Cesium carbonate → (E)-1-(5-(2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)vinyl)-1-methyl-1H-1,2,4-triazol-3-yl)pyrrolidin-2-one

HRID 1055011Notes

Reaction equation

HRID 1055011 reaction equation
Br[C:2]1[N:6]=[C:5](/[CH:7]=[CH:8]/[C:9]2[N:19]=[C:12]3[C:13]([CH3:18])=[N:14][CH:15]=[C:16]([CH3:17])[N:11]3[N:10]=2)[N:4]([CH3:20])[N:3]=1.[NH:21]1[CH2:25][CH2:24][CH2:23][C:22]1=[O:26].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>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].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].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].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>[CH3:17][C:16]1[N:11]2[N:10]=[C:9](/[CH:8]=[CH:7]/[C:5]3[N:4]([CH3:20])[N:3]=[C:2]([N:21]4[CH2:25][CH2:24][CH2:23][C:22]4=[O:26])[N:6]=3)[N:19]=[C:12]2[C:13]([CH3:18])=[N:14][CH:15]=1

Participants

9

Reactant 4

HCID 10796Cesium carbonateHCID 120252-PyrrolidoneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 90025179(E)-2-(2-(3-bromo-1-methyl-1H-1,2,4-triazol-5-yl)vinyl)-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazine

Product 1

HCID 90026269(E)-1-(5-(2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)vinyl)-1-methyl-1H-1,2,4-triazol-3-yl)pyrrolidin-2-oneYield 47.6%

Reagents, catalysts & solvents 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 86718202tris(dibenzylideneacetone)dipalladium Pd2dba3CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

An argon-purged mixture of (E)-2-(2-(3-bromo-1-methyl-1H-1,2,4-triazol-5-yl)vinyl)-5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazine (case 30922, Expl. 9a) p 31) (56 mg, 168 μmol, Eq: 1.00), pyrrolidin-2-one (28.6 mg, 25.7 μl, 336 μmol, Eq: 2), cesium carbonate (76.4 mg, 235 μmol, Eq: 1.4), tris(dibenzylideneacetone)-dipalladium(0)/Pd2(dba)3 (3.07 mg, 3.35 μmol, Eq: 0.02) and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xant-phos) (3.88 mg, 6.7 μmol, Eq: 0.04) in dioxane (3 ml) was heated in a closed vessel for 1.5 hours at 140° C. under argon atmosphere. Up to 4 additional portions of Pd2(dba)3 and 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (xant-phos) are added and heating continued for another 1.5 hours until HPLC shows complete conversion of the Aryl bromide. The crude material was applied on silica gel and purified by flash chromatography over a 20 g silica gel column using ethyl acetate/methanol 5-10% as eluent affording 1-{5-[(E)-2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)-vinyl]-1-methyl-1H-[1,2,4]triazol-3-yl}-pyrrolidin-2-one (27 mg, 47.6%) as an off-white solid. MS: m/z=339.6 (M+H+), MP: 242.5° C.

Workup

  1. customAn argon-purged
  2. temperatureheating
  3. custompurified by flash chromatography over a 20 g silica gel column

Sources & evidence

ORD record
ord-f363e09f8f5f40bca0fa8c5d9a66494f
Source dataset
uspto-grants-2016_07
Patent number
US09394311B2

Reaction notes

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