Methanol → Methyl 2-(4-(diethoxymethyl)phenyl)-3-(4-(4-isobutyrylpiperazine-1-carbonyl)phenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate

HRID 1467550

Reaction equation

HRID 1467550 reaction equation
[C:1]([N:6]1[CH2:11][CH2:10][N:9]([C:12]([C:14]2[CH:21]=[CH:20]C(C=O)=CC=2)=[O:13])[CH2:8][CH2:7]1)(=[O:5])[CH:2]([CH3:4])[CH3:3].[CH2:22]([O:24][CH:25]([O:44][CH2:45][CH3:46])[C:26]1[CH:43]=[CH:42][C:29](/[CH:30]=[N:31]/[C:32]2[CH:40]=[CH:39][CH:38]=[C:37]3[C:33]=2[CH2:34][O:35][C:36]3=[O:41])=[CH:28][CH:27]=1)[CH3:23].[CH3:47][O-:48].[Na+].CO>C(OCC)(=O)CC>[CH2:22]([O:24][CH:25]([O:44][CH2:45][CH3:46])[C:26]1[CH:27]=[CH:28][C:29]([CH:30]2[CH:20]([C:21]3[CH:14]=[CH:12][C:14]([C:12]([N:9]4[CH2:8][CH2:7][N:6]([C:1](=[O:5])[CH:2]([CH3:3])[CH3:4])[CH2:11][CH2:10]4)=[O:13])=[CH:21][CH:20]=3)[C:47](=[O:48])[C:33]3[C:37]([C:36]([O:35][CH3:34])=[O:41])=[CH:38][CH:39]=[CH:40][C:32]=3[NH:31]2)=[CH:42][CH:43]=1)[CH3:23]

Participants

6

Reactant 4

HCID 887MethanolHCID 10942334Sodium MethoxideHCID 866390314-(4-Isobutyrylpiperazine-1-carbonyl)benzaldehydeHCID 178470922HCID 178470922, compound

Product 1

HCID 67261742Methyl 2-(4-(diethoxymethyl)phenyl)-3-(4-(4-isobutyrylpiperazine-1-carbonyl)phenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylateYield 25%

Reagents, catalysts & solvents 1

HCID 7749Ethyl PropionateSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 4-(4-isobutyrylpiperazine-1-carbonyl)benzaldehyde (950 mg, 3.3 mmol) and (E)-4-(4-(diethoxymethyl)benzylideneamino)isobenzofuran-1(3H)-one (1.018 g, 3 mmol) in ethyl propionate (40 mL) was cooled to 0° C. Then a solution of sodium methoxide in methanol [sodium (345 mg, 12 mmol) in methanol (8 mL)] was added dropwise. After the addition, the mixture was stirred at room temperature for 24 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 (100 mL×4). 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 2-(4-(diethoxymethyl)phenyl)-3-(4-(4-isobutyrylpiperazine-1-carbonyl)phenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate (491 mg, yield 25%).

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 (100 mL×4)
  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-209c528b78d944999490ebc666590c75
Source dataset
uspto-grants-2015_04
Patent number
US08999987B2

Linked notes

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