Methanol → HCID 178422524, compound

HRID 492186Notes

Reaction equation

HRID 492186 reaction equation
[Na].CO.Cl.[NH2:5][C:6]([NH2:8])=[NH:7].[Cl:9][C:10]([C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([CH3:21])[CH:19]=2)[N:14]([C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:25]=[CH:24][CH:23]=2)[CH:13]=1)=[O:11]>COCCOC>[ClH:9].[NH:7]([C:10]([C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([CH3:21])[CH:19]=2)[N:14]([C:22]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[N:25]=[CH:24][CH:23]=2)[CH:13]=1)=[O:11])[C:6]([NH2:8])=[NH:5]

Participants

6

Reactant 4

HCID 887MethanolHCID 5742Guanidine HydrochlorideHCID 5360545SodiumHCID 865964073-chlorocarbonyl-5-methyl-1-(quinol-4-yl)-1H-indole

Product 1

HCID 178422524HCID 178422524, compoundYield 55.7%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
22 °C

Procedure

0.365 g (15.9 mmol) of sodium is added at 22° C. under an argon atmosphere to 45 cm3 of methanol. After complete dissolution, 1.4 g (15 mmol) of guanidine hydrochloride are added. After stirring at 22° C. for 2 hours, the reaction mixture is filtered under an argon atmosphere. The filtrate is concentrated to dryness under reduced pressure (2.7 kPa) to give a residue which is dissolved in 25 cm3 of 1,2-dimethoxyethane. 1 g of 3-chlorocarbonyl-5-methyl-1-(quinol-4-yl)-1H-indole, suspended in 20 cm3 of 1,2-dimethoxyethane, is subsequently added at 22° C. under an argon atmosphere. After stirring at 22° C. for 19 hours, the reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa) to give a residue which is triturated in 20 cm3 of water. After stirring at 22° C. for 1 hour, the suspension is filtered and dried to give a beige-coloured powder which is purified by flash chromatography [eluent: cyclohexane/ethyl acetate (7/3 by volume) and then dichloromethane/methanol/20% aqueous ammonia (18/3/0.5 by volume)]. After concentrating the fractions under reduced pressure (2.7 kPa), 1.1 g of a beige-coloured solid are obtained, which solid is triturated in 10 cm3 of N hydrochloric acid for 1 hour. After filtering off, the residue is recrystallised under hot conditions from 180 cm3 of methanol to give 0.66 g of 3-guanidinocarbonyl-5-methyl-1-(quinol-4-yl)-1H-indole hydrochloride in the form of pale yellow crystals melting at 268° C. (Analysis C20H17N5O.HCl; % calculated C, 63.24, H: 4.78, Cl: 9.33, N: 18.44, O: 4.21, % found C: 63.26, H: 4.72, Cl: 9.47, N: 18.57).

Workup

  1. additionare added
  2. filtrationthe reaction mixture is filtered under an argon atmosphere
  3. concentrationThe filtrate is concentrated to dryness under reduced pressure (2.7 kPa)
  4. customto give a residue which
  5. additionis subsequently added at 22° C. under an argon atmosphere
  6. stirringAfter stirring at 22° C. for 19 hours
  7. concentrationthe reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa)
  8. customto give a residue which
  9. customis triturated in 20 cm3 of water
  10. stirringAfter stirring at 22° C. for 1 hour
  11. filtrationthe suspension is filtered
  12. customdried
  13. customto give a beige-coloured powder which
  14. customis purified by flash chromatography [eluent
  15. concentrationAfter concentrating the fractions under reduced pressure (2.7 kPa), 1.1 g of a beige-coloured solid
  16. customare obtained
  17. customwhich solid is triturated in 10 cm3 of N hydrochloric acid for 1 hour
  18. filtrationAfter filtering off
  19. customthe residue is recrystallised under hot conditions from 180 cm3 of methanol

Sources & evidence

ORD record
ord-24f0641f275d441782481d5b59b423fb
Source dataset
uspto-grants-2009_05
Patent number
US07531663B2

Reaction notes

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