Potassium Phosphate, Tribasic → 6-(2-(3,3-Dimethylbut-1-ynyl)-6-methylphenyl)-3-morpholinoquinolin-2-amine

HRID 1029022ノート

反応式

HRID 1029022 の反応式
C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.[O:35]1[CH2:40][CH2:39][N:38]([C:41]2[C:42]([NH2:60])=[N:43][C:44]3[C:49]([CH:50]=2)=[CH:48][C:47](B2OC(C)(C)C(C)(C)O2)=[CH:46][CH:45]=3)[CH2:37][CH2:36]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[C:70]1[C:75]([CH3:76])=[CH:74][CH:73]=[CH:72][C:71]=1[C:77]#[C:78][C:79]([CH3:82])([CH3:81])[CH3:80]>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]>[CH3:80][C:79]([CH3:82])([CH3:81])[C:78]#[C:77][C:71]1[CH:72]=[CH:73][CH:74]=[C:75]([CH3:76])[C:70]=1[C:47]1[CH:48]=[C:49]2[C:44](=[CH:45][CH:46]=1)[N:43]=[C:42]([NH2:60])[C:41]([N:38]1[CH2:37][CH2:36][O:35][CH2:40][CH2:39]1)=[CH:50]2

参加物

6

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 673457182-Bromo-1-(3,3-dimethylbut-1-ynyl)-3-methylbenzeneHCID 673479953-Morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine

生成物 1

HCID 533295376-(2-(3,3-Dimethylbut-1-ynyl)-6-methylphenyl)-3-morpholinoquinolin-2-amine

試薬・触媒・溶媒 1

HCID 9811564Bis(dibenzylideneacetone)palladium触媒

反応条件

温度
140 °C

実験手順

A microwave vial was charged with a mixture of 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (0.040 g, 0.084 mmol), Pd2(dba)3 (0.019 g, 0.021 mmol), 3-morpholino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinolin-2-amine (0.15 g, 0.422 mmol, prepared as in Example 2, Step 1-2) and potassium phosphate (0.175 mL, 2.11 mmol). The vial was evacuated and backfilled with N2. This procedure was repeated twice. Degassed dioxane (2.8 mL) and water (1.4 mL) was added. Then 2-bromo-1-(3,3-dimethylbut-1-ynyl)-3-methylbenzene (0.138 g, 0.549 mmol) was added and the reaction mixture was heated to 140° C. for 12 min in the microwave. The reaction mixture was cooled to RT and partitioned between EtOAc and water. The organic phase was washed with brine and dried over MgSO4. The solvent was removed under reduced pressure and the remaining residue was purified by flash chromatography (50-100% EtOAc/hexanes). The obtained solid was dissolved in MeOH (4 mL) and treated with 1N HCl (1 mL). The solution was eluted on an SCX cartridge with MeOH followed by 2M NH3/MeOH. The basic fraction was concentrated to afford the titled compound as a beige foam. MS (ESI, pos. ion) m/z: 400 (M+1).

後処理

  1. customThe vial was evacuated
  2. additionDegassed dioxane (2.8 mL) and water (1.4 mL) was added
  3. temperatureThe reaction mixture was cooled to RT
  4. custompartitioned between EtOAc and water
  5. washThe organic phase was washed with brine
  6. dry with materialdried over MgSO4
  7. customThe solvent was removed under reduced pressure
  8. customthe remaining residue was purified by flash chromatography (50-100% EtOAc/hexanes)
  9. dissolutionThe obtained solid was dissolved in MeOH (4 mL)
  10. additiontreated with 1N HCl (1 mL)
  11. washThe solution was eluted on an SCX cartridge with MeOH
  12. concentrationThe basic fraction was concentrated

出典と根拠

ORDレコード
ord-3779a013c0564ca48151f0261a1e69c3
出典データセット
uspto-grants-2014_05
特許番号
US08735384B2

反応ノート

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