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

HRID 1774805Notes

Reaction equation

HRID 1774805 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.CCN=C=NCCCN(C)C.OC1C2N=NNC=2C=CC=1.CCN(C(C)C)C(C)C.[CH3:51][O:52][C:53]1[CH:57]=[C:56]([C:58](O)=[O:59])[O:55][N:54]=1.C([O-])(O)=O.[Na+]>C(Cl)Cl.CCOC(C)=O>[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:58]([C:56]4[O:55][N:54]=[C:53]([O:52][CH3:51])[CH:57]=4)=[O:59])[CH:8]=[N:7][CH:6]=3)=[CH:18][CH:17]=2)[CH2:12][CH2:13][C:14]1=[O:20]

Participants

9

Reactant 6

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 3277173-Methoxy-1,2-oxazole-5-carboxylic acidHCID 516892Sodium BicarbonateHCID 715334526-(5-Aminomethyl-pyridin-3-yl)-1-methyl-3,4-dihydro-1H-quinolin-2-oneHCID 178418300HCID 178418300, compound

Product 1

HCID 715334563-Methoxy-isoxazole-5-carboxylic acid [5-(1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-ylmethyl]-amideYield 41%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 6-(5-aminomethyl-pyridin-3-yl)-1-methyl-3,4-dihydro-1H-quinolin-2-one (example 36, 0.05 g, 0.187 mmol) in dry DCM (1 mL) were added EDCI (0.039 g, 0.206 mmol), hydroxybenzotriazole (0.032 g, 0.206 mmol), Hünig's base (0.060 g, 0.468 mmol) and 3-methoxy-isoxazole-5-carboxylic acid (0.040 g, 0.281 mmol) and the resulting solution was stirred at room temperature over night. The reaction mixture was diluted with EtOAc, poured into sat. NaHCO3 solution (5 mL) and extracted with EtOAc (2×10 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 10% MeOH(1% NH4OH)-DCM gradient to give the title compound (0.03 g, 41%) as a white solid. MS: 393.1 (M+H+).

Workup

  1. extractionextracted with EtOAc (2×10 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 10% MeOH(1% NH4OH)-DCM gradient

Sources & evidence

ORD record
ord-6a707f30f0dc4966a92b6a1019d537f9
Source dataset
uspto-grants-2016_02
Patent number
US09260408B2

Reaction notes

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