Triethylamine → 6-chloro-3-methyl-2-(2-methyl-5-pyrrolidin-1-yl-2H-[1,2,4]triazol-3-ylethynyl)-quinoxaline

HRID 1055033Notes

Reaction equation

HRID 1055033 reaction equation
Br[C:2]1[C:11]([CH3:12])=[N:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([Cl:13])[CH:8]=2)[N:3]=1.BrC1C(C)=NC2C(N=1)=CC(Cl)=CC=2.[C:27]([C:29]1[N:33]([CH3:34])[N:32]=[C:31]([N:35]2[CH2:39][CH2:38][CH2:37][CH2:36]2)[N:30]=1)#[CH:28].C(N(CC)CC)C>CN(C)C=O.[Cu]I.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[Cl:13][C:7]1[CH:8]=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]=[C:2]([C:28]#[C:27][C:29]1[N:33]([CH3:34])[N:32]=[C:31]([N:35]3[CH2:39][CH2:38][CH2:37][CH2:36]3)[N:30]=1)[C:11]([CH3:12])=[N:10]2

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 900168702-Bromo-6-chloro-3-methylquinoxalineHCID 900169623-Bromo-6-chloro-2-methylquinoxalineHCID 900255005-ethynyl-1-methyl-3-pyrrolidin-1-yl-1H-[1,2,4]triazole

Product 1

HCID 727037156-chloro-3-methyl-2-(2-methyl-5-pyrrolidin-1-yl-2H-[1,2,4]triazol-3-ylethynyl)-quinoxalineYield 5.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2-bromo-6-chloro-3-methylquinoxaline with 3-bromo-6-chloro-2-methylquinoxaline (250 mg, 485 μmol, Eq: 1.00) and 5-Ethynyl-1-methyl-3-pyrrolidin-1-yl-1H-[1,2,4]triazole (94.1 mg, 534 μmol, Eq: 1.1) at room temperature in N,N-dimethylformamide (7.5 ml) under an argon atmosphere were added triethylamine (98.2 mg, 135 μl, 971 μmol, Eq: 2), copper (I) iodide (4.62 mg, 24.3 μmol, Eq: 0.05) and bis(triphenylphosphine)palladium (II) chloride (17.0 mg, 24.3 μmol, Eq: 0.05). The mixture was purged with argon before it was stirred over weekend at room temperature (dark sol.). The mixture was stirred over an additional night at 80° C. The crude material was applied on silica gel and purified by column chromatography. After separation of the isomers by preparative HPLC gave 6-chloro-3-methyl-2-(2-methyl-5-pyrrolidin-1-yl-2H-[1,2,4]triazol-3-ylethynyl)-quinoxaline (9.3 mg, 5.4%) as a yellow solid. MS: m/z=353.5 (M+H+)

Workup

  1. customThe mixture was purged with argon before it
  2. stirringThe mixture was stirred over an additional night at 80° C
  3. custompurified by column chromatography
  4. customAfter separation of the isomers by preparative HPLC

Sources & evidence

ORD record
ord-687bd762b7d347279f98a4298797f1f3
Source dataset
uspto-grants-2016_07
Patent number
US09394311B2

Reaction notes

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