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

HRID 1530374Notes

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[C:19]([Sn](CCCC)(CCCC)CCCC)=[N:20][CH:21]=[CH:22][CH:23]=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:19]4[C:18]([CH3:17])=[CH:23][CH:22]=[CH:21][N:20]=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), 3-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 100° C. for 1 h 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 0-5% MeOH in EtOAc) affording the title compound as a white solid (135 mg, 74%). LCMS: RT 3.22 min [M+H]+ 355.9/357.9

Workup

customwas purged with nitrogen
custommicrowave irradiation
additionThe reaction mixture was diluted with MeOH (30 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 0-5% MeOH in EtOAc)

Sources & evidence

ORD record: ord-4790dd6a9cc141ce936982a38725ebd9
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090628B2

Reaction notes

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