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

HRID 1453372Notes

Reaction equation

HRID 1453372 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 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

10% Palladium on carbon (200 mg, 0.19 mmol) was added to a solution of 7H-indolo[2,1-a][2]benzazepine-10-carboxamide, 6-[(4-acetyl-1-piperazinyl)carbonyl]-13-cyclohexyl-N-[(dimethylamino)sulfonyl]- (79 mg, 0.13 mmol) in MeOH (10 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 3 d, 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, 6-[(4-acetyl-1-piperazinyl)carbonyl]-13-cyclohexyl-N-[(dimethylamino)sulfonyl]-6,7-dihydro- (16 mg, 0.03 mmol, 20%) as a white powder. Mixture of atrope diastereomers: 1HNMR (500 MHz, CD3OD) δ 8.09 (s. 0.3H), 7.99 (s. 0.7H), 7.91 (d, J=8.6 Hz, 0.3H), 7.89 (d, J=8.6 Hz, 0.7H), 7.63 (d, J=7.9 Hz, 0.3H), 7.59 (d, J=7.9 Hz, 0.7H), 7.52-7.28 (m, 4H), 4.64-4.56 (m, 0.7H), 4.50 (dd, J=6.1, 14.0 Hz, 0.3H), 4.14-4.05 (m, 0.3H), 3.94-3.57 (m, 9H), 3.02 (s, 4H), 3.01 (s, 2H), 2.98-2.91 (m, 1H), 2.88-2.68 (m, 2H), 2.19 (s, 2H), 2.11 (s, 1H), 2.16-1.91 (m, 4H), 1.87-1.76 (m, 2H) 1.67-1.22 (m, 4H). LCMS: m/e 618 (M−H)−, ret time 1.59 min, column A, 3 minute gradient.

Workup

  1. customflushed with nitrogen (3×)
  2. filtrationfiltered through a pad of celite
  3. concentrationconcentrated
  4. customThe residue was purified by preparative HPLC (MeOH/H2O with an NH4OAc buffer)

Sources & evidence

ORD record
ord-1272f700861a4d66b9161eef872c4c75
Source dataset
uspto-grants-2009_01
Patent number
US07473688B2

Reaction notes

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