1,2,3,4-Tetrahydroisoquinoline → 7-(3,4-dihydroisoquinolin-2(1H)-ylcarbonyl)-1-propyl[1,2,4]triazolo[4,3-a]quinoxalin-4(5H)-one

HRID 1807868Notes

Reaction equation

HRID 1807868 reaction equation
[O:1]=[C:2]1[NH:11][C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:12]([OH:14])=O)[CH:9]=2)[N:4]2[C:15]([CH2:18][CH2:19][CH3:20])=[N:16][N:17]=[C:3]12.[CH2:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:24][CH2:23][NH:22]1.C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1>O.CN(C)C=O>[CH2:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH2:24][CH2:23][N:22]1[C:12]([C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[N:4]1[C:15]([CH2:18][CH2:19][CH3:20])=[N:16][N:17]=[C:3]1[C:2](=[O:1])[NH:11]2)=[O:14]

Participants

7

Reactant 4

HCID 70461,2,3,4-TetrahydroisoquinolineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 585752814-Oxo-1-propyl-4,5-dihydro[1,2,4]triazolo[4,3-a]quinoxaline-7-carboxylic acid

Product 1

HCID 585751877-(3,4-dihydroisoquinolin-2(1H)-ylcarbonyl)-1-propyl[1,2,4]triazolo[4,3-a]quinoxalin-4(5H)-oneYield 89.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 125 mg of 4-oxo-1-propyl-4,5-dihydro[1,2,4]triazolo[4,3-a]quinoxaline-7-carboxylic acid, 73 mg of 1,2,3,4-tetrahydroisoquinoline, 0.26 mL of diisopropylethylamine, and 3 mL of N,N-dimethylformamide was added 262 mg of O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate, followed by stirring at room temperature overnight. To the reaction liquid was added water, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and then the solvent was evaporated. The obtained residue was purified by silica gel column chromatography (chloroform/methanol=99/1 to 95/5). The obtained solid was washed with 2 mL of hot methanol to obtain 159 mg of 7-(3,4-dihydroisoquinolin-2(1H)-ylcarbonyl)-1-propyl[1,2,4]triazolo[4,3-a]quinoxalin-4(5H)-one as a white solid.

Workup

  1. customTo the reaction liquid
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated
  6. customThe obtained residue was purified by silica gel column chromatography (chloroform/methanol=99/1 to 95/5)
  7. washThe obtained solid was washed with 2 mL of hot methanol

Sources & evidence

ORD record
ord-7bc3e109a6014e8c9c22382df75b1293
Source dataset
uspto-grants-2013_01
Patent number
US08357688B2

Reaction notes

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