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 1055011노트

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HRID 1055011 반응식
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

참가 물질

9

반응물 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

생성물 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-one수율 47.6%

시약·촉매·용매 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 86718202tris(dibenzylideneacetone)dipalladium Pd2dba3촉매HCID 312751,4-Dioxane용매

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온도
140 °C

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-f363e09f8f5f40bca0fa8c5d9a66494f
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394311B2

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