Dichloromethane → N-(4-methoxyphenyl)-3-(2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)propanamide hydrochloride

HRID 1370405Notes

Reaction equation

HRID 1370405 reaction equation
[CH3:1][O:2][C:3]1[CH:34]=[CH:33][C:6]([NH:7][C:8](=[O:32])[CH2:9][CH2:10][N:11]2[C:19]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:13]3[CH2:20][CH2:21][N:22](C(OC(C)(C)C)=O)[CH2:23][CH2:24][C:12]2=3)=[CH:5][CH:4]=1.FC(F)(F)C(O)=O.C(Cl)[Cl:43]>>[ClH:43].[CH3:1][O:2][C:3]1[CH:34]=[CH:33][C:6]([NH:7][C:8](=[O:32])[CH2:9][CH2:10][N:11]2[C:19]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:13]3[CH2:20][CH2:21][NH:22][CH2:23][CH2:24][C:12]2=3)=[CH:5][CH:4]=1

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 22396876tert-butyl 6-[3-(4-methoxyanilino)-3-oxopropyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate

Product 1

HCID 22396982N-(4-methoxyphenyl)-3-(2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)propanamide hydrochlorideYield 84%

Procedure

tert-butyl 6-[3-(4-methoxyanilino)-3-oxopropyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (0.110 g, 0.238 mmol) was disolved in CH2Cl2 (5 mL) and trifluoroacetic acid (2.0 mL, 2.96 g, 26.0 mmol, 109 equiv.) was added. The resulting solution was stirred at rt for 2.5 h. The reaction mixture was concentrated to dryness, and the residue was partitioned between EtOAc and 1N NaOH. The layers were separated, and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. The crude product (0.0805 g) was combined with EtOAc (2 mL), and 1M HCl in Et2O (2 mL) and the salt was collected by filtration. The salt was dried under vacuum over P2O5. N-(4-methoxyphenyl)-3-(2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)propanamide hydrochloride (0.0796 g) was obtained in 84% yield. 1H NMR (300 MHz, CD3OD) δ 2.76, 3.13-3.17, 3.28-3.39, 3.74, 4.55, 6.82, 7.08, 7.18, 7.26, 7.44, 7.47; MS (ESI+) for C22H25N3O2 m/z 364.1 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. customthe residue was partitioned between EtOAc and 1N NaOH
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. filtrationthe salt was collected by filtration
  10. dry with materialThe salt was dried under vacuum over P2O5

Sources & evidence

ORD record
ord-f5193c6fd4c24644a7454dd29fb712c8
Source dataset
uspto-grants-2003_06
Patent number
US06583135B2

Reaction notes

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