2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → N-(2,5-di-4-morpholinylphenyl)-3-methyl-2-(2-pyridinyl)-1,7-naphthyridin-4-amine

HRID 1431456ノート

反応式

HRID 1431456 の反応式
Cl[C:2]1[C:11]2[C:6](=[CH:7][N:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[C:3]=1[CH3:18].[O:19]1[CH2:24][CH2:23][N:22]([C:25]2[CH:26]=[C:27]3[NH:33]C[C:31]4([CH2:38]COCC4)[C:28]3=[N:29][CH:30]=2)[CH2:21][CH2:20]1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C([CH:70]([CH3:72])C)C=1)C.C[C:74](C)([O-:76])C.[Na+]>C1(C)C=CC=CC=1>[N:29]1([C:28]2[CH:31]=[CH:38][C:25]([N:22]3[CH2:21][CH2:20][O:19][CH2:24][CH2:23]3)=[CH:26][C:27]=2[NH:33][C:2]2[C:11]3[C:6](=[CH:7][N:8]=[CH:9][CH:10]=3)[N:5]=[C:4]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=3)[C:3]=2[CH3:18])[CH2:30][CH2:74][O:76][CH2:70][CH2:72]1

参加物

6

反応物 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 596313804-Chloro-3-methyl-2-(pyridin-2-yl)-1,7-naphthyridineHCID 672847056'-Morpholino-1',2,2',3,5,6-hexahydrospiro[pyran-4,3'-pyrrolo[3,2-b]pyridine]

生成物 1

HCID 59631045N-(2,5-di-4-morpholinylphenyl)-3-methyl-2-(2-pyridinyl)-1,7-naphthyridin-4-amine

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

実験手順

To a stirred solution of 4-chloro-3-methyl-2-(pyridin-2-yl)-1,7-naphthyridine (70 mg, 0.27 mmol), 6′-morpholino-1′,2,2′,3,5,6-hexahydrospiro[pyran-4,3′-pyrrolo[3,2-b]pyridine] (75 mg, 0.27 mmol) and XPhos™ precatalyst (20 mg, 0.03 mmol) in toluene (3 mL) was added sodium tert-butoxide (53 mg, 0.55 mmol) and the reaction was heated at reflux for 2 h. After this time the reaction was allowed to cool to rt and partitioned between EtOAc (60 mL) and water (20 mL). The separated organic layer was dried over MgSO4, filtered and evaporated in vacuo. Purification by reverse phase HPLC (10 to 60% acetonitrile in water) gave N-(2,5-di-4-morpholinylphenyl)-3-methyl-2-(2-pyridinyl)-1,7-naphthyridin-4-amine. H NMR (400 MHz, chloroform-d) δ ppm 9.54 (1H, d, J=1.0 Hz), 8.73-8.78 (1H, m), 8.51 (1H, d, J=5.7 Hz), 7.91-7.99 (2H, m), 7.64 (1H, dd, J=5.8, 1.1 Hz), 7.41 (1H, td, J=4.9, 3.6 Hz), 7.22 (1H, s), 7.12 (1H, d, J=8.6 Hz), 6.48 (1H, dd, J=8.6, 2.7 Hz), 6.03 (1H, d, J=2.7 Hz), 3.89 (4H, t, J=4.6 Hz), 3.69-3.77 (4H, m), 3.01-3.12 (4H, m), 2.88-2.95 (4H, m), 2.45 (3H, s). Mass Spectrum (ESI) m/e=483.2 (M+1).

後処理

  1. temperaturethe reaction was heated
  2. temperatureat reflux for 2 h
  3. custompartitioned between EtOAc (60 mL) and water (20 mL)
  4. dry with materialThe separated organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customPurification by reverse phase HPLC (10 to 60% acetonitrile in water)

出典と根拠

ORDレコード
ord-b1a8d55f8eff473b94745e5eb136848f
出典データセット
uspto-grants-2015_01
特許番号
US08940724B2

反応ノート

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