Cyclohexylamine → 2-chloro-N-cyclohexyl-5,6-dimethylpyrimidin-4-amine

HRID 63095

Reaction equation

HRID 63095 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([CH3:9])=[C:4]([CH3:10])[N:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH:17]1([NH2:23])[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1>CN(C)C=O>[Cl:1][C:2]1[N:7]=[C:6]([NH:23][CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[C:5]([CH3:9])=[C:4]([CH3:10])[N:3]=1

Participants

5

Reactant 3

HCID 7965CyclohexylamineHCID 10796Cesium carbonateHCID 2415532,4-Dichloro-5,6-dimethylpyrimidine

Product 1

HCID 824606262-chloro-N-cyclohexyl-5,6-dimethylpyrimidin-4-amineYield 40.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 2,4-dichloro-5,6-dimethylpyrimidine (9.3 g, 0.05 mol, Step C) in dimethylformamide (100 mL) was added cesium carbonate (37.6 g, 0.12 mol). Cyclohexylamine (5.7 g, 0.058 mol) was then added, keeping the temperature of the reaction mixture at 70° C. After 48 hours, the reaction mixture was concentrated, and the residue was quenched with water (200 mL). The resulting mixture was extracted with dichloromethane (3×120 mL). The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, and concentrated. The solvent was removed by distillation, and the crude product was purified by column chromatography on silica gel eluting with ethyl acetate/methanol (10:1-10:2) to yield 4.9 g (38.9%) of the titled compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.05-1.14 (m, 1H), 1.28-1.33 (m, 4H), 1.61 (d, J=12.36 Hz, 1H), 1.72 (s, 2H), 1.80 (s, 2H), 1.93 (s, 3H), 2.19 (s, 3H), 3.85 (d, J=7.52 Hz, 1H), 6.66 (d, J=7.79 Hz, 1H); MS (ESI) m/z 240.3 (M+1)+.

Workup

  1. customat 70° C
  2. concentrationthe reaction mixture was concentrated
  3. customthe residue was quenched with water (200 mL)
  4. extractionThe resulting mixture was extracted with dichloromethane (3×120 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe solvent was removed by distillation
  10. customthe crude product was purified by column chromatography on silica gel eluting with ethyl acetate/methanol (10:1-10:2)

Sources & evidence

ORD record
ord-c32e305dc41f4a9c81047dfc1db2c379
Source dataset
uspto-grants-2016_09
Patent number
US09447051B2

Linked notes

Loading…