(E)-5-bromomethylene-8-fluoro-10,11-dihydro-benzo[4,5]cyclohepta[1,2-b]pyridine → (E)-N-[3-Fluoro-5-(8-fluoro-10,11-dihydro-benzo[4,5]cyclohepta[1,2-b]pyridin-5-ylidenemethyl)-phenyl]-methanesulfonamide

HRID 2218760Notes

Reaction equation

HRID 2218760 reaction equation
Br/[CH:2]=[C:3]1\[C:4]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:5]=2[CH2:6][CH2:7][C:8]2[C:13]\1=[CH:12][CH:11]=[CH:10][N:9]=2.[F:19][C:20]1[CH:21]=[C:22]([NH:35][S:36]([CH3:39])(=[O:38])=[O:37])[CH:23]=[C:24](B2OC(C)(C)C(C)(C)O2)[CH:25]=1>>[F:19][C:20]1[CH:21]=[C:22]([NH:35][S:36]([CH3:39])(=[O:37])=[O:38])[CH:23]=[C:24](/[CH:2]=[C:3]2\[C:4]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:5]=3[CH2:6][CH2:7][C:8]3[C:13]\2=[CH:12][CH:11]=[CH:10][N:9]=3)[CH:25]=1

Participants

3

Reactant 2

HCID 59770460(E)-5-bromomethylene-8-fluoro-10,11-dihydro-benzo[4,5]cyclohepta[1,2-b]pyridineHCID 59770533N-[3-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanesulfonamide

Product 1

HCID 10093093(E)-N-[3-Fluoro-5-(8-fluoro-10,11-dihydro-benzo[4,5]cyclohepta[1,2-b]pyridin-5-ylidenemethyl)-phenyl]-methanesulfonamideYield 66.7%

Procedure

Following procedures essentially as desctribed in Example 219, beginning with (E)-5-bromomethylene-8-fluoro-10,11-dihydro-benzo[4,5]cyclohepta[1,2-b]pyridine (50 mg, 0.16 mmol) and N-[3-fluoro-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-methanesulfonamide (62 mg, 0.20 mmol). After work-up, purify the crude product by flash chromatography (50% ethyl acetate/hexanes to 75% ethyl acetate/hexanes) to provide 44 mg (65%) of purified product. LCMS (APCI-pos): 413.0 (M+H). LCMS (APCI-neg): 411.0 (M−H). Purity by LCMS 1 Area percent) 98%. 1HNMR (d6-DMSO, 400 MHz): δ9.91 (s, 1H), 8.42 (dd, 1H), 7.91 (dd, 1H), 7.29-7.25 (m, 2H), 6.92 (s, 2H), 6.90 (d, 1H), 6.77-6.74 (m, 2H), 6.52-6.49(m, 1H), 3.4-2.8 (m, 4H), 2.87 (s, 3H).

Workup

  1. customAfter work-up, purify the crude product by flash chromatography (50% ethyl acetate/hexanes to 75% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-523753eb0efd40b39fe5196b60acb744
Source dataset
uspto-grants-2008_08
Patent number
US07411072B2

Reaction notes

Loading…