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

HRID 592645Notes

Reaction equation

HRID 592645 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 129b (0.8 g, 5.76 mmol), xantophos (360 mg, 0.623 mmol), Pd2dba3 (384 mg, 0.42 mmol), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (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 132a (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-ba26f28631c541f291fd5a8eae03d750
Source dataset
uspto-grants-2016_01
Patent number
US09238655B2

Reaction notes

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