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

HRID 1071048Notes

Reaction equation

HRID 1071048 reaction equation
[CH3:1][C:2]1[C:32]([CH3:33])=[CH:31][CH:30]=[CH:29][C:3]=1[NH:4][C:5](=[O:28])[CH2:6][N:7]1[C:15]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:9]2[CH2:16][CH2:17][N:18](C(OC(C)(C)C)=O)[CH2:19][CH2:20][C:8]1=2.FC(F)(F)C(O)=O.C(Cl)[Cl:42]>>[ClH:42].[CH3:1][C:2]1[C:32]([CH3:33])=[CH:31][CH:30]=[CH:29][C:3]=1[NH:4][C:5](=[O:28])[CH2:6][N:7]1[C:15]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:9]2[CH2:16][CH2:17][NH:18][CH2:19][CH2:20][C:8]1=2

Participants

4

Reactant 3

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 22396686tert-butyl 6-[2-(2,3-dimethylanilino)-2-oxoethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate

Product 1

HCID 22396810N-(2,3-dimethylphenyl)-2-(2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)acetamide hydrochlorideYield 89%

Procedure

tert-Butyl 6-[2-(2,3-dimethylanilino)-2-oxoethyl]-1,4,5,6-tetrahydroazepino[4,5-b]indole-3(2H)-carboxylate (1.02 g, 2.27 mmol) was disolved in CH2Cl2 (15 mL), then trifluoroacetic acid (3.0 mL, 4.44 g, 38.9 mmol, 17.2 equiv.) was added. The resulting solution was stirred at rt for 1.5 h. The reaction mixture was concentrated to dryness, then the residue was partitioned between EtOAc (100 mL) and 1N NaOH (50 mL). The layers were separated, and the aqueous layer was extracted with EtOAc (50 mL) The combined organic layers were washed with brine (25 mL), dried over MgSO4, filtered, and concentrated. The residue was combined with EtOAc (20 mL) and 1M HCl in Et2O (20 mL), then the salt was collected by filtration. The salt was dried under vacuum over P2O5. N-(2,3-dimethylphenyl)-2-(2,3,4,5-tetrahydroazepino[4,5-b]indol-6(1H)-yl)acetamide hydrochloride (0.7739 g) was obtained in 89% yield. 1H NMR (300 MHz, CD3OD) δ 2.11, 2.29, 3.23-3.26, 3.32-3.35, 3.47-3.56, 5.12, 7.06-7.15, 7.22, 7.44, 7.53; MS (ESI+) for C22H25N3O m/z 348.3 (M+H)+.

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. customthe residue was partitioned between EtOAc (100 mL) and 1N NaOH (50 mL)
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (50 mL) The combined organic layers
  5. washwere washed with brine (25 mL)
  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-84bcae1c31884f549ddc0c67c3059491
Source dataset
uspto-grants-2005_06
Patent number
US06903090B2

Reaction notes

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