p-Toluenesulfonic acid → HCID 136348015, compound

HRID 591787Notes

Reaction equation

HRID 591787 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([CH3:18])[C:9]=1[O:10][CH2:11][C@@H:12]1[CH2:16][CH2:15][C:14](=[O:17])[NH:13]1)[CH:5]=O.[NH2:19][C:20]1[CH:28]=[C:27]([O:29][CH3:30])[CH:26]=[C:25]([O:31][CH3:32])[C:21]=1[C:22]([NH2:24])=[O:23].OS([O-])=O.[Na+].CC1C=CC(S(O)(=O)=O)=CC=1>CC(N(C)C)=O.C(OCC)(=O)C>[CH3:1][C:2]1[CH:3]=[C:4]([C:5]2[NH:24][C:22](=[O:23])[C:21]3[C:20](=[CH:28][C:27]([O:29][CH3:30])=[CH:26][C:25]=3[O:31][CH3:32])[N:19]=2)[CH:7]=[C:8]([CH3:18])[C:9]=1[O:10][CH2:11][C@@H:12]1[CH2:16][CH2:15][C:14](=[O:17])[NH:13]1

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium BisulfiteHCID 86662034HCID 86662034, compound

Product 1

HCID 136348015HCID 136348015, compoundYield 31.5%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of (S)-3,5-dimethyl-4-((5-oxopyrrolidin-2-yl)methoxy)benzaldehyde (0.200 g, 0.81 mmol), 2-amino-4,6-dimethoxybenzamide (0.159 g, 0.81 mmol), NaHSO3 (0.093 g, 0.89 mmol), and p-TsOH (0.015 g, 0.08 mmol) in DMA (10 mL) was heated at 150° C. for 48 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (200 mL), washed with water (2×200 mL), dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by flash chromatography on silica gel, eluting with 1:1 CH2Cl2/92:7:1 CHCl3/MeOH/concentrated NH4OH to 100% 92:7:1 CHCl3/MeOH/concentrated NH4OH to 6:3:1 CHCl3/MeOH/concentrated NH4OH, to afford the title compound as an off-white solid (0.108 g, 31%). 1H NMR (300 MHz, DMSO-d6): δ 11.85 (s, 1H), 7.79-7.91 (m, 3H), 6.74 (d, J=2.2 Hz, 1H), 6.52 (d, J=2.2 Hz, 1H), 3.88-3.94 (m, 4H), 3.84 (s, 3H), 3.63-3.75 (m, 2H), 2.30 (s, 6H), 2.09-2.27 (m, 3H), 1.91-2.00 (m, 1H). APCI MS m/z 424 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with water (2×200 mL)
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography on silica gel
  7. washeluting with 1:1 CH2Cl2/92:7:1 CHCl3/MeOH/concentrated NH4OH to 100% 92:7:1 CHCl3/MeOH/concentrated NH4OH to 6:3:1 CHCl3/MeOH/concentrated NH4OH

Sources & evidence

ORD record
ord-606568f1457645548c490aa2b49f892c
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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