Acetic Anhydride → HCID 11993403, compound

HRID 2266316Notes

Reaction equation

HRID 2266316 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]([C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=2)=[CH:10][C:11]2[N:12]([C:14]([C:17]34[CH2:24][CH2:23][C:20]([O:25]C)([CH2:21][CH2:22]3)[CH2:19][CH2:18]4)=[N:15][N:16]=2)[N:13]=1.C(OC(=O)C)(=O)C.C([O-])(O)=O.[Na+]>Br>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]([C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][CH:28]=2)=[CH:10][C:11]2[N:12]([C:14]([C:17]34[CH2:24][CH2:23][C:20]([OH:25])([CH2:19][CH2:18]3)[CH2:21][CH2:22]4)=[N:15][N:16]=2)[N:13]=1

Participants

5

Reactant 3

HCID 7918Acetic AnhydrideHCID 516892Sodium BicarbonateHCID 11993207HCID 11993207, compound

Product 1

HCID 11993403HCID 11993403, compoundYield 75.2%

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Conditions

Temperature
120 °C

Procedure

To a suspension of 6-(2-chlorophenyl)-7-(4-chlorophenyl)-3-(4-methoxybicyclo[2.2.2]octan-1-yl)-[1,2,4]triazolo[4,3-b]pyridazine (Example 18) (48 mg, 0.1 mmol) in aqueous (48%) hydrobromic acid solution (0.37 mL) was added dropwise acetic anhydride (0.33 mL). After addition, the reaction tube was sealed, and heated at 120° C. for 16 h. After cooling to room temperature, the reaction mixture was adjusted to pH 7-8 by careful addition of saturated aqueous NaHCO3, then extracted with EtOAc (10 mL×2). The combined organic was washed with water, saturated aqueous NaCl, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude product was purified using reverse phase preparative HPLC (Conditions: Phenomenex Luna 5μ C18 21.2×100 mm; Eluted with 70% to 100% B, 18 min gradient, 100% B hold for 3 min, (A=90% H2O, 10% MeOH and B=10% H2O, 90% MeOH); Flow rate at 20 mL/min, UV detection at 220 nm) to afford 35 mg (75%) of the title compound as a white solid. HPLC/MS (method A): retention time 3.61 min, (M+H)+=465.2.

Workup

  1. additionAfter addition
  2. customthe reaction tube was sealed
  3. temperatureAfter cooling to room temperature
  4. extractionextracted with EtOAc (10 mL×2)
  5. washThe combined organic was washed with water, saturated aqueous NaCl
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified
  10. washEluted with 70% to 100% B, 18 min gradient, 100% B hold for 3 min

Sources & evidence

ORD record
ord-30fb317be5a9472e8da08e4124e87c1b
Source dataset
uspto-grants-2010_12
Patent number
US07858639B2

Reaction notes

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