Acetoxyacetyl chloride → Acetic acid [5-(1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-ylcarbamoyl]-methyl ester

HRID 1774784Notes

Reaction equation

HRID 1774784 reaction equation
Cl.[NH2:2][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.[C:21]([O:24][CH2:25][C:26](Cl)=[O:27])(=[O:23])[CH3:22].C([O-])(O)=O.[Na+]>C(Cl)Cl>[CH3:19][N:15]1[C:16]2[C:11](=[CH:10][C:9]([C:5]3[CH:4]=[C:3]([NH:2][C:26]([CH2:25][O:24][C:21](=[O:23])[CH3:22])=[O:27])[CH:8]=[N:7][CH:6]=3)=[CH:18][CH:17]=2)[CH2:12][CH2:13][C:14]1=[O:20]

Participants

5

Reactant 3

HCID 26297Acetoxyacetyl chlorideHCID 516892Sodium BicarbonateHCID 866791056-(5-Amino-pyridin-3-yl)-1-methyl-3,4-dihydro-1H-quinolin-2-one hydrochloride

Product 1

HCID 71533146Acetic acid [5-(1-methyl-2-oxo-1,2,3,4-tetrahydro-quinolin-6-yl)-pyridin-3-ylcarbamoyl]-methyl esterYield 57.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 6-(5-amino-pyridin-3-yl)-1-methyl-3,4-dihydro-1H-quinolin-2-one hydrochloride (intermediate A-2, 0.045 g, 0.155 mmol) in DCM (1.5 mL) was added TEA (0.039 g, 0.388 mmol) followed by 2-chloro-2-oxoethyl acetate (0.017 g, 0.124 mmol) in DCM (1 mL) and the reaction mixture was stirred at room temperature for 2 h. The mixture was diluted with DCM, poured into aq. NaHCO3 (10 mL) and the aqueous layer was extracted with DCM (2×25 mL). Combined organics were washed with brine, 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 (0.025 g, 46%) as a light brown solid. MS: 354.2 (M+H+).

Workup

  1. extractionthe aqueous layer was extracted with DCM (2×25 mL)
  2. washCombined organics were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe residue was purified by silica gel flash chromatography
  7. washeluting with a 0 to 5% MeOH-DCM gradient

Sources & evidence

ORD record
ord-0324b29dbad34793a323365e3d759e11
Source dataset
uspto-grants-2016_02
Patent number
US09260408B2

Reaction notes

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