Hydrochloric Acid → HCID 70817808, compound

HRID 1501355Notes

Reaction equation

HRID 1501355 reaction equation
[C:1]1([C:7]2[N:11]3[N:12]=[C:13]([O:16][CH3:17])[CH:14]=[CH:15][C:10]3=[N:9][C:8]=2[C:18]2[CH:23]=[CH:22][C:21]([C:24]3([NH:28]C(=O)OC(C)(C)C)[CH2:27][CH2:26][CH2:25]3)=[CH:20][CH:19]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.O1CCOCC1.[OH-].[Na+]>C(Cl)Cl.CO>[CH3:17][O:16][C:13]1[CH:14]=[CH:15][C:10]2[N:11]([C:7]([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)=[C:8]([C:18]3[CH:19]=[CH:20][C:21]([C:24]4([NH2:28])[CH2:25][CH2:26][CH2:27]4)=[CH:22][CH:23]=3)[N:9]=2)[N:12]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 86716496HCID 86716496, compound

Product 1

HCID 70817808HCID 70817808, compoundYield 83%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of tert-butyl (1-{4-[3-phenyl-6-methoxyimidazo[1,2-b]pyridazin-2-yl]phenyl}cyclobutyl)carbamate that was prepared in a manner analgous to that described for Intermediate Example Int-5 (550 mg, 1.17 mmol) in DCM (7.5 mL) and MeOH (0.8 mL) was added a 4 M hydrogen chloride solution in dioxane (5.8 mL, 23.4 mmol, 20.0 eq), and the resulting mixture was stirred at room temperature for 12 h. The resulting mixture was added to ice water, made alkaline with aqueous sodium hydroxide (2 N), and extracted with EtOAc (3×25 mL). The combined organic phases were washed, dried (Na2SO4 anh.) and concentrated under reduced pressure. The resulting material was purified using MPLC (Biotage Isolera; 100 g SNAP cartridge: 100% DCM 3.5 min., gradient to 95% DCM/5% MeOH 1 min., 95% DCM/5% MeOH 3.5 min., gradient to 90% DCM/10% MeOH 1 min., 90% DCM/10% MeOH 4.5 min.) to give 1-[4-(6-methyloxy-3-phenylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutanamine (379 mg, 83% yield):

Workup

  1. customwas prepared in a manner analgous to
  2. extractionextracted with EtOAc (3×25 mL)
  3. washThe combined organic phases were washed
  4. dry with materialdried (Na2SO4 anh.)
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting material was purified
  7. customMPLC (Biotage Isolera; 100 g SNAP cartridge: 100% DCM 3.5 min., gradient to 95% DCM/5% MeOH 1 min., 95% DCM/5% MeOH 3.5 min., gradient to 90% DCM/10% MeOH 1 min., 90% DCM/10% MeOH 4.5 min.)

Sources & evidence

ORD record
ord-e7e2f646987644a7a9fab6bfef131d00
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

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