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

HRID 1431708ノート

反応式

HRID 1431708 の反応式
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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 54751079XPhos Palladacycle触媒HCID 1140Toluene溶媒

実験手順

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).

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

出典と根拠

ORDレコード
ord-fa23f99980484dccaf1371d1ab3ad735
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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