Phosphorus oxychloride → 4-chloro-N-[2-(diethylamino)ethyl]-6-iodoquinoline-3-carboxamide

HRID 2273661Notes

Reaction equation

HRID 2273661 reaction equation
[CH2:1]([N:3]([CH2:21][CH3:22])[CH2:4][CH2:5][NH:6][C:7]([C:9]1[C:18](=O)[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([I:20])[CH:16]=2)[NH:11][CH:10]=1)=[O:8])[CH3:2].P(Cl)(Cl)([Cl:25])=O>>[Cl:25][C:18]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([I:20])[CH:16]=2)[N:11]=[CH:10][C:9]=1[C:7]([NH:6][CH2:5][CH2:4][N:3]([CH2:21][CH3:22])[CH2:1][CH3:2])=[O:8]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 59228685N-(2-diethylaminoethyl)-1,4-dihydro-6-iodo-4-oxoquinoline-3-carboxamide

Product 1

HCID 669425004-chloro-N-[2-(diethylamino)ethyl]-6-iodoquinoline-3-carboxamideYield 76%

Procedure

A stirred solution of compound 94 (9.00 g, 21.8 mmol) in phosphorus oxychloride (50 mL) was heated at 100° C. for 20 min. After cooling to room temperature, the solvent was evaporated under vacuum. The residue was poured into crushed ice (100 g). A 10% aqueous sodium hydrogenocarbonate solution (100 mL) and dichloromethane (100 mL) were added successively at 0° C. The mixture was stirred until the brown oil was totally dissolved. The solution was decanted and the aqueous layer was then extracted with dichloromethane (3×200 mL). The organic layers were combined, dried on magnesium sulfate, filtered and evaporated under reduced pressure. The residue was chromatographed (Al2O3, AcOEt/cyclohexane, 9/1, v/v) to give compound 95 (7.12 g, 16.5 mmol) as a yellow solid. Yield 76%; Rf (Al2O3, AcOEt/cyclohexane, 9/1, v/v) 0.34; mp 76-78° C.: IR (KBr) ν 1329, 1477, 1558, 1636, 2798, 2966, 3300 cm−1; 1H NMR (400 MHz, CDCl3) δ 1.01 (t, 6H, J=7.1 Hz), 2.58 (q, 4H, J=7.1 Hz), 2.70 (t, 2H, J=5.8 Hz), 3.55 (q, 2H, J=5.8 Hz), 7.39 (se, 1H), 7.73 (d, 1H, J=8.8 Hz), 7.96 (dd, 1H, J=1.8, 8.8 Hz), 8.55 (d, 1H, J=1.8 Hz), 8.93 (s, 1H); MS m/z 433 (M+2, 2), 431 (M+, 6), 417 (3), 415 (8), 317 (6), 315 (20), 289 (2), 287 (6), 189 (6), 161 (9), 128 (5), 99 (6), 86 (100), 72 (6), 56 (13).

Workup

  1. customthe solvent was evaporated under vacuum
  2. additionThe residue was poured
  3. custominto crushed ice (100 g)
  4. additionA 10% aqueous sodium hydrogenocarbonate solution (100 mL) and dichloromethane (100 mL) were added successively at 0° C
  5. dissolutionwas totally dissolved
  6. customThe solution was decanted
  7. extractionthe aqueous layer was then extracted with dichloromethane (3×200 mL)
  8. customdried on magnesium sulfate
  9. filtrationfiltered
  10. customevaporated under reduced pressure
  11. customThe residue was chromatographed (Al2O3, AcOEt/cyclohexane, 9/1

Sources & evidence

ORD record
ord-b6dcc744e78b4768b7eeeba6dc21092f
Source dataset
uspto-grants-2015_09
Patent number
US09125937B2

Reaction notes

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