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

HRID 1774859Notes

Reaction equation

HRID 1774859 reaction equation
Cl.[NH2:2][CH2:3][C:4]1[C:5]([Cl:22])=[C:6]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]([CH3:20])[C:15](=[O:21])[CH2:14][CH2:13]3)[CH:7]=[N:8][CH:9]=1.CCN=C=NCCCN(C)C.OC1C2N=NNC=2C=CC=1.CCN(C(C)C)C(C)C.[CH3:53][C:54]1[C:58]([C:59](O)=[O:60])=[C:57]([CH3:62])[O:56][N:55]=1.C([O-])(O)=O.[Na+]>CN(C=O)C.CCOC(C)=O>[Cl:22][C:5]1[C:6]([C:10]2[CH:11]=[C:12]3[C:17](=[CH:18][CH:19]=2)[N:16]([CH3:20])[C:15](=[O:21])[CH2:14][CH2:13]3)=[CH:7][N:8]=[CH:9][C:4]=1[CH2:3][NH:2][C:59]([C:58]1[C:54]([CH3:53])=[N:55][O:56][C:57]=1[CH3:62])=[O:60]

Participants

9

Reactant 6

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 756363,5-Dimethylisoxazole-4-carboxylic acidHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 866792006-(5-Aminomethyl-4-chloro-pyridin-3-yl)-1-methyl-3,4-dihydro-1H-quinolin-2-one hydrochlorideHCID 178418300HCID 178418300, compound

Product 1

HCID 866792023,5-Dimethyl-isoxazole-4-carboxylic acid [4-chloro-5-(1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-ylmethyl]-amideYield 48%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-(5-aminomethyl-4-chloro-pyridin-3-yl)-1-methyl-3,4-dihydro-1H-quinolin-2-one hydrochloride (example 218, 0.05 g, 0.148 mmol) in dry DMF (1 mL) were added EDCI (0.034 g, 0.077 mmol), hydroxybenzotriazole (0.017 g, 0.077 mmol), Hünig's base (0.057 g, 0.443 mmol) and 3,5-dimethyl-isoxazole-4-carboxylic acid (0.021 g, 0.148 mmol) and the resulting solution was stirred at room temperature for 2 h. The reaction mixture was diluted with EtOAc, poured into sat. NaHCO3 solution (10 mL) and extracted with EtOAc (2×20 mL). Combined organics were dried over Na2SO4, filtered and evaporated to dryness. The residue was purified by silica gel flash chromatography eluting with a 0 to 5% MeOH-DCM gradient to give the title compound (0.03 g, 48%) as a colorless solid. MS: 425.4 (M+H+).

Workup

  1. extractionextracted with EtOAc (2×20 mL)
  2. dry with materialCombined organics were dried over Na2SO4
  3. filtrationfiltered
  4. customevaporated to dryness
  5. customThe residue was purified by silica gel flash chromatography
  6. washeluting with a 0 to 5% MeOH-DCM gradient

Sources & evidence

ORD record
ord-14236c5db8b24e8283b2ac4e2a664f9f
Source dataset
uspto-grants-2016_02
Patent number
US09260408B2

Reaction notes

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