4-Methylmorpholine → HCID 68512418、化合物

HRID 2241403ノート

反応式

HRID 2241403 の反応式
[O:1]=[C:2]1[C:7]([C:8]([OH:10])=O)=[CH:6][CH:5]=[N:4][N:3]1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.CN1CCOCC1.[F:45][C:46]1[CH:47]=[C:48]([CH:50]=[CH:51][C:52]=1[O:53][C:54]1[CH:59]=[CH:58][N:57]=[C:56]2[N:60]([CH2:70][C:71]3[CH:76]=[CH:75][C:74]([O:77][CH3:78])=[CH:73][CH:72]=3)[N:61]=[C:62]([N:63]3[CH2:68][CH2:67][N:66]([CH3:69])[CH2:65][CH2:64]3)[C:55]=12)[NH2:49]>C(Cl)Cl.C(Cl)Cl.CN(C=O)C>[CH3:78][O:77][C:74]1[CH:73]=[CH:72][C:71]([CH2:70][N:60]2[C:56]3=[N:57][CH:58]=[CH:59][C:54]([O:53][C:52]4[CH:51]=[CH:50][C:48]([NH:49][C:8]([C:7]5[C:2](=[O:1])[N:3]([C:11]6[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=6)[N:4]=[CH:5][CH:6]=5)=[O:10])=[CH:47][C:46]=4[F:45])=[C:55]3[C:62]([N:63]3[CH2:68][CH2:67][N:66]([CH3:69])[CH2:65][CH2:64]3)=[N:61]2)=[CH:76][CH:75]=1

参加物

8

反応物 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 68512039HCID 68512039、化合物HCID 685129493-fluoro-4-(1-(4-methoxybenzyl)-3-(4-methylpiperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)aniline

生成物 1

HCID 68512418HCID 68512418、化合物

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 22350042dichloromethane N,N-dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

3-Oxo-2-(pyridin-2-yl)-2,3-dihydropyridazine-4-carboxylic acid (0.0282 g, 0.130 mmol; prepared as in Example 141, Steps A-C) was dissolved in 5 mL of CH2Cl2 and cooled to 0° C. HOBt (0.0351 g, 0.259 mmol), EDCI (0.0497 g, 0.259 mmol), and NMM (0.0333 ml, 0.303 mmol) were added and the reaction mixture was stirred under N2(g) for 15 minutes. 4-(1-(4-Methoxybenzyl)-3-(4-methylpiperazin-1-yl)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (0.020 g, 0.0432 mmol; prepared according to Example 86, Step A) in 2 mL of 1:1 CH2Cl2/DMF was added and the reaction was stirred at ambient temperature for 5 hours. The mixture was partitioned between EtOAc and aqueous NaHCO3. The organic layer washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography (Flash 5 g) eluting with 3% MeOH/CH2Cl2 to afford the desired product as yellow semi-solid. Yield: 25.8 mg, 86%. LRMS (APCI pos) m/e 662 (M+H).

後処理

  1. stirringthe reaction was stirred at ambient temperature for 5 hours
  2. customThe mixture was partitioned between EtOAc and aqueous NaHCO3
  3. washThe organic layer washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography (Flash 5 g)
  8. washeluting with 3% MeOH/CH2Cl2

出典と根拠

ORDレコード
ord-4e4a378deaa942c7a84c4b14760bb843
出典データセット
uspto-grants-2010_05
特許番号
US07723330B2

反応ノート

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