Hydrochloric Acid → US9604989, Example 1

HRID 1501350Notes

Reaction equation

HRID 1501350 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([C:17]4([NH:21]C(=O)OC(C)(C)C)[CH2:20][CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[N:10]=2)[N:7]=1.Cl.O1CCOCC1.[OH-].[Na+]>C(Cl)Cl.CO>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[C:9]([C:11]3[CH:12]=[CH:13][C:14]([C:17]4([NH2:21])[CH2:18][CH2:19][CH2:20]4)=[CH:15][CH:16]=3)[N:10]=2)[N:7]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 86716494Tert-butyl {1-[4-(6-methyl-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]-cyclobutyl}carbamate

Product 1

HCID 70817920US9604989, Example 1Yield 83%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of tert-butyl {1-[4-(6-methyl-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]-cyclobutyl}carbamate that was prepared in a manner analgous to that described for Intermediate Example Int-1 (200 mg, 0.440 mmol, 1.0 eq) in DCM (2.2 mL) and methanol (1.8 mL) was added a solution of 4 M hydrogen chloride in dioxane (2.2 mL, 8.80 mmol, 20.0 eq) and the mixture was stirred for overnight at rt. The mixture was poured onto ice, made alkaline with aqueous sodium hydroxide (2 N) and extracted with DCM. The combined organic phases were washed with brine, dried and concentrated in vacuo. Purification was achieved by crystallization from diisopropyl ether. The resulting solid was filtered and dried under high vacuum overnight to give 130 mg (83% yield) of the title compound.

Workup

  1. customwas prepared in a manner analgous to
  2. additionThe mixture was poured onto ice
  3. extractionextracted with DCM
  4. washThe combined organic phases were washed with brine
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customPurification
  8. customwas achieved by crystallization from diisopropyl ether
  9. filtrationThe resulting solid was filtered
  10. customdried under high vacuum overnight

Sources & evidence

ORD record
ord-c7be0dbe433f441fb01e90777b2cefc1
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

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