Sodium bis(trimethylsilyl)amide → 6-Chloro-5-fluoro-9H-pyrrolo[2,3-b:5,4-c']dipyridine

HRID 60238Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:9]2[C:10](F)=[N:11][CH:12]=[CH:13][CH:14]=2)[C:3]=1[F:16].C[Si]([N-][Si](C)(C)C)(C)C.[Na+]>C1COCC1>[Cl:1][C:2]1[N:7]=[CH:6][C:5]2[NH:8][C:10]3[N:11]=[CH:12][CH:13]=[CH:14][C:9]=3[C:4]=2[C:3]=1[F:16]

Participants

Conditions

Temperature: 40 °C

Procedure

A solution of 6′-chloro-2,5′-difluoro-[3,4′]bipyridinyl-3′-ylamine (70 g, 290 mmol) in THF (300 mL) was added dropwise to a solution of sodium bis(trimethylsilyl)amide (720 mL, 1M in THF, 720 mmol) at such a rate that the reaction temperature was maintained at 40° C. When the addition was complete the mixture was stirred for ca. 1 hour at ambient temperature. The bulk of the solvent was evaporated in-vacuo and the residue poured into ice-cold 1N hydrochloric acid. The resulting slurry was filtered and the solid washed with water. The filter cake was collected and triturated with acetone followed by diethyl ether to afford the title compound as a beige solid (40.9 g, 64%). The trituration liquors were evaporated and the residue triturated with methanol followed by diethyl ether to afford a second crop of title compound as a brown solid (6.1 g, 10%). Total yield=47 g, 74%. 1H NMR (400 MHz, DMSO-d6): 13.24 (s, 1H), 8.91 (d, J=2.5 Hz, 1H), 8.77 (dd, J=4.8, 1.7 Hz, 1H), 8.65 (dd, J=7.9, 1.7 Hz, 1H), 7.50 (dd, J=7.9, 4.8 Hz, 1H).

Workup

additionWhen the addition
customThe bulk of the solvent was evaporated in-vacuo
additionthe residue poured into ice-cold 1N hydrochloric acid
filtrationThe resulting slurry was filtered
washthe solid washed with water
customThe filter cake was collected
customtriturated with acetone

Sources & evidence

ORD record: ord-3a4d1ea9cc0045229b7e520b5d7f1371
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440976B2

Reaction notes

Loading…