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

HRID 63095

反応式

HRID 63095 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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)+.

後処理

  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)

出典と根拠

ORDレコード
ord-c32e305dc41f4a9c81047dfc1db2c379
出典データセット
uspto-grants-2016_09
特許番号
US09447051B2

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