4-Toluenesulfonyl chloride → 5-bromo-3-iodo-1-tosyl-1H-pyrrolo[2,3-b]pyridine

HRID 901478Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([I:11])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=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>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([I:11])=[CH:9][N:8]([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:6][CH:7]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Into a 250 mL round bottomed flask were added 5-bromo-3-iodo-1H-pyrrolo[2,3-b]pyridine (8.00 g, 40.6 mmol) and 120 mL dry THF. The solution was cooled in an ice bath at 0° C. and NaH (2.40 g, 60.0 mmol) was added in three portions. After 20 min, p-toluenesulfonyl chloride (8.70 g, 45.63 mmol) was added, and the reaction mixture was allowed to warm to rt over 30 min. The reaction mixture was concentrated and hexanes was added to obtain a precipitate, which was collected and washed with ice cold 2M NaOH. The crude product was recrystallized from EtOAc/hexanes to afford 17.8 g (92%) of the title compound as a light tan powder. 1H-NMR (500 MHz, d6-DMSO) δ 8.49 (d, J=2.5 Hz, 1H), 8.21 (s, 1H), 7.99 (d, J=2.0 Hz, 1H), 7.98(d, J=8.5 Hz, 2H), 7.42 (d, J=8.5 Hz, 2.32(s, 3H); MS: m/z 476.8/478.8 [MH+].

Workup

temperatureto warm to rt over 30 min
concentrationThe reaction mixture was concentrated
additionhexanes was added
customto obtain a precipitate, which
customwas collected
washwashed with ice cold 2M NaOH
customThe crude product was recrystallized from EtOAc/hexanes

Sources & evidence

ORD record: ord-af5f6c1969f041e2abd0776db0e1af6d
Source dataset: uspto-grants-2008_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07361764B2

Reaction notes

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