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

HRID 1431707노트

반응식

HRID 1431707 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:31]=[CH:30][C:29]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)=[CH:28][C:26]=2[NH2:27])[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>[N:22]1([C:25]2[CH:31]=[CH:30][C:29]([N:32]3[CH2:33][CH2:34][O:35][CH2:36][CH2:37]3)=[CH:28][C:26]=2[NH:27][C:2]2[C:11]3[C:6](=[N:7][CH: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])[CH2:23][CH2:24][O:19][CH2:20][CH2:21]1

참가 물질

6

반응물 3

HCID 23676156Sodium t-butoxideHCID 288098152,5-DimorpholinobenzenamineHCID 596310684-Chloro-3-methyl-2-(pyridin-2-yl)-1,8-naphthyridine

생성물 1

HCID 59631158N-(2,5-di-4-morpholinylphenyl)-3-methyl-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 (48.6 mg, 0.19 mmol), 2,5-dimorpholinoaniline (50 mg, 0.19 mmol) and XPhos precatalyst (14 mg, 0.019 mmol) in toluene (4 mL) was added sodium tert-butoxide (36 mg, 0.38 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 N-(2,5-di-4-morpholinylphenyl)-3-methyl-2-(2-pyridinyl)-1,8-naphthyridin-4-amine. H NMR (500 MHz, CDCl3) δ ppm 9.08 (1H, dd, J=3.9, 1.7 Hz), 8.71 (1H, br. s.), 8.26 (1H, dd, J=8.3, 1.7 Hz), 8.16 (1H, d, J=7.8 Hz), 7.88-7.96 (1H, m), 7.39 (2H, dd, J=8.3, 4.2 Hz), 7.11 (1H, d, J=8.8 Hz), 6.45 (1H, dd, J=8.7, 2.6 Hz), 5.99 (1H, d, J=2.7 Hz), 3.90 (4H, t, J=4.4 Hz), 3.66-3.77 (4H, m), 3.05 (4H, br. s.), 2.82-2.93 (4H, m), 2.51 (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

출처 및 근거

ORD 기록
ord-0b45eb71562e4d5a8419dfdaa183faa1
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08940724B2

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