Iodo benzene diacetate → HCID 136377153, compound

HRID 1027220Notes

Reaction equation

HRID 1027220 reaction equation
[F:1][C:2]([F:34])([F:33])[S:3]([O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[N:15][C:16]([N:19]([CH3:30])[CH:20]3[CH2:25][C:24]([CH3:27])([CH3:26])[NH:23][C:22]([CH3:29])([CH3:28])[CH2:21]3)=[CH:17][CH:18]=2)=[C:9]([O:31][CH3:32])[CH:8]=1)(=[O:5])=[O:4].C(O)(=[O:37])C.C(O)(=O)C.IC1C=CC=CC=1.C(O)(=O)C.C(OC(=O)C)(=O)C>CC([O-])=O.CC([O-])=O.[Pd+2]>[F:34][C:2]([F:33])([F:1])[S:3]([O:6][C:7]1[CH:8]=[C:9]([O:31][CH3:32])[C:10]([C:13]2[N:14]=[N:15][C:16]([N:19]([CH3:30])[CH:20]3[CH2:21][C:22]([CH3:28])([CH3:29])[NH:23][C:24]([CH3:26])([CH3:27])[CH2:25]3)=[CH:17][CH:18]=2)=[C:11]([OH:37])[CH:12]=1)(=[O:4])=[O:5]

Participants

5

Reactant 3

HCID 12217721Iodo benzene diacetateHCID 21895370AcOH AcOAcHCID 86710574HCID 86710574, compound

Product 1

HCID 136377153HCID 136377153, compound

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Conditions

Temperature
50 °C

Procedure

A mixture of 3-methoxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl trifluoromethanesulfonate (2.6 g, 5.17 mmol), Pd(OAc)2 (58 mg, 0.259 mmol), and iodobenzene diacetate (2.33 g, 7.24 mmol) in 1:1 acetic acid/acetic anhydride (42 mL) was heated at 50° C. for 8 h. The mixture was cooled to RT and concentrated under reduced pressure. Flash chromatography (10-100% EtOH in DCM, followed by 7:1 EtOH/7 N ammonia in MeOH elution) provided a mixture of the title compound and the corresponding acetate (3-methoxy-2-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(((trifluoromethyl)sulfonyl)oxy)phenyl acetate). After concentration, the mixture was taken up in methanol and heated at 70° C. for 4 h. The solvent was evaporated to provide 3-hydroxy-5-methoxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)phenyl trifluoro-methanesulfonate as a tan-colored solid (1.25 g). MS (M+1)=519.4. 1H NMR (400 MHz, METHANOL-d4) δ ppm 8.08 (d, J=10.1 Hz, 1H), 7.23 (d, J=10.1 Hz, 1H), 6.57 (s, 2H), 5.16 (t, J=12.1 Hz, 1H), 3.89 (s, 3H), 3.02 (s, 3H), 1.69-1.77 (m, 2H), 1.56-1.67 (m, 2H), 1.41 (s, 6H), 1.27 (s, 6H).

Workup

  1. temperatureThe mixture was cooled to RT
  2. concentrationconcentrated under reduced pressure
  3. washFlash chromatography (10-100% EtOH in DCM, followed by 7:1 EtOH/7 N ammonia in MeOH elution)
  4. customprovided

Sources & evidence

ORD record
ord-16f17e78b83b4b488a290ae5e5620f97
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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