Triethylamine → N-[5-(3-fluoro-phenylethynyl)-pyridin-2-yl]-2-methoxy-2-methyl-propionamide

HRID 40543

Reaction equation

[CH3:1][O:2][C:3]([CH3:20])([CH3:19])[C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]#[C:14][Si](C)(C)C)=[CH:9][N:8]=1)=[O:5].[F:21][C:22]1[CH:27]=[CH:26][CH:25]=[C:24](I)[CH:23]=1.CCN(CC)CC.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1.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.[Cu]I>[F:21][C:22]1[CH:23]=[C:24]([C:14]#[C:13][C:10]2[CH:11]=[CH:12][C:7]([NH:6][C:4](=[O:5])[C:3]([O:2][CH3:1])([CH3:20])[CH3:19])=[N:8][CH:9]=2)[CH:25]=[CH:26][CH:27]=1

Participants

Conditions

Temperature: 70 °C

Procedure

2-Methoxy-2-methyl-N-(5-trimethylsilanylethynyl-pyridin-2-yl)-propionamide (Example 13, step 2) (90 mg, 0.31 mmol) was dissolved in THF (8 ml). 1-Fluoro-3-iodobenzene (83 mg, 0.37 mmol, 1.2 equiv.), Et3N (130 μl, 0.93 mmol, 3 equiv.), bis-(triphenylphosphine)-palladium(II)dichloride (11 mg, 15 μmol, 0.05 equiv.) and copper(I)iodide (1.8 mg, 10 μmol, 0.03 equiv.) were added under nitrogen and the mixture was heated to 70° C. TBAF 1M in THF (370 μl, 0.37 mmol, 1.2 equiv.) was added dropwise at 70° C. The reaction mixture was stirred for 1 hour at 70° C., filtered through celite and the filtrate evaporated to dryness. The crude product was purified by flash chromatography with a silica gel column eluting with heptane:ethyl acetate 100:0->90:10. The desired N-[5-(3-fluoro-phenylethynyl)-pyridin-2-yl]-2-methoxy-2-methyl-propionamide (64 mg, 66% yield) was obtained as a yellow oil, MS: m/e=313.0 (M+H+).

Workup

filtrationfiltered through celite
customthe filtrate evaporated to dryness
customThe crude product was purified by flash chromatography with a silica gel column
washeluting with heptane:ethyl acetate 100:0->90:10

Sources & evidence

ORD record: ord-3f2aab5138514f34974511fae9fc787b
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08530472B2

Linked notes

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