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

HRID 2361273Notes

Reaction equation

HRID 2361273 reaction equation
[NH2:1][CH2:2][CH:3]([C:18]1[C:19]([CH3:35])=[C:20]([NH:24][C:25](=[O:34])[O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:21]=[CH:22][CH:23]=1)[C:4]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=2)[NH:6][CH:5]=1.O=[CH:37][C:38]([O:40][CH2:41][CH3:42])=[O:39].C1(C)C=CC=CC=1.Cl.O1CCOCC1>C(OCC)(=O)C.C(Cl)Cl>[CH2:27]([O:26][C:25]([NH:24][C:20]1[C:19]([CH3:35])=[C:18]([C:3]2[C:4]3[C:12]4[C:7](=[CH:8][C:9]([O:13][CH2:14][CH2:15][O:16][CH3:17])=[CH:10][CH:11]=4)[NH:6][C:5]=3[C:37]([C:38]([O:40][CH2:41][CH3:42])=[O:39])=[N:1][CH:2]=2)[CH:23]=[CH:22][CH:21]=1)=[O:34])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 312751,4-DioxaneHCID 70211Ethyl oxoacetateHCID 67994818Benzyl 3-(2-amino-1-(6-(2-methoxyethoxy)-1H-indol-3-yl)ethyl)-2-methylphenylcarbamate

Product 1

HCID 67994870Ethyl 4-(3-(benzyloxycarbonylamino)-2-methylphenyl)-7-(2-methoxyethoxy)-9H-pyrido[3,4-b]indole-1-carboxylateYield 43.8%

Reagents, catalysts & solvents 1

HCID 21226138Dichloromethane ethylacetateSolvent

Procedure

To a solution of benzyl 3-(2-amino-1-(6-(2-methoxyethoxy)-1H-indol-3-yl)ethyl)-2-methylphenylcarbamate (0.780 g, 1.647 mmol) and ethyl 2-oxoacetate in toluene (50%) (0.653 mL, 3.29 mmol) at room temperature was added hydrogen chloride in 1,4-dioxane (4.0 M) (0.494 mL, 1.977 mmol). The mixture was stirred room temperature for 16 hr. The volatiles were removed under vacuum. The residue was diluted with water (50 mL), basified with NaHCO3 solution to pH 10, and extracted with ethyl acetate (4×50 mL). The combined extract was washed with brine (40 ml), dried over anhydrous MgSO4, and concentrated to dryness under vacuum. To the residue were added p-xylene (60 mL) and 10% Pd/C (0.46 g), and the mixture was heated at 125° C. under an ambient atmosphere for 4.5 hr. The solid phase was removed by suction filtration. The filtrate was diluted with ethyl acetate (120 ml), washed with brine (40 ml), and dried over anhydrous MgSO4. The desired product (0.399 g, 0.721 mmol, 43.8% yield) was isolated by ISCO (40 g silica gel, solid loading, 15-35% ethyl acetate/CH2Cl2).

Workup

  1. customThe volatiles were removed under vacuum
  2. additionThe residue was diluted with water (50 mL)
  3. extractionextracted with ethyl acetate (4×50 mL)
  4. extractionThe combined extract
  5. washwas washed with brine (40 ml)
  6. dry with materialdried over anhydrous MgSO4
  7. concentrationconcentrated to dryness under vacuum
  8. additionTo the residue were added p-xylene (60 mL) and 10% Pd/C (0.46 g)
  9. temperaturethe mixture was heated at 125° C. under an ambient atmosphere for 4.5 hr
  10. customThe solid phase was removed by suction filtration
  11. additionThe filtrate was diluted with ethyl acetate (120 ml)
  12. washwashed with brine (40 ml)
  13. dry with materialdried over anhydrous MgSO4

Sources & evidence

ORD record
ord-e15171e4f7d243c88daecf5070147753
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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