Sodium Hydroxide → HCID 76282687, compound

HRID 1501360Notes

Reaction equation

HRID 1501360 reaction equation
[CH3:1][O:2][C:3]1[C:4]2[N:5]([C:11]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([C:20]4([NH:24]C(=O)OC(C)(C)C)[CH2:23][CH2:22][CH2:21]4)=[CH:16][CH:15]=3)[N:13]=2)[N:6]=[C:7]([CH:9]=[CH2:10])[CH:8]=1.FC(F)(F)S(O)(=O)=O.[OH-].[Na+]>O1CCOCC1>[CH3:1][O:2][C:3]1[C:4]2[N:5]([C:11]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([C:20]4([NH2:24])[CH2:23][CH2:22][CH2:21]4)=[CH:16][CH:15]=3)[N:13]=2)[N:6]=[C:7]([CH:9]=[CH2:10])[CH:8]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 62406Trifluoromethanesulfonic acidHCID 86716500HCID 86716500, compound

Product 1

HCID 76282687HCID 76282687, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of tert-butyl {1-[4-(8-methoxy-3-phenyl-6-vinylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutyl}carbamate that was prepared in a manner analgous to that described for Intermediate Example Int-12 (40 mg, 0.081 mmol) in dioxane (1.7 mL) was added trifluoromethanesulfonic acid (0.61 mL, 1.8 mmol, 10.0 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; 10 g SNAP cartridge: 100% DCM 3.0 min., gradient to 95% DCM/5% MeOH 1 min., 95% DCM/5% MeOH 2.5 min., gradient to 90% DCM/10% MeOH 3 min., 90% DCM/10% MeOH 3.5 min.) to give 1-[4-(8-methoxy-3-phenyl-6-vinylimidazo[1,2-b]pyridazin-2-yl)phenyl]cyclobutanamine (0.022 g, 70%):

Workup

  1. extractionextracted with EtOAc (3×25 mL)
  2. washThe combined organic phases were washed
  3. dry with materialdried (Na2SO4 anh.)
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting material was purified
  6. customMPLC (Biotage Isolera; 10 g SNAP cartridge: 100% DCM 3.0 min., gradient to 95% DCM/5% MeOH 1 min., 95% DCM/5% MeOH 2.5 min., gradient to 90% DCM/10% MeOH 3 min., 90% DCM/10% MeOH 3.5 min.)

Sources & evidence

ORD record
ord-c0921f6add534dd89b091d4ad9997cff
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

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