Cesium carbonate → 6-Chloro-2-methyl-4-({5-[(morpholin-4-yl)carbonyl]pyridin-2-yl}amino)-2,3-dihydropyridazin-3-one

HRID 1431040Notes

Reaction equation

HRID 1431040 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[O:9])=[CH:4][CH:3]=1.Br[C:17]1[C:18](=[O:25])[N:19]([CH3:24])[N:20]=[C:21]([Cl:23])[CH:22]=1.C(=O)([O-])[O-].[Cs+].[Cs+].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>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:23][C:21]1[CH:22]=[C:17]([NH:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]([N:10]3[CH2:15][CH2:14][O:13][CH2:12][CH2:11]3)=[O:9])=[CH:6][N:7]=2)[C:18](=[O:25])[N:19]([CH3:24])[N:20]=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 59259223(6-Aminopyridin-3-yl)(morpholino)methanone

Product 1

HCID 576627786-Chloro-2-methyl-4-({5-[(morpholin-4-yl)carbonyl]pyridin-2-yl}amino)-2,3-dihydropyridazin-3-oneYield 30.3%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

6-aminopyridin-3-yl-morpholino-methanone (800 mg, 3.86 mmol, Eq: 1.00), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (1 g, 4.48 mmol, Eq: 1.16), cesium carbonate (4.4 g, 13.5 mmol, Eq: 3.5) and xantphos (335 mg, 579 μmol, Eq: 0.15) were suspended in dioxane (40 ml). The suspension was degassed with argon. Finally Pd2(dba)3 (265 mg, 290 μmol, Eq: 0.075) was added and the reaction mixture was stirred at 90° C. over night under an argon atmosphere. The reaction mixture was allowed to cool to room temperature, and then filtered over celite. Filtrate was concentrated in vacuo to give a light brown solid. The crude material was purified by flash chromatography (silica gel, 110 g, 0% to 10% MeOH in (EtOAc 1:1 Hex) to afford a light yellow solid (408 mg, 1.17 mmol). MS (H+)=350.0 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 3.60-3.80 (m, 8H) 3.83 (s, 3H) 6.96 (d, J=8.69 Hz, 1H) 7.77 (dd, J=8.50, 2.45 Hz, 1H) 8.35-8.44 (m, 2H) 8.47 (d, J=2.27 Hz, 1H)

Workup

  1. customThe suspension was degassed with argon
  2. temperatureto cool to room temperature
  3. filtrationfiltered over celite
  4. concentrationFiltrate was concentrated in vacuo
  5. customto give a light brown solid
  6. customThe crude material was purified by flash chromatography (silica gel, 110 g, 0% to 10% MeOH in (EtOAc 1:1 Hex)

Sources & evidence

ORD record
ord-a16dc524680246d486928b99e9b4ec20
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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