2,4,6-Trimethylaniline → HCID 11452287, compound

HRID 2216301Notes

Reaction equation

HRID 2216301 reaction equation
[CH3:1][C:2]1[CH:8]=[C:7]([CH3:9])[CH:6]=[C:5]([CH3:10])[C:3]=1[NH2:4].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Cl[C:22]1[C:27]([S:28]([C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)(=[O:30])=[O:29])=[CH:26][N:25]=[C:24]([CH3:39])[N:23]=1>C1COCC1>[CH3:38][O:37][C:34]1[CH:33]=[CH:32][C:31]([S:28]([C:27]2[C:26]([NH:4][C:3]3[C:5]([CH3:10])=[CH:6][C:7]([CH3:9])=[CH:8][C:2]=3[CH3:1])=[N:25][C:24]([CH3:39])=[N:23][CH:22]=2)(=[O:29])=[O:30])=[CH:36][CH:35]=1

Participants

5

Reactant 3

HCID 69132,4,6-TrimethylanilineHCID 2724254Sodium bis(trimethylsilyl)amideHCID 21941670HCID 21941670, compound

Product 1

HCID 11452287HCID 11452287, compoundYield 45.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 2,4,6-trimethylaniline (0.089 mL, 0.64 mmol) in THF (2 mL), NaHMDS (1.0 M in THF, 0.64 mL, 0.64 mmol) was added dropwise at 0° C. The mixture was stirred under N2 at 0° C. for 10 min, and then 4-chloro-5-(4-methoxy-benzenesulfonyl)-2-methyl-pyrimidine (158 mg, 0.53 mmol) in THF (3 mL) was added dropwise at 0° C. The reaction mixture was stirred at room temperature for 1 h, and then quenched with saturated ammonium chloride. The organic layer was separated and the aqueous layer was extracted with ethyl acetate (2×). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel (1:2 ethyl acetate/hexanes) to provide the target compound (95 mg, 45%) as a light yellow solid: mp 153–155° C.; 1H NMR (300 MHz, CDCl3) δ 8.74 (s 1H), 8.22 (br s, 1H), 7.88 (d, J=7.0 Hz, 2H), 6.98 (d, J=7.0 Hz, 1H), 6.91 (s, 2H), 3.86 (s, 3H), 2.38 (s, 3H), 2.30 (s, 3H), 2.01 (s, 6H); ESI MS m/z 398 [(M+H)+, calcd for C21H24N3O3S, 398.2].

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 1 h
  2. customquenched with saturated ammonium chloride
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with ethyl acetate (2×)
  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 by chromatography on silica gel (1:2 ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-955bd7e86fd44bfdb0062bd459a4a00b
Source dataset
uspto-grants-2006_09
Patent number
US07112585B2

Reaction notes

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