Iodo benzene diacetate → HCID 136377151, compound

HRID 1027218Notes

Reaction equation

HRID 1027218 reaction equation
[F:1][C:2]([F:37])([F:36])[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][C:32]([F:35])([F:34])[F:33])[CH:8]=1)(=[O:5])=[O:4].C(O)(=[O:40])C.C(O)(=O)C.IC1C=CC=CC=1>CC(O)=O.CC(OC(C)=O)=O.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:37][C:2]([F:36])([F:1])[S:3]([O:6][C:7]1[CH:8]=[C:9]([O:31][C:32]([F:33])([F:34])[F:35])[C:10]([C:13]2[N:14]=[N:15][C:16]([N:19]([CH3:30])[CH:20]3[CH2:21][C:22]([CH3:29])([CH3:28])[NH:23][C:24]([CH3:26])([CH3:27])[CH2:25]3)=[CH:17][CH:18]=2)=[C:11]([OH:40])[CH:12]=1)(=[O:4])=[O:5]

Participants

6

Reactant 2

HCID 12217721Iodo benzene diacetateHCID 86710620HCID 86710620, compound

Product 1

HCID 136377151HCID 136377151, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 176Acetic AcidSolventHCID 7918Acetic AnhydrideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-3-(trifluoromethoxy)phenyl trifluoromethanesulfonate (360 mg, 0.647 mmol), iodobenzene diacetate (375 mg, 1.164 mmol) and Pd(OAc)2 (7.3 mg, 0.032 mmol) in AcOH (3.0 mL) and Ac2O (3.0 mL) was heated at 60° C. overnight. The reaction mixture was cooled to room temperature and concentrated. The residue was basified with aqueous NaHCO3 solution and extracted with DCM. The combined organic layers were dried over Na2SO4, and concentrated. The crude material was loaded onto a SCX column, washed with MeOH and diluted with 2 M NH3 in MeOH. The product-containing fractions were concentrated. Compound 3-hydroxy-4-(6-(methyl(2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-5-(trifluoromethoxy)phenyl trifluoromethanesulfonate was obtained as a yellow solid (110 mg, 28%) after flash column chromatography and HPLC purification. MS (M+1)=573.2.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. concentrationconcentrated
  3. extractionextracted with DCM
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. concentrationconcentrated
  6. washwashed with MeOH
  7. additiondiluted with 2 M NH3 in MeOH
  8. concentrationThe product-containing fractions were concentrated

Sources & evidence

ORD record
ord-f6c722d8137b498782a6750d822d1bf9
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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