Imidazole → HCID 22347277, compound

HRID 897841Notes

Reaction equation

HRID 897841 reaction equation
CS(O[CH2:6][CH2:7][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.[NH:39]1[CH:43]=[CH:42][N:41]=[CH:40]1.C(N(CC)CC)C.[I-].[Na+]>CN(C=O)C.C(OCC)(=O)C>[NH2:17][C:16]1[N:15]=[CH:14][N:13]=[C:12]2[N:8]([CH2:7][CH2:6][N:39]3[CH:43]=[CH:42][N:41]=[CH:40]3)[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

7

Reactant 4

HCID 795Imidazole2×HCID 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 22347277HCID 22347277, compoundYield 44.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

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), imidazole (0.011 g, 0.15 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. Imidazole (0.011 g, 0.15 mmol) was added and the reaction mixture was heated at 70° C. for 60 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. Water (5 mL) was added and the resulting precipitate was collected by filtration to afford a beige solid which was taken up in hot ethyl acetate then allowed to slowly cool to ambient temperature. The filtrate was concentrated to afford N2-(4-{4-amino-1-[2-(1H-1-imidazolyl)ethyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-1-methyl-1H-2-indolecarboxamide (0.034 g, 0.067 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 10.45 min. MS: M+ 508.2.

Workup

  1. temperaturethe reaction mixture was heated at 70° C. for 60 h
  2. temperatureThe reaction mixture was cooled to ambient temperature
  3. concentrationconcentrated in vacuo
  4. additionWater (5 mL) was added
  5. filtrationthe resulting precipitate was collected by filtration
  6. customto afford a beige solid which
  7. temperatureto slowly cool to ambient temperature
  8. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-bc2d6fddb88941c38bdae85acfdcc777
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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