Water → HCID 11011968, compound

HRID 398855Notes

Reaction equation

HRID 398855 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.[CH:18]1([C:21](Cl)=[O:22])[CH2:20][CH2:19]1.O>N1C=CC=CC=1>[CH:18]1([C:21]([NH:1][C:2]2[N:7]=[C:6]3[C:8]([CH:11]4[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]4)=[CH:9][NH:10][C:5]3=[CH:4][CH:3]=2)=[O:22])[CH2:20][CH2:19]1

Participants

5

Reactant 3

HCID 962WaterHCID 77637Cyclopropanecarbonyl chloride2×HCID 102202303-(1-Methyl-piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-5-ylamine

Product 1

HCID 11011968HCID 11011968, compoundYield 56.7%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of 0.300 gm (1.30 mMol) 5-amino-3-(1-methylpiperidin-4-yl)pyrrolo[3,2-b]pyridine in 40 mL pyridine was heated to 50° C. To this solution was added 0.13 mL (1.43 mMol) cyclopropanecarbonyl chloride and the reaction mixture was stirred for 1.5 hours. An additional 0.10 mL of cyclopropanecarbonyl chloride were added and the reaction mixture was stirred for an additional hour. The reaction mixture was treated with 1.0 mL of water and was then concentrated under reduced pressure. The residue was diluted with 3:1 chloroform:isopropanol and the solution washed sequentially with water, dilute aqueous sodium hydroxide, and saturated aqueous sodium chloride. The organic phase was then dried over sodium sulfate and concentrated under reduced pressure. The residue was subjected to radial chromatography (silica gel, 1 mm), eluting with a gradient of dichloromethane (5-10% methanol) containing 1% ammonium hydroxide. Fractions containing product were combined and concentrated under reduced pressure. The residue was recrystallized from ethanol/water to provide 0.22 gm (55.9%) of the title compound as a crystalline solid.

Workup

  1. stirringthe reaction mixture was stirred for an additional hour
  2. concentrationwas then concentrated under reduced pressure
  3. additionThe residue was diluted with 3:1 chloroform
  4. washisopropanol and the solution washed sequentially with water, dilute aqueous sodium hydroxide, and saturated aqueous sodium chloride
  5. dry with materialThe organic phase was then dried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. washeluting with a gradient of dichloromethane (5-10% methanol)
  8. additioncontaining 1% ammonium hydroxide
  9. additionFractions containing product
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was recrystallized from ethanol/water

Sources & evidence

ORD record
ord-f9abb3688bd142f898e019aea63e2e02
Source dataset
uspto-grants-1998_10
Patent number
US05817671

Reaction notes

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