Ethanol → 4-(2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

HRID 1811836Notes

Reaction equation

HRID 1811836 reaction equation
C([O-])(=O)C.[K+].[F:6][C:7]1[C:12](B(O)O)=[CH:11][CH:10]=[CH:9][N:8]=1.Cl[C:17]1[N:22]=[C:21]([CH3:23])[N:20]=[C:19]([N:24]([CH2:34][C:35]2[CH:40]=[CH:39][C:38]([O:41][CH3:42])=[CH:37][CH:36]=2)[CH2:25][C:26]2[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=2)[N:18]=1.CCO>C(Cl)Cl.O>[F:6][C:7]1[C:12]([C:17]2[N:22]=[C:21]([CH3:23])[N:20]=[C:19]([N:24]([CH2:25][C:26]3[CH:27]=[CH:28][C:29]([O:32][CH3:33])=[CH:30][CH:31]=3)[CH2:34][C:35]3[CH:36]=[CH:37][C:38]([O:41][CH3:42])=[CH:39][CH:40]=3)[N:18]=2)=[CH:11][CH:10]=[CH:9][N:8]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 517044Potassium AcetateHCID 27832702-Fluoropyridine-3-boronic acidHCID 595482094-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 595482404-(2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineYield 11.52%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
80 °C

Procedure

A mixture of potassium acetate (0.38 g, 3.87 mmol), 2-fluoro-3-pyridineboronic acid (0.28 g, 1.987 mmol) and 4-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (0.60 g, 1.559 mmol) in DCM (8.0 mL) was evaporated under nitrogen to dryness. THF (5.0 mL) was added followed by the addition of bis[4-(di-tert-butylphosphino)-N,N-dimethylaniline]palladium dichloride (Am-phos) (0.060 g, 0.085 mmol). The mixture was heated in an oil bath at 80° C. After 1 h, EtOH (5 mL) was added and heating was continued overnight. The mixture was cooled to rt. Water (10 mL) and DCM (10 mL) were added. The organic layer was separated. The aqueous layer was extracted with CH2CL2 and the organic layer was dried over MgSO4. The solution was filtered and concentrated in vacuo. The orange oil was adsorbed onto a plug of silica gel and purified by chromatography eluting with 2:1 hexane-acetone to provide 4-(2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (80 mg, 0.180 mmol, 11.52% yield) as a white foam. LCMS (ES, pos.): calcd for C25H24FN5O2: 445.2; found: 446.2 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.49-8.62 (m, 1H); 7.86-7.99 (m, 1H); 7.27-7.36 (m, 1H); 7.23 (dd, J=8.31, 4.99 Hz, 4H); 6.87 (t, J=8.51 Hz, 4H); 3.81 (s, 3H) 4.81 (s, 4H); 3.80 (s, 3H); 2.55 (s, 3H).

Workup

  1. customwas evaporated under nitrogen to dryness
  2. additionTHF (5.0 mL) was added
  3. temperatureheating
  4. waitwas continued overnight
  5. temperatureThe mixture was cooled to rt
  6. customThe organic layer was separated
  7. extractionThe aqueous layer was extracted with CH2CL2
  8. dry with materialthe organic layer was dried over MgSO4
  9. filtrationThe solution was filtered
  10. concentrationconcentrated in vacuo
  11. custompurified by chromatography
  12. washeluting with 2:1 hexane-acetone

Sources & evidence

ORD record
ord-2104166a12af4e82a35ee157853f061d
Source dataset
uspto-grants-2013_01
Patent number
US08362241B2

Reaction notes

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