6-Bromo-4-fluoro-2,3-dihydro-1H-inden-1-one → (R)-3-(6-Cyclopropylmethoxy-pyridin-3-yloxy)-1-(7-fluoro-3-oxo-indan-5-yl)-pyrrolidin-2-one

HRID 533891Notes

Reaction equation

[CH2:1]1[CH2:3][CH:2]1[CH2:4][O:5][C:6]1[N:11]=[CH:10][C:9]([O:12][C@@H:13]2[CH2:17][CH2:16][NH:15][C:14]2=[O:18])=[CH:8][CH:7]=1.Br[C:20]1[CH:28]=[C:27]2[C:23]([CH2:24][CH2:25][C:26]2=[O:29])=[C:22]([F:30])[CH:21]=1>O1CCOCC1>[CH:2]1([CH2:4][O:5][C:6]2[N:11]=[CH:10][C:9]([O:12][C@@H:13]3[CH2:17][CH2:16][N:15]([C:20]4[CH:28]=[C:27]5[C:23](=[C:22]([F:30])[CH:21]=4)[CH2:24][CH2:25][C:26]5=[O:29])[C:14]3=[O:18])=[CH:8][CH:7]=2)[CH2:3][CH2:1]1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of (R)-3-[6-(2-cyclopropyl-methoxy)-pyridin-3-yloxy]-pyrrolidin-2-one (100 mg), 6-bromo-4-fluoro-2,3-dihydro-1H-inden-1-one (92 mg) and 1,4-dioxane (2 mL) was purged with argon. N,N′-Dimethyl-ethylene-diamine (355 mg), cesium carbonate (263 mg) and copper(I) iodide (8 mg) were added. The mixture was heated to 80° C. for 4 hours. After cooling to r.t. the mixture was filtered and the filtrate purified by preparative HPLC to provide Example 1-11. 1H-NMR (400 MHz, DMSO) δ 7.99 (1H, dd, J=11.2, 1.8 Hz), 7.95 (1H, d, J=3.1 Hz), 7.77 (1H, d, J=1.8 Hz), 7.53 (1H, dd, J=9.0, 3.1 Hz), 6.79 (1H, d, J=9.0 Hz), 5.22 (1H, dd, J=8.3, 8.3 Hz), 4.03 (2H, d, J=7.1 Hz), 3.96 (1H, m), 3.86 (1H, m), 3.10 (2H, m), 2.72 (2H, m), 2.68 (1H, m), 2.13 (1H, m), 1.22 (1H, m), 0.54 (2H, m), 0.30 (2H, m).

Workup

customwas purged with argon
additionN,N′-Dimethyl-ethylene-diamine (355 mg), cesium carbonate (263 mg) and copper(I) iodide (8 mg) were added
temperatureAfter cooling to r.t. the mixture
filtrationwas filtered
customthe filtrate purified by preparative HPLC
customto provide Example 1-11

Sources & evidence

ORD record: ord-d14ee5ebe67e402c8e7bfefbeb6d70b6
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08853412B2

Reaction notes

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