Bromotrimethylsilane → 6-Bromo-3-(4-piperidin-1-ylmethyl-phenyl)-9H-dipyrido[2,3-b;4',3'-d]pyrrole

HRID 1506017Notes

Reaction equation

Cl[C:2]1[N:7]=[CH:6][C:5]([NH2:8])=[C:4]([C:9]2[C:10](F)=[N:11][CH:12]=[C:13]([C:15]3[CH:20]=[CH:19][C:18]([CH2:21][N:22]4[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]4)=[CH:17][CH:16]=3)[CH:14]=2)[CH:3]=1.[Br:29][Si](C)(C)C>O1CCOCC1>[Br:29][C:2]1[N:7]=[CH:6][C:5]2[NH:8][C:10]3[N:11]=[CH:12][C:13]([C:15]4[CH:20]=[CH:19][C:18]([CH2:21][N:22]5[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]5)=[CH:17][CH:16]=4)=[CH:14][C:9]=3[C:4]=2[CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 6′-chloro-2-fluoro-5-(4-piperidin-1-ylmethyl-phenyl)-[3,4]bipyridinyl-3′-ylamine (1.6 g, 0.004 mol) in 1,4-dioxane (30 mL) was added bromotrimethylsilane (27 mL, 0.2 mol) which immediately produced a white precipitate. The reaction was heated at 100° C. for 48 h. The solid from the cooled reaction mixture was collected by filtration and washed with ethyl acetate (2×20 mL). The resultant solid was then purified by flash chromotagraphy (silica, 25 g column, Biotage, 040% methanol in (DCM containing 1% 2M ammonia in methanol)) to afford the title compound as an off-white solid (1.1 g, 45%). 1H NMR (DMSO-D6, 500 MHz,): 8.62 (s, 1H), 8.25 (d, J=7.3 Hz, 1H), 7.90 (s, 1H), 7.74 (d, J=6.5 Hz, 2H), 7.42 (d, J=6.5 Hz), 7.35 (s, 1H), 5.57 (s, 2H), 3.47 (s, 2H), 2.34 (s, 4H), 1.51 (s, 4H), 1.40 (s, 2H).

Workup

customimmediately produced a white precipitate
customThe solid from the cooled reaction mixture
filtrationwas collected by filtration
washwashed with ethyl acetate (2×20 mL)
customThe resultant solid was then purified by flash chromotagraphy (silica, 25 g column, Biotage, 040% methanol in (DCM containing 1% 2M ammonia in methanol))

Sources & evidence

ORD record: ord-1f0fe8b55e38439f9209b11e247e3447
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09216980B2

Reaction notes

Loading…