2-(Bromomethyl)tetrahydro-2H-pyran → 5-fluoro-6-methoxy-1'-(pyridin-2-ylmethyl)spiro[1-benzofuran-3,3'-indol]-2'(1'H)-one

Reaction equation

[F:1][C:2]1[C:3]([O:20][CH3:21])=[CH:4][C:5]2[O:19][CH2:18][C:8]3([C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[NH:10][C:9]3=[O:17])[C:6]=2[CH:7]=1.Br.Br[CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=1.BrCC1CCCCO1>>[F:1][C:2]1[C:3]([O:20][CH3:21])=[CH:4][C:5]2[O:19][CH2:18][C:8]3([C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[N:10]([CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=4)[C:9]3=[O:17])[C:6]=2[CH:7]=1

Participants

Reactant 3

HCID 1419172-(Bromomethyl)tetrahydro-2H-pyran

HCID 27347202-(Bromomethyl)pyridine hydrobromide

HCID 461940485-fluoro-6-methoxyspiro[1-benzofuran-3,3'-indol]-2'(1'H)-one

Product 1

HCID 593523175-fluoro-6-methoxy-1'-(pyridin-2-ylmethyl)spiro[1-benzofuran-3,3'-indol]-2'(1'H)-one

Procedure

Following the procedure as described in EXAMPLE 4 and making non-critical variations using 5-fluoro-6-methoxyspiro[1-benzofuran-3,3′-indol]-2′(1′H)-one to replace 5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2″(1′H)-one, and 2(bromomethyl)pyridine hydrobromide to replace 2-(bromomethyl)tetrahydro-2H-pyran, 5-fluoro-6-methoxy-1′-(pyridin-2-ylmethyl)spiro[1-benzofuran-3,3′-indol]-2′(1′H)-one was obtained (77%) as a colorless solid: mp 142-144° C.; 1H NMR (300 MHz, CDCl3) δ 8.59-8.53 (m, 1H), 7.65 (ddd, J=7.7, 7.7, 1.7 Hz, 1H), 7.28-7.10 (m, 4H), 7.01 (dd, J=7.5, 7.5 Hz, 1H), 6.88 (d, J=7.8 Hz, 1H), 6.60 (d, J=6.8 Hz, 1H), 6.52 (d, J=10.1 Hz, 1H), 5.20 (d, J=15.8 Hz, 1H), 5.03-4.90 (m, 2H), 4.72 (d, J=9.0 Hz, 1H), 3.86 (s, 3H); 13C NMR (75 MHz, CDCl3) δ177.3, 157.2 (d), 155.4, 149.6, 149.3, 149.1, 149.0, 146.1, 142.1, 137.1, 131.8, 129.0, 123.8, 123.6, 122.8, 121.6, 119.0 (d), 110.7, 110.4, 109.6, 96.3, 80.5, 58.1, 56.4, 46.0; MS (ES+) m/z 377.2 (M+1).