Tetrahydrofuran → HCID 11098166, compound

HRID 610598Notes

Reaction equation

HRID 610598 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]2[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]3)=[CH:9][NH:10][C:5]2=[CH:4][CH:3]=1.[CH3:18][N:19]=[C:20]=[O:21].O1CCCC1>CN(C)C=O>[CH3:18][NH:19][C:20]([NH:1][C:2]1[N:7]=[C:6]2[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]3)=[CH:9][NH:10][C:5]2=[CH:4][CH:3]=1)=[O:21]

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 12228Methyl Isocyanate2×HCID 102202303-(1-Methyl-piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-5-ylamine

Product 1

HCID 11098166HCID 11098166, compoundYield 34%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 0.15 gm (0.65 mMol) 5-amino-3-(1-methyl-piperidin-4yl)pyrrolo[3,2-b]pyridine and 0.046 mL (0.78 mMol) methyl isocyanate in 6 mL 5:1 tetrahydrofuran: dimethylformamide was stirred at room temperature for 5 hours. At this point an additional 0.020 mL methyl isocyanate were added and stirring continued for another 3.5 hours. The reaction mixture was then concentrated under reduced pressure. The residue was partitioned between 3:1 chloroform:isopropanol and 1N sodium hydroxide. The phases were separated and the aqueous phase extracted well with 3:1 chloroform:isopropanol. The organic phases were combined, washed with saturated aqueous sodium chloride, dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to radial chromatography (2mm silica gel plate), eluting with dichloromethane containing from 20-40% methanol and 1% ammonium hydroxide. Fractions shown to contain produce were combined and concentrated under reduced pressure. The residue was crystallized from aqueous ethanol to provide 0.043 gm (34%) of the title compound. m.p.=228.8-230.4° C. MS(m/e): 288(M+1) Calculated for C15H21N5O: Theory: C, 62.70; H, 7.37; N, 24.37. Found: C, 62.49; H, 7.29; N, 24.40.

Workup

  1. concentrationThe reaction mixture was then concentrated under reduced pressure
  2. customThe residue was partitioned between 3:1 chloroform
  3. customThe phases were separated
  4. extractionthe aqueous phase extracted well with 3:1 chloroform
  5. washwashed with saturated aqueous sodium chloride
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. washeluting with dichloromethane containing from 20-40% methanol and 1% ammonium hydroxide
  9. customto contain produce
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was crystallized from aqueous ethanol

Sources & evidence

ORD record
ord-1368c63b1cc146e193c7fc6fec40d298
Source dataset
uspto-grants-1999_12
Patent number
US05998622

Reaction notes

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