Aniline → 4,6-dichloro-N-phenyl-1,3,5-triazin-2-amine

HRID 2245227Notes

Reaction equation

HRID 2245227 reaction equation
[N:1]1[C:8]([Cl:9])=[N:7][C:5](Cl)=[N:4][C:2]=1[Cl:3].[NH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(=O)(O)[O-].[Na+]>CC(C)=O>[Cl:9][C:8]1[N:1]=[C:2]([Cl:3])[N:4]=[C:5]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:7]=1

Participants

5

Reactant 3

HCID 6115AnilineHCID 7954Cyanuric chlorideHCID 516892Sodium Bicarbonate

Product 1

HCID 167664,6-dichloro-N-phenyl-1,3,5-triazin-2-amineYield 94.2%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent2×

Procedure

To a suspension of cyanuric chloride (20 g, 108 mmol) in acetone (120 mL) and ice (50 mL) at 0° C. was added dropwise a solution of aniline (10 g, 107 mmol) in acetone (45 mL). At the end of the addition, the pH of the solution was adjusted from 1 to 7 with 5% aqueous sodium bicarbonate (150 mL). The precipitate was filtered, washed several times with water and dried in vacuo. This gave 2,4-dichloro-6-phenylamino-1,3,5-triazine as an off-white solid (24.3 g, 93% yield). The product was used in the next step without further purification. To a solution of the dichlorotriazine (6.2 g, 25.7 mmol) in THF (300 mL) at room temperature was added a solution of 2-(4-hydroxyphenyl)ethylamine (3.6 g, 25.9 mmol) in acetone (100 mL) and water (100 mL), followed by 5% aqueous sodium bicarbonate (50 mL). After 20 h reaction at room temperature, the solution was diluted with water (50 mL) and ethyl acetate (50 mL). The aqueous layer was extracted with ethyl acetate (2×50 mL). The organic layers were washed with brine (150 mL), dried over anhydrous sodium sulphate, filtered and evaporated to dryness. This gave 2-chloro-4-(2-[4-hydroxyphenyl]ethylamino)-6-phenylamino-1,3,5-triazine as an off-white solid (8.5 g, 97% yield). The product was used for the next step without further purification. This triazine derivative (384 mg, 1.1 mmol) was dissolved in THF (11 mL) at room temperature. To this solution was added ethylenediamine (68 μL, 1.0 mmol) followed by diisopropylethylamine (355 μL, 2.0 mmol). After 20 h at 50° C., the solution was diluted with methanol (10 mL) and concentrated under reduced pressure. The crude residue was purified on a Biotage™ 25S column (silica, hexane/AcOEt 9:1 to 0:1) to yield compound 1 as a white solid. Yield of product: 267 mg (78%); 1H NMR (300 MHz, CD3OD) δ 7.63 (m, 4H), 7.21 (t, 4H, J=7.6 Hz), 6.98 (m, 6H), 6.68 (d, 4H, J=7.9 Hz), 3.48 (m, 8H), 2.84 (m, 4H); LRMS (FAB+): m/z 672.0 (MH+); HRMS: Calc. for MH+ C36H39N12O2, 671.33191; found 671.33060; HPLC (method 1): 8.0 min.

Workup

  1. additionAt the end of the addition
  2. filtrationThe precipitate was filtered
  3. washwashed several times with water
  4. customdried in vacuo

Sources & evidence

ORD record
ord-6131292970ac4275ba0834eb9933b81c
Source dataset
uspto-grants-2010_03
Patent number
US07683061B2

Reaction notes

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