Methanol → HCID 178422526, compound

HRID 492180Notes

Reaction equation

HRID 492180 reaction equation
[Na].CO.Cl.[NH2:5][C:6]([NH2:8])=[NH:7].Cl.[Cl:10][C:11]([C:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([CH3:22])[CH:20]=2)[N:15]([C:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH:26]=[CH:25][N:24]=2)[CH:14]=1)=[O:12]>COCCOC>[ClH:10].[NH:7]([C:11]([C:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([CH3:22])[CH:20]=2)[N:15]([C:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH:26]=[CH:25][N:24]=2)[CH:14]=1)=[O:12])[C:6]([NH2:8])=[NH:5]

Participants

6

Reactant 4

HCID 887MethanolHCID 5742Guanidine HydrochlorideHCID 5360545SodiumHCID 86596403HCID 86596403, compound

Product 1

HCID 178422526HCID 178422526, compoundYield 69.4%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
20 °C

Procedure

0.457 g (19.8 mmol) of sodium is added at 20° C. under an argon atmosphere to 60 cm3 of methanol. After complete dissolution, 1.79 g (18.75 mmol) of guanidine hydrochloride are added. After stirring at 20° 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 20 cm3 of 1,2-dimethoxyethane. 1.2 g of 3-chlorocarbonyl-1-(isoquinol-1-yl)-5-methyl-1H-indole hydrochloride, suspended in 40 cm3 of 1,2-dimethoxyethane, are subsequently added at 20° C. under an argon atmosphere. After stirring at 20° C. for 17.5 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 then dried to give a beige-coloured solid 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, 1.2 g of a beige-coloured solid are obtained, which solid is triturated in 12 cm3 of N hydrochloric acid for 1 hour. After filtering off, the residue is recrystallised under hot conditions from 80 cm3 of methanol to give 0.885 g of 3-guanidinocarbonyl-1-(isoquinol-1-yl)-5-methyl-1H-indole hydrochloride in the form of beige-coloured crystals melting at 268° C. IR spectrum (KBr): 3350, 3092, 1693, 1625, 1524, 1462, 1406, 1216 and 832 cm−1.

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. additionare subsequently added at 20° C. under an argon atmosphere
  6. stirringAfter stirring at 20° C. for 17.5 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 solid which
  14. customis purified by flash chromatography [eluent
  15. concentrationAfter concentrating the fractions under reduced pressure, 1.2 g of a beige-coloured solid
  16. customare obtained
  17. customwhich solid is triturated in 12 cm3 of N hydrochloric acid for 1 hour
  18. filtrationAfter filtering off
  19. customthe residue is recrystallised under hot conditions from 80 cm3 of methanol

Sources & evidence

ORD record
ord-db07f18d9a4b4a688322a914b75ecd7a
Source dataset
uspto-grants-2009_05
Patent number
US07531663B2

Reaction notes

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