Dimethylformamide → Kv3 modulator 1

HRID 2278334Notes

Reaction equation

HRID 2278334 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([OH:13])=[C:6]2[C:10]3([CH2:12][CH2:11]3)[CH2:9][O:8][C:7]=12.CN(C=O)C.Cl[C:20]1[N:25]=[CH:24][C:23]([N:26]2[C:30](=[O:31])[C:29]([CH3:33])([CH3:32])[NH:28][C:27]2=[O:34])=[CH:22][N:21]=1>>[CH3:32][C:29]1([CH3:33])[NH:28][C:27](=[O:34])[N:26]([C:23]2[CH:24]=[N:25][C:20]([O:13][C:5]3[C:6]4[C:10]5([CH2:9][O:8][C:7]=4[C:2]([CH3:1])=[CH:3][CH:4]=3)[CH2:12][CH2:11]5)=[N:21][CH:22]=2)[C:30]1=[O:31]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 574113017-methylspiro[2H-benzofuran-3,1-cyclopropane]-4-ol2×HCID 866984523-(2-Chloropyrimidin-5-yl)-5,5-dimethyl-imidazolidine-2,4-dione2×

Product 1

HCID 57411069Kv3 modulator 1Yield 57%

Conditions

Temperature
80 °C

Procedure

To a solution of 7-methylspiro[2H-benzofuran-3,1′-cyclopropane]-4-ol (Intermediate 13, 18 mg, 0.1 mmol) in dry DMF (1 ml) potassium carbonate (27.6 mg, 0.2 mmol) and then 3-(2-chloropyrimidin-5-yl)-5,5-dimethyl-imidazolidine-2,4-dione (Intermediate 23, 20 mg, 0.083 mmol) were added and the reaction mixture was stirred for 2 hours at 80° C. After cooling the reaction mixture was quenched with water (1 ml), diluted with brine (5 ml) and extracted with ethyl acetate (2×10 ml). The organic layer was dried over sodium sulfate, filtered and evaporated and the residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and cyclohexane/ethyl acetate 7:3 to cyclohexane/ethyl acetate 3:7 as eluents affording the title compound (18 mg) as a light beige solid.

Workup

  1. temperatureAfter cooling the reaction mixture
  2. customwas quenched with water (1 ml)
  3. additiondiluted with brine (5 ml)
  4. extractionextracted with ethyl acetate (2×10 ml)
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customthe residue was purified by flash chromatography (Biotage system) on silica gel using a 10 g SNAP column and cyclohexane/ethyl acetate 7:3 to cyclohexane/ethyl acetate 3:7 as eluents

Sources & evidence

ORD record
ord-ac7e11821fe34cb6a0013f95fc375378
Source dataset
uspto-grants-2015_09
Patent number
US09133175B2

Reaction notes

Loading…