Diisopropylethylamine → HCID 67974943, compound

HRID 1502377Notes

Reaction equation

[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:25])=[C:6]([C:8]2[N+:9]([O-])=[CH:10][C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([NH:18][C:19]([CH:21]2[CH2:23][CH2:22]2)=[O:20])[CH:12]=3)[CH:7]=1.[CH:26]([N:29](CC)C(C)C)(C)C.C[Si](C#N)(C)C>C(#N)C.C(OCC)(=O)C>[C:26]([C:10]1[N:9]=[C:8]([C:6]2[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=2[CH3:25])[CH:17]=[C:16]2[C:11]=1[CH:12]=[C:13]([NH:18][C:19]([CH:21]1[CH2:23][CH2:22]1)=[O:20])[N:14]=[CH:15]2)#[N:29]

Participants

Conditions

Temperature: 100 °C

Procedure

To a slurry of 3-(5-fluoro-2-methylphenyl)-7-(cyclopropanecarboxamido)-2,6-naphthyridine 2-oxide (50 mg, 0.1 mmol) in acetonitrile (0.4 mL) was added N,N-diisopropylethylamine (0.05 mL, 0.3 mmol), followed by trimethylsilyl cyanide (0.06 mL, 0.44 mmol). The mixture was heated at 100° C. for 2 hours. The cooled reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (20 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min) to afford the title compound as a white solid (10 mg, 20%). 1H NMR (400 MHz, DMSO) δ 11.47 (s, 1H), 9.52 (s, 1H), 8.84 (s, 1H), 8.56 (s, 1H), 7.48-7.35 (m, 2H), 7.26 (td, J=8.5, 2.8 Hz, 1H), 2.37 (s, 3H), 2.13 (m, 1H), 0.99-0.83 (m, 4H). LCMS (Method E): RT=5.495 min, M+H+=347.1.

Workup

customThe cooled reaction mixture
washwashed with water (20 mL)
customThe organic layer was separated
dry with materialdried over sodium sulfate
filtrationfiltered
customevaporated in vacuo
customto afford a residue that
customwas purified by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min)

Sources & evidence

ORD record: ord-196aa94b7dae423fa6cb9d4a3b9ac3ec
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09206175B2

Reaction notes

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