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

HRID 1748283Notes

Reaction equation

HRID 1748283 reaction equation
C(OC([NH:8][CH2:9][CH:10]([CH3:31])[CH2:11][N:12]1[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:19]=2)[CH:14]=[C:13]1[C:26](OCC)=[O:27])=O)(C)(C)C.N1C2C(=CC=C(C(OCC)=O)C=2)C=C1C(OCC)=O.C(O)(C(F)(F)F)=O.C(N(CC)CC)C.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.C(O)C.O>[CH3:31][CH:10]1[CH2:11][N:12]2[C:20]3[CH:19]=[C:18]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:17]=[CH:16][C:15]=3[CH:14]=[C:13]2[C:26](=[O:27])[NH:8][CH2:9]1

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 44754779Diethyl 1H-indole-2,6-dicarboxylateHCID 67235256HCID 67235256, compound

Product 1

HCID 67235919ethyl 4-methyl-1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxylateYield 66%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a mixture of diethyl 1-{3-[(tert-butoxycarbonyl)amino]-2-methylpropyl}-1H-indole-2,6-dicarboxylate and diethyl 1H-indole-2,6-dicarboxylate (3.2 g, 7.4 mmol) in CH2Cl2 (70 mL) is added TFA (30 mL). The mixture is stirred at room temperature for 2 h. The reaction is concentrated and the residue is dried in vacuo for 1 h. To a solution of the residue in ethanol (150 mL) are added triethylamine (3.1 mL, 22.2 mmol) and K2CO3 (6.1 g, 44.2 mmol). The mixture is heated at 80° C. for 5 h. Water (300 mL) is added and the mixture is extracted with EtOAc (3×200 mL). The organic layers are combined, dried (Na2SO4) and concentrated and the crude compound is purified by flash column chromatography to afford the title compound (1.4 g, 66% for 3 steps).

Workup

  1. concentrationThe reaction is concentrated
  2. customthe residue is dried in vacuo for 1 h
  3. temperatureThe mixture is heated at 80° C. for 5 h
  4. extractionthe mixture is extracted with EtOAc (3×200 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customthe crude compound is purified by flash column chromatography

Sources & evidence

ORD record
ord-690cc275e5c24425b2245c89ff570365
Source dataset
uspto-grants-2015_10
Patent number
US09150577B2

Reaction notes

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