1-Methylimidazole → Methyl 4-(3-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamido)-2-methoxybenzoate

HRID 1755373Notes

Reaction equation

HRID 1755373 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([NH:11][C:12]2[C:13]3[N:14]([CH:27]=[CH:28][N:29]=3)[N:15]=[C:16]([C:18]3[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=3)[C:21](O)=[O:22])[CH:17]=2)=[N:7][C:8]=1[O:9][CH3:10].[NH2:30][C:31]1[CH:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[C:33]([O:41][CH3:42])[CH:32]=1.CN1C=CN=C1.CCN=C=NCCCN(C)C>CN(C=O)C.O.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([NH:11][C:12]2[C:13]3[N:14]([CH:27]=[CH:28][N:29]=3)[N:15]=[C:16]([C:18]3[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=3)[C:21]([NH:30][C:31]3[CH:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[C:33]([O:41][CH3:42])[CH:32]=3)=[O:22])[CH:17]=2)=[N:7][C:8]=1[O:9][CH3:10]

Participants

8

Reactant 4

HCID 13901-MethylimidazoleHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 168705Methyl 4-amino-o-anisateHCID 715343363-(8-(5,6-Dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid

Product 1

HCID 86682729Methyl 4-(3-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamido)-2-methoxybenzoateYield 47.5%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (150 mg, 0.38 mmol), methyl 4-amino-2-methoxybenzoate (70 mg, 0.38 mmol), 1-methyl-1H-imidazole (126 mg, 1.53 mmol) and EDCI (293 mg, 1.53 mmol) in DMF (3 mL) was stirred for 16 h at room temperature. Ethyl acetate (5 mL) and water (5 mL) were added. The organic layer was separated and the aqueous phase was extracted with ethyl acetate (20 mL). The combined organic phases were washed with brine (10 mL) and dried over Na2SO4. The residue was concentrated and purified by chromatography (silica gel, 200-300 mesh, dichloromethane:MeOH=50:1) to give methyl 4-(3-(8-(5,6-dimethoxypyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamido)-2-methoxybenzoate (100 mg, 47%) as brown liquid. LC-MS: [M+H]+, 555.1, tR=1.701 min

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous phase was extracted with ethyl acetate (20 mL)
  3. washThe combined organic phases were washed with brine (10 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationThe residue was concentrated
  6. custompurified by chromatography (silica gel, 200-300 mesh, dichloromethane:MeOH=50:1)

Sources & evidence

ORD record
ord-4679959645be4779b68ded550df3f8ad
Source dataset
uspto-grants-2015_10
Patent number
US09169259B2

Reaction notes

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