Methanol → Methyl 3-(3-(4-isobutyryl piperazine-1-carbonyl)phenyl)-4-oxo-2-(pyridin-4-yl)-1,2,3,4-tetrahydroquinoline-5-carboxylate

HRID 1467571Notes

Reaction equation

HRID 1467571 reaction equation
[C:1]([N:6]1[CH2:11][CH2:10][N:9]([C:12]([C:14]2[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=2)[CH:17]=O)=[O:13])[CH2:8][CH2:7]1)(=[O:5])[CH:2]([CH3:4])[CH3:3].[N:22]1[CH:27]=[CH:26][C:25](/[CH:28]=[N:29]/[C:30]2[CH:38]=[CH:37][CH:36]=C3C=2COC3=O)=[CH:24][CH:23]=1.[CH3:40][O-:41].[Na+].CO.[C:45]([O:49][CH2:50]C)(=[O:48])[CH2:46][CH3:47]>>[C:1]([N:6]1[CH2:11][CH2:10][N:9]([C:12]([C:14]2[CH:15]=[C:16]([CH:17]3[C:40](=[O:41])[C:47]4[C:46]([C:45]([O:49][CH3:50])=[O:48])=[CH:36][CH:37]=[CH:38][C:30]=4[NH:29][CH:28]3[C:25]3[CH:24]=[CH:23][N:22]=[CH:27][CH:26]=3)[CH:19]=[CH:20][CH:21]=2)=[O:13])[CH2:8][CH2:7]1)(=[O:5])[CH:2]([CH3:4])[CH3:3]

Participants

6

Reactant 5

HCID 887MethanolHCID 7749Ethyl PropionateHCID 10942334Sodium MethoxideHCID 866390283-(4-Isobutyrylpiperazine-1-carbonyl)benzaldehydeHCID 178519078HCID 178519078, compound

Product 1

HCID 67259841Methyl 3-(3-(4-isobutyryl piperazine-1-carbonyl)phenyl)-4-oxo-2-(pyridin-4-yl)-1,2,3,4-tetrahydroquinoline-5-carboxylateYield 26%

Conditions

Temperature
0 °C

Procedure

A mixture of 3-(4-isobutyrylpiperazine-1-carbonyl)benzaldehyde (288 mg, 1 mmol) and (E)-4-(pyridin-4-ylmethyleneamino)-isobenzofuran-1(3H)-one (238 mg, 1 mmol) in ethyl propionate (7.5 mL) was cooled to 0° C. Then a solution of sodium methoxide in methanol [sodium (92 mg, 4 mmol) in methanol (7.5 mL)] was added drop-wise. After the addition, the mixture was stirred at 25° C. for 18 hr. The mixture was quenched with water (10 mL) and solvent was removed in vacuum. The residue was dissolved in water, and then extracted with ethyl acetate (50 mL×3). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate, and concentrated to give crude product. The crude product was purified by chromatography (silica gel, petroleum ether/ethyl acetate=10:1 to 1:10) to give methyl 3-(3-(4-isobutyryl piperazine-1-carbonyl)phenyl)-4-oxo-2-(pyridin-4-yl)-1,2,3,4-tetrahydroquinoline-5-carboxylate (140 mg, yield 26%). LC-MS (ESI) m/z: 541 (M+1)+.

Workup

  1. additionAfter the addition
  2. customThe mixture was quenched with water (10 mL) and solvent
  3. customwas removed in vacuum
  4. dissolutionThe residue was dissolved in water
  5. extractionextracted with ethyl acetate (50 mL×3)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated
  9. customto give crude product
  10. customThe crude product was purified by chromatography (silica gel, petroleum ether/ethyl acetate=10:1 to 1:10)

Sources & evidence

ORD record
ord-d9fad32aa9094866805bf49d75791186
Source dataset
uspto-grants-2015_04
Patent number
US08999987B2

Reaction notes

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