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

HRID 1431456노트

반응식

HRID 1431456 반응식
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

참가 물질

6

반응물 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]

생성물 1

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

시약·촉매·용매 1

HCID 1140Toluene용매

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-b1a8d55f8eff473b94745e5eb136848f
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940724B2

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