Methanol → HCID 178513077, compound

HRID 1766146Notes

Reaction equation

HRID 1766146 reaction equation
CO.C[O-].[Na+].Cl.[NH2:7][C:8]([NH2:10])=[NH:9].Cl.Cl[C:13]([C:15]1[C:23]2[C:18](=[N:19][CH:20]=[CH:21][CH:22]=2)[N:17]([C:24]2[CH:29]=[CH:28][N:27]=[CH:26][CH:25]=2)[CH:16]=1)=[O:14]>O1CCCC1.ClCCl>[N:27]1[CH:28]=[CH:29][C:24]([N:17]2[C:18]3=[N:19][CH:20]=[CH:21][CH:22]=[C:23]3[C:15]([C:13]([NH:9][C:8]([NH2:10])=[NH:7])=[O:14])=[CH:16]2)=[CH:25][CH:26]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 5742Guanidine HydrochlorideHCID 10942334Sodium MethoxideHCID 21110070HCID 21110070, compound

Product 1

HCID 178513077HCID 178513077, compoundYield 2.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
20 °C

Procedure

20 cm3 of methanol and then a solution of 70 cm3 of 0.5M sodium methoxide were added, at a temperature in the region of 20° C. under an argon atmosphere, to 3.34 g (35 mmol) of guanidine hydrochloride and the reaction mixture was stirred at a temperature in the region of 20° C. for 1 h. The reaction mixture was subsequently concentrated to dryness under reduced pressure (2.7 kPa) and the residue was 3 times in succession taken up in 20 cm3 of dichloromethane (stabilized over amylene) and concentrated to dryness under reduced pressure (2.7 kPa). The residue obtained was taken up in 50 cm3 of tetrahydrofuran under an argon atmosphere at a temperature in the region of 20° C. and 1.8 g (7 mmol) of 3-chlorocarbonyl-1-(pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine hydrochloride, in suspension in 50 cm3 of dichloromethane, were added with stirring, followed by 50 cm3 of tetrahydrofuran and 50 cm3 of dichloromethane. After stirring at a temperature in the region of 20° C. for 15 h, the reaction mixture was concentrated to dryness under reduced pressure (2.7 kPa). The residue was taken up in 50 cm3 of ethanol and the mixture was heated at reflux for 5 minutes and then reconcentrated to dryness under reduced pressure (2.7 kPa). The residue was purified by flash chromatography on a column of silica gel (0.04–0.06 mm), elution being carried out with an ethyl acetate/methanol/aqueous ammonia (80/20/5 by volume) mixture. The fractions comprising the expected product were combined and concentrated to dryness under reduced pressure (2.7 kPa). The residue was taken up in 30 cm3 of water and the solution was basified with 1N sodium hydroxide and then 50 cm3 of ethyl acetate were added. After filtration, the organic phase was separated by settling, dried over magnesium sulfate and then concentrated to dryness under reduced pressure (2.7 kPa). The residue was triturated in 20 cm3 of diisopropyl ether, filtered and dried under reduced pressure (2.7 kPa) at a temperature in the region of 40° C. 45 mg of N-[1-(pyridin-4-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonyl]guanidine were thus obtained in the form of a white powder melting at 210° C. Mass spectrum: EI: m/z=280 M+ base peak.

Workup

  1. concentrationThe reaction mixture was subsequently concentrated to dryness under reduced pressure (2.7 kPa)
  2. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  3. customThe residue obtained
  4. additionwere added
  5. stirringwith stirring
  6. stirringAfter stirring at a temperature in the region of 20° C. for 15 h
  7. concentrationthe reaction mixture was concentrated to dryness under reduced pressure (2.7 kPa)
  8. temperaturethe mixture was heated
  9. temperatureat reflux for 5 minutes
  10. customThe residue was purified by flash chromatography on a column of silica gel (0.04–0.06 mm), elution
  11. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  12. addition50 cm3 of ethyl acetate were added
  13. filtrationAfter filtration
  14. customthe organic phase was separated
  15. dry with materialdried over magnesium sulfate
  16. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  17. customThe residue was triturated in 20 cm3 of diisopropyl ether
  18. filtrationfiltered
  19. customdried under reduced pressure (2.7 kPa) at a temperature in the region of 40° C

Sources & evidence

ORD record
ord-db219ab38de94296ab958a2e4baabfa9
Source dataset
uspto-grants-2007_06
Patent number
US07230007B2

Reaction notes

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