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

HRID 1621910Notes

Reaction equation

HRID 1621910 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](B(O)O)[C:5]([F:8])=[N:6][CH:7]=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+]>C(O)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>[Cl:1][C:2]1[CH:3]=[C:4]([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)[C:5]([F:8])=[N:6][CH:7]=1

Participants

7

Reactant 3

HCID 517044Potassium AcetateHCID 249017795-Chloro-2-fluoropyridine-3-boronic AcidHCID 595482094-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

Product 1

HCID 666005044-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineYield 55.4%

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-chloro-2-fluoropyridin-3-ylboronic acid (Combi Blocks, 2.507 g, 14.30 mmol), 4-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (Example 51; 5.24 g, 13.62 mmol), bis-(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (Aldrich; 0.482 g, 0.681 mmol) and potassium acetate (4.10 g, 41.8 mmol) in ethanol (100 mL) and water (10 mL) was degassed and stirred under N2 at 100° C. for 16 h. The reaction mixture was cooled, concentrated, and the residue was partitioned between water (50 mL) and EtOAc (50 mL). The aqueous phase was extracted with EtOAc (2×20 mL) and the combined organic layers were washed with saturated aqueous sodium chloride (100 mL). The organic phase was dried over sodium sulfate, filtered and concentrated. Chromatographic purification of the residue (silica gel, 15% to 50% EtOAc/hexanes) provided 4-(5-chloro-2-fluoropyridin-3-yl)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (3.62 g, 7.54 mmol, 55.4% yield). m/z (ESI, +ve ion) 480 (M+H)+.

Workup

  1. customwas degassed
  2. temperatureThe reaction mixture was cooled
  3. concentrationconcentrated
  4. customthe residue was partitioned between water (50 mL) and EtOAc (50 mL)
  5. extractionThe aqueous phase was extracted with EtOAc (2×20 mL)
  6. washthe combined organic layers were washed with saturated aqueous sodium chloride (100 mL)
  7. dry with materialThe organic phase was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customChromatographic purification of the residue (silica gel, 15% to 50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-fca3b3fa40374a3e850acca66578f41b
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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