Sodium Iodide → 4-(4-Chloro-2-fluoro-5-hydroxy-phenylamino)-6-methoxy-7-(2-morpholin-4-yl-ethoxy)-quinoline-3-carbonitrile

HRID 612044Notes

Reaction equation

[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24]Cl)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:26]#[N:27])=[C:4]([F:28])[CH:3]=1.[NH:29]1[CH2:34][CH2:33][O:32][CH2:31][CH2:30]1.[I-].[Na+]>COCCOC>[Cl:1][C:2]1[C:7]([OH:8])=[CH:6][C:5]([NH:9][C:10]2[C:19]3[C:14](=[CH:15][C:16]([O:22][CH2:23][CH2:24][N:29]4[CH2:34][CH2:33][O:32][CH2:31][CH2:30]4)=[C:17]([O:20][CH3:21])[CH:18]=3)[N:13]=[CH:12][C:11]=2[C:26]#[N:27])=[C:4]([F:28])[CH:3]=1

Participants

Conditions

Temperature: 135 °C

Procedure

A mixture of 0.8 g (1.83 mmol) of 4-(4-chloro-2-fluoro-5-hydroxy-phenylamino)-7-(2-chloro-ethoxy)-6-methoxy-quinoline-3-carbonitrile, 2.4 g (27.5 mmol) of morpholine, and 0.11 g of sodium iodide in 15 ml ethylene glycol dimethyl ether heated in a sealed tube at 135° C. for 12 hr. The solvent was removed and the residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution. The organic layer was separated and dried over magnesium sulfate. Solvent was removed and the residue was chromatographed on silica gel eluting with ethyl acetate-methanol-triethylamine 70:30:1 giving 0.43 g of the title compound as a tan solid: mass spectrum (electrospray, m/e) M+H 470.0; (M+2H)+2 237.0.

Workup

customThe solvent was removed
additionthe residue was mixed with warm ethyl acetate and saturated sodium bicarbonate solution
customThe organic layer was separated
dry with materialdried over magnesium sulfate
customSolvent was removed
customthe residue was chromatographed on silica gel eluting with ethyl acetate-methanol-triethylamine 70:30:1 giving 0.43 g of the title compound as a tan solid

Sources & evidence

ORD record: ord-8fe91af07453432782c880a1330a32c8
Source dataset: uspto-grants-1999_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06002008

Reaction notes

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