3-Amino-4-methylbenzamide → HCID 86729625, compound

HRID 2284899Notes

Reaction equation

HRID 2284899 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[NH:15][C:16](=[O:19])[CH:17]=[CH2:18])[C:5]([Cl:20])=[CH:4][N:3]=1.[NH2:21][C:22]1[CH:23]=[C:24]([CH:28]=[CH:29][C:30]=1[CH3:31])[C:25]([NH2:27])=[O:26].CO.C(Cl)Cl>CC1C=CC(S(O)(=O)=O)=CC=1.O1CCOCC1>[C:16]([NH:15][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=1[NH:8][C:6]1[C:5]([Cl:20])=[CH:4][N:3]=[C:2]([NH:21][C:22]2[CH:23]=[C:24]([CH:28]=[CH:29][C:30]=2[CH3:31])[C:25]([NH2:27])=[O:26])[N:7]=1)(=[O:19])[CH:17]=[CH2:18]

Participants

6

Reactant 3

HCID 880433-Amino-4-methylbenzamideHCID 21226129Dichloromethane methanolHCID 86729624HCID 86729624, compound

Product 1

HCID 86729625HCID 86729625, compoundYield 31.4%

Reagents, catalysts & solvents 2

HCID 6101p-Toluenesulfonic acidSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of Intermediate 1 (1 g, 3.24 mmol) and 3-amino-4-methylbenzamide (584 mg, 3.89 mmol) in 0.08 M PTSA in 1,4-dioxane was heated to 90° C. for 48 h. TLC showed the completion of starting material (TLC system: 10% methanol/DCM, (Rf): 0.5). The reaction mixture was concentrated, quenched with water, and the precipitated solid was filtered and dried under vacuum. The crude solid was purified by silica gel column chromatography by using 3% methanol/DCM as eluents. The purified solid was further triturated with ether, filtered and dried under vacuum to get the title compound as an off-white solid (430 mg, 31%). 1HNMR (400 MHz, D6-DMSO) δ 2.17 (s, 3H), 5.78-5.81 (dd, 1H J=1.8, 10.1 Hz), 6.28-6.32 (dd, 1H J=1.8, 17 Hz), 6.43-6.50 (dd, 1H J=10.1, 17 Hz), 7.04-7.08 (m, 2H), 7.18-7.24 (m, 2H), 7.27 (br s, 1H), 7.52-7.54 (dd, 1H J=1.7, 7.9 Hz), 7.73-7.76 (m, 1H), 7.87 (br s, 1H), 7.92 (d, 1H), 8.03 (s, 1H), 8.39 (s, 1H), 8.62 (s, 1H), 10.19 (s, 1H). MS m/z: 423.5 (ES+, M+H).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customquenched with water
  3. filtrationthe precipitated solid was filtered
  4. customdried under vacuum
  5. customThe crude solid was purified by silica gel column chromatography
  6. customThe purified solid was further triturated with ether
  7. filtrationfiltered
  8. customdried under vacuum

Sources & evidence

ORD record
ord-f9a5ce3ea0824588b53c2cbb0e528efd
Source dataset
uspto-grants-2015_09
Patent number
US09145387B2

Reaction notes

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