8-chloro-1,7-Naphthyridine-3-carbonitrile synthesis

8synthesis methods

Product Name:8-chloro-1,7-Naphthyridine-3-carbonitrile
CAS Number:1600511-81-6
Molecular formula:C9H4ClN3
Molecular Weight:189.6

557-21-1 Synthesis

557-21-1
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1393575-76-2 Synthesis

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8-chloro-1,7-Naphthyridine-3-carbonitrile

1600511-81-6
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Yield:1600511-81-6 50 mg

Reaction Conditions:

Stage #1: zinc(II) cyanide;3-chloro-1,7-naphthyridin-8(7H)-onewith dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane;tris-(dibenzylideneacetone)dipalladium⁽⁰⁾ in water;N,N-dimethyl-formamide at 110; for 1 h;Inert atmosphere;Sealed tube;
Stage #2: with N-ethyl-N,N-diisopropylamine;trichlorophosphate in toluene at 120; for 1.5 h;

Steps:

4 8-chloro-1,7-naphthyridine-3-carbonitrile

A screw-cap vial was charged with 3-chloro-l,7-naphthyridin-8(7//)-one (100 mg, 0.554 mmol), zinc cyanide (52.7 μ, 0.831 mmol), 2-dicyclohexylphosphino-2',6'- dimethoxybiphenyl (45.5 mg, 0.111 mmol), tris(dibenzylideneacetone)dipalladium(0) (40.6 mg, 0.044 mmol), DMF (2.74 mL) and water (28 μ). The vial was purged with argon, sealed, and stirred at 110 °C for 1 hour. The mixture was filtered through a pad of Celite, which was rinsed with methanol and dimethylsulfoxide. The combined filtrates were concentrated, and a few drops of water were added. The resulting solids were collected by vacuum filtration, rinsed with water and dried. The solids were suspended in A-1813-WO-PCT - 142 - toluene (3.5 mL), and phosphorus oxychloride (98 μ,, 1.052 mmol) and DIPEA (122 μ,, 0.701 mmol) were added. The reaction was stirred at 120 °C for 1.5 hours, cooled to RT, diluted with EtOAc, and washed with 2 M aqueous sodium carbonate. The organic portion was dried over anhydrous sodium sulfate, filtered and concentrated. The crude material was purified by silica gel chromatography, eluting with 5-50% EtOAc in heptanes, to provide the title compound (50 mg, 0.264 mmol) as a white solid. LC/MS (ESI⁺) m/z = 190 (M+H) ⁺

References:

WO2014/138484,2014,A1 Location in patent:Page/Page column 141; 142

657408-07-6 Synthesis