Diisopropylethylamine → 1-(4,4-difluorocyclohexyl)-7-[(5-fluoro-2,3-dihydro-1H-indol-1-yl)carbonyl]-8-methyl[1,2,4]triazolo[4,3-a]quinoxalin-4(5H)-one

HRID 1807876Notes

Reaction equation

HRID 1807876 reaction equation
[F:1][C:2]1([F:26])[CH2:7][CH2:6][CH:5]([C:8]2[N:12]3[C:13]4[C:18]([NH:19][C:20](=[O:21])[C:11]3=[N:10][N:9]=2)=[CH:17][C:16]([C:22](O)=[O:23])=[C:15]([CH3:25])[CH:14]=4)[CH2:4][CH2:3]1.[F:27][C:28]1[CH:29]=[C:30]2[C:34](=[CH:35][CH:36]=1)[NH:33][CH2:32][CH2:31]2.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>O.CN(C)C=O>[F:26][C:2]1([F:1])[CH2:3][CH2:4][CH:5]([C:8]2[N:12]3[C:13]4[C:18]([NH:19][C:20](=[O:21])[C:11]3=[N:10][N:9]=2)=[CH:17][C:16]([C:22]([N:33]2[C:34]3[C:30](=[CH:29][C:28]([F:27])=[CH:36][CH:35]=3)[CH2:31][CH2:32]2)=[O:23])=[C:15]([CH3:25])[CH:14]=4)[CH2:6][CH2:7]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 27744635-FluoroindolineHCID 58575300HCID 58575300, compound

Product 1

HCID 469101431-(4,4-difluorocyclohexyl)-7-[(5-fluoro-2,3-dihydro-1H-indol-1-yl)carbonyl]-8-methyl[1,2,4]triazolo[4,3-a]quinoxalin-4(5H)-oneYield 54.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of 150 mg of 1-(4,4-difluorocyclohexyl)-8-methyl-4-oxo-4,5-dihydro[1,2,4]triazolo[4,3-a]quinoxaline-7-carboxylic acid, 62.5 mg of 5-fluoroindoline, 0.25 mL of diisopropylethylamine, and 3 mL of N,N-dimethylformamide was added 146 mg of TBTU, followed by stirring at room temperature overnight. To the reaction liquid were added water and a saturated aqueous sodium hydrogen carbonate solution, followed by extraction with chloroform. 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=100/0 to 95/5). The obtained solid was washed with a mixed solution of hot diethyl ether and normal hexane to obtain 108 mg of 1-(4,4-difluorocyclohexyl)-7-[(5-fluoro-2,3-dihydro-1H-indol-1-yl)carbonyl]-8-methyl[1,2,4]triazolo[4,3-a]quinoxalin-4(5H)-one.

Workup

  1. customTo the reaction liquid
  2. extractiona saturated aqueous sodium hydrogen carbonate solution, followed by extraction with chloroform
  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=100/0 to 95/5)
  7. washThe obtained solid was washed with a mixed solution of hot diethyl ether and normal hexane

Sources & evidence

ORD record
ord-b9a78c5ef9bb41328d786e2de55cca10
Source dataset
uspto-grants-2013_01
Patent number
US08357688B2

Reaction notes

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