Acetonitrile → 2-(2-Methylpyridin-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carbonitrile

HRID 1190317Notes

Reaction equation

HRID 1190317 reaction equation
Br[C:2]1[S:11][C:10]2[C:9]3[CH:12]=[CH:13][C:14]([C:16]#[N:17])=[CH:15][C:8]=3[O:7][CH2:6][CH2:5][C:4]=2[CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:24](#[N:26])[CH3:25]>CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:25][C:24]1[CH:10]=[C:4]([C:2]2[S:11][C:10]3[C:9]4[CH:12]=[CH:13][C:14]([C:16]#[N:17])=[CH:15][C:8]=4[O:7][CH2:6][CH2:5][C:4]=3[CH:3]=2)[CH:3]=[CH:2][N:26]=1

Participants

6

Reactant 3

HCID 6342AcetonitrileHCID 10340Sodium CarbonateHCID 582038742-Bromo-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carbonitrile

Product 1

HCID 582041812-(2-Methylpyridin-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carbonitrileYield 17%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

A 2 ml microwave vial was loaded with a slurry of 2-Bromo-4,5-dihydro-6-oxa-1-thia-benzo[e]azulene-8-carbonitrile (170 mg, 0.55 mmol) and pyridine-2-amino boronic acid pinacolester (130 mg, 0.61 mmol) in 0.800 ml of aqueous 2M Sodium carbonate and 1.2 ml of ACN. The reaction mixture was degassed by bubbling nitrogen through the solution for several minutes. Next palladium tetrakis (51 mg, 2 mmol) was added to the reaction mixture and the vial was tightly capped and flash heated a Biotage microwave at 180 C for 10 minutes. The cooled reaction mixture was diluted with a large volume of EtOAc and the organic was washed with water and saline and concentrated in vacuo. The resulting residue was taken into DMF and purified by preparative RP-HPLC to give 32 mg (17%) of 2-(2-methylpyridin-4-yl)-4,5-dihydrobenzo[b]thieno[2,3-d]oxepine-8-carbonitrile

Workup

  1. customThe reaction mixture was degassed
  2. customby bubbling nitrogen through the solution for several minutes
  3. customthe vial was tightly capped
  4. temperatureflash heated a Biotage microwave at 180 C for 10 minutes
  5. customThe cooled reaction mixture
  6. washthe organic was washed with water and saline
  7. concentrationconcentrated in vacuo
  8. custompurified by preparative RP-HPLC

Sources & evidence

ORD record
ord-9508a52c96aa4b45b2a97166a60d8c5e
Source dataset
uspto-grants-2014_03
Patent number
US08673952B2

Reaction notes

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