Hydrochloric Acid → 1-[4-(7-Phenyl-imidazo[1,2-b]pyridazin-6-yl)-phenyl]-cyclobutylamine

HRID 876871Notes

Reaction equation

HRID 876871 reaction equation
C(OC(=O)[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[C:19]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[CH:20][C:21]4[N:22]([CH:24]=[CH:25][N:26]=4)[N:23]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)(C)(C)C.Cl>O1CCOCC1>[C:27]1([C:19]2[C:18]([C:15]3[CH:14]=[CH:13][C:12]([C:8]4([NH2:7])[CH2:9][CH2:10][CH2:11]4)=[CH:17][CH:16]=3)=[N:23][N:22]3[CH:24]=[CH:25][N:26]=[C:21]3[CH:20]=2)[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 66714313HCID 66714313, compound

Product 1

HCID 566443461-[4-(7-Phenyl-imidazo[1,2-b]pyridazin-6-yl)-phenyl]-cyclobutylamineYield 60.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

105 mg (0.24 mmol) {1-[4-(7-Phenyl-imidazo[1,2-b]pyridazin-6-yl)-phenyl]-cyclobutyl}-carbamic acid tert.-butyl ester, (intermediate example Int-2-0, slightly contaminated), were stirred with 2.3 mL 4M hydrogen chloride in dioxane for 10 days at room temperature. After evaporation of the solvent the residue was brought to pH 9 with saturated aqueous sodium bicarbonate solution. The mixture was stirred for four hours. The precipitate was sucked off and washed with water. The solid substance was dissolved in dichloromethane and purified by chromatography on silicagel (eluents: dichloromethane/methanol) resulting in 49.6 mg of the desired compound which was however yet contaminated. Due to these impurities the compound was again purified by HPLC yielding 21.1 mg (23.7%) of the title compound.

Workup

  1. customAfter evaporation of the solvent the residue
  2. washwashed with water
  3. dissolutionThe solid substance was dissolved in dichloromethane
  4. custompurified by chromatography on silicagel (eluents: dichloromethane/methanol)

Sources & evidence

ORD record
ord-6a969e3af23741ff84ce9a2d6f7582e3
Source dataset
uspto-grants-2015_03
Patent number
US08987273B2

Reaction notes

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