p-Toluenesulfonic acid → HCID 135939122, compound

HRID 591656Notes

Reaction equation

HRID 591656 reaction equation
[CH:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH:12]([N:15]([CH:19]([CH3:21])[CH3:20])[C:16](=[O:18])[CH3:17])[CH2:11][CH2:10]2)=[CH:5][CH:4]=1)=O.[NH2:22][C:23]1[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=[C:28]([O:34][CH3:35])[C:24]=1[C:25]([NH2:27])=[O:26].OS([O-])=O.[Na+].CC1C=CC(S(O)(=O)=O)=CC=1>CC(N(C)C)=O.O>[CH3:35][O:34][C:28]1[CH:29]=[C:30]([O:32][CH3:33])[CH:31]=[C:23]2[C:24]=1[C:25](=[O:26])[NH:27][C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]3[CH2:14][CH2:13][CH:12]([N:15]([CH:19]([CH3:21])[CH3:20])[C:16](=[O:18])[CH3:17])[CH2:11][CH2:10]3)=[CH:5][CH:4]=1)=[N:22]2

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium BisulfiteHCID 86662023N-[1-(4-Formylphenyl)-4-piperidinyl]-N-(1-methylethyl)acetamide

Product 1

HCID 135939122HCID 135939122, compoundYield 20.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
155 °C

Procedure

To a solution of N-(1-(4-formylphenyl)piperidin-4-yl)-N-isopropylacetamide (0.300 g, 1.04 mmol) in DMA (10 mL) was added 2-amino-4,6-dimethoxybenzamide (0.204 g, 1.04 mmol), NaHSO3 (0.129 g, 1.24 mmol) and p-TsOH (0.019 g, 0.10 mmol). The resulting solution was heated to 155° C. overnight and then cooled to room temperature. The solution was diluted with water, extracted with CH2Cl2, washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The material was purified by flash chromatography on silica gel eluting, with 30% to 100% of 92:7:1 CHCl3/MeOH/concentrated NH4OH in CH2Cl2, to afford the title compound (0.100 g, 20%). 1H NMR (300 MHz, DMSO-d6): mixture of rotamers δ 11.66 (s, 1H), 8.07 (d, J=8.3 Hz, 2H), 6.89-7.15 (m, 2H), 6.67 (s, 1H), 6.46 (s, 1H), 3.90-4.11 (m, 3H), 3.88 (s, 3H), 3.83 (s, 3H), 2.80-3.02 (m, 2H), 2.39-2.66 (m, 1H), 1.92-2.06 (m, 3H), 1.63-1.82 (m, 2H), 1.32-1.47 (m, 1H), 1.21-1.32 (m, 3H), 1.08-1.21 (m, 4H). ESI MS m/z 463 [M−H]−.

Workup

  1. temperaturecooled to room temperature
  2. extractionextracted with CH2Cl2
  3. washwashed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe material was purified by flash chromatography on silica gel eluting, with 30% to 100% of 92:7:1 CHCl3/MeOH/concentrated NH4OH in CH2Cl2

Sources & evidence

ORD record
ord-d488a2be768146a7a2ad178a35481e57
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

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