Cesium carbonate → 6-Chloro-4-[6-(2-dimethylamino-1,1-dimethyl-ethoxy)-pyridazin-3-ylamino]-2-methyl-2H-pyridazin-3-one

HRID 449645Notes

Reaction equation

HRID 449645 reaction equation
[CH3:1][N:2]([CH3:15])[CH2:3][C:4]([CH3:14])([O:6][C:7]1[N:12]=[N:11][C:10]([NH2:13])=[CH:9][CH:8]=1)[CH3:5].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.[Pd]>[Cl:23][C:21]1[CH:22]=[C:17]([NH:13][C:10]2[N:11]=[N:12][C:7]([O:6][C:4]([CH3:5])([CH3:14])[CH2:3][N:2]([CH3:1])[CH3:15])=[CH:8][CH:9]=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 667429246-(2-Dimethylamino-1,1-dimethyl-ethoxy)-pyridazin-3-ylamine

Product 1

HCID 667429116-Chloro-4-[6-(2-dimethylamino-1,1-dimethyl-ethoxy)-pyridazin-3-ylamino]-2-methyl-2H-pyridazin-3-oneYield 70.5%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

In a 15 mL microwave reaction vial was added a solution of 6-(1-(dimethylamino)-2-methylpropan-2-yloxy)pyridazin-3-amine (110 mg, 523 μmol, Eq: 1.00) in dioxane (5 ml) under argon. To the solution was added 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (152 mg, 680 μmol, Eq: 1.3), Cs2CO3 (511 mg, 1.57 mmol, Eq: 3), xantphos (45.4 mg, 78.5 μmol, Eq: 0.15) and bis(dibenzylideneacetone)palladium (22.6 mg, 39.2 μmol, Eq: 0.075). The reaction tube was sealed and heated in oil bath at 110° C. (bath temp) for 7 hrs, then was cooled to room temperature and stirred overnight. The reaction mixture was filtered and the solid was washed with THF (20 mL). The combined filtrate and washes were concentrated in vacuo. The reaction mixture was absorbed on to silica and purified by LC chromatography eluting with 0-5% (MeOH) in 1/1 EtOAc/heptane to afford 130 mg (70%) of the title compound.

Workup

  1. customIn a 15 mL microwave reaction
  2. customThe reaction tube was sealed
  3. temperaturewas cooled to room temperature
  4. filtrationThe reaction mixture was filtered
  5. washthe solid was washed with THF (20 mL)
  6. concentrationThe combined filtrate and washes were concentrated in vacuo
  7. customThe reaction mixture was absorbed on to silica
  8. custompurified by LC chromatography
  9. washeluting with 0-5% (MeOH) in 1/1 EtOAc/heptane

Sources & evidence

ORD record
ord-8ebff60018e346b89d648786f33706de
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

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