Cesium carbonate → 6-chloro-4-(5-(4-isopropylpiperazin-1-yl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one

HRID 1431102Notes

Reaction equation

HRID 1431102 reaction equation
[CH:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10]2[CH:11]=[CH:12][C:13]([NH2:16])=[N:14][CH:15]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2].Br[C:18]1[C:19](=[O:26])[N:20]([CH3:25])[N:21]=[C:22]([Cl:24])[CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C3OC4C(=CC=CC=4P(C4C=CC=CC=4)C4C=CC=CC=4)C(C)(C)C=3C=CC=2)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Cl:24][C:22]1[CH:23]=[C:18]([NH:16][C:13]2[CH:12]=[CH:11][C:10]([N:7]3[CH2:6][CH2:5][N:4]([CH:1]([CH3:3])[CH3:2])[CH2:9][CH2:8]3)=[CH:15][N:14]=2)[C:19](=[O:26])[N:20]([CH3:25])[N:21]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 434619445-(4-(Propan-2-yl)piperazin-1-yl)pyridin-2-amineHCID 592164744-Bromo-6-chloro-2-methyl-2,3-dihydropyridazin-3-one

Product 1

HCID 667422216-chloro-4-(5-(4-isopropylpiperazin-1-yl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-oneYield 83%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

In a 50 mL round-bottomed flask, 5-(4-isopropylpiperazin-1-yl)pyridin-2-amine (200 mg, 908 μmol, Eq: 1.00), 4-bromo-6-chloro-2-methylpyridazin-3(2H)-one (243 mg, 1.09 mmol, Eq: 1.2) and cesium carbonate (887 mg, 2.72 mmol, Eq: 3) were combined with dioxane (20 ml) to give a orange suspension. 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (78.8 mg, 136 μmol, eq: 0.15) was added. Tris(dibenzylideneacetone)dipalladium(0) (41.6 mg, 45.4 μmol, Eq: 0.05) was added. The solution was degassed with Ar for 10 min. The solution was heated at 95-105° C. for 48 h. The solution was diluted with 200 ml DCM. MgSO4 was added and the suspension stirred for 10 min. The solid was filtered and washed several times with DCM. The organics were concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 40 g, 50% to 100% EtOAc/hexanes gradient) to give 6-chloro-4-(5-(4-isopropylpiperazin-1-yl)pyridin-2-ylamino)-2-methylpyridazin-3(2H)-one (273 mg, 83%). LC/MS-ESI observed [M+H]+ 363.

Workup

  1. customto give a orange suspension
  2. customThe solution was degassed with Ar for 10 min
  3. additionThe solution was diluted with 200 ml DCM
  4. additionMgSO4 was added
  5. filtrationThe solid was filtered
  6. washwashed several times with DCM
  7. concentrationThe organics were concentrated in vacuo
  8. customThe crude material was purified by flash chromatography (silica gel, 40 g, 50% to 100% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-82307d6101374ab48eb8cb22edda59b1
Source dataset
uspto-grants-2015_01
Patent number
US08940741B2

Reaction notes

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