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

HRID 1621695Notes

Reaction equation

HRID 1621695 reaction equation
[F:1][C:2]1[C:7](B(O)O)=[CH:6][CH:5]=[C:4]([CH3:11])[N:3]=1.Cl[C:13]1[N:18]=[C:17]([CH3:19])[N:16]=[C:15]([N:20]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)[N:14]=1.C([O-])(=O)C.[K+]>O1CCOCC1.O.CCOC(C)=O.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl>[F:1][C:2]1[C:7]([C:13]2[N:18]=[C:17]([CH3:19])[N:16]=[C:15]([N:20]([CH2:21][C:22]3[CH:23]=[CH:24][C:25]([O:28][CH3:29])=[CH:26][CH:27]=3)[CH2:30][C:31]3[CH:32]=[CH:33][C:34]([O:37][CH3:38])=[CH:35][CH:36]=3)[N:14]=2)=[CH:6][CH:5]=[C:4]([CH3:11])[N:3]=1

Participants

8

Reactant 3

HCID 517044Potassium AcetateHCID 27631322-Fluoro-6-methylpyridine-3-boronic acidHCID 595482094-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 666001774-(2-fluoro-6-methylpyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineYield 81.1%

Reagents, catalysts & solvents 4

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 2-fluoro-6-picoline-3-boronic acid (Asynchem Laboratories, Inc.) (430 mg, 2.77 mmol), 4-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (970 mg, 2.52), potassium acetate (742 mg, 7.56 mmol) and bis(di-tert-butyl (4-dimethylaminophenyl)phosphine)dichloropalladium(II) (Aldrich) (89 mg, 0.126 mmol) in 8 mL of dioxane and 2 mL of water was heated in a microwave at 110° C. for 30 min. It was diluted with EtOAc and washed with 1 N NaOH. The organic layer was dried and concentrated. The residue was purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 25-50% EtOAc in hexanes to give 4-(2-fluoro-6-methylpyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (939 mg, 2.043 mmol, 81% yield) as a yellow amorphous solid. 1H NMR (400 MHz, d6-DMSO) δ 8.53 (1H, m); 7.37 (1H, d, J=6.5 Hz); 7.24 (4H, dd, J=8.6, 1.2 Hz); 6.89 (4H, t, J=Hz); 4.75 (4H, d, J=6.5 Hz); 3.74 (3H, s); 3.72 (s, 3H); 2.51 (3H, s); 2.45 (3H, s). m/z (ESI, +ve ion) 460 (M+H)+.

Workup

  1. washwashed with 1 N NaOH
  2. customThe organic layer was dried
  3. concentrationconcentrated
  4. customThe residue was purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g)
  5. washeluting with a gradient of 25-50% EtOAc in hexanes

Sources & evidence

ORD record
ord-33ed5f172fc0491eaf87f58be72e750a
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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