Hydrochloric Acid → methyl 4-methyl-3-(4-oxo-6-piperazin-1-ylquinazolin-3(4H)-yl)benzoate

HRID 641974ノート

反応式

HRID 641974 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[CH:7][N:6]([C:12]1[CH:13]=[C:14]([CH:19]=[CH:20][C:21]=1[CH3:22])[C:15]([O:17][CH3:18])=[O:16])[C:5]2=[O:23].C([O-])([O-])=O.[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([N:83]1[CH2:88][CH2:87][NH:86][CH2:85][CH2:84]1)(OC(C)(C)C)=O.Cl>C1(C)C=CC=CC=1.CO.O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:22][C:21]1[CH:20]=[CH:19][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][C:12]=1[N:6]1[C:5](=[O:23])[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([N:83]3[CH2:88][CH2:87][NH:86][CH2:85][CH2:84]3)[CH:3]=2)[N:8]=[CH:7]1

参加物

10

反応物 5

HCID 313Hydrochloric Acid2 回HCID 10796Cesium carbonateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-HCID 66919066Methyl 3-(6-bromo-4-oxoquinazolin-3(4H)-yl)-4-methylbenzoate

生成物 1

HCID 68604387methyl 4-methyl-3-(4-oxo-6-piperazin-1-ylquinazolin-3(4H)-yl)benzoate収率 69.5%

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒HCID 887Methanol溶媒HCID 1140Toluene溶媒HCID 312751,4-Dioxane溶媒2 回

反応条件

温度
100 °C

実験手順

Methyl 3-(6-bromo-4-oxoquinazolin-3(4H)-yl)-4-methylbenzoate (2 g), Cs2CO3 (4.4 g), racemic 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.67 g), palladium acetate (0.12 g) in anhydrous toluene (20 ml) at ambient temperature was added N-boc piperazine (2.5 g). The mixture was heated to 100° C. and stirred for 16 hours. Inorganic solids were removed via a hot filtration and the filtrate concentrated to give an oil. The oil was resuspended in MeOH (16 ml), 4N HCl in dioxane (10 ml) was added and the reaction mixture stirred at 50° C. for 1 hour when additional 4N HCl in dioxane (2 ml) was added and heating continued for a further 30 minutes. The reaction mixture was cooled to room temperature and the solid collected by filteration, washed with ethyl acetate (×2) and ether and dried. The resultant solid was suspended in saturated K2CO3 solution and extracted with ethyl acetate (×5). The organic layers combined, dried (magnesium sulphate) and concentrated to yield methyl 4-methyl-3-(4-oxo-6-piperazin-1-ylquinazolin-3(4H)-yl)benzoate as a yellow foam (1.41 g); NMR Spectrum: (DMSOd6) 2.17 (s, 3H), 2.31 (m, 1H), 2.87 (m, 4H), 3.19 (m, 4H), 3.87 (s, 3H), 7.46 (s, 1H), 7.61 (m, 3H), 7.97 (s, 1H), 8.02 (d, 1H), 8.08 (s, 1H); Mass Spectrum: M+H+ 379.

後処理

  1. customInorganic solids were removed via a hot filtration
  2. concentrationthe filtrate concentrated
  3. customto give an oil
  4. additionwas added
  5. temperatureheating
  6. waitcontinued for a further 30 minutes
  7. temperatureThe reaction mixture was cooled to room temperature
  8. customthe solid collected by filteration
  9. washwashed with ethyl acetate (×2) and ether
  10. customdried
  11. extractionextracted with ethyl acetate (×5)
  12. dry with materialdried (magnesium sulphate)
  13. concentrationconcentrated

出典と根拠

ORDレコード
ord-74dd4906a32f40829566b4c2c69c0a90
出典データセット
uspto-grants-2010_04
特許番号
US07696215B2

反応ノート

読み込み中…