1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 67169559, compound

HRID 545181Notes

Reaction equation

HRID 545181 reaction equation
CCN=C=NCCCN(C)C.[C:12]([NH:19][NH2:20])([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].C1C=CC2N(O)N=NC=2C=1.[CH3:31][O:32][C:33]1[C:42]2[C:37](=[C:38]([O:43][CH3:44])[CH:39]=[CH:40][CH:41]=2)[N:36]=[C:35]([C:45]([N:47]2[CH2:52][CH2:51][C:50]3([CH2:61][C:60](=[O:62])[C:59]4[C:54](=[CH:55][CH:56]=[C:57]([C:63](O)=[O:64])[CH:58]=4)[O:53]3)[CH2:49][CH2:48]2)=[O:46])[CH:34]=1>C(OCC)(=O)C.CN(C=O)C>[CH3:31][O:32][C:33]1[C:42]2[C:37](=[C:38]([O:43][CH3:44])[CH:39]=[CH:40][CH:41]=2)[N:36]=[C:35]([C:45]([N:47]2[CH2:52][CH2:51][C:50]3([CH2:61][C:60](=[O:62])[C:59]4[C:54](=[CH:55][CH:56]=[C:57]([C:63]([NH:20][NH:19][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[O:64])[CH:58]=4)[O:53]3)[CH2:49][CH2:48]2)=[O:46])[CH:34]=1

Participants

7

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 70091tert-Butyl carbazateHCID 757711-HydroxybenzotriazoleHCID 16042340HCID 16042340, compound

Product 1

HCID 67169559HCID 67169559, compoundYield 91.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

50.6 mg of EDCI was added to a mixture of 29.1 mg of Boc-hydrazine, 33.7 mg of HOBT, 105 mg of 1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-6-(carboxy)spiro[chroman-2,4′-piperidin]-4-one and 2.2 mL of DMF, and the resulting mixture was stirred at room temperature for 14 hours. The reaction mixture was diluted with 15 mL of ethyl acetate, washed with water and aqueous saturated NaHCO3 solution, and dried over sodium sulfate. The residue was purified through silica gel chromatography (2% MeOH/CHCl3) to obtain 119 mg of tert-butyl 2-({1′-[(4,8-dimethoxyquinolin-2-yl)carbonyl]-4-oxospiro[chroman-2,4′-piperidin]-6-yl}carbonyl)hydrazinecarboxylate. 2 mL of 4 N HCl in dioxane was added to 59.1 mg of the product, and stirred at room temperature for 1 hour, and then concentrated. The residue was suspended in 2.5 mL of THF, and 0.049 μL of triethylamine and 24.3 mg of CDI were added thereto at 0° C., and stirred at room temperature for 14 hours. Water was added to the reaction solution, and extracted with chloroform, and the organic layer was dried over sodium sulfate and concentrated. The residue was purified through silica gel thin-layer chromatography (17% MeOH/CHCl3) to obtain the intended compound. 1H-NMR (CDCl3) δ: 8.85 (1H, br s), 8.38 (1H, d, J=2.2 Hz), 7.97 (1H, dd, J=2.2, 8.8 Hz), 7.77 (1H, dd, J=8.5, 1.0 Hz), 7.47 (1H, dd, J=7.8, 8.5 Hz), 7.20 (1H, s), 7.13 (1H, d, J=8.8 Hz), 7.08 (1H, dd, J=1.0, 7.8 Hz), 4.64-4.56 (1H, m), 4.24-4.16 (1H, m), 4.09 (3H, s), 4.03 (3H, s), 3.67-3.58 (1H, m), 3.43-3.34 (1H, m), 2.87 (1H, d, J=16.8 Hz), 2.81 (1H, d, J=16.8 Hz), 2.26-2.18 (1H, m), 2.11-2.04 (1H, m), 2.01-1.87 (2H, m). MS [M+H]+=517.

Workup

  1. washwashed with water and aqueous saturated NaHCO3 solution
  2. dry with materialdried over sodium sulfate
  3. customThe residue was purified through silica gel chromatography (2% MeOH/CHCl3)

Sources & evidence

ORD record
ord-8e5807ab5d1f42899d201430a1d84486
Source dataset
uspto-grants-2011_05
Patent number
US07935712B2

Reaction notes

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