1,2-Dibromoethane → 9-(3-Chloro-4-fluoroanilino)-2,3-dihydro-1H-[1,4]oxazino[3,2-g]quinoline-8-carbonitrile

HRID 396181

Reaction equation

HRID 396181 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[OH:12])[N:8]=[CH:7][C:6]([C:13]#[N:14])=[C:5]2[NH:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[C:18]([Cl:23])[CH:17]=1.Br[CH2:25][CH2:26]Br.C(=O)([O-])[O-].[K+].[K+]>C(OCCO)C>[Cl:23][C:18]1[CH:17]=[C:16]([CH:21]=[CH:20][C:19]=1[F:22])[NH:15][C:5]1[C:4]2[CH:3]=[C:2]3[NH:1][CH2:25][CH2:26][O:12][C:11]3=[CH:10][C:9]=2[N:8]=[CH:7][C:6]=1[C:13]#[N:14]

Participants

5

Reactant 3

HCID 78391,2-DibromoethaneHCID 11430Potassium CarbonateHCID 1358250776-Amino-4-(3-chloro-4-fluoro-phenylamino)-7-hydroxy-quinoline-3-carbonitrile

Product 1

HCID 99685229-(3-Chloro-4-fluoroanilino)-2,3-dihydro-1H-[1,4]oxazino[3,2-g]quinoline-8-carbonitrileYield 45.1%

Reagents, catalysts & solvents 1

HCID 8076Glycol monoethyl etherSolvent

Conditions

Temperature
135 °C

Procedure

An amount of 6-amino-4-(3-chloro-4-fluoro-phenylamino)-7-hydroxy-quinoline-3-carbonitrile (4 g, 12.2 mmol) was stirred in 2-ethoxyethanol (480 mL), and to this were added 1,2-dibromoethane (22.9 g, 12.2 mmol), and potassium carbonate (10.1 g, 73 mmol), and the mixture was heated at 135° C. for 0.5 hours. After cooling to room temperature, the mixture was filtered over a thin silica pad and evaporated to an oil. To this was added ethyl acetate and saturated brine solution, and the layers were separated. The organic layer was dried on sodium sulfate and evaporated to a brown oil. Purification was carried out by flash chromatography (70% ethyl acetate in hexane) to yield a yellow solid (1.95 g, 45% yield), m.p. 244-245° C.; 1H NMR (DMSO-d6) δ 9.32 (s, 1H), 8.29 (s, 1H), 7.36 (m, 2H), 7.19 (s, 1H), 7.12 (m, 2H), 6.59 (s, 1H), 4.27 (m, 2H), 3.37 (m, 2H); HRMS (EI) m/z 355.07512 (M+1). Analysis for C18H12ClFN4.O0.1H2O.0.4CH3CO2C2H5: Found: C, 59.59; H, 3.66; N, 14.69. Calcd: C, 59.97; H, 3.93; N, 14.29.

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe mixture was filtered over a thin silica pad
  3. customevaporated to an oil
  4. additionTo this was added ethyl acetate and saturated brine solution
  5. customthe layers were separated
  6. customThe organic layer was dried on sodium sulfate
  7. customevaporated to a brown oil
  8. customPurification

Sources & evidence

ORD record
ord-61a1e7f2c08747c3979ecb5de0eec882
Source dataset
uspto-grants-2003_08
Patent number
US06608048B2

Linked notes

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