Tetrahydrofuran → HCID 86639156, compound

HRID 1666915Notes

Reaction equation

HRID 1666915 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:14]3[C:15]([CH3:20])=[C:16]([CH:18]=[O:19])[S:17][C:13]=3[N:12]3[C:21]([CH3:24])=[N:22][N:23]=[C:11]3[C@H:10]([CH2:25][C:26]([O:28][CH3:29])=[O:27])[N:9]=2)=[CH:4][CH:3]=1.[F-].[K+].[C:32]([C:34]1[CH:35]=[C:36](B(O)O)[CH:37]=[CH:38][CH:39]=1)#[N:33].O1CCCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.O>[C:32]([C:34]1[CH:39]=[C:38]([C:2]2[CH:3]=[CH:4][C:5]([C:8]3[C:14]4[C:15]([CH3:20])=[C:16]([CH:18]=[O:19])[S:17][C:13]=4[N:12]4[C:21]([CH3:24])=[N:22][N:23]=[C:11]4[C@H:10]([CH2:25][C:26]([O:28][CH3:29])=[O:27])[N:9]=3)=[CH:6][CH:7]=2)[CH:37]=[CH:36][CH:35]=1)#[N:33]

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 522689Potassium FluorideHCID 27343253-Cyanophenylboronic acidHCID 86639154HCID 86639154, compound

Product 1

HCID 86639156HCID 86639156, compoundYield 118.6%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 27342152-(Di-tert-butylphosphino)biphenylCatalystHCID 962WaterSolvent

Procedure

To a mixture of methyl (S)-{4-(4-chlorophenyl)-2-formyl-3,9-dimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl}acetate (429 mg) synthesized in Example 342 as an intermediate, palladium acetate (11 mg), 2-(di-tert-butylphosphino)biphenyl (30 mg), potassium fluoride (349 mg) and 3-cyanophenylboronic acid (441 mg) was added tetrahydrofuran (4 mL), and the mixture was heated under reflux for 6 hr. After cooling, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was purified by column chromatography (chloroform:methanol=100:1) to give methyl (S)-{4-(3′-cyanobiphenyl-4-yl)-2-formyl-3,9-dimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl}acetate (588 mg). The obtained methyl (S)-{4-(3′-cyanobiphenyl-4-yl)-2-formyl-3,9-dimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl}acetate (564 mg) was dissolved in acetonitrile (4 mL), and aqueous sodium dihydrogen phosphate solution (128 mg/1.6 mL) was added. To the reaction mixture were successively added 35% hydrogen peroxide solution (0.5 mL) and aqueous sodium chlorite solution (174 mg/0.6 mL) at 0° C., and the mixture was stirred for 1 hr on a water bath. After completion of the reaction, water was added, and the mixture was worked up with sodium sulfite. The aqueous layer was acidified and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated to give (S)-4-(3′-cyanobiphenyl-4-yl)-6-methoxycarbonylmethyl-3,9-dimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-2-carboxylic acid (500 mg). The obtained (S)-4-(3′-cyanobiphenyl-4-yl)-6-methoxycarbonylmethyl-3,9-dimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-2-carboxylic acid (487 mg) and copper (50 mg) were reacted at 150° C. for 30 min in quinoline. After completion of the reaction, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was purified by column chromatography (chloroform:methanol=100:1) and recrystallized from ethyl acetate to give the title compound (217 mg).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 6 hr
  3. temperatureAfter cooling
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customthe solvent was evaporated
  8. customThe residue was purified by column chromatography (chloroform:methanol=100:1)

Sources & evidence

ORD record
ord-70398bafd55043ddb09ac131c970d61d
Source dataset
uspto-grants-2011_10
Patent number
US08044042B2

Reaction notes

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