2-Methyl-4-methoxyaniline → HCID 11454340, compound

HRID 2216305Notes

Reaction equation

HRID 2216305 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([S:15]([C:18]2[C:19](Cl)=[N:20][C:21]([CH3:24])=[N:22][CH:23]=2)(=[O:17])=[O:16])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:26][C:27]1[CH:33]=[C:32]([O:34][CH3:35])[CH:31]=[CH:30][C:28]=1[NH2:29]>C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([S:15]([C:18]2[C:19]([NH:29][C:28]3[CH:30]=[CH:31][C:32]([O:34][CH3:35])=[CH:33][C:27]=3[CH3:26])=[N:20][C:21]([CH3:24])=[N:22][CH:23]=2)(=[O:17])=[O:16])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 76102-Methyl-4-methoxyanilineHCID 21941677HCID 21941677, compound

Product 1

HCID 11454340HCID 11454340, compoundYield 95%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 1140TolueneSolvent

Procedure

To a solution of 5-(4-benzyloxy-benzenesulfonyl)-4-chloro-2-methyl-pyrimidine (38 mg, 0.106 mmol) and 2-methyl-4-methoxy aniline (31 mg, 0.23 mmol) in toluene (1 mL) was added p-toluenesulfonic acid monohydrate (1.6 mg, 0.0081 mmol). The resulting mixture was heated at reflux under N2 for 1 h and then cooled to room temperature. The mixture was quenched by addition of water, and extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified using preparative TLC on silica (1:1 hexanes/EtOAc) to provide the desired product (46 mg, 95%) as a pale yellow solid: mp 110–114° C.; 1H NMR (500 MHz, CDCl3) δ 8.71 (s, 1H), 8.61 (s, 1H), 7.86 (d, J=9.1 Hz, 2H), 7.49 (d, J=8.6 Hz, 1H), 7.38–7.33 (m, 4H), 7.07–7.04 (m, 2H), 6.79–6.75 (m, 2H), 5.12 (s, 2H), 3.81 (s, 3H), 2.46 (s, 3H), 2.17 (s, 3H); ESI MS m/z 476 [(M+H)+, calcd for C26H26N3O4S, 476.2].

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux under N2 for 1 h
  3. customThe mixture was quenched by addition of water
  4. extractionextracted with EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified

Sources & evidence

ORD record
ord-73d9d8a0bb1749579733d28d91299337
Source dataset
uspto-grants-2006_09
Patent number
US07112585B2

Reaction notes

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