Potassium Acetate → 4-(2-fluoro-5-(1-(4-(methylthio)phenyl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

HRID 1621587Notes

Reaction equation

HRID 1621587 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=2)[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[N:3]=1.[F:28][C:29]1[C:34](B(O)O)=[CH:33][C:32]([CH:38]([C:40]2[CH:45]=[CH:44][C:43]([S:46][CH3:47])=[CH:42][CH:41]=2)[CH3:39])=[CH:31][N:30]=1.C([O-])(=O)C.[K+]>O1CCOCC1>[F:28][C:29]1[C:34]([C:2]2[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([N:9]([CH2:19][C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[CH2:10][C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)[N:3]=2)=[CH:33][C:32]([CH:38]([C:40]2[CH:41]=[CH:42][C:43]([S:46][CH3:47])=[CH:44][CH:45]=2)[CH3:39])=[CH:31][N:30]=1

Participants

5

Reactant 3

HCID 517044Potassium AcetateHCID 595482094-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineHCID 666000612-Fluoro-5-(1-(4-(methylthio)phenyl)ethyl)pyridin-3-ylboronic acid

Product 1

HCID 666112674-(2-fluoro-5-(1-(4-(methylthio)phenyl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineYield 82.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

4-Chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (1.4126 g, 3.6704 mmol), 2-fluoro-5-(1-(4-(methylthio)phenyl)ethyl)pyridin-3-ylboronic acid (1.2342 g, 4.2390 mmol), Am-Phos (140.4 mg, 0.1983 mmol), and potassium acetate (1.531 g, 15.60 mmol) were suspended in 1,4-dioxane (20 mL) and water (4 mL), and nitrogen was bubbled through the suspension for 15 s. Then, the flask was fitted with a reflux condenser and placed in a preheated oil bath (100° C.), and stirred under nitrogen overnight. Then, the reaction was cooled to room temperature, diluted with water (40 mL), and extracted with EtOAc. The organic extracts were combined, dried over sodium sulfate, filtered through a Celite® (diatomaceous earth) pad, concentrated, and purified on a silica gel filter (600 mL fritted filter with about 3 inches of silica gel; DCM to 100:1 DCM/MeOH to 75:1 DCM/MeOH). The fractions with product were collected, concentrated, and dried under high vacuum, first at room temperature, and then in a water bath (about 50° C.) to give 4-(2-fluoro-5-(1-(4-(methylthio)phenyl)ethyl)pyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (1.797 g). 1H NMR (CDCl3, 400 MHz) δ 8.34 (dd, J=8.90 Hz, 2.45 Hz, 1H), 8.15 (d, J=1.96 Hz, 1H), 7.24-7.17 (m, 6H), 7.16-7.11 (m, 2H), 6.86 (dd, J=10.17 Hz, 8.61 Hz, 4H), 4.82 (s, 2H), 4.78 (s, 2H), 4.20 (q, J=7.30 Hz, 1H), 3.82 (s, 3H), 3.81 (s, 3H), 2.53 (s, 3H), 2.45 (s, 3H), 1.67 (d, J=7.24 Hz, 3H). m/z (ESI, pos. ion) 596 (M+H)+.

Workup

  1. customwater (4 mL), and nitrogen was bubbled through the suspension for 15 s
  2. customThen, the flask was fitted with a reflux condenser
  3. customplaced in a preheated oil bath
  4. temperatureThen, the reaction was cooled to room temperature
  5. additiondiluted with water (40 mL)
  6. extractionextracted with EtOAc
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered through a Celite® (diatomaceous earth) pad
  9. concentrationconcentrated
  10. custompurified on a silica gel
  11. filtrationfilter (600 mL fritted filter with about 3 inches of silica gel; DCM to 100:1 DCM/MeOH to 75:1 DCM/MeOH)
  12. customThe fractions with product were collected
  13. concentrationconcentrated
  14. customdried under high vacuum, first at room temperature

Sources & evidence

ORD record
ord-0963e7ee3c0c40fd9caf995a758d3bfc
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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