Water → HCID 178487563, compound

HRID 1501369Notes

Reaction equation

HRID 1501369 reaction equation
Cl[C:2]1[CH:3]=[C:4]([C:28]2[CH:32]=[CH:31][NH:30][N:29]=2)[C:5]2[N:6]([C:8]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([C:17]4([NH2:21])[CH2:20][CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[N:10]=2)[N:7]=1.[CH3:33][O-:34].[Na+].O>CO>[CH3:33][O:34][C:2]1[CH:3]=[C:4]([C:28]2[CH:32]=[CH:31][NH:30][N:29]=2)[C:5]2[N:6]([C:8]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([C:17]4([NH2:21])[CH2:20][CH2:19][CH2:18]4)=[CH:13][CH:12]=3)[N:10]=2)[N:7]=1

Participants

5

Reactant 3

HCID 962WaterHCID 10942334Sodium MethoxideHCID 178507119HCID 178507119, compound

Product 1

HCID 178487563HCID 178487563, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 1-{4-[6-chloro-3-phenyl-8-(1H-pyrazol-3-yl)imidazo[1,2-b]pyridazin-2-yl]phenyl}cyclobutanamine that was prepared in a manner analgous to that described for Example 19 (0.14 g, 0.32 mmol) and sodium methoxide (0.051 g, 0.95 mmol, 3.0 equiv) in MeOH (0.8 mL) was irradiated in a microwave apparatus at 120° C. for 90 min. The resulting mixture was added to water 10 mL. The aqueous mixture was extracted with DCM (3×15 mL), dried (Na2SO4 anh.) and concentrated under reduced pressure. The resulting material was purified using MPLC (Biotage Isolera; Snap 10 g cartridge, 100% hexane 2.0 min, gradient to 80% hexane/20% EtOAc 1.0 min, 80% hexane/20% EtOAc 3.0 min, gradient to 50% hexane/50% EtOAc 2.5 min, 50% hexane/50% EtOAc 3.5 min, gradient to 100% EtOAc 3.0 min, 100% EtOAc 4.8 min) to give an oil which was triturated with MeOH to give 1-{4-[6-methoxy-3-phenyl-8-(1H-pyrazol-3-yl)imidazo[1,2-b]pyridazin-2-yl]phenyl}cyclobutanamine (0.052 g, 36%):

Workup

  1. customwas irradiated in a microwave apparatus at 120° C. for 90 min
  2. extractionThe aqueous mixture was extracted with DCM (3×15 mL)
  3. dry with materialdried (Na2SO4 anh.)
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting material was purified
  6. customMPLC (Biotage Isolera; Snap 10 g cartridge, 100% hexane 2.0 min, gradient to 80% hexane/20% EtOAc 1.0 min, 80% hexane/20% EtOAc 3.0 min, gradient to 50% hexane/50% EtOAc 2.5 min, 50% hexane/50% EtOAc 3.5 min, gradient to 100% EtOAc 3.0 min, 100% EtOAc 4.8 min)
  7. customto give an oil which
  8. customwas triturated with MeOH

Sources & evidence

ORD record
ord-d65174145f714e258656bbb01be44531
Source dataset
uspto-grants-2015_12
Patent number
US09206185B2

Reaction notes

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