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HuagongsheHuagongshe Chemistry Print Report · For research reference only
HRID 2374092Generated: October 30, 2026

Toluene → HCID 59853008, compound

https://huagongshe.com/reaction/2374092

Reaction equation

Participants

RoleNameHCIDCharge
ReactantTolueneHCID 1140—
ReactantDiethyl EtherHCID 3283—
ReactantPhosgeneHCID 6371—
ReactantDiisopropylethylamineHCID 81531—
Reactant4-(4-Amino-2-fluorophenoxy)picolinamideHCID 23153205—
ReactantHCID 56919414HCID 56919414—
ReactantN-(4-(6-(4-(Benzyloxy)phenylamino)pyrimidin-4-yloxy)-3-fluorophenyl)-N3-(4-fluorophenyl)malonamideHCID 59853038—
ReactantHCID 178418348HCID 178418348—
SolventDimethylformamideHCID 6228—
SolventTetrahydrofuranHCID 8028—
ProductHCID 59853008HCID 5985300833%

Reaction Conditions

Temperature-78 °C

Reaction Steps

To a solution of 2-(4-fluorophenyl)-N-methylacetamide (89 mg, 0.53 mmol) in 2 mL of THF at −78° C. was added MeLi in Et2O (1.6 M, 0.34 mL, 0.55 mmol). The solution was stirred at −78° C. for 5 min and then 20% phosgene in toluene (1.9 M, 0.29 mL, 0.55 mmol) was introduced quickly. After 2 min, 4-(4-amino-2-fluorophenoxy)picolinamide (Compound B′ of Example 24, 100 mg, 0.40 mmol) was added, followed by the addition of DMF (2 mL) and DIEA (0.4 mL). The reaction mixture was stirred at room temperature for 1 h and quenched with H2O. The solution was then extracted with EtOAc and the organic layer was washed with brine, dried over MgSO4. After filtration and concentration, the residue was purified by silica gel chromatography to give the title compound (77 mg, 33%). MS(ESI+) m/z 441 (M+H)+.

Provenance & Evidence

DOI10.6084/m9.figshare.5104873.v1
Patent numberUS07459562B2
Source datasetuspto-grants-2008_12
ORD IDord-ec628043c22a4e22824d862415d30303
Source noteuspto-grants-2008_12