4-Methyl-2-(tributylstannyl)pyridine → 9-Bromo-2-(4-methylpyridin-2-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene

HRID 1530388Notes

Reaction equation

HRID 1530388 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][N:11]3[C:7](=[N:8][C:9](I)=[CH:10]3)[C:6]=2[CH:16]=1.[CH3:17][C:18]1[CH:23]=[CH:22][N:21]=[C:20]([Sn](CCCC)(CCCC)CCCC)[CH:19]=1>CN(C=O)C.[Cu](I)I>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:14][CH2:13][CH2:12][N:11]3[C:7](=[N:8][C:9]([C:20]4[CH:19]=[C:18]([CH3:17])[CH:23]=[CH:22][N:21]=4)=[CH:10]3)[C:6]=2[CH:16]=1

Participants

5

Reactant 2

HCID 112227754-Methyl-2-(tributylstannyl)pyridineHCID 5820440710-Bromo-2-iodo-5,6-dihydrobenzo[F]imidazo[1,2-D][1,4]oxazepine

Product 1

HCID 683126959-Bromo-2-(4-methylpyridin-2-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azuleneYield 87.2%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 9-bromo-2-iodo-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (200 mg, 0.512 mmol), 4-methyl-2-tributylstannanylpyridine (235 mg, 0.614 mmol), Pd2(PPh3)2Cl2 (36 mg, 0.051 mmol) and copper iodide (29 mg, 0.153 mmol) in DMF (4 mL) was purged with nitrogen and then heated at 120° C. for 45 min using microwave irradiation. The reaction mixture was diluted with MeOH (30 mL) and then loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH and the product eluted with 0.5M NH3/MeOH. The product containing fractions were combined and concentrated in vacuo and the resulting residue was purified by column chromatography (Si-PCC, gradient 0-10% MeOH in DCM followed by Si-PCC, gradient 0-3% MeOH in EtOAc) affording 9-Bromo-2-(4-methylpyridin-2-yl)-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene as a colorless solid (159 mg, 87%). LCMS: RT 2.44 min [M+H]+ 355.9/357.8

Workup

  1. customwas purged with nitrogen
  2. custommicrowave irradiation
  3. additionThe reaction mixture was diluted with MeOH (30 mL)
  4. washwas washed with MeOH
  5. washthe product eluted with 0.5M NH3/MeOH
  6. additionThe product containing fractions
  7. concentrationconcentrated in vacuo
  8. customthe resulting residue was purified by column chromatography (Si-PCC, gradient 0-10% MeOH in DCM followed by Si-PCC, gradient 0-3% MeOH in EtOAc)

Sources & evidence

ORD record
ord-dd7abf9bc81341dea1fa38a682c8e5fb
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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