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 897837Notes

Reaction equation

HRID 897837 reaction equation
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

Participants

6

Reactant 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 methanesulfonate2×

Product 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-indolecarboxamideYield 13.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

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). Rt 9.39 min. MS: M+ 501.3.

Workup

  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

Sources & evidence

ORD record
ord-57401fa42c714d3e8077844c615ced19
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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