Sodium Hydroxide → 7-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-2-(2,4-dimethoxybenzyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one

HRID 1055986Notes

Reaction equation

HRID 1055986 reaction equation
[C:1]([NH:5][C:6]1[C:15]([CH3:16])=[N:14][C:13]2[C:8](=[C:9](B3OC(C)(C)C(C)(C)O3)[CH:10]=[CH:11][CH:12]=2)[N:7]=1)([CH3:4])([CH3:3])[CH3:2].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.Br[C:61]1[CH:62]=[C:63]2[C:68](=[O:69])[N:67]([CH2:70][C:71]3[CH:76]=[CH:75][C:74]([O:77][CH3:78])=[CH:73][C:72]=3[O:79][CH3:80])[CH2:66][CH2:65][N:64]2[CH:81]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[OH-].[Na+]>O1CCOCC1.O.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]>[C:1]([NH:5][C:6]1[C:15]([CH3:16])=[N:14][C:13]2[C:8]([N:7]=1)=[C:9]([C:61]1[CH:62]=[C:63]3[C:68](=[O:69])[N:67]([CH2:70][C:71]4[CH:76]=[CH:75][C:74]([O:77][CH3:78])=[CH:73][C:72]=4[O:79][CH3:80])[CH2:66][CH2:65][N:64]3[CH:81]=1)[CH:10]=[CH:11][CH:12]=2)([CH3:2])([CH3:3])[CH3:4]

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 897836627-bromo-2-(2,4-dimethoxybenzyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-oneHCID 89783758N-(tert-butyl)-3-methyl-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoxalin-2-amine

Product 1

HCID 897850897-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-2-(2,4-dimethoxybenzyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-oneYield 26.1%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
135 °C

Procedure

A mixture of N-(tert-butyl)-3-methyl-8-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoxalin-2-amine (Example 174b; 187 mg, 0.55 mmol), XPhos (Strem, Newburyport, Mass.; 13 mg, 0.027 mmol), Pd2(dba)3 (12 mg, 0.014 mmol), 7-bromo-2-(2,4-dimethoxybenzyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (Example 165b; 167 mg, 0.46 mmol) and potassium phosphate (291 mg, 1.37 mmol) in 2 mL of dioxane and 0.5 mL of water was heated in a microwave at 135° C. for 45 min. The mixture was then treated with 2 mL of 1 N NaOH, and extracted with EtOAc (2×5 mL). The organic extracts were concentrated. Purification of the brown residue on a silica gel column (eluted with 25-75% EtOAc in hexanes) afforded 7-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-2-(2,4-dimethoxybenzyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (60 mg) as a brown amorphous solid. m/z (ESI, +ve) 500.1 (M+H)+.

Workup

  1. extractionextracted with EtOAc (2×5 mL)
  2. concentrationThe organic extracts were concentrated
  3. customPurification of the brown residue
  4. washon a silica gel column (eluted with 25-75% EtOAc in hexanes)

Sources & evidence

ORD record
ord-f76814b563ac4f1b830728d5ce834200
Source dataset
uspto-grants-2016_07
Patent number
US09394297B2

Reaction notes

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