(R)-1-Pyridin-2-yl-ethylamine → 7-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-N4-[(1R)-1-(2-pyridinyl)ethyl]-3,4-quinolinediamine

HRID 1042999ノート

反応式

HRID 1042999 の反応式
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:14]3[C:15]([CH3:20])=[N:16][O:17][C:18]=3[CH3:19])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[N+:21]([O-])=O.[N:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[C@H:30]([NH2:32])[CH3:31]>C(#N)C>[CH3:20][C:15]1[C:14]([C:8]2[CH:7]=[C:6]3[C:11]([C:2]([NH:32][C@@H:30]([C:25]4[CH:26]=[CH:27][CH:28]=[CH:29][N:24]=4)[CH3:31])=[C:3]([NH2:21])[CH:4]=[N:5]3)=[CH:10][C:9]=2[O:12][CH3:13])=[C:18]([CH3:19])[O:17][N:16]=1

参加物

4

反応物 2

HCID 1084918(R)-1-Pyridin-2-yl-ethylamineHCID 574655804-(4-Chloro-6-methoxy-3-nitroquinolin-7-yl)-3,5-dimethylisoxazole2 回

生成物 1

HCID 672077397-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-N4-[(1R)-1-(2-pyridinyl)ethyl]-3,4-quinolinediamine

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
40 °C

実験手順

A solution of 4-chloro-7-(3,5-dimethyl-4-isoxazolyl)-6-(methoxy)-3-nitroquinoline (for a preparation see Intermediate 18, 400 mg,) and (R)-1-(pyridin-2-yl)ethanamine (293 mg) in acetonitrile (30 ml) was heated at 60° C. for 2 h. The reaction mixture was extracted with DCM and washed with a saturated solution of sodium hydrogen carbonate. The organic was dried over Na2SO4, filtered and concentrated to dryness. The resulting compound was taken-up in ether, filtered and dried in vacuo. The residue was dissolved in ethanol (20 ml) and HCl (3.8 ml). Tin (II) chloride dihydrate (0.89 g) was then added in four portions and the reaction mixture was stirred for 1 h at 40° C. The reaction mixture was hydrolysed using a solution of sodium hydroxide (1N). The mixture was extracted with DCM, the organic dried over Na2SO4, filtered over Celite and concentrated to dryness. The crude product was purified via flash column chromatography on silica gel eluting with DCM/MeOH (95/5) and the obtained product was taken-up in diisopropylether to give 7-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-N4-[(1R)-1-(2-pyridinyl)ethyl]-3,4-quinolinediamine (250 mg) as a brown powder. LC/MS: Rt 2.62 min.

後処理

  1. extractionThe reaction mixture was extracted with DCM
  2. washwashed with a saturated solution of sodium hydrogen carbonate
  3. dry with materialThe organic was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated to dryness
  6. filtrationfiltered
  7. customdried in vacuo
  8. dissolutionThe residue was dissolved in ethanol (20 ml)
  9. additionTin (II) chloride dihydrate (0.89 g) was then added in four portions
  10. extractionThe mixture was extracted with DCM
  11. dry with materialthe organic dried over Na2SO4
  12. filtrationfiltered over Celite
  13. concentrationconcentrated to dryness
  14. customThe crude product was purified via flash column chromatography on silica gel eluting with DCM/MeOH (95/5)

出典と根拠

ORDレコード
ord-3fc215738cb646b5890698dccd71952e
出典データセット
uspto-grants-2013_10
特許番号
US08557984B2

反応ノート

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