Water → HCID 86683475, compound

HRID 515815Notes

Reaction equation

HRID 515815 reaction equation
C[Si](I)(C)C.[F:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[C:20](=[S:21])[N:19]([C:22]3[CH:23]=[C:24]([C:30]([F:33])([F:32])[F:31])[C:25]([C:28]#[N:29])=[N:26][CH:27]=3)[C:18](=[O:34])[C:14]32[CH2:17][CH2:16][CH2:15]3)=[CH:9][C:8]=1[O:35]C.O>C(#N)C>[F:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[C:20](=[S:21])[N:19]([C:22]3[CH:23]=[C:24]([C:30]([F:32])([F:33])[F:31])[C:25]([C:28]#[N:29])=[N:26][CH:27]=3)[C:18](=[O:34])[C:14]32[CH2:15][CH2:16][CH2:17]3)=[CH:9][C:8]=1[OH:35]

Participants

5

Reactant 3

HCID 962WaterHCID 85247Trimethylsilyl iodideHCID 86683476HCID 86683476, compound2×

Product 1

HCID 86683475HCID 86683475, compoundYield 49.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Trimethylsilyl iodide (7.0 ml, 51.1 mmol) was added to a solution of 5-(5-(4-fluoro-3-methoxyphenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-(trifluoromethyl)picolinonitrile (Compound 32, 3 g, 5.1 mmol) in acetonitrile (50 mL) and the mixture was refluxed for 24 h. The mixture was cooled to room temperature, poured into water, and extracted with EtOAc (3×). The organics were combined, washed with sat'd solution of NaHSO3, dried over MgSO4, and evaporated to dryness. The residue was purified by column chromatography on silica gel eluting with EtOAc/Hexane=1/5 to afford 1.1 g of 5-(5-(4-fluoro-3-hydroxyphenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-(trifluoromethyl)picolinonitrile. 1H NMR (400 MHz, CDCl3) δ 9.10 (d, 1H), 8.38 (d, 1H), 7.27-7.22 (m, 1H), 6.93 (dd, 1H), 6.78 (m, 1H), 2.74-2.55 (m, 1H), 2.23 (m, 1H), 1.80-1.59 (m, 4H).

Workup

  1. temperaturethe mixture was refluxed for 24 h
  2. extractionextracted with EtOAc (3×)
  3. washwashed with sat'd solution of NaHSO3
  4. dry with materialdried over MgSO4
  5. customevaporated to dryness
  6. customThe residue was purified by column chromatography on silica gel eluting with EtOAc/Hexane=1/5

Sources & evidence

ORD record
ord-f775b385db9547f3a53f1a92a89f80fb
Source dataset
uspto-grants-2015_08
Patent number
US09108944B2

Reaction notes

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