1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-(3-chloro-4-(quinolin-2-ylmethoxy)phenyl)-4-(pyridin-4-yl)furan-2(5H)-one

HRID 446828Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([CH2:20][C:21]([OH:23])=[O:22])[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:19]=[CH:18][C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]=1.Br.Br[CH2:26][C:27]([C:29]1[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=1)=O.C1CCN2C(=NCCC2)CC1>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:20]2[C:21](=[O:23])[O:22][CH2:26][C:27]=2[C:29]2[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:19]=[CH:18][C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[N:11]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a stirred solution of 2-(3-chloro-4-(quinolin-2-ylmethoxy)phenyl)acetic acid (6.0 g, 0.01 mol) in acetonitrile (50 mL) were added TEA (2.58 mL, 0.02 mol) and 2-bromo-1-(pyridin-4-yl)ethanone hydrobromide (6.16 g, 0.02 mol) at RT under an inert atmosphere. The reaction mixture was stirred for 30 minutes, cooled to 0° C., and then DBU (5.5 mL, 0.03 mol) was added. The reaction was stirred for an additional 15 minutes and then quenched with HCl (1 N) and extracted with DCM (2×300 mL). The combined organic layers were washed with water, dried over Na2SO4, and concentrated in vacuo to obtain the crude product. The crude material was purified via silica gel column chromatography to afford 3-(3-chloro-4-(quinolin-2-ylmethoxy)phenyl)-4-(pyridin-4-yl)furan-2(5H)-one (500 mg) as a solid. 1H NMR (500 MHz, d6-DMSO): δ 8.64 (d, J=7.8 Hz, 2H), 8.50-8.44 (m, 1H), 8.04-7.98 (m, 2H), 7.8 (t, J=7.2 Hz, 1H), 7.74 (d, J=7.6 Hz, 1H), 7.64 (t, J=7.2 Hz, 1H), 7.50 (s, 1H), 7.38-7.32 (m, 3H), 7.26-7.22 (m, 1H), 5.55 (s, 2H), 5.38 (s, 2H). MS: M+H: m/z=429.1. HPLC: 90%, (Condition-I).

Workup

stirringThe reaction was stirred for an additional 15 minutes
customquenched with HCl (1 N)
extractionextracted with DCM (2×300 mL)
washThe combined organic layers were washed with water
dry with materialdried over Na2SO4
concentrationconcentrated in vacuo
customto obtain the crude product
customThe crude material was purified via silica gel column chromatography

Sources & evidence

ORD record: ord-f6a05b6d01764f42be1a691c5798c50e
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08481534B2

Reaction notes

Loading…