Diisopropylethylamine → HCID 67974943, compound

HRID 468860Notes

Reaction equation

HRID 468860 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

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 82115Trimethylsilyl cyanideHCID 67974365HCID 67974365, compound

Product 1

HCID 67974943HCID 67974943, compoundYield 28.9%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

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

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

Sources & evidence

ORD record
ord-6bd6b41fe95d4c5ba9527375a8d544ce
Source dataset
uspto-grants-2014_01
Patent number
US08623889B2

Reaction notes

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