Trifluoroacetic acid → 4-(Benzyloxy)-1-(10-methyl-1,2,3,4,5,10-hexahydroazepino[3,4-b]indol-8-yl)pyridin-2(1H)-one

HRID 474899Notes

Reaction equation

HRID 474899 reaction equation
FC(F)(F)C(O)=O.C(OC([N:15]1[CH2:28][CH2:27][CH2:26][C:25]2[C:24]3[C:19](=[CH:20][C:21]([N:29]4[CH:34]=[CH:33][C:32]([O:35][CH2:36][C:37]5[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=5)=[CH:31][C:30]4=[O:43])=[CH:22][CH:23]=3)[N:18]([CH3:44])[C:17]=2[CH2:16]1)=O)(C)(C)C>C(Cl)Cl>[CH2:36]([O:35][C:32]1[CH:33]=[CH:34][N:29]([C:21]2[CH:20]=[C:19]3[C:24]([C:25]4[CH2:26][CH2:27][CH2:28][NH:15][CH2:16][C:17]=4[N:18]3[CH3:44])=[CH:23][CH:22]=2)[C:30](=[O:43])[CH:31]=1)[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 58093460tert-Butyl-8-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-10-methyl-3,4,5,10-tetrahydroazepino[3,4-b]indole-2(1H)-carboxylate

Product 1

HCID 498694884-(Benzyloxy)-1-(10-methyl-1,2,3,4,5,10-hexahydroazepino[3,4-b]indol-8-yl)pyridin-2(1H)-oneYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (1.0 mL) was added to a solution of tert-butyl-8-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-10-methyl-3,4,5,10-tetrahydroazepino[3,4-b]indole-2(1H)-carboxylate (54 mg, 0.11 mmol) in CH2Cl2 (2.0 mL), and the resulting solution was stirred at ambient temperature for 30 min. The mixture was carefully quenched with saturated NaHCO3 solution until the solution was basic. The mixture was extracted with CH2Cl2 (3×25 mL). The combined organic extracts were washed with brine (50 mL), dried over Na2SO4 and concentrated to dryness under reduced pressure. Flash chromatography (12 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 5 column volumes, increased to 0:100 over 20 column volumes and held for 15 column volumes) provided the title compound (31 mg, 73%) as an off-white solid: 1H NMR (500 MHz, CDCl3) δ 7.53 (d, J=8.5 Hz, 1H), 7.43-7.36 (m, 5H), 7.30 (d, J=7.5 Hz, 1H), 7.23 (d, J=2.0 Hz, 1H), 6.99 (dd, J=8.0, 1.5 Hz, 1H), 6.08 (d, J=2.5 Hz, 1H), 6.03 (dd, J=7.5, 3.0 Hz, 1H), 5.05 (s, 2H), 4.10 (s, 2H), 3.64 (s, 3H), 3.23 (t, J=5.5 Hz, 2H), 2.92 (t, J=6.0 Hz, 2H), 1.90-1.86 (s, 2H); ESI MS m/z 400 [M+H]+.

Workup

  1. customThe mixture was carefully quenched with saturated NaHCO3 solution until the solution
  2. extractionThe mixture was extracted with CH2Cl2 (3×25 mL)
  3. washThe combined organic extracts were washed with brine (50 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated to dryness under reduced pressure
  6. temperatureFlash chromatography (12 g ISCO column, CH2Cl2/(80:18:2 CH2Cl2/MeOH/NH4OH), 100:0 for 5 column volumes, increased to 0:100 over 20 column volumes and held for 15 column volumes)

Sources & evidence

ORD record
ord-c5c8ebd3f301446caac0b0716d8ada00
Source dataset
uspto-grants-2014_01
Patent number
US08637501B2

Reaction notes

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