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

HRID 2361301Notes

Reaction equation

HRID 2361301 reaction equation
[NH2:1][CH2:2][CH:3]([C:19]1[C:20]([CH3:36])=[C:21]([NH:25][C:26](=[O:35])[O:27][CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH:22]=[CH:23][CH:24]=1)[C:4]1[C:12]2[C:7](=[CH:8][C:9]([O:13][CH:14]3[CH2:18][CH2:17][O:16][CH2:15]3)=[CH:10][CH:11]=2)[NH:6][CH:5]=1.O=[CH:38][C:39]([O:41][CH2:42][CH3:43])=[O:40].C1(C)C=CC=CC=1.Cl.O1CCOCC1>C(OCC)(=O)C.C(Cl)Cl>[CH2:28]([O:27][C:26]([NH:25][C:21]1[C:20]([CH3:36])=[C:19]([C:3]2[C:4]3[C:12]4[C:7](=[CH:8][C:9]([O:13][CH:14]5[CH2:18][CH2:17][O:16][CH2:15]5)=[CH:10][CH:11]=4)[NH:6][C:5]=3[C:38]([C:39]([O:41][CH2:42][CH3:43])=[O:40])=[N:1][CH:2]=2)[CH:24]=[CH:23][CH:22]=1)=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 1140TolueneHCID 312751,4-DioxaneHCID 70211Ethyl oxoacetateHCID 67995033Benzyl 3-(2-amino-1-(6-(tetrahydrofuran-3-yloxy)-1H-indol-3-yl)ethyl)-2-methylphenylcarbamate

Product 1

HCID 67995012Ethyl 4-(3-(benzyloxycarbonylamino)-2-methylphenyl)-7-(tetrahydrofuran-3-yloxy)-9H-pyrido[3,4-b]indole-1-carboxylateYield 30.4%

Reagents, catalysts & solvents 1

HCID 21226138Dichloromethane ethylacetateSolvent

Procedure

To a solution of benzyl 3-(2-amino-1-(6-(tetrahydrofuran-3-yloxy)-1H-indol-3-yl)ethyl)-2-methylphenylcarbamate (0.678 g, 1.396 mmol) and ethyl 2-oxoacetate in toluene (50%) (0.554 mL, 2.79 mmol) at room temperature was added hydrogen chloride in 1,4-dioxane (4.0 M) (0.419 mL, 1.676 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 (0.240 g, 0.424 mmol, 30.4% 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-1cc140e5003f43a78c8a01d33f92facd
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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