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

HRID 2218288Notes

Reaction equation

HRID 2218288 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 mL 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-edab7439646d4b54b9e37b5380b9c1d7
Source dataset
uspto-grants-2008_08
Patent number
US07410976B2

Reaction notes

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