1-Hydroxybenzotriazole → HCID 57526693, compound

HRID 1453396Notes

Reaction equation

HRID 1453396 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.CN(C)CCCN=C=NCC.ON1C2C=CC=CC=2N=N1.[CH2:73]([NH2:79])[C@H:74]1[O:78][CH2:77][CH2:76][CH2:75]1>C(Cl)Cl.CCOCC>[CH:1]1([C:7]2[C:8]3[CH:9]=[CH:10][C:11]([C:39]([NH:79][CH2:73][C@H:74]4[CH2:75][CH2:76][CH2:77][O:78]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[CH2:30][CH2:31][O:32][CH2:33][CH2:34]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)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 641530(S)-(+)-TetrahydrofurfurylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 5752668313-cyclohexyl-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid

Product 1

HCID 57526693HCID 57526693, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Procedure

13-cyclohexyl-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-N-[[(2S)-tetrahydro-2-furanyl]methyl-7H-indolo[2,1-a[2]benzazepine-10-carboxamide. A solution of 13-cyclohexyl-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxylic acid (40 mg, 0.07 mmol), N,N-diisopropylethylamine (60 μL, 0.34 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (19 mg, 0.1 mmol), 1-hydroxybenzotriazole (14 mg, 0.1 mmol), and (S)-(+)-tetrahydrofurfurylamine (10 mg, 0.1 mmol) in CH2Cl2 (1.5 mL) was stirred at r.t. overnight, diluted with CH2Cl2 (5 mL), and chromatographed on silica gel (gradient elution: 0%→10% MeOH in CH2Cl2) to afford a yellow oil. Et2O (5 mL) was added to dissolve the oil, and concentration afforded the title compound as an off-white solid (32 mg, 72% yield). LC/MS (ESI) retention time: 1.73 min, m/z 637 (MH+); 1H NMR (400 MHz, CDCl3) δ 1.27-1.43 (m, 3 H) 1.47-1.57 (m, 1 H) 1.58-1.70 (m, 2 H) 1.70-1.81 (m, 2 H) 1.86-1.97 (m, 3 H) 1.98-2.12 (m, 4 H) 2.25-2.35 (m, 1 H) 2.42 (s, 3 H) 2.63-2.77 (m, 1 H) 2.78-2.89 (m, 1 H) 3.29-3.46 (m, 1 H) 3.65 (s, 4 H) 3.74-3.85 (m, 2 H) 3.85-3.98 (m, 1 H) 4.09 (ddd, J=14.16, 7.11, 3.40 Hz, 1 H) 4.39 (s, 1 H) 5.08 (s, 1 H) 6.67-6.75 (m, 1 H) 6.82 (s, 1 H) 7.34-7.39 (m, 1 H) 7.40-7.50 (m, 3 H) 7.52-7.59 (m, 1 H) 7.86 (d, J=8.56 Hz, 1 H) 7.99 (s, 1 H).

Workup

  1. customchromatographed on silica gel (gradient elution: 0%→10% MeOH in CH2Cl2)
  2. customto afford a yellow oil
  3. dissolutionto dissolve
  4. concentrationthe oil, and concentration

Sources & evidence

ORD record
ord-3723a858daa648658f11f9ef9a3037d4
Source dataset
uspto-grants-2009_01
Patent number
US07473688B2

Reaction notes

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