Trifluoroacetic acid → ethyl 5-methyl-1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxylate

HRID 1748270Notes

Reaction equation

HRID 1748270 reaction equation
C(OC([NH:8][CH2:9][CH2:10][CH:11]([N:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:20]=2)[CH:15]=[C:14]1[C:27](OCC)=[O:28])[CH3:12])=O)(C)(C)C.C(O)(C(F)(F)F)=O.C(N(CC)CC)C.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.C(O)C>[CH3:12][CH:11]1[N:13]2[C:21]3[CH:20]=[C:19]([C:22]([O:24][CH2:25][CH3:26])=[O:23])[CH:18]=[CH:17][C:16]=3[CH:15]=[C:14]2[C:27](=[O:28])[NH:8][CH2:9][CH2:10]1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 67236468diethyl 1-{4-[(tert-butoxycarbonyl)amino]butan-2-yl}-1H-indole-2,6-dicarboxylate

Product 1

HCID 67235486ethyl 5-methyl-1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxylateYield 59%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of diethyl 1-{4-[(tert-butoxycarbonyl)amino]butan-2-yl}-1H-indole-2,6-dicarboxylate (1.04 g, 1.8 mmol) in CH2Cl2 (4 mL) is added TFA (4 mL). The reaction mixture is stirred for 1 h and the solvent is removed under vacuum. To a solution of the residue in ethanol (10 mL) is added triethylamine (0.75 mL, 5.4 mmol) and K2CO3 (742 mg, 5.4 mmol). The reaction mixture is refluxed for 3 h. Then the solvent is evaporated, the residue is partitioned between EtOAc and water. The organic layer is then separated, dried (MgSO4) and concentrated to afford crude compound which is purified by flash column chromatography to afford the title compound (300 mg, 59% for two steps).

Workup

  1. customthe solvent is removed under vacuum
  2. temperatureThe reaction mixture is refluxed for 3 h
  3. customThen the solvent is evaporated
  4. customthe residue is partitioned between EtOAc and water
  5. customThe organic layer is then separated
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated
  8. customto afford crude compound which
  9. customis purified by flash column chromatography

Sources & evidence

ORD record
ord-43639a56a94a4e46a595ace36c56ff31
Source dataset
uspto-grants-2015_10
Patent number
US09150577B2

Reaction notes

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