Hydrochloric Acid → 1-[4-(6-Chloro-7,8-dimethyl-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]-cyclobutanamine

HRID 1501361Notes

Reaction equation

HRID 1501361 reaction equation
[Cl:1][C:2]1[C:3]([CH3:36])=[C:4]([CH3:35])[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>[Cl:1][C:2]1[C:3]([CH3:36])=[C:4]([CH3:35])[C:5]2[N:6]([C:8]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=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 86716516HCID 86716516, compound

Product 1

HCID 762841871-[4-(6-Chloro-7,8-dimethyl-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]-cyclobutanamineYield 44%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of the tert-butyl {1-[4-(6-chloro-7,8-dimethyl-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-32 (179 mg, 0.360 mmol, 1.0 eq) in DCM (2.29 mL) and MeOH (1.44 mL) was added a solution of 4 M hydrogen chloride in dioxane (1.78 mL, 7.12 mmol, 20.0 eq) and the mixture was stirred 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. The crude mixture was purified via MPLC (Biotage Isolera; 10 g SNAP cartridge: DCM→DCM/ethanol 95/5) to give 64 mg (44% 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. customThe crude mixture was purified via MPLC (Biotage Isolera; 10 g SNAP cartridge: DCM→DCM/ethanol 95/5)

Sources & evidence

ORD record
ord-cebfd9ff8bd14423a00fa29a072011e9
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

Loading…