spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-one → 7'-fluoro-1'-((3-(trifluoromethyl)pyridin-2-yl)methyl)-3,7-dihydro-2H-spiro[benzofuro[5,6-b][1,4]dioxine-8,3'-indolin]-2'-one

HRID 2385351Notes

Reaction equation

HRID 2385351 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.N1C2C(=CC=CC=2)C2(C3=CC4OCOC=4C=C3OC2)C1=O.Cl.Cl[CH2:47][C:48]1[C:53]([C:54]([F:57])([F:56])[F:55])=[CH:52][CH:51]=[CH:50][N:49]=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]([CH2:47][C:48]1[C:53]([C:54]([F:56])([F:55])[F:57])=[CH:52][CH:51]=[CH:50][N:49]=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 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)-oneHCID 667065662-(Chloromethyl)-3-(trifluoromethyl)pyridine hydrochloride

Product 1

HCID 593520897'-fluoro-1'-((3-(trifluoromethyl)pyridin-2-yl)methyl)-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-(chloromethyl)-3-(trifluoromethyl)pyridine hydrochloride to replace (R)-(1,4-dioxan-2-yl)methyl 4-methylbenzenesulfonate, 7′-fluoro-1′-((3-(trifluoromethyl)pyridin-2-yl)methyl)-3,7-dihydro-2H-spiro[benzofuro[5,6-b][1,4]dioxine-8,3′-indolin]-2′-one was obtained (40%) as a colorless solid: mp 241-243° C. (dichloromethane); 1H NMR (300 MHz, CDCl3) δ8.62 (d, J=4.7 Hz, 1H), 7.97 (d, J=7.8 Hz, 1H), 7.34-7.30 (m, 1H), 7.00-6.86 (m, 3H), 6.68 (s, 1H), 6.50 (s, 1H), 5.54 (d, J=17.1 Hz, 1H), 5.37 (d, J=17.1 Hz, 1H), 4.99 (d, J=9.0 Hz, 1H), 4.73 (d, J=9.0 Hz, 1H), 4.21-4.19 (m, 2H), 4.15-4.14 (m, 2H); 13C NMR (75 MHz, CDCl3) δ177.9, 155.1, 153.0, 151.9, 149.2, 145.9, 144.7, 138.3, 135.5, 134.3, 129.2, 123.9, 121.9, 121.3, 119.6, 116.4, 116.2, 112.5, 99.2, 80.2, 64.6, 63.9, 58.5, 44.2; MS (ES+) m/z 473.0 (M+1).

Sources & evidence

ORD record
ord-39fefe22623e4deb94fcede10a728ec5
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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