p-Toluenesulfonic acid monohydrate → HCID 135939049, compound

HRID 591708Notes

Reaction equation

HRID 591708 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]([O:13][CH3:14])[C:3]=1[C:4]([NH2:6])=[O:5].[CH3:15][N:16]([CH3:34])[C:17]([N:19]1[CH2:24][CH2:23][CH:22]([O:25][C:26]2[CH:31]=[CH:30][C:29]([CH:32]=O)=[CH:28][CH:27]=2)[CH2:21][CH2:20]1)=[O:18].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.S([O-])(O)=O.[Na+]>O.CC(N(C)C)=O>[CH3:14][O:13][C:7]1[CH:8]=[C:9]([O:11][CH3:12])[CH:10]=[C:2]2[C:3]=1[C:4](=[O:5])[NH:6][C:32]([C:29]1[CH:28]=[CH:27][C:26]([O:25][CH:22]3[CH2:23][CH2:24][N:19]([C:17]([N:16]([CH3:15])[CH3:34])=[O:18])[CH2:20][CH2:21]3)=[CH:31][CH:30]=1)=[N:1]2

Participants

7

Reactant 4

HCID 521998p-Toluenesulfonic acid monohydrateHCID 203490162-Amino-4,6-dimethoxybenzamideHCID 23665763Sodium BisulfiteHCID 86662033HCID 86662033, compound

Product 1

HCID 135939049HCID 135939049, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
115 °C

Procedure

To a 100 mL round-bottom flask was added 2-amino-4,6-dimethoxybenzamide (196 mg, 1.00 mmol), 4-(4-formylphenoxy)-piperidine-1-carboxylic acid dimethylamide (300 mg, 1.10 mmol), p-toluenesulfonic acid monohydrate (21 mg, 0.10 mmol), sodium hydrogensulfite (216 mg, 1.20 mmol) and dimethylacetamide (5 mL). The mixture was stirred at 115° C. under N2 for 17 hours and cooled to room temperature. Water (20 mL) was added and stirred for 0.5 hours. The precipitate was filtered off, washed with water, and air dried. The crude product was purified by column chromatography (SiO2, neat ethyl acetate, then ethyl acetate/methanol=19:1, then CH2Cl2/methanol=19:1) to afford the title compound as a white solid. Yield: 110 mg (24%). MP 248-249° C. 1H NMR (400 MHz, DMSO-d6): δ 11.91 (s, 1H), 8.15 (d, J=8.8 Hz, 2H), 7.10 (d, J=8.8 Hz, 2H), 6.72 (s, 1H), 6.51 (s, 1H), 4.71-4.69 (m, 1H), 3.89 (s, 3H), 3.85 (s, 3H), 3.44-3.39 (m, 2H), 3.06-2.99 (m, 2H), 2.74 (s, 6H), 2.00-1.96 (m, 2H), 1.64-1.59 (m, 2H).

Workup

  1. temperaturecooled to room temperature
  2. stirringstirred for 0.5 hours
  3. filtrationThe precipitate was filtered off
  4. washwashed with water, and air
  5. customdried
  6. customThe crude product was purified by column chromatography (SiO2, neat ethyl acetate

Sources & evidence

ORD record
ord-b98ef7d21b6f4339a9bf1487c5863067
Source dataset
uspto-grants-2016_01
Patent number
US09238640B2

Reaction notes

Loading…