4-Chloroquinazoline → 4-Piperazin-1-ylquinazoline

HRID 1192283ノート

反応式

HRID 1192283 の反応式
Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.CCN(C(C)C)C(C)C.C([N:28]1[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1)(OC(C)(C)C)=O.Cl.O1CCOCC1>CC(O)C>[N:28]1([C:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]=[CH:4][N:3]=2)[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]1

参加物

6

反応物 4

HCID 788644-ChloroquinazolineHCID 81531DiisopropylethylamineHCID 143452tert-Butyl piperazine-1-carboxylateHCID 204431481,4-Dioxane hydrochloride

生成物 1

HCID 18585334-Piperazin-1-ylquinazoline収率 96%

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

実験手順

To a solution of 4-chloroquinazoline (2.0 g, 12.2 mmol) (Tobe, Masanori, et al., Bioorg. Med. Chem. 2003, 11(3), 383) and DIEA (3.2 mL, 18.2 mmol) in 40 mL IPA was added Boc-piperazine (1.96 g, 12.81 mmol). The reaction mixture was heated to reflux and stirred for 20 hours, after which it was cooled to room temperature and concentrated by rotary evaporation. The residue was dissolved in dichloromethane (DCM) and washed with 1N NaOH. The organic layer was dried (Na2SO4), filtered, and concentrated by rotary evaporation. The resulting oil was dissolved in 25 mL dioxane, and 4M HCl/dioxane (46 mL, 182 mmol) was added dropwise. The suspension was sonicated for 2 minutes and stirred 13 hours at room temperature, after which the reaction mixture was concentrated to dryness by rotary evaporation. The resulting amine HCl salt was dissolved in 2N NaOH and extracted with DCM. The organic layer was dried (Na2SO4), filtered, and concentrated by rotary evaporation. The resulting oil was purified on silica (9:1:0.02 DCM/MeOH/NR4OH) to give 4-piperazinylquinazoline as a yellow oil (2.5 g, 96%). 1H NMR (CDCl3, 400 MHz) δ 8.74 (s, 1H), 7.92-7.86 (m, 2H), 7.76-7.70 (m, 1H), 7.48-7.42 (m, 1H), 3.75 (t, J=4.9 Hz, 4H), 3.09 (t, J=4.9 Hz, 4H), 1.89 (br s, 1H). Rt 0.70. MS (ESI+) [M+H]+ 215.

後処理

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux
  3. concentrationconcentrated by rotary evaporation
  4. dissolutionThe residue was dissolved in dichloromethane (DCM)
  5. washwashed with 1N NaOH
  6. dry with materialThe organic layer was dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated by rotary evaporation
  9. dissolutionThe resulting oil was dissolved in 25 mL dioxane
  10. customThe suspension was sonicated for 2 minutes
  11. stirringstirred 13 hours at room temperature
  12. concentrationafter which the reaction mixture was concentrated to dryness by rotary evaporation
  13. dissolutionThe resulting amine HCl salt was dissolved in 2N NaOH
  14. extractionextracted with DCM
  15. dry with materialThe organic layer was dried (Na2SO4)
  16. filtrationfiltered
  17. concentrationconcentrated by rotary evaporation
  18. customThe resulting oil was purified on silica (9:1:0.02 DCM/MeOH/NR4OH)

出典と根拠

ORDレコード
ord-c11e9b2bc0b54d3b8e7b436725b5e70f
出典データセット
uspto-grants-2014_03
特許番号
US08680114B2

反応ノート

読み込み中…