Methyl p-toluenesulfonate → HCID 86683472, compound

HRID 515813Notes

Reaction equation

HRID 515813 reaction equation
[C:1]([C:3]1[N:8]=[CH:7][C:6]([N:9]2[C:16](=[O:17])[C:12]3([CH2:15][CH2:14][CH2:13]3)[N:11]([C:18]3[CH:23]=[CH:22][C:21]([S:24]([NH2:27])(=[O:26])=[O:25])=[CH:20][CH:19]=3)[C:10]2=[S:28])=[CH:5][C:4]=1[C:29]([F:32])([F:31])[F:30])#[N:2].S(C1C=CC(C)=CC=1)(O[CH3:37])(=O)=O.C([O-])([O-])=O.[Cs+].[Cs+]>C(#N)C.O>[C:1]([C:3]1[N:8]=[CH:7][C:6]([N:9]2[C:16](=[O:17])[C:12]3([CH2:15][CH2:14][CH2:13]3)[N:11]([C:18]3[CH:23]=[CH:22][C:21]([S:24]([NH:27][CH3:37])(=[O:26])=[O:25])=[CH:20][CH:19]=3)[C:10]2=[S:28])=[CH:5][C:4]=1[C:29]([F:32])([F:30])[F:31])#[N:2]

Participants

6

Reactant 3

HCID 6645Methyl p-toluenesulfonateHCID 10796Cesium carbonateHCID 86683473HCID 86683473, compound2×

Product 1

HCID 86683472HCID 86683472, compoundYield 30.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro-[3.4]octan-5-yl)benzenesulfonamide (Compound 81, 97 mg, 0.20 mmol), methyl tosylate (37 mg, 0.20 mmol), and Cs2CO3 (65 mg, 0.20 mmol) in acetonitrile (1 mL) was heated at 50° C. for 20 h in a sealed tube. After being cooled room temperature, the reaction mixture was diluted with water and extracted with EtOAc (3×). The organic layer was dried over magnesium sulfate and concentrated to give a residue that was purified by column chromatography on silica gel (hexanes:DCM:acetone=5:9:1) to afford 30 mg of 4-(7-(6-cyano-5-(trifluoromethyl)pyridin-3-yl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]-octan-5-yl)-N-methylbenzenesulfonamide as a white solid. 1H NMR (400 MHz, CDCl3) δ 9.11 (s, 1H), 8.37 (s, 1H), 8.10 (dd, 2H), 7.58-7.49 (m, 2H), 4.52 (d, 1H), 2.80 (m, 3H), 2.78-2.69 (m, 2H), 2.63-2.47 (m, 2H), 2.29 (m, 1H), 1.74 (m, 1H). LCMS [M+1+Na]+ 518.0.

Workup

  1. temperatureAfter being cooled room temperature
  2. extractionextracted with EtOAc (3×)
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. concentrationconcentrated
  5. customto give a residue that
  6. customwas purified by column chromatography on silica gel (hexanes:DCM:acetone=5:9:1)

Sources & evidence

ORD record
ord-9a402d95914a480183c152dc533ae513
Source dataset
uspto-grants-2015_08
Patent number
US09108944B2

Reaction notes

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