1-Hydroxybenzotriazole → 13-cyclohexyl-N-(imidazo[1,2-a]pyridin-2-ylmethyl)-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxamide

HRID 1453392Notes

Reaction equation

HRID 1453392 reaction equation
[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:39](O)=[O:40])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]([N:23]4[CH2:28][CH2:27][CH:26]([N:29]5[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)[CH2:25][CH2:24]4)=[O:22])=[CH:18][C:17]4[CH:35]=[CH:36][CH:37]=[CH:38][C:16]=4[C:15]=23)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.Cl.Cl.[NH2:53][CH2:54][C:55]1[N:56]=[C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][N:58]2[CH:63]=1.Cl.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1>C(Cl)Cl>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:39]([NH:53][CH2:54][C:55]4[N:56]=[C:57]5[CH:62]=[CH:61][CH:60]=[CH:59][N:58]5[CH:63]=4)=[O:40])=[CH:12][C:13]=3[N:14]3[CH2:20][C:19]([C:21]([N:23]4[CH2:24][CH2:25][CH:26]([N:29]5[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)[CH2:27][CH2:28]4)=[O:22])=[CH:18][C:17]4[CH:35]=[CH:36][CH:37]=[CH:38][C:16]=4[C:15]=23)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2771120Imidazo[1,2-a]pyridin-2-ylmethanamine dihydrochlorideHCID 5752668313-cyclohexyl-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

Product 1

HCID 1666716713-cyclohexyl-N-(imidazo[1,2-a]pyridin-2-ylmethyl)-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxamideYield 35%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 13-cyclohexyl-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid (70 mg, 0.13 mmol) in CH2Cl2 (1 mL) were added N,N-diisopropylethylamine (85 μL, 0.49 mmol), 2-aminomethylimidazo[1,2-a]pyridine dihydrochloride (36 mg, 0.16 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (34 mg, 0. 18 mmol), and 1-hydroxybenzotriazole (24 mg, 0.18 mmol). The suspension was allowed to stir at r.t. for 17 hr, and the solvent was removed under reduced pressure. The resulting solid was suspended in DMF (1 mL) and stirred for an additional 4 hr before being concentrated under reduced pressure, dissolved in CH2Cl2, filtered through Celite, and chromatographed on silica gel (gradient elution: 0%→20% MeOH in CH2Cl2) to afford the title compound as a yellow solid (22 mg, 35% yield). LC/MS (ESI) retention time: 1.53 min, m/z 683 (MH+); 1H NMR (400 MHz, CDCl3) δ 1.13-1.21 (m, 1 H) 1.29-1.45 (m, 4 H) 1.57-1.67 (m, 1 H) 1.69-1.79 (m,2 H) 1.84-1.95 (m, 1 H) 1.96-2.12 (m, 3 H) 2.30-2.31 (m, 4 H) 2.57-2.75 (m, 2 H) 2.80-2.81 (m, 1 H) 3.60 (s, 4 H) 4.36 (s, 1 H) 4.80 (s, 2 H) 5.06 (s, 1 H) 6.74 (t, J=6.42 Hz, 1 H) 6.79 (s, 1 H) 7.07-7.18 (m, 1 H) 7.32-7.37 (m, 2 H) 7.39-7.46 (m, 2 H) 7.47-7.56 (m, 3 H) 7.60 (s, 1 H) 7.84 (d, J=8.56 Hz, 1 H) 7.99-8.10 (m, 2 H).

Workup

  1. customthe solvent was removed under reduced pressure
  2. stirringstirred for an additional 4 hr
  3. concentrationbefore being concentrated under reduced pressure
  4. dissolutiondissolved in CH2Cl2
  5. filtrationfiltered through Celite
  6. customchromatographed on silica gel (gradient elution: 0%→20% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-2fb490c2f263413f9f4aadc909814460
Source dataset
uspto-grants-2009_01
Patent number
US07473688B2

Reaction notes

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