Hydrochloric Acid → HCID 21968278, compound

HRID 1106509Notes

Reaction equation

HRID 1106509 reaction equation
N#N.[C:3]1([CH2:9][N:10]2[CH2:22][CH2:21][C:13]3[NH:14][C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=4[C:12]=3[CH2:11]2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.Cl>C1COCC1>[C:3]1([CH2:9][N:10]2[CH2:22][CH2:21][C@H:13]3[NH:14][C:15]4[CH:16]=[CH:17][CH:18]=[CH:19][C:20]=4[C@@H:12]3[CH2:11]2)[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 947NitrogenHCID 2754382-Benzyl-2,3,4,5-tetrahydro-1H-pyrido(4,3-b)indole

Product 1

HCID 21968278HCID 21968278, compoundYield 14.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Borane-THF complex (1:1) (400 ml) was transferred into a 4 necked flask with a syringe (under N2 flow). This solution was cooled to 0° C. A solution of 2,3,4,5-tetra-hydro-2-(phenylmethyl)-1H-pyrido[4,3-b]indole (52.5 g), prepared as described in J. Med. Chem. 9:436-438 (1966), in THF (400 ml) was added over a 1 hour period at 0-5° C. The reaction mixture was stirred for 1 hour at room temperature. The reaction mixture was stirred and refluxed for 4 hours, then cooled to room temperature. 6N HCl (300 ml) was added. The organic solvent was removed by evaporation. Dioxane (400 ml) was added to the residue and the mixture was stirred and refluxed for 1 hour. The solvent was evaporated. Water (300 ml) was added to the residue and this mixture was alkalized with a diluted NaOH solution. This mixture was extracted with DCM. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CHCl3 /CH3OH 95/5). The pure fractions were collected and the solvent was evaporated. The residue (20 g) was crystallized from DIPE (100 ml). The crystals were filtered off and dried, yielding 7.5 g (14%) of (±)-trans-1,3,4,4a,5,9b-hexahydro-2-(phenylmethyl)-2H-pyrido[4,3-b]indole (intermediate 13).

Workup

  1. customBorane-THF complex (1:1) (400 ml) was transferred into a 4 necked flask with a syringe
  2. stirringThe reaction mixture was stirred
  3. temperaturerefluxed for 4 hours
  4. temperaturecooled to room temperature
  5. customThe organic solvent was removed by evaporation
  6. additionDioxane (400 ml) was added to the residue
  7. stirringthe mixture was stirred
  8. temperaturerefluxed for 1 hour
  9. customThe solvent was evaporated
  10. additionWater (300 ml) was added to the residue
  11. extractionThis mixture was extracted with DCM
  12. customThe organic layer was separated
  13. customdried
  14. filtrationfiltered
  15. customthe solvent was evaporated
  16. customThe residue was purified by column chromatography over silica gel (eluent: CHCl3 /CH3OH 95/5)
  17. customThe pure fractions were collected
  18. customthe solvent was evaporated
  19. customThe residue (20 g) was crystallized from DIPE (100 ml)
  20. filtrationThe crystals were filtered off
  21. customdried

Sources & evidence

ORD record
ord-0d4aad6d6808402fad83c307104dc651
Source dataset
uspto-grants-2000_05
Patent number
US06057325

Reaction notes

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