Succinic anhydride → HCID 53372815, compound

HRID 515829Notes

Reaction equation

HRID 515829 reaction equation
[O:1]1C(=O)C[CH2:3][C:2]1=O.[OH:8][C:9]1[CH:14]=[CH:13][C:12]([N:15]2[C:22](=[S:23])[N:21]([C:24]3[CH:25]=[C:26]([CH3:32])[C:27]([C:30]#[N:31])=[N:28][CH:29]=3)[C:20](=[O:33])[C:16]32[CH2:19][CH2:18][CH2:17]3)=[CH:11][CH:10]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[OH:1][CH2:2][CH2:3][O:8][C:9]1[CH:10]=[CH:11][C:12]([N:15]2[C:22](=[S:23])[N:21]([C:24]3[CH:25]=[C:26]([CH3:32])[C:27]([C:30]#[N:31])=[N:28][CH:29]=3)[C:20](=[O:33])[C:16]32[CH2:19][CH2:18][CH2:17]3)=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 7922Succinic anhydrideHCID 11430Potassium CarbonateHCID 86683487HCID 86683487, compound

Product 1

HCID 53372815HCID 53372815, compoundYield 70.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
85 °C

Procedure

Dihydrofuran-2,5-dione (604 mg, 6.87 mmol) in DMF (5 mL) was added to a mixture of 5-(5-(4-hydroxyphenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-methylpicolinonitrile (500 mg, 1.37 mmol) and potassium carbonate (378 mg, 2.74 mmol) in DMF (10 mL) and the resulting mixture was heated to 85° C. overnight. The mixture was cooled to room temperature and partitioned between water and EtOAc. The aqueous was extracted further with EtOAc (2×) and the combined organics were washed with water, then brine. The organics were dried over sodium sulfate, filtered, and concentrated. Column chromatography on silica gel (50 to 100% EtOAc/hexanes) afforded 396 mg of 5-(5-(4-(2-hydroxyethoxy)phenyl)-8-oxo-6-thioxo-5,7-diazaspiro[3.4]octan-7-yl)-3-methylpicolinonitrile as a white solid. 1H NMR (300 MHz, DMSO-d6) δ 8.71 (d, 1H), 8.14 (d, 1H), 7.33 (d, 2H), 7.13 (d, 2H), 4.92 (t, 1H), 4.11-4.05 (m, 2H), 3.78-3.73 (m, 2H), 2.63-2.5 (m, 5H), 2.49-2.37 (m, 2H), 2.00-1.90 (m, 1H), 1.56-1.51 (m, 1H). LCMS [M+1]+ 409.0.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. custompartitioned between water and EtOAc
  3. extractionThe aqueous was extracted further with EtOAc (2×)
  4. washthe combined organics were washed with water
  5. dry with materialThe organics were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-9404dd70110a40779ff2cf7445317169
Source dataset
uspto-grants-2015_08
Patent number
US09108944B2

Reaction notes

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