Heptane → N-(2-diethylaminoethyl)-1,4-dihydro-6-iodo-4-oxoquinoline-3-carboxamide

HRID 2273660Notes

Reaction equation

HRID 2273660 reaction equation
C[Al](C)C.CCCCCCC.[CH2:12]([N:14]([CH2:18][CH3:19])[CH2:15][CH2:16][NH2:17])[CH3:13].[I:20][C:21]1[CH:22]=[C:23]2[C:28](=[CH:29][CH:30]=1)[NH:27][CH:26]=[C:25]([C:31](OCC)=[O:32])[C:24]2=[O:36].NC(C1C=CC2C(=CC=CC=2)N=1)=O>ClCCl.O>[CH2:12]([N:14]([CH2:18][CH3:19])[CH2:15][CH2:16][NH:17][C:31]([C:25]1[C:24](=[O:36])[C:23]2[C:28](=[CH:29][CH:30]=[C:21]([I:20])[CH:22]=2)[NH:27][CH:26]=1)=[O:32])[CH3:13]

Participants

8

Reactant 5

HCID 8900HeptaneHCID 60993N,N-DiethylethylenediamineHCID 1457872-QuinolinecarboxamideHCID 719682Ethyl 6-iodo-4-oxo-1,4-dihydro-3-quinolinecarboxylateHCID 16682925Trimethylaluminum

Product 1

HCID 59228685N-(2-diethylaminoethyl)-1,4-dihydro-6-iodo-4-oxoquinoline-3-carboxamideYield 81%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of a 2.0 M trimethylaluminium solution in heptane (20.8 mL, 41.6 mmol) in anhydrous dichloromethane (350 mL) was added at 0° C., under argon, N,N-diethylethylenediamine (5.78 mL, 41.1 mmol) dropwise. After 10 min, ethyl 6-iodo-4-oxo-1,4-dihydroquinoline-3-carboxylate (93) (10.0 g, 31.4 mmol) (Edlin, C.; Eldred, C. D.; Lunniss, C. J.; Redgrave, A. J.; Robinson, J. E.; Woodrow, M. Preparation of aminocarbonylquinoline derivatives as phosphodiesterase type IV (PDE4) inhibitors. Patent WO2005030725, 2005) was added. The mixture was refluxed for 12 h. After cooling to room temperature, water (500 mL) was added and the precipitate was filtered and washed with ethanol (2×100 mL). The filtrate was evaporated under vacuum. The residue was chromatographed (Al2O3, CH2Cl2/EtOH, 94/6, v/v) to give amide 94 (9.70 g, 23.5 mmol) as a beige solid. Yield 81%; Rf (Al2O3, CH2Cl2/EtOH, 94/6, v/v) 0.32; mp 243-245° C.; IR (KBr) ν 1466, 1507, 1551, 1633, 2800-3000, 3062 cm−1; 1H NMR (200 MHz, DMSO-d6) δ 1.23 (t, 6H, J=7.1 Hz), 3.17 (q, 4H, J=7.1 Hz), 3.23 (t, 2H, J=6.8 Hz), 3.71 (q, 2H, J=6.4 Hz), 7.59 (d, 1H, J=8.6 Hz), 8.05 (dd, 1H, J=2.0, 8.6 Hz), 8.51 (d, 1H, J=2.0 Hz), 8.72 (s, 1H), 10.04 (t, 1H, J=5.8 Hz), 10.13 (se, 1H); ESI-MS m/z 413.8 [M+H]+.

Workup

  1. additionPatent WO2005030725, 2005) was added
  2. temperatureThe mixture was refluxed for 12 h
  3. filtrationthe precipitate was filtered
  4. washwashed with ethanol (2×100 mL)
  5. customThe filtrate was evaporated under vacuum
  6. customThe residue was chromatographed (Al2O3, CH2Cl2/EtOH, 94/6, v/v)

Sources & evidence

ORD record
ord-6922f14d6f4a4406a1f796d74514efab
Source dataset
uspto-grants-2015_09
Patent number
US09125937B2

Reaction notes

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