Sodium Bicarbonate → 7-Chloro-4-(4-chloro-5-methoxy-2-methylanilino)-6-nitro-3-quinolinecarbonitrile

HRID 2213727Notes

Reaction equation

HRID 2213727 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:15])=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:16]#[N:17].Cl.N1C=CC=CC=1.[Cl:25][C:26]1[C:32]([O:33][CH3:34])=[CH:31][C:29]([NH2:30])=[C:28]([CH3:35])[CH:27]=1.C(=O)(O)[O-].[Na+]>C(OCCO)C.O>[Cl:15][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:30][C:29]3[CH:31]=[C:32]([O:33][CH3:34])[C:26]([Cl:25])=[CH:27][C:28]=3[CH3:35])=[C:3]([C:16]#[N:17])[CH:4]=[N:5]2)=[CH:10][C:9]=1[N+:12]([O-:14])=[O:13]

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 10176127Pyridinium chlorideHCID 123258794-Chloro-5-methoxy-2-methylanilineHCID 219564524,7-Dichloro-6-nitroquinoline-3-carbonitrile

Product 1

HCID 219563917-Chloro-4-(4-chloro-5-methoxy-2-methylanilino)-6-nitro-3-quinolinecarbonitrileYield 82.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8076Glycol monoethyl etherSolvent

Conditions

Temperature
120 °C

Procedure

To a stirred suspension of 0.9 g (3.3 mmol) of 4,7-dichloro-6-nitro-3-quinolinecarbonitrile and pyridine hydrochloride (0.381 g, 3.3 mmol) in 2-ethoxyethanol (10 mL) under nitrogen, is added 0.634 g (3.69 mmol) of 4-chloro-5-methoxy-2-methylaniline (WO 8501939 A1). The reaction is stirred at 120° C. for 4 hours. The mixture is then cooled to room temperature and solid sodium bicarbonate is added until foaming subsided. Water is added to the reaction mixture (40 mL), which is subsequently extracted with 3×30 mL ethyl acetate. After combining the organic portions and drying with sodium sulfate, the solvents are removed in vacuo. The residue obtained is purified by flash chromatography, eluting with 99.5:0.5 methylene chloride/methanol. The solid obtained is recrystallized from hot ethyl acetate to afford 1.1 g of an orange crystalline solid, mp 217–219° C.

Workup

  1. temperatureThe mixture is then cooled to room temperature
  2. extractionis subsequently extracted with 3×30 mL ethyl acetate
  3. dry with materialdrying with sodium sulfate
  4. customthe solvents are removed in vacuo
  5. customThe residue obtained
  6. customis purified by flash chromatography
  7. washeluting with 99.5:0.5 methylene chloride/methanol
  8. customThe solid obtained
  9. customis recrystallized from hot ethyl acetate

Sources & evidence

ORD record
ord-75cea26743284a65b9b248790b865816
Source dataset
uspto-grants-2006_09
Patent number
US07105531B2

Reaction notes

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