2,3-Dimethylaniline → tert-butyl 6-[2-(2,3-dimethylanilino)-2-oxoethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate

HRID 2306939Notes

Reaction equation

HRID 2306939 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:21][CH2:20][C:19]2[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[N:12]([CH2:22][C:23](O)=[O:24])[C:11]=2[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:26][C:27]1[C:33]([CH3:34])=[CH:32][CH:31]=[CH:30][C:28]=1[NH2:29].CN(C1C=CC=CN=1)C.C(N=C=NC(C)C)(C)C>C1COCC1.CCOC(C)=O>[CH3:26][C:27]1[C:33]([CH3:34])=[CH:32][CH:31]=[CH:30][C:28]=1[NH:29][C:23](=[O:24])[CH2:22][N:12]1[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=2[C:19]2[CH2:20][CH2:21][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:9][CH2:10][C:11]1=2

Participants

7

Reactant 4

HCID 68932,3-DimethylanilineHCID 12734DiisopropylcarbodiimideHCID 218852-DimethylaminopyridineHCID 22396950(3-(tert-butoxycarbonyl)-2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)acetic acid

Product 1

HCID 22396686tert-butyl 6-[2-(2,3-dimethylanilino)-2-oxoethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylateYield 73.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

(3-(tert-butoxycarbonyl)-2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)acetic acid (3.38 mmol) was dissolved in THF (20 mL) and 2,3-dimethylaniline (0.43 mL, 0.43 g, 3.6 mmol, 1.05 equiv.), dimethylaminopyridine (0.415 g, 3.40 mmol, 1.01 equiv.), and diisopropylcarbodiimide (0.60 mL, 0.48 g, 3.8 mmol, 1.13 equiv.) were added. The reaction mixture was stirred at rt under N2 for 18 h. The reaction mixture was taken up in EtOAc (100 mL) and this solution was washed with 10% aqueous citric acid (2×50 mL), 5% aqueous NaHCO3 (2×50 mL), and brine (50 mL). The organic layer was dried over MgSO4, filtered, and concentrated. The crude product (1.7223 g) was chromatographed (SiO2 187 g, eluted with 10:1 toluene:acetone followed by 9:1 toluene:acetone) to give tert-butyl 6-[2-(2,3-dimethylanilino)-2-oxoethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (1.1066 g) in 67% yield. 1H NMR (300 MHz, CD3OD) δ 1.50, 2.01-2.03, 2.27, 2.29-3.12, 3.66-3.75, 3.75-3.83, 5.03, 7.04-7.19, 7.37, 7.49; MS (ESI+) for C27H33N3O3 m/z 448.1 (M+H)+.

Workup

  1. washthis solution was washed with 10% aqueous citric acid (2×50 mL), 5% aqueous NaHCO3 (2×50 mL), and brine (50 mL)
  2. dry with materialThe organic layer was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude product (1.7223 g) was chromatographed
  6. wash(SiO2 187 g, eluted with 10:1 toluene:acetone followed by 9:1 toluene:acetone)

Sources & evidence

ORD record
ord-8c146b34c2a84b61a8e8c0fa1eb88e98
Source dataset
uspto-grants-2004_12
Patent number
US06828314B2

Reaction notes

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