Ethanolamine → N2-[4-(4-amino-1-{2-[(2-hydroxyethyl)amino]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-methoxyphenyl]-1-methyl-1H-2-indolecarboxamide

HRID 2056034노트

반응식

HRID 2056034 반응식
CS(OCC[N:8]1[C:12]2=[N:13][CH:14]=[N:15][C:16]([NH2:17])=[C:11]2[C:10]([C:18]2[CH:23]=[CH:22][C:21]([NH:24][C:25]([C:27]3[N:28]([CH3:36])[C:29]4[C:34]([CH:35]=3)=[CH:33][CH:32]=[CH:31][CH:30]=4)=[O:26])=[C:20]([O:37][CH3:38])[CH:19]=2)=[N:9]1)(=O)=O.[CH2:39]([CH2:41][NH2:42])[OH:40].[CH2:43](N(CC)CC)[CH3:44].[I-].[Na+]>CN(C=O)C>[NH2:17][C:16]1[N:15]=[CH:14][N:13]=[C:12]2[N:8]([CH2:43][CH2:44][NH:42][CH2:41][CH2:39][OH:40])[N:9]=[C:10]([C:18]3[CH:23]=[CH:22][C:21]([NH:24][C:25]([C:27]4[N:28]([CH3:36])[C:29]5[C:34]([CH:35]=4)=[CH:33][CH:32]=[CH:31][CH:30]=5)=[O:26])=[C:20]([O:37][CH3:38])[CH:19]=3)[C:11]=12

참가 물질

6

반응물 4

HCID 700EthanolamineHCID 5238Sodium IodideHCID 8471TriethylamineHCID 223468312-[4-amino-3-(3-methoxy-4-{[(1-methyl-1H-2-indolyl)carbonyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]ethyl methanesulfonate2회

생성물 1

HCID 22347107N2-[4-(4-amino-1-{2-[(2-hydroxyethyl)amino]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-methoxyphenyl]-1-methyl-1H-2-indolecarboxamide수율 13.3%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
70 °C

실험 절차

A mixture of 2-[4-amino-3-(3-methoxy-4-{[(1-methyl-1H-2-indolyl)carbonyl]amino}phenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]ethyl methanesulfonate (Intermediate 4) (0.080 g, 0.15 mmol), ethanolamine (0.05 mL, 0.82 mmol), triethylamine (0.021 mL, 0.15 mmol), and sodium iodide (0.021 g, 0.15 mmol) in DMF (2.5 mL) was heated at 70° C. for 15 h. The reaction mixture was cooled to ambient temperature and concentrated; water (5 mL) was added and the resulting precipitate was collected by filtration and rinsed with water (5 mL). The crude solid was purified by silica gel column chromatography (elution with 20% MeOH—CH2Cl2). The appropriate fractions were combined and the solvent removed in vacuo to afford N2-[4-(4-amino-1-{2-[(2-hydroxyethyl)amino]ethyl}-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-2-methoxyphenyl]-1-methyl-1H-2-indolecarboxamide as a white solid (0.009 g, 0.02 mmol). RP-HPLC (Hypersil C18, 5 μm, 100 Å, 15 cm; 5%-100% acetonitrile—0.1 M ammonium acetate over 15 min, 1 mL/min). Rt9.39 min. MS: M+501.3.

후처리

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. concentrationconcentrated
  3. additionwater (5 mL) was added
  4. filtrationthe resulting precipitate was collected by filtration
  5. washrinsed with water (5 mL)
  6. customThe crude solid was purified by silica gel column chromatography (elution with 20% MeOH—CH2Cl2)
  7. customthe solvent removed in vacuo

출처 및 근거

ORD 기록
ord-de1df55ab61a429fac7827ba6993ab02
출처 데이터셋
uspto-grants-2008_02
특허 번호
US07332497B2

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