Hydrochloric Acid → Ethyl 4-(3-(benzyloxycarbonylamino)-2-methylphenyl)-7-bromo-9H-pyrido[3,4-b]indole-1-carboxylate

HRID 2361360Notes

Reaction equation

HRID 2361360 reaction equation
[NH2:1][CH2:2][CH:3]([C:14]1[C:15]([CH3:31])=[C:16]([NH:20][C:21](=[O:30])[O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:17]=[CH:18][CH:19]=1)[C:4]1[C:12]2[C:7](=[CH:8][C:9]([Br:13])=[CH:10][CH:11]=2)[NH:6][CH:5]=1.O=[CH:33][C:34]([O:36][CH2:37][CH3:38])=[O:35].C1(C)C=CC=CC=1.Cl.O1CCOCC1>O1CCCC1>[CH2:23]([O:22][C:21]([NH:20][C:16]1[C:15]([CH3:31])=[C:14]([C:3]2[C:4]3[C:12]4[C:7](=[CH:8][C:9]([Br:13])=[CH:10][CH:11]=4)[NH:6][C:5]=3[C:33]([C:34]([O:36][CH2:37][CH3:38])=[O:35])=[N:1][CH:2]=2)[CH:19]=[CH:18][CH:17]=1)=[O:30])[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 312751,4-DioxaneHCID 70211Ethyl oxoacetateHCID 67995178Benzyl 3-(2-amino-1-(6-bromo-1H-indol-3-yl)ethyl)-2-methylphenylcarbamate

Product 1

HCID 67994617Ethyl 4-(3-(benzyloxycarbonylamino)-2-methylphenyl)-7-bromo-9H-pyrido[3,4-b]indole-1-carboxylateYield 36%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a mixture of benzyl 3-(2-amino-1-(6-bromo-1H-indol-3-yl)ethyl)-2-methylphenylcarbamate (2.320 g, 4.85 mmol) and 4 angstrom molecular sieves (powder, activated, <5 mesh, 1.80 g) in tetrahydrofuran (100 mL) at room temperature was added ethyl 2-oxoacetate in toluene (1.923 mL, 9.70 mmol), followed by hydrogen chloride in 1,4-dioxane (1.334 mL, 5.33 mmol). The mixture was stirred at room temperature for 24 h. The solid phase was removed by suction filtration through CELITE®, and the filtrate was concentrated under vacuum. The residue was diluted with water (60 mL), basified with saturated NaHCO3 solution, and extracted with ethyl acetate (3×80 mL). The combined extract was washed with brine (60 mL) and dried over anhydrous MgSO4. The solvent was removed under vacuum. To the residue was added p-xylene (200 mL) and 10% Pd/C (1.5 g), and the mixture was heated under atmosphere at 125° C. for 16 hr. The solid phase was removed by suction filtration through CELITE®. The filtrate was concentrated under vacuum, and the residue was purified by ISCO (220 g silica gel, solid loading, 20-50% ethyl acetate/hexane) to provide the desired product (0.977 g, 36% yield) as a beige solid.

Workup

  1. customThe solid phase was removed by suction filtration through CELITE®
  2. concentrationthe filtrate was concentrated under vacuum
  3. additionThe residue was diluted with water (60 mL)
  4. extractionextracted with ethyl acetate (3×80 mL)
  5. extractionThe combined extract
  6. washwas washed with brine (60 mL)
  7. dry with materialdried over anhydrous MgSO4
  8. customThe solvent was removed under vacuum
  9. additionTo the residue was added p-xylene (200 mL) and 10% Pd/C (1.5 g)
  10. temperaturethe mixture was heated under atmosphere at 125° C. for 16 hr
  11. customThe solid phase was removed by suction filtration through CELITE®
  12. concentrationThe filtrate was concentrated under vacuum
  13. customthe residue was purified by ISCO (220 g silica gel, solid loading, 20-50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-c205752ed735491da41ddd1b1a6ed373
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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