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

HRID 2361293Notes

Reaction equation

HRID 2361293 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]([N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]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.C1(C)C=CC=CC=1>O1CCOCC1.CCOC(C)=O.[Pd]>[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]([N:13]5[CH2:14][CH2:15][O:16][CH2:17][CH2:18]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:30]=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

8

Reactant 4

HCID 1140TolueneHCID 204431481,4-Dioxane hydrochlorideHCID 67994601Benzyl 3-(2-amino-1-(6-morpholino-1H-indol-3-yl)ethyl)-2-methylphenylcarbamateHCID 86599969Ethyl glyoxylate toluene2×

Product 1

HCID 67994966Ethyl 4-(3-(benzyloxycarbonylamino)-2-methylphenyl)-7-morpholino-9H-pyrido[3,4-b]indole-1-carboxylateYield 20.4%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

To a homogeneous solution of benzyl 3-(2-amino-1-(6-morpholino-1H-indol-3-yl)ethyl)-2-methylphenylcarbamate (1.4934 g, 3.08 mmol) in dioxane (154 ml) were added 50% ethyl 2-oxoacetate/toluene (1.222 ml, 6.16 mmol) and 4N HCl/dioxane (1.541 ml, 6.16 mmol) under nitrogen. The reaction was stirred overnight. More 50% ethyl 2-oxoacetate/toluene (1.222 ml, 6.16 mmol) was added, and the reaction was stirred overnight. The reaction was concentrated in vacuo, dissolved in EtOAc (100 mL) and washed with water (25 mL) and brine (25 mL) successively, dried over MgSO4, and concentrated in vacuo to give a crude product, which was used in the subsequent step. To this crude were added 10% Pd/C (0.819 g, 0.770 mmol) and toluene (77 ml), and the mixture was refluxed overnight. The reaction was cooled to room temperature, diluted with EtOAc (200 mL), and filtered through a pad of CELITE®. The filtrate was washed with water (75 mL) and brine (75 mL), dried over MgSO4, and concentrated in vacuo. The residue was purified by flash chromatography using an ISCO 120 g column eluting with 15-70% EtOAc/CH2Cl2 to give the desired product (0.354 g, 0.627 mmol, 20.4% yield) as a tan solid.

Workup

  1. stirringthe reaction was stirred overnight
  2. concentrationThe reaction was concentrated in vacuo
  3. dissolutiondissolved in EtOAc (100 mL)
  4. washwashed with water (25 mL) and brine (25 mL) successively
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customto give a crude product, which
  8. temperaturethe mixture was refluxed overnight
  9. filtrationfiltered through a pad of CELITE®
  10. washThe filtrate was washed with water (75 mL) and brine (75 mL)
  11. dry with materialdried over MgSO4
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by flash chromatography
  14. washeluting with 15-70% EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-2bc3d4b8359f4267b61d6c9bc111939e
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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