Tributylvinyltin → 2-(6-chloro-3-vinylpyridazin-4-yl)-4-fluoro-1H-indole

HRID 595709Notes

Reaction equation

Cl[C:2]1[N:3]=[N:4][C:5]([Cl:18])=[CH:6][C:7]=1[C:8]1[NH:9][C:10]2[C:15]([CH:16]=1)=[C:14]([F:17])[CH:13]=[CH:12][CH:11]=2.[CH2:19]([Sn](CCCC)(CCCC)C=C)[CH2:20]CC.[Li+].[Cl-]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:18][C:5]1[N:4]=[N:3][C:2]([CH:19]=[CH2:20])=[C:7]([C:8]2[NH:9][C:10]3[C:15]([CH:16]=2)=[C:14]([F:17])[CH:13]=[CH:12][CH:11]=3)[CH:6]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a degassed solution of 2-(3,6-dichloropyridazin-4-yl)-4-fluoro-1H-indole (500 mg, 1.7 mmol), tributyl(vinyl)stannane (560 mg, 1.7 mmol) and LiCl (375 mg, 8.9 mmol) in DMF (5 mL) was added Pd(PPh3)2Cl2 (30 mg) under N2, and the mixture was stirred at 80° C. for 12 h. After the solvent was removed, the residue was purified by prep-TLC (PE:EtOAc=2:1) to give the product of 2-(6-chloro-3-vinylpyridazin-4-yl)-4-fluoro-1H-indole (140 mg, yield: 29%). 1H-NMR (CDCl3, 400 MHz) δ 8.71 (s, 1H), 7.61 (s, 1H), 7.16 (dd, J=10.8, 16.8 Hz, 2H), 7.03 (s, 1H), 6.87 (d, J=6.8 Hz, 2H), 6.68 (s, 1H), 5.79 (s, 1H). MS (M+H)+: 274/276.

Workup

customAfter the solvent was removed
customthe residue was purified by prep-TLC (PE:EtOAc=2:1)

Sources & evidence

ORD record: ord-58f237958662498393f24fb2e0c14e1c
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09243002B2

Reaction notes

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