3,5-Dimethylisoxazole-4-carboxylic acid → 3,5-Dimethyl-isoxazole-4-carboxylic acid [5-(1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-ylmethyl]-amide

HRID 1774820Notes

Reaction equation

HRID 1774820 reaction equation
[NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([C:9]2[CH:10]=[C:11]3[C:16](=[CH:17][CH:18]=2)[N:15]([CH3:19])[C:14](=[O:20])[CH2:13][CH2:12]3)[CH:6]=[N:7][CH:8]=1.[CH3:21][C:22]1[C:26]([C:27](O)=[O:28])=[C:25]([CH3:30])[O:24][N:23]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:19][N:15]1[C:16]2[C:11](=[CH:10][C:9]([C:5]3[CH:4]=[C:3]([CH2:2][NH:1][C:27]([C:26]4[C:22]([CH3:21])=[N:23][O:24][C:25]=4[CH3:30])=[O:28])[CH:8]=[N:7][CH:6]=3)=[CH:18][CH:17]=2)[CH2:12][CH2:13][C:14]1=[O:20]

Participants

6

Reactant 4

HCID 756363,5-Dimethylisoxazole-4-carboxylic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 715334526-(5-Aminomethyl-pyridin-3-yl)-1-methyl-3,4-dihydro-1H-quinolin-2-one

Product 1

HCID 715336373,5-Dimethyl-isoxazole-4-carboxylic acid [5-(1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-ylmethyl]-amideYield 59.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-(5-aminomethyl-pyridin-3-yl)-1-methyl-3,4-dihydro-1H-quinolin-2-one (example 36, 0.047 g, 0.177 mmol) in DMF (1 mL) were added 3,5-dimethylisoxazole-4-carboxylic acid (0.037 g, 0.266 mmol) and TBTU (0.063 g, 0.195 mmol) followed by Hünig's base (0.048 g, 0.372 mmol) and the reaction mixture was stirred at room temperature over night. The mixture was purified directly by reverse phase HPLC on a Gemini-NX column, eluting with a 20 to 98% MeOH—H2O (0.05% TEA) gradient to give the title compound (0.041 g, 59%) as a colorless solid. MS: 391.3 (M+H+).

Workup

  1. customThe mixture was purified directly by reverse phase HPLC on a Gemini-NX column
  2. washeluting with a 20 to 98% MeOH—H2O (0.05% TEA) gradient

Sources & evidence

ORD record
ord-48c379ccdaac461e94e86f681573e939
Source dataset
uspto-grants-2016_02
Patent number
US09260408B2

Reaction notes

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