Hydrochloric Acid → 2-t-Butoxycarbonyl-9-methylcarbamoylmethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole

HRID 2301084Notes

Reaction equation

HRID 2301084 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:20][CH2:19][C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:21][C:22]([O:24]C)=O)[C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].Cl.O[N:30]1[C:34]2C=CC=CC=2N=N1.CN>O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:20][CH2:19][C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=3)[N:11]([CH2:21][C:22](=[O:24])[NH:30][CH3:34])[C:10]=2[CH2:9]1)=[O:7])([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 6329MethylamineHCID 14798Sodium HydroxideHCID 757711-HydroxybenzotriazoleHCID 110784542-Tert-butoxycarbonyl-9-methoxycarbonylmethyl-1,2,3,4-tetrahydropyrido[3,4-b]indole

Product 1

HCID 108608372-t-Butoxycarbonyl-9-methylcarbamoylmethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indoleYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 10 ml portion of tetrahydrofuran solution containing 0.62 g (1.80 mmol) of 2-t-butoxycarbonyl-9-methoxycarbonylmethyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole was mixed with 2 ml of aqueous solution containing 0.22 g (5.40 mmol) of sodium hydroxide and stirred overnight at room temperature. This was acidified by adding 1 N hydrochloric acid and extracted with chloroform. The extract was washed with water and dried (Na2SO4), and then the solvent was removed by evaporation under a reduced pressure. The thus obtained residue was dissolved in 12 ml of acetonitrile, and the solution was mixed with 557 mg (2.70 mmol) of N,N-dicyclohexylcarbodiimide and 365 mg (2.70 mmol) of 1-hydroxybenzotriazole and stirred at room temperature for 2 hours. The reaction solution was cooled to 0° C., mixed with 2 ml of 40% methylamine aqueous solution and again stirred at room temperature for 30 minutes. The insoluble matter was removed by filtration, the solvent was removed by evaporation under a reduced pressure and then the resulting residue was purified by a silica gel column chromatography (130 cc; elution by chloroform-methanol=30:1) to obtain 542 mg of the title compound (88% in yield).

Workup

  1. extractionextracted with chloroform
  2. washThe extract was washed with water
  3. dry with materialdried (Na2SO4)
  4. customthe solvent was removed by evaporation under a reduced pressure
  5. dissolutionThe thus obtained residue was dissolved in 12 ml of acetonitrile
  6. stirringstirred at room temperature for 2 hours
  7. temperatureThe reaction solution was cooled to 0° C.
  8. stirringagain stirred at room temperature for 30 minutes
  9. customThe insoluble matter was removed by filtration
  10. customthe solvent was removed by evaporation under a reduced pressure
  11. customthe resulting residue was purified by a silica gel column chromatography (130 cc; elution by chloroform-methanol=30:1)

Sources & evidence

ORD record
ord-24d966a4108f49a28f32bc3af8cf65f0
Source dataset
uspto-grants-2002_12
Patent number
US06498251B1

Reaction notes

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