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

HRID 1530366Notes

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.C([Sn](CCCC)(CCCC)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=1)CCC>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:22]4[CH:27]=[CH:26][CH:25]=[CH:24][N:23]=4)=[CH:10]3)[C:6]=2[CH:16]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 9-bromo-2-iodo-4,5-dihydro-6-oxa-1,3a-diazabenzo[e]azulene (200 mg, 0.512 mmol), 2-tributylstannanylpyridine (226 g, 0.614 mmol), Pd2(PPh3)2Cl2 (36 mg, 0.05 mmol) and copper iodide (29 mg, 0.15 mmol) in DMF (4 mL) was purged with nitrogen and then heated at 100° C. for 1 h using microwave irradiation. The reaction mixture was diluted with MeOH (20 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. The resulting residue was purified by column chromatography (Si-PCC, gradient 0-8% MeOH in DCM followed by Si-PCC, gradient 0-7% MeOH in EtOAc) affording the title compound as a cream solid (140 mg, 80%). LCMS: RT 2.52 min [M+H]+ 341.8/343.8.

Workup

customwas purged with nitrogen
custommicrowave irradiation
additionThe reaction mixture was diluted with MeOH (20 mL)
washwas washed with MeOH
washthe product eluted with 0.5M NH3/MeOH
additionThe product containing fractions
concentrationconcentrated in vacuo
customThe resulting residue was purified by column chromatography (Si-PCC, gradient 0-8% MeOH in DCM followed by Si-PCC, gradient 0-7% MeOH in EtOAc)

Sources & evidence

ORD record: ord-b09588498cdb4a50ac35b63bdb5f76b0
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090628B2

Reaction notes

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