7H-indolo[2,1-a][2]benzazepine-10-carboxamide → 5H-indolo[2,1-a][2]benzazepine-10-carboxamide

HRID 1453373Notes

Reaction equation

HRID 1453373 reaction equation
[CH:1]1[C:11]2[C:10]3=[CH:12][C:13]4[CH:14]=[CH:15][C:16]([C:19]([NH2:21])=[O:20])=[CH:17][C:18]=4[N:9]3[CH2:8][CH:7]=[CH:6][C:5]=2[CH:4]=[CH:3][CH:2]=1>[Pd].CO>[CH:1]1[C:11]2[C:10]3=[CH:12][C:13]4[CH:14]=[CH:15][C:16]([C:19]([NH2:21])=[O:20])=[CH:17][C:18]=4[N:9]3[CH:8]=[CH:7][CH2:6][C:5]=2[CH:4]=[CH:3][CH:2]=1

Participants

4

Reactant 1

HCID 666396907H-indolo[2,1-a][2]benzazepine-10-carboxamide

Product 1

HCID 668140775H-indolo[2,1-a][2]benzazepine-10-carboxamide

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalyst2×HCID 887MethanolSolvent

Procedure

10% Palladium on carbon (84 mg, 0.08 mmol) was added to a solution of 7H-indolo[2,1-a][2]benzazepine-10-carboxamide, 13-cyclohexyl-N-[(dimethylamino)sulfonyl]-6-[[4-(methylsulfonyl)-1-piperazinyl]carbonyl]- (84 mg, 0.14 mmol) in MeOH (6 mL) and the reaction mixture was vacuum flushed with nitrogen (3×) and then with hydrogen (3×). The reaction mixture was stirred under a balloon of hydrogen for 1 d. Additional 10% palladium on carbon (100 mg, 0.9 mmol) was added and the reaction mixture was vacuum flushed with nitrogen (3×), with hydrogen (3×) and then stirred under a balloon of hydrogen for 3 d. The reaction mixture was filtered through a pad of celite and concentrated. The residue was purified by preparative HPLC (MeOH/H2O with an NH4OAc buffer) to yield 5H-indolo[2,1-a][2]benzazepine-10-carboxamide, 13-cyclohexyl-N-[(dimethylamino)sulfonyl]-6,7-dihydro-6-[[4-(methylsulfonyl)-1-piperazinyl]carbonyl]- (39 mg, 0.06 mmol, 44%) as a yellow solid. Mixture of atrope diastereomers: 1HNMR (500 MHz, CD3OD) δ 8.10 (s. 0.3H), 8.02 (s. 0.7H), 7.92 (d, J=8.6 Hz, 0.3H), 7.90 (d, J=8.6 Hz, 0.7H), 7.63 (d, J=8.5 Hz, 0.3H), 7.58 (d, J=8.5 Hz, 0.7H), 7.53-7.31 (m, 4H), 4.64-4.47 (m, 1H), 4.15-3.64 (m, 5H), 3.55-3.27 (m, 5H), 3.04-2.96 (m, 9H), 2.94-2.76 (m, 3H), 2.19-1.23 (m, 10H). LCMS: m/e 654 (M−H)−, ret time 1.73 min, column A, 3 minute gradient.

Workup

  1. customflushed with nitrogen (3×)
  2. customflushed with nitrogen (3×), with hydrogen (3×)
  3. stirringstirred under a balloon of hydrogen for 3 d
  4. filtrationThe reaction mixture was filtered through a pad of celite
  5. concentrationconcentrated
  6. customThe residue was purified by preparative HPLC (MeOH/H2O with an NH4OAc buffer)

Sources & evidence

ORD record
ord-ef91596f502e4270ae34d01e1a200733
Source dataset
uspto-grants-2009_01
Patent number
US07473688B2

Reaction notes

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