Cesium carbonate → HCID 66743342, compound

HRID 1431123Notes

Reaction equation

HRID 1431123 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C@@H: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]([C@@H: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 66742578HCID 66742578, compound

Product 1

HCID 66743342HCID 66743342, compoundYield 96%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

(S)-tert-Butyl 3-(6-aminopyridin-3-yl)pyrrolidine-1-carboxylate (307 mg, 1.17 mmol, Eq: 1.00) and 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (313 mg, 1.4 mmol, Eq: 1.20) were combined with 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (101 mg, 175 μmol, eq: 0.15), cesium carbonate (1.14 g, 3.5 mmol, eq: 3) and tris(dibenzylideneacetone)dipalladium(0) (53.4 mg, 58.3 μmol, Eq: 0.05) in dioxane (8.0 ml). The solution was degassed with Ar. The reaction mixture heated at 100° C. for 18 h. The solution was cooled to room temperature and diluted with 100 ml DCM. The organic layer was washed with water, and then dried over MgSO4. Concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 24 g, 50% to 100% EtOAc/Hex gradient) to give (S)-tert-butyl 3-(6-(6-chloro-2-methyl-3-oxo-2,3-dihydropyridazin-4-ylamino)pyridin-3-yl)pyrrolidine-1-carboxylate (456 mg, 96%). LC/MS-ESI observed [M+H]+ 405.

Workup

  1. customThe solution was degassed with Ar
  2. temperatureThe solution was cooled to room temperature
  3. additiondiluted with 100 ml DCM
  4. washThe organic layer was washed with water
  5. dry with materialdried over MgSO4
  6. concentrationConcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel, 24 g, 50% to 100% EtOAc/Hex gradient)

Sources & evidence

ORD record
ord-ef2dda504e0f4df49f76044706a14e8d
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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