Triethylamine → 2-(5-Chloro-2-fluoro-phenyl)-4-(5-triethylsilanylethynyl-pyridin-3-yl)-[1,8]naphthyridine

HRID 1404305Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([C:8]2[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[N:11]=[C:10]([C:18]3[CH:23]=[C:22]([Cl:24])[CH:21]=[CH:20][C:19]=3[F:25])[CH:9]=2)[CH:5]=[N:6][CH:7]=1.C(N(CC)CC)C.[CH2:33]([Si:35]([C:40]#[CH:41])([CH2:38][CH3:39])[CH2:36][CH3:37])[CH3:34]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl>[Cl:24][C:22]1[CH:21]=[CH:20][C:19]([F:25])=[C:18]([C:10]2[CH:9]=[C:8]([C:4]3[CH:5]=[N:6][CH:7]=[C:2]([C:34]#[C:33][Si:35]([CH2:40][CH3:41])([CH2:38][CH3:39])[CH2:36][CH3:37])[CH:3]=3)[C:17]3[C:12](=[N:13][CH:14]=[CH:15][CH:16]=3)[N:11]=2)[CH:23]=1

Participants

Conditions

Temperature: 120 °C

Procedure

A solution of 415 mg (1.00 mmol) 4-(5-bromo-pyridin-3-yl)-2-(5-chloro-2-fluoro-phenyl)-[1,8]naphthyridine in 5 ml DMF was flushed with nitrogen and subsequently treated with 70 mg (0.10 mmol) bis-(triphenylphosphine)-palladium(II)-chloride, 6.0 mg (0.03 mmol) cuprous iodide, 0.42 ml (3.0 mmol) triethylamine and 450 μl (2.5 mmol) triethylsilyl acetylene. The resulting slurry was stirred at 120° C. for two hours. The reaction mixture was cooled to room temperature and partitioned between ethylacetate and brine. The combined organic phases were dried with sodium sulfate and evaporated yielding 2-(5-chloro-2-fluoro-phenyl)-4-(5-triethylsilanylethynyl-pyridin-3-yl)-[1,8]naphthyridine as brown solid; HPLC-MS: 2.73 min, [M+H] 474.

Workup

temperatureThe reaction mixture was cooled to room temperature
custompartitioned between ethylacetate and brine
dry with materialThe combined organic phases were dried with sodium sulfate
customevaporated

Sources & evidence

ORD record: ord-32c5655ea7814615aff949f3e1dd1202
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08912216B2

Reaction notes

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