Trifluoroacetic acid → 4-(4-Chlorobenzyloxy)-1-(6-methyl-1,2,3,4,5,6-hexahydroazepino[4,3-b]indol-8-yl)pyridin-2(1H)-one hydrochloride

HRID 475010Notes

Reaction equation

HRID 475010 reaction equation
[Cl:1][C:2]1[CH:38]=[CH:37][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][N:11]([C:14]3[CH:15]=[CH:16][C:17]4[C:18]5[CH2:28][N:27](C(OC(C)(C)C)=O)[CH2:26][CH2:25][CH2:24][C:19]=5[N:20]([CH3:23])[C:21]=4[CH:22]=3)[C:10](=[O:36])[CH:9]=2)=[CH:4][CH:3]=1.FC(F)(F)C(O)=O>ClCCl>[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][O:7][C:8]2[CH:13]=[CH:12][N:11]([C:14]3[CH:15]=[CH:16][C:17]4[C:18]5[CH2:28][NH:27][CH2:26][CH2:25][CH2:24][C:19]=5[N:20]([CH3:23])[C:21]=4[CH:22]=3)[C:10](=[O:36])[CH:9]=2)=[CH:37][CH:38]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 70805149tert-butyl 8-(4-(4-chlorobenzyloxy)-2-oxopyridin-1(2H)-yl)-6-methyl-3,4,5,6-tetrahydroazepino[4,3-b]indole-2(1H)-carboxylate

Product 1

HCID 668746694-(4-Chlorobenzyloxy)-1-(6-methyl-1,2,3,4,5,6-hexahydroazepino[4,3-b]indol-8-yl)pyridin-2(1H)-one hydrochlorideYield 78.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 8-(4-(4-chlorobenzyloxy)-2-oxopyridin-1(2H)-yl)-6-methyl-3,4,5,6-tetrahydroazepino[4,3-b]indole-2(1H)-carboxylate (100 mg, 0.19 mmol) in dichloromethane (20 mL) was trifluoroacetic acid (0.5 mL). The reaction mixture was stirred at room temperature for 2 h and then concentrated under reduced pressure. The residue was purified by preparative HPLC (Phenomenex Luna C18 (2), 250.0×50.0 mm, 10 micron, H2O with 0.05% TFA and CH3CN with 0.05% TFA). The clean fractions were combined and concentrated under reduced pressure. The trifluoracetate salt was converted to the HCl salt by dissolving in 1.25 M HCl in methanol and concentrating the resulting solution to dryness. This process was repeated three times afforded the title compound (35 mg, 39%) as an off-white solid: 1H NMR (500 MHz, CD3OD) δ 7.64 (d, J=8.0 Hz, 2H), 7.48-7.42 (m, 5H), 7.07 (dd, J=8.0, 2.0 Hz, 1H), 6.37 (dd, J=7.5, 2.5 Hz, 1H), 6.17 (d, J=3.0 Hz, 1H), 5.20 (s, 2H), 4.55 (s, 2H), 3.77 (s, 3H), 3.59-3.57 (m, 2H), 3.22-3.19 (m, 2H), 2.26-2.18 (m, 2H); ESI MS m/z 434 [M+H]+.

Workup

  1. concentrationconcentrated under reduced pressure
  2. customThe residue was purified by preparative HPLC (Phenomenex Luna C18 (2), 250.0×50.0 mm, 10 micron, H2O with 0.05% TFA and CH3CN with 0.05% TFA)
  3. concentrationconcentrated under reduced pressure
  4. dissolutionby dissolving in 1.25 M HCl in methanol
  5. concentrationconcentrating the resulting solution to dryness

Sources & evidence

ORD record
ord-a49a555879874185b9a5c858361b738c
Source dataset
uspto-grants-2014_01
Patent number
US08637501B2

Reaction notes

Loading…