Cesium carbonate → 6-chloro-4-(5-(ethylsulfonyl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one

HRID 449603Notes

Reaction equation

HRID 449603 reaction equation
[CH2:1]([S:3]([C:6]1[CH:7]=[CH:8][C:9]([NH2:12])=[N:10][CH:11]=1)(=[O:5])=[O:4])[CH3:2].Br[C:14]1[C:15](=[O:22])[N:16]([CH3:21])[N:17]=[C:18]([Cl:20])[CH:19]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>C(Cl)Cl.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:20][C:18]1[CH:19]=[C:14]([NH:12][C:9]2[CH:8]=[CH:7][C:6]([S:3]([CH2:1][CH3:2])(=[O:4])=[O:5])=[CH:11][N:10]=2)[C:15](=[O:22])[N:16]([CH3:21])[N:17]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 284117055-(Ethylsulfonyl)pyridin-2-amineHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

Product 1

HCID 667424096-chloro-4-(5-(ethylsulfonyl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-oneYield 83.3%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

In a 250 mL round-bottomed flask, 5-(ethylsulfonyl)pyridin-2-amine (183 mg, 983 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (263 mg, 1.18 mmol), xantphos (85.3 mg, 147 μmol) and Cs2CO3 (960 mg, 2.95 mmol) were combined with dioxane (10 mL) to give a light brown suspension. The flask was evacuated and filled with argon. Pd2(dba)3 (45.0 mg, 49.1 mmol) was added and the reaction mixture was stirred at 100° C. for 20 h under argon. Cooled to 25° C. and diluted with DCM. The reaction mixture was filtered through celite and the filter cake was washed with DCM until clear. The filtrate was concentrated and purified by flash chromatography (silica gel, 40 g, 0% to 2% MeOH in DCM) to afford 0.323 g (25%) of the title compound as a tan powder. (M+H)+=329/331 m/e. 1H NMR (300 MHz, DMSO-d6) δ: 10.18 (s, 1H), 8.78 (d, J=2.3 Hz, 1H), 8.12 (dd, J=8.9, 2.5 Hz, 1H), 7.74 (d, J=9.1 Hz, 1H), 3.69 (s, 3H), 3.32 (q, J=7.4 Hz, 2H), 1.11 (t, J=7.4 Hz, 3H).

Workup

  1. customto give a light brown suspension
  2. customThe flask was evacuated
  3. additionfilled with argon
  4. temperatureCooled to 25° C.
  5. filtrationThe reaction mixture was filtered through celite
  6. washthe filter cake was washed with DCM until clear
  7. concentrationThe filtrate was concentrated
  8. custompurified by flash chromatography (silica gel, 40 g, 0% to 2% MeOH in DCM)

Sources & evidence

ORD record
ord-7a092c57e7834c9a9cddcb7260af09a9
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

Loading…