1,4-Dioxane → (2-(2-Amino-3-morpholinoquinolin-6-yl)-3-methylphenyl)(o-tolyl)methanone

HRID 1028939ノート

反応式

HRID 1028939 の反応式
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.Br[C:36]1[C:41]([CH3:42])=[CH:40][CH:39]=[CH:38][C:37]=1[C:43]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=1[CH3:51])=[O:44].[O:52]1[CH2:57][CH2:56][N:55]([C:58]2[C:59]([NH2:77])=[N:60][C:61]3[C:66]([CH:67]=2)=[CH:65][C:64](B2OC(C)(C)C(C)(C)O2)=[CH:63][CH:62]=3)[CH2:54][CH2:53]1.O1CCOCC1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[NH2:77][C:59]1[C:58]([N:55]2[CH2:56][CH2:57][O:52][CH2:53][CH2:54]2)=[CH:67][C:66]2[C:61](=[CH:62][CH:63]=[C:64]([C:36]3[C:41]([CH3:42])=[CH:40][CH:39]=[CH:38][C:37]=3[C:43]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=3[CH3:51])=[O:44])[CH:65]=2)[N:60]=1

参加物

7

反応物 4

HCID 312751,4-DioxaneHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67326275(2-Bromo-3-methylphenyl)(o-tolyl)methanoneHCID 673479953-Morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine

生成物 1

HCID 67325352(2-(2-Amino-3-morpholinoquinolin-6-yl)-3-methylphenyl)(o-tolyl)methanone

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒

反応条件

温度
140 °C

実験手順

A mixture of 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (0.013 g, 0.028 mmol), (2-bromo-3-methylphenyl)(o-tolyl)methanone (0.16 g, 0.563 mmol), 3-morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (0.050 g, 0.141 mmol), Pd2(dba)3 (6.44 mg, 7.04 μmol) were treated with dioxane (0.94 mL) and water (0.47 mL) in a medium-sized Smith synthesizer vial. The mixture was heated to 140° C. for 12 min in a microwave reactor. The reaction mixture was filtered then partitioned between EtOAc and water. The organic layer was washed with water and brine and then concentrated in vacuo. The crude product was purified first by column chromatography (1-10% MeOH:DCM) and then by HPLC (10-90% CH3CN/H2O; TFA modifier). A single fraction was treated with NH4OH, concentrated, filtered and air-dried to afford (2-(2-amino-3-morpholinoquinolin-6-yl)-3-methylphenyl)(o-tolyl)methanone. MS (ESI, pos. ion) m/z: 438 (M+1).

後処理

  1. filtrationThe reaction mixture was filtered
  2. customthen partitioned between EtOAc and water
  3. washThe organic layer was washed with water and brine
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified first by column chromatography (1-10% MeOH:DCM)
  6. additionA single fraction was treated with NH4OH
  7. concentrationconcentrated
  8. filtrationfiltered
  9. customair-dried

出典と根拠

ORDレコード
ord-55607327fa5240309e549266d24cbacb
出典データセット
uspto-grants-2014_05
特許番号
US08735384B2

反応ノート

読み込み中…