Sodium t-butoxide → 3-methyl-N-(5-(4-morpholinyl)-3-pyridinyl)-2-(2-pyridinyl)-1,8-naphthyridin-4-amine

HRID 1431708노트

반응식

HRID 1431708 반응식
Cl[C:2]1[C:11]2[C:6](=[N:7][CH: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]([NH2:31])[CH:28]=[N:29][CH:30]=2)[CH2:21][CH2:20]1.CC(C)([O-])C.[Na+]>CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].C1(C)C=CC=CC=1>[CH3:18][C:3]1[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)=[N:5][C:6]2[C:11]([C:2]=1[NH:31][C:27]1[CH:28]=[N:29][CH:30]=[C:25]([N:22]3[CH2:23][CH2:24][O:19][CH2:20][CH2:21]3)[CH:26]=1)=[CH:10][CH:9]=[CH:8][N:7]=2

참가 물질

6

반응물 3

HCID 23676156Sodium t-butoxideHCID 583477375-Morpholinopyridin-3-amineHCID 596310684-Chloro-3-methyl-2-(pyridin-2-yl)-1,8-naphthyridine

생성물 1

HCID 596313703-methyl-N-(5-(4-morpholinyl)-3-pyridinyl)-2-(2-pyridinyl)-1,8-naphthyridin-4-amine

시약·촉매·용매 2

HCID 54751079XPhos Palladacycle촉매HCID 1140Toluene용매

실험 절차

To a stirred solution of 4-chloro-3-methyl-2-(pyridin-2-yl)-1,8-naphthyridine (70 mg, 0.27 mmol), 5-morpholinopyridin-3-amine (49 mg, 0.27 mmol) and XPhos precatalyst (20 mg, 0.027 mmol) in toluene (4 mL) was added sodium tert-butoxide (52 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 gave 3-methyl-N-(5-(4-morpholinyl)-3-pyridinyl)-2-(2-pyridinyl)-1,8-naphthyridin-4-amine. H NMR (400 MHz, CDCl3) δ ppm 9.03 (1H, dd, J=4.1, 2.0 Hz), 8.69 (1H, ddd, J=4.8, 1.7, 1.1 Hz), 8.20 (1H, dd, J=8.3, 1.9 Hz), 8.08 (1H, dt, J=7.9, 1.1 Hz), 7.84-7.93 (2H, m), 7.78 (1H, d, J=2.3 Hz), 7.31-7.42 (2H, m), 6.51-6.61 (1H, m), 6.37 (1H, t, J=2.4 Hz), 3.74-3.87 (4H, m), 3.00-3.10 (4H, m), 2.47 (3H, s). Mass Spectrum (ESI) m/e=399.2 (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

출처 및 근거

ORD 기록
ord-fa23f99980484dccaf1371d1ab3ad735
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940724B2

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