Cesium carbonate → 6-Chloro-4-(5-cyclobutylaminomethyl-pyrazin-2-ylamino)-2-methyl-2H-pyridazin-3-one

HRID 1431130Notes

Reaction equation

HRID 1431130 reaction equation
[CH:1]1([NH:5][CH2:6][C:7]2[N:8]=[CH:9][C:10]([NH2:13])=[N:11][CH:12]=2)[CH2:4][CH2:3][CH2:2]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+].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.[Pd]>[Cl:21][C:19]1[CH:20]=[C:15]([NH:13][C:10]2[CH:9]=[N:8][C:7]([CH2:6][NH:5][CH:1]3[CH2:2][CH2:3][CH2:4]3)=[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 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-oneHCID 667422585-Cyclobutylaminomethyl-pyrazin-2-ylamine

Product 1

HCID 667421676-Chloro-4-(5-cyclobutylaminomethyl-pyrazin-2-ylamino)-2-methyl-2H-pyridazin-3-oneYield 39.1%

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

In a 15 mL microwave reaction vial was added a solution of 5-((cyclobutylamino)methyl)pyrazin-2-amine (280 mg, 1.57 mmol, Eq: 1.00) in dioxane (7 ml) under argon bubbling. To the solution was added 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (456 mg, 2.04 mmol, Eq: 1.3), Cs2CO3 (1.3 g, 3.99 mmol, Eq: 2.54), xantphos (136 mg, 236 μmol, Eq: 0.15) and bis(dibenzylideneacetone)palladium (67.7 mg, 118 μmol, Eq: 0.075). The reaction tube was sealed and heated in oil bath at 105° C. (bath temp) for 7 hrs then stirred at room temperature overnight. The crude reaction mixture was filtered and the solid was washed with dioxane (20 mL) and DCM (5 mL). The combined filtrate and washes were concentrated and absorbed on silica gel. The mixture was purified by LC chromatography (silica gel, 60 g) and eluted with 0-10% (10% NH4OH in MeOH) in (1/1) EtOAc/Heptane to afford 197 mg (39%) of the title compound.

Workup

  1. customIn a 15 mL microwave reaction
  2. customThe reaction tube was sealed
  3. customThe crude reaction mixture
  4. filtrationwas filtered
  5. washthe solid was washed with dioxane (20 mL) and DCM (5 mL)
  6. concentrationThe combined filtrate and washes were concentrated
  7. customabsorbed on silica gel
  8. customThe mixture was purified by LC chromatography (silica gel, 60 g)
  9. washeluted with 0-10% (10% NH4OH in MeOH) in (1/1) EtOAc/Heptane

Sources & evidence

ORD record
ord-b26ff58c32be49b0aed52d61c0b268a1
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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