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

HRID 1453394Notes

Reaction equation

HRID 1453394 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:74]1[O:78][CH:77]=[CH:76][CH: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:74]4[O:78][CH:77]=[CH:76][CH:75]=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 3438FurfurylamineHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 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 1666716813-cyclohexyl-N-(2-furanylmethyl)-6-[[4-(4-morpholinyl)-1-piperidinyl]carbonyl]-7H-indolo[2,1-a][2]benzazepine-10-carboxamideYield 95%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Procedure

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 furfuryl amine (10 mg, 0.1 mmol) in CH2Cl2 (1.5 mL) was stirred at r.t. overnight, diluted with CH2Cl2 (3 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 a pale yellow solid (42 mg, 95% yield). LC/MS (ESI) retention time: 1.74 min, m/z 633 (MH+); 1H NMR (400 MHz, CDCl3 ) δ 1.29-1.44 (m, 3 H) 1.46-1.57 (m, 1 H) 1.69-1.81 (m,3 H) 1.86-1.97 (m, 1 H) 1.98-2.11 (m, 3 H) 2.27-2.37 (m, 1 H) 2.38-2.49 (m, 4 H) 2.61-2.78 (m, 2 H) 2.78-2.89 (m, 1 H) 3.66 (s, 4 H) 4.38 (s, 1 H) 4.66 (d, J=5.29 Hz, 2 H) 5.06 (s, 1 H) 6.22-6.41 (m, 2 H) 6.64 (t, J=5.04 Hz, 1 H) 6.81 (s, 1 H) 7.33-7.50 (m, 5 H) 7.51-7.61 (m, 1 H) 7.85 (d, J=8.31 Hz, 1 H) 7.97 (s, 1 H); 13C NMR (101 MHz, CDCl3) δ 26.20, 27.02, 33.27, 36.73, 37.04, 41.92, 49.45, 61.67, 66.94, 107.54, 108.90, 110.48, 116.84, 120.05, 121.19, 127.05, 127.95, 128.21, 129.24, 130.08, 130.96, 131.24, 133.24, 134.00, 135.18, 136.39, 142.15, 151.57, 167.74, 168.88.

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-dadf323bce9e4759a400f3b0c6fb35a5
Source dataset
uspto-grants-2009_01
Patent number
US07473688B2

Reaction notes

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