Iodo benzene diacetate → HCID 136377161, compound

HRID 1027240Notes

Reaction equation

HRID 1027240 reaction equation
[F:1][C:2]([F:36])([F:35])[S:3]([O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[N:14]=[N:15][C:16]([NH:19][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:30][C:31]([F:34])([F:33])[F:32])[CH:8]=1)(=[O:5])=[O:4].C(O)(=[O:39])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:36][C:2]([F:35])([F:1])[S:3]([O:6][C:7]1[CH:8]=[C:9]([O:30][C:31]([F:32])([F:33])[F:34])[C:10]([C:13]2[N:14]=[N:15][C:16]([NH:19][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:39])[CH:12]=1)(=[O:4])=[O:5]

Participants

6

Reactant 2

HCID 12217721Iodo benzene diacetate2×HCID 86710647HCID 86710647, compound

Product 1

HCID 136377161HCID 136377161, compoundYield 36.1%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
75 °C

Procedure

A mixture of 4-(6-((2,2,6,6-tetramethylpiperidin-4-yl)amino)pyridazin-3-yl)-3-(trifluoromethoxy)phenyl trifluoromethanesulfonate (86 mg, 0.16 mmol), iodobenzene diacetate (71.5 mg, 0.222 mmol) and Pd(OAc)2 (3.6 mg, 0.016 mmol) in AcOH (0.6 mL) and Ac2O (0.6 mL) was heated at 75° C. for 3 hours. The mixture was then heated at 80° C. overnight after addition of another 40 mg of iodobenzene diacetate. The reaction mixture was cooled to room temperature and concentrated. The residue was loaded onto an SCX column, washed with MeOH and diluted with 2 M NH3 in MeOH. The product-containing fractions were concentrated. The residue was treated with 7 M NH3/MeOH and stirred at 40° C. for 4 h. The crude material was purified via flash column chromatography to give the title compound as a beige solid (32 mg, 36.1%). MS (M+1)=559.4.

Workup

  1. temperatureThe mixture was then heated at 80° C. overnight
  2. temperatureThe reaction mixture was cooled to room temperature
  3. concentrationconcentrated
  4. washwashed with MeOH
  5. additiondiluted with 2 M NH3 in MeOH
  6. concentrationThe product-containing fractions were concentrated
  7. additionThe residue was treated with 7 M NH3/MeOH
  8. customThe crude material was purified via flash column chromatography

Sources & evidence

ORD record
ord-574ea430430544d88df90a967bd1322e
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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