Cesium carbonate → 4-(5-(Difluoromethoxy)-2-fluoropyridin-3-YL)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amine

HRID 1621778Notes

Reaction equation

HRID 1621778 reaction equation
[CH3:1][O:2][C:3]1[CH:34]=[CH:33][C:6]([CH2:7][N:8]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[C:9]2[N:14]=[C:13]([CH3:15])[N:12]=[C:11]([C:16]3[CH:17]=[C:18]([OH:23])[CH:19]=[N:20][C:21]=3[F:22])[N:10]=2)=[CH:5][CH:4]=1.Cl[C:36]([F:41])([F:40])C([O-])=O.[Na+].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[F:40][CH:36]([F:41])[O:23][C:18]1[CH:17]=[C:16]([C:11]2[N:12]=[C:13]([CH3:15])[N:14]=[C:9]([N:8]([CH2:7][C:6]3[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:34][CH:33]=3)[CH2:24][C:25]3[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=3)[N:10]=2)[C:21]([F:22])=[N:20][CH:19]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 2734985Sodium chlorodifluoroacetateHCID 666121165-(4-(Bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-YL)-6-fluoropyridin-3-OL

Product 1

HCID 666114724-(5-(Difluoromethoxy)-2-fluoropyridin-3-YL)-N,N-bis(4-methoxybenzyl)-6-methyl-1,3,5-triazin-2-amineYield 54.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 5-(4-(bis(4-methoxybenzyl)amino)-6-methyl-1,3,5-triazin-2-yl)-6-fluoropyridin-3-ol (0.050 g, 0.108 mmol) in DMF (3 mL) was treated with sodium 2-chloro-2,2-difluoroacetate (Aldrich) (0.033 g, 0.217 mmol) and cesium carbonate (Aldrich) (0.053 g, 0.163 mmol). The reaction mixture was heated at 100° C. under N2 for 2 h. The reaction mixture was cooled to rt and partitioned between EtOAc and water. The organic layer was washed with sat. NaHCO3, water, brine, dried over MgSO4 and concentrated. The crude product was purified by column chromatography (12 g, 10% to 20% EtOAc in hexanes) to give the product as a white solid (0.030 g). m/z (ESI, +ve ion) 512.0 (M+H)+. 1H NMR (300 MHz, CDCl3) δ 8.39 (d, J=7.45 Hz, 1H); 8.18 (br. s., 1H); 7.23 (d, J=7.89 Hz, 4H); 6.87 (t, J=7.60Hz, 4H); 6.23-6.83 (m, 1H); 4.82 (d, J=8.04 Hz, 4H); 3.81 (d, J=4.82 Hz, 6H); 2.55 (s, 3H).

Workup

  1. temperatureThe reaction mixture was cooled to rt
  2. custompartitioned between EtOAc and water
  3. washThe organic layer was washed with sat. NaHCO3, water, brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customThe crude product was purified by column chromatography (12 g, 10% to 20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-9f4face2147047cb844325fce37d8d39
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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