Cesium carbonate → HCID 66743083, compound

HRID 337281Notes

Reaction equation

HRID 337281 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 argon for 10 min and heated at 95-105° C. for 4 h. No aniline starting material remained. The reaction mixture was diluted with 200 ml CH2Cl2. MgSO4 was added and the mixture was stirred for 5 min. The reaction was filtered and the filtercake was washed several times with CH2Cl2. 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 CH2Cl2) 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 argon for 10 min
  3. additionThe reaction mixture was diluted with 200 ml CH2Cl2
  4. additionMgSO4 was added
  5. filtrationThe reaction was filtered
  6. washthe filtercake was washed several times with CH2Cl2
  7. concentrationThe combined filtrate and washes were concentrated in vacuo
  8. customThe crude material was purified by flash chromatography (silica gel, 40 g, 1% to 2% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-42d128ab54bd4691be8622cfb3f66c5d
Source dataset
uspto-grants-2014_11
Patent number
US08889682B2

Reaction notes

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