Cesium carbonate → 6-Chloro-4-(6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-ylamino)-2-methylpyridazin-3(2H)-one

HRID 1918885Notes

Reaction equation

HRID 1918885 reaction equation
[N:1]1[N:9]2[C:4]([CH2:5][O:6][CH2:7][CH2:8]2)=[CH:3][C:2]=1[NH2:10].Br[C:12]1[C:13](=[O:20])[N:14]([CH3:19])[N:15]=[C:16]([Cl:18])[CH:17]=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]>[Cl:18][C:16]1[CH:17]=[C:12]([NH:10][C:2]2[CH:3]=[C:4]3[CH2:5][O:6][CH2:7][CH2:8][N:9]3[N:1]=2)[C:13](=[O:20])[N:14]([CH3:19])[N:15]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 580437996,7-dihydro-4H-pyrazolo(5,1-c)(1,4)oxazin-2-amineHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

Product 1

HCID 580437886-Chloro-4-(6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-ylamino)-2-methylpyridazin-3(2H)-oneYield 81%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of 6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazin-2-amine 110b (0.8 g, 5.76 mmol), xantophos (360 mg, 0.623 mmol), Pd2 dba3 (384 mg, 0.42 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one 103e (1.28 g, 5.76 mmol) and Cs2CO3 (5.05 g. 17.3 mmol) in 1,4-dioxane (40 mL) was heated at reflux for 2 h. After the completion of the reaction, the mixture was filtered off, and washed with MeOH (60 mL). The filtrate was evaporated in vacuo. The residue was purified on reverse phase Combi-flash to give 147a (1.3 g, 81%). MS: [M+H]+ 282.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 2 h
  3. customAfter the completion of the reaction
  4. filtrationthe mixture was filtered off
  5. washwashed with MeOH (60 mL)
  6. customThe filtrate was evaporated in vacuo
  7. customThe residue was purified on reverse phase Combi-flash

Sources & evidence

ORD record
ord-b79172c0798341ceaeb787b8ac3ea924
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

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