Morpholine → HCID 50906574、化合物

HRID 1431320ノート

反応式

HRID 1431320 の反応式
Br[C:2]1[CH:3]=[C:4]([N:14]([CH3:34])[C:15]2[C:24]3[C:19](=[CH:20][C:21]([F:26])=[CH:22][C:23]=3[F:25])[N:18]=[C:17]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=3)[C:16]=2[CH3:33])[C:5]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[N:6][CH:7]=1.C1(P(C2CCCCC2)C2(C(C)C)CC(C(C)C)=CC(C(C)C)=C2C2C=CC=CC=2)CCCCC1.CC(C)([O-])C.[Na+].[NH:75]1[CH2:80][CH2:79][O:78][CH2:77][CH2:76]1>C1(C)C=CC=CC=1.O.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]>[N:8]1([C:5]2[C:4]([N:14]([CH3:34])[C:15]3[C:24]4[C:19](=[CH:20][C:21]([F:26])=[CH:22][C:23]=4[F:25])[N:18]=[C:17]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=4)[C:16]=3[CH3:33])=[CH:3][C:2]([N:75]3[CH2:80][CH2:79][O:78][CH2:77][CH2:76]3)=[CH:7][N:6]=2)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1

参加物

8

反応物 4

HCID 8083MorpholineHCID 23676156Sodium t-butoxideHCID 59631098HCID 59631098、化合物HCID 672859322-Dicyclohexylphosphino-2,4,6-triisopropylbiphenyl

生成物 1

HCID 50906574HCID 50906574、化合物

試薬・触媒・溶媒 3

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 1140Toluene溶媒

反応条件

温度
100 °C

実験手順

A stirred mixture of N-(5-bromo-2-morpholinopyridin-3-yl)-5,7-difluoro-N,3-dimethyl-2-(pyridin-2-yl)quinolin-4-amine (12.0 mg, 0.023 mmol), tris(dibenzylideneacetone)dipalladium (0) (2.1 mg, 2.280 μmol), 2-dicyclohexylphosphino-2,4,6,-triisopropylbiphenyl (2.2 mg, 4.56 μmol), and sodium tert-butoxide (15 mg, 0.153 mmol) in toluene (2 mL) was purged three times with argon and placed under vacuum three times. Before heating, morpholine (9.93 μL, 0.114 mmol) was added and the mixture was heated to 100° C. Stirring continued for 21 h. After which the reaction was cooled to rt, diluted with water and extracted with EtOAc (3×10 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was dissolved in MeOH and purified by HPLC (10-90% of 0.1% TFA acetonitrile solution in 0.1% TFA water solution) to yield N-(2,5-di-4-morpholinyl-3-pyridinyl)-5,7-difluoro-N,3-dimethyl-2-(2-pyridinyl)-4-quinolinamine. 1H NMR (400 MHz, CD3OD) δ ppm 8.66 (1H, d, J=4.7 Hz), 8.01 (1H, m), 7.78 (1H, d, J=7.8 Hz), 7.61-7.67 (1H, m), 7.60 (1H, d, J=2.7 Hz), 7.51 (1H, m), 7.23 (1H, m), 7.10 (1H, br. s.), 3.82-3.92 (4H, m), 3.35-3.44 (4H, m), 3.31 (4H, m), 3.17-3.28 (4H, m), 2.46 (3H, br. s.), 1.94-2.04 (3H, s); Mass Spectrum (ESI) m/e=533.2 (M+1).

後処理

  1. customwas purged three times with argon
  2. temperatureBefore heating
  3. temperatureAfter which the reaction was cooled to rt
  4. extractionextracted with EtOAc (3×10 mL)
  5. dry with materialThe combined organic layers were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. dissolutionThe crude product was dissolved in MeOH
  9. custompurified by HPLC (10-90% of 0.1% TFA acetonitrile solution in 0.1% TFA water solution)

出典と根拠

ORDレコード
ord-2e039179f81547888888d1100ac5bc79
出典データセット
uspto-grants-2015_01
特許番号
US08940724B2

反応ノート

読み込み中…