH:12][C:11]=1[C:21]1[N:22]=[N:23][C:24]([O:27][CH:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[CH:25][CH:26]=1.C([O-])([O-])=O.[K+].[K+]>CN1C(=O)CCC1>[NH:31]1[CH2:32][CH2:33][CH:28]([O:27][C:24]2[N:23]=[N:22][C:21]([C:11]3[CH:12]=[CH:13][C:14]([N:16]4[CH:20]=[CH:19][CH:18]=[N:17]4)=[CH:15][C:10]=3[OH:9])=[CH:26][CH:25]=2)[CH2:29][CH2:30]1

Participants

5

Reactant 3

HCID 7969Thiophenol2×HCID 11430Potassium CarbonateHCID 867105813-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-6-(piperidin-4-yloxy)pyridazine

Product 1

HCID 1362530612-(6-(piperidin-4-yloxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenolYield 18%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Following GENERAL METHOD 3-1 for methoxy deprotection with thiophenol, 3-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)-6-(piperidin-4-yloxy)pyridazine (70 mg, 0.20 mmol) was treated with thiophenol (27 mg, 0.24 mmol) and K2CO3 (25 mg, 0.18 mmol) in NMP (1.3 mL) for 15 min at 190° C. HPLC purification (0.1% trifluoroacetic acid as modifier) afforded 2-(6-(piperidin-4-yloxy)pyridazin-3-yl)-5-(1H-pyrazol-1-yl)phenol (12 mg, 18%) as a yellow solid. LCMS Rt=0.50 min (LCMS method Q); [M+H]: 338.16; 1H NMR (400 MHz, DMSO-d6) δ 13.01 (bs, 1H), 8.53 (d, J=2.5 Hz, 1H), 8.46 (bs, 2H), 8.45 (d, J=9.5 Hz, 1H), 7.50 (d, J=2.0 Hz, 1H), 7.47 (dd, J=8.5, 2.5 Hz, 2H), 7.44 (d, J=9.5 Hz, 1H), 6.51-6.62 (m, 1H), 5.51 (tt, J=7.5, 3.5 Hz, 1H), 3.33 (br. s, 2H), 3.20 (br. s, 2H), 2.18-2.31 (m, 2H), 2.01 (ddt, J=13.5, 8.5, 4.0 Hz, 2H).

Workup

  1. customHPLC purification (0.1% trifluoroacetic acid as modifier)

Sources & evidence

ORD record
ord-9690283df7324ed2ae52390d1d8ef193
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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