4-Toluenesulfonyl chloride → 2-Bromo-7-iodo-5-tosyl-5H-pyrrolo[2,3-B]pyrazine

HRID 85028Notes

Reaction equation

[Br:1][C:2]1[N:7]=[C:6]2[C:8]([I:11])=[CH:9][NH:10][C:5]2=[N:4][CH:3]=1.[H-].[Na+].[C:14]1([CH3:24])[CH:19]=[CH:18][C:17]([S:20](Cl)(=[O:22])=[O:21])=[CH:16][CH:15]=1>C1COCC1.CCOC(C)=O>[Br:1][C:2]1[N:7]=[C:6]2[C:8]([I:11])=[CH:9][N:10]([S:20]([C:17]3[CH:18]=[CH:19][C:14]([CH3:24])=[CH:15][CH:16]=3)(=[O:22])=[O:21])[C:5]2=[N:4][CH:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a stirred solution of 2-bromo-7-iodo-5H-pyrrolo[3,2-b]pyrazine [Intermediate AT] (1.1 g, 3.5 mmol) in anhydrous THF (20 mL) cooled to 0° C. was added NaH [60% dispersion in mineral oil] (0.17 g, 4.3 mmol). The reaction mixture was stirred for 20 min at 0° C., after which p-toluenesulfonyl chloride (0.73 g, 3.8 mmol) in THF (8 mL) was added. The resulting mixture was stirred at rt for 3 hr, after which it was diluted with EtOAc and washed with H2O and brine. The organic layer was separated, dried over Na2SO4, filtered, and evaporated in vacuo to yield a residue that was triturated with hexanes to yield the title compound (1.6 g, 94%) as a light yellow powder. 1H NMR (DMSO-d6, 300 MHz) δ 8.62 (d, J=7.5 Hz, 2H), 8.03 (s, 1H), 8.00 (s, 1H), 7.47 (d, J=8.1 Hz, 2H), 2.37 (s, 3H). HPLC retention time: 2.84 minutes. MS ESI (m/z): 478.0/480.0 (M+H)+, calc. 477.

Workup

stirringThe resulting mixture was stirred at rt for 3 hr
washwashed with H2O and brine
customThe organic layer was separated
dry with materialdried over Na2SO4
filtrationfiltered
customevaporated in vacuo
customto yield a residue that
customwas triturated with hexanes

Sources & evidence

ORD record: ord-c76a993244d74ec999a16f5502c7a755
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846909B2

Reaction notes

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