Cesium carbonate → Tert-butyl 4-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylate

HRID 449619Notes

Reaction equation

HRID 449619 reaction equation
Br[C:2]1[C:3](=[O:10])[N:4]([CH3:9])[N:5]=[C:6]([Cl:8])[CH:7]=1.[NH2:11][C:12]1[N:17]=[CH:16][C:15]([CH:18]2[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]2)=[CH:14][CH:13]=1.C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:8][C:6]1[CH:7]=[C:2]([NH:11][C:12]2[N:17]=[CH:16][C:15]([CH:18]3[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]3)=[CH:14][CH:13]=2)[C:3](=[O:10])[N:4]([CH3:9])[N:5]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 49839963tert-Butyl 4-(6-aminopyridin-3-yl)piperidine-1-carboxylateHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

Product 1

HCID 66742247Tert-butyl 4-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylateYield 82%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

4-Bromo-6-chloro-2-methylpyridazin-3(2H)-one (509 mg, 2.28 mmol, Eq: 1.00), tert-butyl 4-(6-aminopyridin-3-yl)piperidine-1-carboxylate (632 mg, 2.28 mmol, Eq: 1.00), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (198 mg, 342 μmol, Eq: 0.15) and cesium carbonate (2.6 g, 7.98 mmol, Eq: 3.5) were suspended in dioxane (20 ml) under argon. Finally tris(dibenzylideneacetone)dipalladium(0) (156 mg, 171 μmol, Eq: 0.075) was added. The reaction mixture was heated to 90° C. for 18 h. The reaction mixture was filtered over celite; washed with dioxane, and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 24 g, 20% to 50% EtOAc/Hex gradient) to give tert-butyl 4-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)piperidine-1-carboxylate (782 mg, 82%). LC/MS-ESI observed [M+H]+ 420.

Workup

  1. filtrationThe reaction mixture was filtered over celite
  2. washwashed with dioxane
  3. concentrationconcentrated in vacuo
  4. customThe crude material was purified by flash chromatography (silica gel, 24 g, 20% to 50% EtOAc/Hex gradient)

Sources & evidence

ORD record
ord-72d246af21ea4e15835e5727dbbed3b3
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

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