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

HRID 1431107Notes

Reaction equation

HRID 1431107 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9]2)=[CH:4][CH:3]=1.Br[C:21]1[C:22](=[O:29])[N:23]([CH3:28])[N:24]=[C:25]([Cl:27])[CH:26]=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:27][C:25]1[CH:26]=[C:21]([NH:1][C:2]2[N:7]=[CH:6][C:5]([CH:8]3[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9]3)=[CH:4][CH:3]=2)[C:22](=[O:29])[N:23]([CH3:28])[N:24]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-oneHCID 66742238Tert-butyl 3-(6-aminopyridin-3-yl)pyrrolidine-1-carboxylate

Product 1

HCID 66742790Tert-butyl 3-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)pyrrolidine-1-carboxylateYield 50%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

Tert-butyl 3-(6-aminopyridin-3-yl)pyrrolidine-1-carboxylate (422 mg, 1.6 mmol, Eq: 1.00), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (430 mg, 1.92 mmol, Eq: 1.20), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (139 mg, 240 μmol, Eq: 0.15), cesium carbonate (1.57 g, 4.81 mmol, Eq: 3) and tris(dibenzylideneacetone)dipalladium(0) (73.4 mg, 80.1 μmol, Eq: 0.05) were combined in dioxane (10 ml). The solution was degassed with Ar for 10 min. The mixture was heated at 100° C. for 18 h. The solution was cooled to room temperature then diluted with 100 ml DCM. The organics washed with water, then dried over MgSO4. The solution was filtered. Concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 50% to 100% EtOAC/Hex gradient) to give tert-butyl 3-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)pyrrolidine-1-carboxylate (325 mg, 50%) LC/MS-ESI observed [M+H]+ 406.

Workup

  1. customThe solution was degassed with Ar for 10 min
  2. temperatureThe solution was cooled to room temperature
  3. additionthen diluted with 100 ml DCM
  4. washThe organics washed with water
  5. dry with materialdried over MgSO4
  6. filtrationThe solution was filtered
  7. concentrationConcentrated in vacuo
  8. customThe crude material was purified by flash chromatography (silica gel, 40 g, 50% to 100% EtOAC/Hex gradient)

Sources & evidence

ORD record
ord-9f2d504ba05c4e03adda819caa8fb9c3
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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