2-(Bromomethyl)pyridine hydrobromide → 7'-fluoro-1'-(pyridin-2-ylmethyl)-3,7-dihydro-2H-spiro[benzofuro[5,6-b][1,4]dioxine-8,3'-indolin]-2'-one

HRID 1407757Notes

Reaction equation

HRID 1407757 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][C:8](=[O:11])[C:7]12[C:23]2[C:14](=[CH:15][C:16]3[O:21][CH2:20][CH2:19][O:18][C:17]=3[CH:22]=2)[O:13][CH2:12]1.[NH:24]1[C:32]2[C:27](=CC=C[CH:31]=2)[C:26]2([C:36]3=[CH:37]C4OCOC=4C=C3OC2)C1=O.Br.BrCC1C=CC=CN=1.CC1C=CC(S(OC[C@H]2COCCO2)(=O)=O)=CC=1>>[F:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH2:31][C:32]1[CH:27]=[CH:26][CH:36]=[CH:37][N:24]=1)[C:8](=[O:11])[C:7]12[C:23]2=[CH:22][C:17]3[O:18][CH2:19][CH2:20][O:21][C:16]=3[CH:15]=[C:14]2[O:13][CH2:12]1

Participants

5

Reactant 4

HCID 27347202-(Bromomethyl)pyridine hydrobromideHCID 53375495spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-oneHCID 59253203(R)-(1,4-dioxan-2-yl)methyl 4-methylbenzenesulfonateHCID 593525427'-fluoro-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-one

Product 1

HCID 593526527'-fluoro-1'-(pyridin-2-ylmethyl)-3,7-dihydro-2H-spiro[benzofuro[5,6-b][1,4]dioxine-8,3'-indolin]-2'-one

Procedure

Following the procedure as described in EXAMPLE 8 and making non-critical variations using 7′-fluoro-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one to replace spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one, and 2-(bromomethyl)pyridine hydrobromide to replace (R)-(1,4-dioxan-2-yl)methyl 4-methylbenzenesulfonate, 7′-fluoro-1′-(pyridin-2-ylmethyl)-3,7-dihydro-2H-spiro[benzofuro[5,6-b][1,4]dioxine-8,3′-indolin]-2′-one was obtained (38%) as a colorless solid: mp 205-207° C. (dichloromethane); 1H NMR (300 MHz, CDCl3) δ8.55 (d, J=4.8 Hz, 1H), 7.69-7.63 (m, 1H), 7.23-7.16 (m, 2H), 6.99-6.89 (m, 3H), 6.50 (s, 2H), 5.35 (d, J=16.4 Hz, 1H), 5.17 (d, J=16.4 Hz, 1H), 4.97 (d, J=8.9 Hz, 1H), 4.70 (d, J=8.9 Hz, 1H), 4.22-4.19 (m, 2H), 4.15-4.13 (m, 2H); 13C NMR (75 MHz, CDCl3) δ177.5, 155.7, 155.1, 149.6, 144.7, 138.4, 136.7, 124.0, 124.0, 122.4, 121.0, 120.7, 119.7, 119.6, 116.7, 116.5, 112.1, 99.3, 80.3, 64.5, 63.9, 58.4, 47.0; MS (ES+) m/z 405.0 (M+1).

Sources & evidence

ORD record
ord-0cf567ff5c744aac860bb551578cb12b
Source dataset
uspto-grants-2014_12
Patent number
US08916580B2

Reaction notes

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