Water → HCID 70977554、化合物

HRID 628954

反応式

HRID 628954 の反応式
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10](Br)=[CH:11][CH:12]=2)[C@H:7]([NH2:15])[CH2:6][C@@H:5]1[CH3:16])(=[O:3])[CH3:2].[CH3:17][O:18][CH2:19][CH2:20][N:21]1[CH:25]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:23]=[N:22]1.C([O-])([O-])=O.[K+].[K+].O>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH2:15][C@H:7]1[C:8]2[C:13](=[CH:12][CH:11]=[C:10]([C:24]3[CH:23]=[N:22][N:21]([CH2:20][CH2:19][O:18][CH3:17])[CH:25]=3)[CH:9]=2)[N:4]([C:1](=[O:3])[CH3:2])[C@@H:5]([CH3:16])[CH2:6]1

参加物

7

反応物 4

HCID 962Water2 回HCID 11430Potassium Carbonate2 回HCID 112304911-(2-Methoxyethyl)-1H-pyrazole-4-boronic acid, pinacol esterHCID 67194540HCID 67194540、化合物

生成物 1

HCID 70977554HCID 70977554、化合物収率 68%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒2 回HCID 312751,4-Dioxane溶媒

反応条件

温度
110 °C

実験手順

(2S,4R)-1-Acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinamine (for a preparation see Intermediate 7) (900 mg, 2.82 mmol), 1-(2-methoxyethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (852 mg, 3.38 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (309 mg, 0.422 mmol) and K2CO3 (895 mg, 6.48 mmol) were combined in 1,4-dioxane (12 ml) and water (4.0 ml) and heated at 110° C. for 60 min (microwave). The reaction was heated for a further 10 min and then, for a further 30 min under the same conditions. PdCl2(dppf) (309 mg, 0.422 mmol), K2CO3 (895 mg, 6.48 mmol) and water (1.5 ml) were added and the mixture heated at 110° C. for 30 min (microwave). The reaction mixture was partitioned between saturated aqueous sodium hydrogen carbonate (150 ml) and DCM (3×150 ml). The organics were combined, dried (hydrophobic frit) and evaporated under vacuum. The residue was dissolved in DCM, the solution applied to a silica cartridge (100 g) and purified the cartridge eluted with an ethyl acetate/cyclohexane gradient (0-100% over 10 CV followed by 100% ethyl acetate for 5 CV). The cartridge was washed using a methanol/DCM gradient (0-20% over 10 CV, followed by holding at 20% methanol/DCM for 5 CV). The cartridge was further washed using a gradient 2M ammonia in methanol/DCM (0-20% over 10 CV, followed by 2M ammonia in methanol/DCM 20% for 5 CV). The appropriate fractions were combined and evaporated under vacuum to leave 1-((2S,4R)-4-amino-6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone (631 mg, 1.921 mmol, 68% yield) as a brown glass. LCMS (HpH), Rt 0.68 min, MH+ 329

後処理

  1. temperatureThe reaction was heated for a further 10 min
  2. customThe reaction mixture was partitioned between saturated aqueous sodium hydrogen carbonate (150 ml) and DCM (3×150 ml)
  3. customdried (hydrophobic frit)
  4. customevaporated under vacuum
  5. dissolutionThe residue was dissolved in DCM
  6. custompurified the cartridge
  7. washeluted with an ethyl acetate/cyclohexane gradient (0-100% over 10 CV followed by 100% ethyl acetate for 5 CV)
  8. washThe cartridge was washed
  9. washThe cartridge was further washed
  10. customevaporated under vacuum

出典と根拠

ORDレコード
ord-b1f958541af549b49752109eb3d1b943
出典データセット
uspto-grants-2016_04
特許番号
US09315487B2

関連ノート

読み込み中…