Cesium carbonate → HCID 66743083, compound

HRID 449587Notes

Reaction equation

HRID 449587 reaction equation
[CH3:1][N:2]1[CH2:6][CH2:5][CH2:4][C@H:3]1[C:7]1[CH:8]=[CH:9][C:10]([NH2:13])=[N:11][CH:12]=1.Br[C:15]1[C:16](=[O:23])[N:17]([CH3:22])[N:18]=[C:19]([Cl:21])[CH:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+].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>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].O1CCOCC1>[Cl:21][C:19]1[CH:20]=[C:15]([NH:13][C:10]2[CH:9]=[CH:8][C:7]([C@@H:3]3[CH2:4][CH2:5][CH2:6][N:2]3[CH3:1])=[CH:12][N:11]=2)[C:16](=[O:23])[N:17]([CH3:22])[N:18]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 769989AC1LGF1FHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

Product 1

HCID 66743083HCID 66743083, compoundYield 52%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

In a 50 mL round-bottomed flask, 5-((S)-1-methyl-pyrrolidin-2-yl)-pyridin-2-ylamine (560 mg, 3.16 mmol)], 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (847 mg, 3.79 mmol) and cesium carbonate (3.09 g, 9.48 mmol) were combined with dioxane (25 ml) to give a orange suspension. 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (274 mg, 474 μmol, Eq: 0.15) was added followed by tris(dibenzylideneacetone)dipalladium(0) (145 mg, 158 μmol, Eq: 0.05). The reaction was degassed with Ar for 10 min and heated at 95-105° C. for 4 h. No aniline starting material was left. The reaction mixture was diluted with 200 ml DCM. MgSO4 was added and stirred. The reaction was filtered and the filtercake was washed several times with DCM. The combined filtrate and washes were concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 1% to 2% MeOH in DCM) to afford the desired product (522 mg, 52%). (M+H)+=320 m/e.

Workup

  1. customto give a orange suspension
  2. customThe reaction was degassed with Ar for 10 min
  3. waitNo aniline starting material was left
  4. additionThe reaction mixture was diluted with 200 ml DCM
  5. additionMgSO4 was added
  6. filtrationThe reaction was filtered
  7. washthe filtercake was washed several times with DCM
  8. concentrationThe combined filtrate and washes were concentrated in vacuo
  9. customThe crude material was purified by flash chromatography (silica gel, 40 g, 1% to 2% MeOH in DCM)

Sources & evidence

ORD record
ord-971c4c903f2f475fbc952d5c6375fcef
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

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