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

HRID 1467543Notes

Reaction equation

HRID 1467543 reaction equation
[CH:1]1([C:4]([N:6]2[CH2:11][CH2:10][N:9]([C:12]([C:14]3[CH:21]=[CH:20][C:17](C=O)=[CH:16][CH:15]=3)=[O:13])[CH2:8][CH2:7]2)=[O:5])[CH2:3][CH2:2]1.[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+].[CH3:50]O>C(OCC)(=O)CC>[CH:1]1([C:4]([N:6]2[CH2:11][CH2:10][N:9]([C:12]([C:14]3[CH:21]=[CH:20][C:17]([CH:50]4[C:47](=[O:48])[C:33]5[C:37]([C:36]([O:35][CH3:34])=[O:41])=[CH:38][CH:39]=[CH:40][C:32]=5[NH:31][CH:30]4[C:29]4[CH:28]=[CH:27][C:26]([CH:25]([O:44][CH2:45][CH3:46])[O:24][CH2:22][CH3:23])=[CH:43][CH:42]=4)=[CH:16][CH:15]=3)=[O:13])[CH2:8][CH2:7]2)=[O:5])[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 887MethanolHCID 10942334Sodium MethoxideHCID 672585054-(4-(diethoxymethyl)benzylideneamino)isobenzofuran-1(3H)-oneHCID 866390294-(4-(Cyclopropanecarbonyl)piperazine-1-carbonyl)benzaldehyde

Product 1

HCID 67258880Methyl 3-(4-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)phenyl)-2-(4-(diethoxymethyl)phenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylateYield 26%

Reagents, catalysts & solvents 1

HCID 7749Ethyl PropionateSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 4-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)benzaldehyde (859 mg, 3 mmol) and 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 (276 mg, 12 mmol) in methanol (8 mL)] was added dropwise. After the addition, the mixture was stirred at room temperature for 20 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 3-(4-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)phenyl)-2-(4-(diethoxymethyl)phenyl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate (500 mg, yield 26%). LC-MS (ESI) m/z: 640 (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 (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-e536b9c4dca848b491599edcd32630a2
Source dataset
uspto-grants-2015_04
Patent number
US08999987B2

Reaction notes

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