Hydrochloric Acid → HCID 70817817, compound

HRID 1501352Notes

Reaction equation

HRID 1501352 reaction equation
[C:1]1([C:7]2[N:11]3[N:12]=[C:13]([C:16]([F:19])([F:18])[F:17])[CH:14]=[CH:15][C:10]3=[N:9][C:8]=2[C:20]2[CH:25]=[CH:24][C:23]([C:26]3([NH:30]C(=O)OC(C)(C)C)[CH2:29][CH2:28][CH2:27]3)=[CH:22][CH:21]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.O1CCOCC1.[OH-].[Na+]>C(Cl)Cl.CO>[C:1]1([C:7]2[N:11]3[N:12]=[C:13]([C:16]([F:19])([F:17])[F:18])[CH:14]=[CH:15][C:10]3=[N:9][C:8]=2[C:20]2[CH:21]=[CH:22][C:23]([C:26]3([NH2:30])[CH2:29][CH2:28][CH2:27]3)=[CH:24][CH:25]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 86716495HCID 86716495, compound

Product 1

HCID 70817817HCID 70817817, compoundYield 92%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of tert-butyl (1-{4-[3-phenyl-6-(trifluoromethyl)imidazo[1,2-b]pyridazin-2-yl]phenyl}cyclobutyl)carbamate that was prepared in a manner analgous to that described for Intermediate Example Int-3 (680 mg, 1.177 mmol, 1.0 eq) in DCM (7.6 mL) and methanol (4.8 mL) was added a solution of 4 M hydrogen chloride in dioxane (5.9 mL, 23.5 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 EtOAc (3×). 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 440 mg (92% yield) of the title compound.

Workup

  1. customwas prepared in a manner analgous to
  2. additionThe mixture was poured onto ice
  3. extractionextracted with EtOAc (3×)
  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-d0fc4f978c92432ba8e696ee1f7879ac
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

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