Pyridine → HCID 178488195、化合物

HRID 432413

反応式

HRID 432413 の反応式
[C:1]1([C@H:7]([CH3:12])[CH2:8]C(O)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:13](Cl)(=[O:17])C(Cl)=O.N[C:20]1[CH:25]=[CH:24][C:23]([C:26]2[C:34]3[C:29](=[N:30][CH:31]=[N:32][C:33]=3[NH2:35])[N:28]([C@H:36]3[CH2:41][CH2:40][C@H:39]([N:42]4[CH2:47][CH2:46][N:45]([CH3:48])[CH2:44][CH2:43]4)[CH2:38][CH2:37]3)[N:27]=2)=[CH:22][C:21]=1[O:49][CH3:50].C(OCC)(=O)C.[N:57]1C=CC=CC=1>ClCCl.CN(C=O)C>[C:1]1([C@@H:7]([CH3:12])[CH2:8][NH:57][C:13](=[O:17])[C:20]2[CH:25]=[CH:24][C:23]([C:26]3[C:34]4[C:29](=[N:30][CH:31]=[N:32][C:33]=4[NH2:35])[N:28]([C@H:36]4[CH2:41][CH2:40][C@H:39]([N:42]5[CH2:47][CH2:46][N:45]([CH3:48])[CH2:44][CH2:43]5)[CH2:38][CH2:37]4)[N:27]=3)=[CH:22][C:21]=2[O:49][CH3:50])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

参加物

8

反応物 5

HCID 1049PyridineHCID 8857Ethyl AcetateHCID 65578Oxalyl chlorideHCID 852992(3R)-3-phenylbutanoic acidHCID 178488198HCID 178488198、化合物

生成物 1

HCID 178488195HCID 178488195、化合物収率 64%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide触媒HCID 6344Dichloromethane溶媒2 回

実験手順

To (3R)-3-phenylbutanoic acid (376 mg, 2.29 mmol) in dichloromethane (7 mL) was added oxalyl chloride (2 mL, 22.9 mmol) and DMF (1 drop). The reaction mixture was stirred overnight. Solvent was evaporated and the residue was dissolved in dichloromethane (3 mL). The dichloromethane solution was added to a solution of trans-3-(4-amino-3-methoxyphenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (448 mg, 1.026 mmol) in pyridine (6 mL) at 0° C. After 2 hours, the reaction mixture was poured to ethyl acetate (60 ml) and the solid as collected by filtration. Water was then added to the solid and the pH of the solution was adjusted to 10 with sodium hydroxide (1.0N). The aqueous was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (80:20) as mobile phase to give trans-N1-[(2R)-2-phenylpropyl]-4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxybenzamide (383 mg, 64%). 1H NMR (CDCl3) δ 1.40 (d, J=6.96, 3H), 1.57 (m, 2H), 2.08-2.21 (m, 6H), 2.30 (s, 3H), 2.50 (m, 5H), 2.63-2.74 (m, 6H), 3.40 (m, 1H), 3.88 (s, 3H), 4.74 (m, 1H), 5.69 (bs, 2H), 7.16-7.34 (m, 7H), 7.66 (s, 1H), 8.34 (s, 1H), 8.49 (d, J=8.21, 1H).

後処理

  1. customSolvent was evaporated
  2. dissolutionthe residue was dissolved in dichloromethane (3 mL)
  3. waitAfter 2 hours
  4. filtrationthe solid as collected by filtration
  5. additionWater was then added to the solid
  6. extractionThe aqueous was extracted with dichloromethane
  7. washThe combined organic layer was washed with water
  8. dry with materialbrine, dried over MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by flash column chromatography

出典と根拠

ORDレコード
ord-467258d7343346eda7b8f51d658c9429
出典データセット
uspto-grants-2003_12
特許番号
US06660744B1

関連ノート

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