Cesium carbonate → HCID 66742549, compound

HRID 337315Notes

Reaction equation

HRID 337315 reaction equation
[CH2:1]([O:3][C:4](=[O:16])[C:5]([O:8][C:9]1[CH:10]=[N:11][C:12]([NH2:15])=[CH:13][CH:14]=1)([CH3:7])[CH3:6])[CH3:2].Br[C:18]1[C:19](=[O:26])[N:20]([CH3:25])[N:21]=[C:22]([Cl:24])[CH:23]=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]>[CH2:1]([O:3][C:4](=[O:16])[C:5]([O:8][C:9]1[CH:10]=[N:11][C:12]([NH:15][C:18]2[C:19](=[O:26])[N:20]([CH3:25])[N:21]=[C:22]([Cl:24])[CH:23]=2)=[CH:13][CH:14]=1)([CH3:7])[CH3:6])[CH3:2]

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 66742761HCID 66742761, compound

Product 1

HCID 66742549HCID 66742549, compoundYield 91.1%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

A flask containing 2-(6-amino-pyridin-3-yloxy)-2-methyl-propionic acid ethyl ester (1.365 g, 6.09 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (1.77 g, 7.91 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (528 mg, 0.913 mmol) and cesium carbonate (6.94 g, 21.3 mmol) in dry dioxane (60 ml) was evacuated under vacuum and back filled with argon (repeat 3 times). Tris(dibenzylideneacetone)dipalladium (0) (418 mg, 0.457 mmol) was added and the flask evacuated under vacuum and back filled with argon (repeat 3 times). The flask was place in an oil bath heated to 90° C. and stirred for 16 hours under argon atmosphere. The flask was cooled to ambient and the material was filtered through a plug of celite, rinsing well with dioxane. The volatiles were concentrated in vacuo and the residue was purified by silica gel chromatography, eluting with 5% to 25% ethyl acetate/hexane to provide the desired product as a light yellow-brown powder (2.035 g). (M+H)+=367 m/e. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.30 (t, J=7.18 Hz, 3 H) 1.59 (s, 6 H) 3.80 (s, 3 H) 4.26 (q, J=7.18 Hz, 2 H) 6.83 (d, J=9.06 Hz, 1 H) 7.26-7.30 (m, 1 H) 8.04 (d, J=3.02 Hz, 1 H) 8.18 (s, 1 H) 8.22 (s, 1 H).

Workup

  1. customwas evacuated under vacuum
  2. additionback filled with argon (repeat 3 times)
  3. customthe flask evacuated under vacuum
  4. additionback filled with argon (repeat 3 times)
  5. temperatureThe flask was cooled to ambient and the material
  6. filtrationwas filtered through a plug of celite
  7. washrinsing well with dioxane
  8. concentrationThe volatiles were concentrated in vacuo
  9. customthe residue was purified by silica gel chromatography
  10. washeluting with 5% to 25% ethyl acetate/hexane

Sources & evidence

ORD record
ord-182f7ef59eef457d8d1c6ff7f12c4019
Source dataset
uspto-grants-2014_11
Patent number
US08889682B2

Reaction notes

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