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

HRID 1621661Notes

Reaction equation

HRID 1621661 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+].B(O)O.[NH4+].[Cl-]>O1CCOCC1.O>[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

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 61668Boronic AcidHCID 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 80.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 5-chloro-2-fluoropyridin-3-ylboronic acid (1220 mg, 6.96 mmol) (Asymchem Laboratories, Inc.), 4-chloro-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine (2300 mg, 5.98 mmol), and potassium acetate (1200 mg, 12.23 mmol) in dioxane (10 mL)-water (2.0 mL) was placed in a 100 mL flask under argon. A-Phos-PdCl2 (150 mg, 0.212 mmol) was added and the mixture was heated to 95° C. under nitrogen. After 2 h, more boronic acid (600 mg) was added and the mixture was heated for another hour. The mixture was cooled to rt. Saturated NH4Cl was added. The mixture was partitioned between water (5 mL) and EtOAc (30 mL). The organic layer was dried over Na2SO4 and concentrated. The residue was purified on silica gel using 10-50% EtOAc in hexane to give the desired product as a light yellow solid (2.3 g). LCMS (ES, pos.): calcd for C25H23ClFN5O2: 479.2. found: 480.1 (M+H)+. 1H NMR (400 MHz, CDCl3) δ 8.53 (dd, J=8.02, 2.74 Hz, 1H); 8.25 (d, J=1.37 Hz, 1H); 7.21 (d, J=8.41 Hz, 4H); 6.86 (t, J=8.22 Hz, 4H); 4.81 (d, J=7.24 Hz, 4H); 3.80 (2s, 6H); 2.54 (s, 3H).

Workup

  1. customwas placed in a 100 mL flask under argon
  2. temperaturethe mixture was heated for another hour
  3. temperatureThe mixture was cooled to rt
  4. customThe mixture was partitioned between water (5 mL) and EtOAc (30 mL)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated
  7. customThe residue was purified on silica gel using 10-50% EtOAc in hexane

Sources & evidence

ORD record
ord-05b3859c9a3e4939b9510bd2ecd07332
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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