Guanidine Hydrochloride → HCID 178478912, compound

HRID 1869174Notes

Reaction equation

HRID 1869174 reaction equation
[Na].Cl.[NH2:3][C:4]([NH2:6])=[NH:5].O1CCCC1.Cl.[Cl:13][C:14]([C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:18]([C:25]2[C:26]3[CH:33]=[CH:32][N:31]([CH3:34])[C:27]=3[N:28]=[CH:29][N:30]=2)[CH:17]=1)=[O:15]>CO.ClCCl>[ClH:13].[NH:5]([C:14]([C:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[N:18]([C:25]2[C:26]3[CH:33]=[CH:32][N:31]([CH3:34])[C:27]=3[N:28]=[CH:29][N:30]=2)[CH:17]=1)=[O:15])[C:4]([NH2:6])=[NH:3]

Participants

7

Reactant 4

HCID 5742Guanidine HydrochlorideHCID 8028TetrahydrofuranHCID 5360545SodiumHCID 865948063-chlorocarbonyl-1-(7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-indole hydrochloride

Product 1

HCID 178478912HCID 178478912, compoundYield 40.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

0.345 g (15 mmol) of sodium (prewashed in toluene) is added gradually to 100 cm3 of methanol at a temperature in the region of 20° C. under an argon atmosphere. After dissolution with stirring, 1.43 g (15 mmol) of guanidine hydrochloride are added, and the reaction mixture is stirred at a temperature in the region of 20° C. for 2 hours. The reaction mixture is then concentrated to dryness under reduced pressure (2.7 kPa), and the residue is taken up twice successively with 70 cm3 of dichloromethane (stabilized with amylene) and concentrated to dryness under reduced pressure (2.7 kPa). 50 cm3 of tetrahydrofuran and 50 cm3 of dichloromethane are then added, under an argon atmosphere, at a temperature in the region of 20° C., and 3 mmol of 3-chlorocarbonyl-1-(7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-indole hydrochloride, are then added with stirring. After stirring for 15 hours at a temperature in the region of 20° C., the reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa). The residue is purified by flash chromatography on silica gel [eluent: ethyl acetate/methanol (80/20 by volume)]. After the various fractions containing the expected product have been concentrated to dryness under reduced pressure (2.7 kPa), the solid obtained is taken up in methanol, and the mixture is refluxed for 10 minutes. After cooling to a temperature in the region of 20° C. and filtered, the solid is dried at a temperature in the region of 40° C. under reduced pressure (2.7 kPa), giving 0.45 g of 3-guanidinocarbonyl-1-(7-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-indole hydrochloride in the form of an off-white solid melting at 244° C. Mass spectrum (DCI): m/e 334 (MH+) (base peak).

Workup

  1. dissolutionAfter dissolution
  2. stirringthe reaction mixture is stirred at a temperature in the region of 20° C. for 2 hours
  3. concentrationThe reaction mixture is then concentrated to dryness under reduced pressure (2.7 kPa)
  4. concentrationconcentrated to dryness under reduced pressure (2.7 kPa)
  5. additionare then added
  6. stirringwith stirring
  7. stirringAfter stirring for 15 hours at a temperature in the region of 20° C.
  8. concentrationthe reaction mixture is concentrated to dryness under reduced pressure (2.7 kPa)
  9. customThe residue is purified by flash chromatography on silica gel [eluent: ethyl acetate/methanol (80/20 by volume)]
  10. additionAfter the various fractions containing the expected product
  11. concentrationhave been concentrated to dryness under reduced pressure (2.7 kPa)
  12. customthe solid obtained
  13. temperaturethe mixture is refluxed for 10 minutes
  14. filtrationfiltered
  15. customthe solid is dried at a temperature in the region of 40° C. under reduced pressure (2.7 kPa)

Sources & evidence

ORD record
ord-7b9a16b84c004ba0b63595e39b6b0bcd
Source dataset
uspto-grants-2009_12
Patent number
US07638521B2

Reaction notes

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