spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-one → 1'-[(5-fluoropyridin-3-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-one

HRID 2385353Notes

Reaction equation

HRID 2385353 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([C:21]3[C:12](=[CH:13][C:14]4[O:19][CH2:18][CH2:17][O:16][C:15]=4[CH:20]=3)[O:11][CH2:10]2)[C:2]1=[O:22].N1C2C(=CC=CC=2)C2(C3=CC4OCOC=4C=C3OC2)C1=O.Cl.Cl[CH2:46][C:47]1[CH:48]=[N:49][CH:50]=[C:51]([F:53])[CH:52]=1.CC1C=CC(S(OC[C@H]2COCCO2)(=O)=O)=CC=1>>[F:53][C:51]1[CH:52]=[C:47]([CH2:46][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]3([C:21]4[C:12](=[CH:13][C:14]5[O:19][CH2:18][CH2:17][O:16][C:15]=5[CH:20]=4)[O:11][CH2:10]3)[C:2]2=[O:22])[CH:48]=[N:49][CH:50]=1

Participants

5

Reactant 4

HCID 53375495spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-oneHCID 567764533-(Chloromethyl)-5-fluoropyridine hydrochlorideHCID 58224164Spiro[furo[2,3-g]-1,4-benzodioxin-8(7H),3'-[3H]indol]-2'(1'H)-one, 2,3-dihydroHCID 59253203(R)-(1,4-dioxan-2-yl)methyl 4-methylbenzenesulfonate

Product 1

HCID 593524761'-[(5-fluoropyridin-3-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-one

Procedure

Following the procedure as described in EXAMPLE 8 and making non-critical variations using 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 3-(chloromethyl)-5-fluoropyridine hydrochloride (Carlson et al., Acta Pharmaceutica Suecica, 1972, 9, 411-414) to replace (R)-(1,4-dioxan-2-yl)methyl 4-methylbenzenesulfonate, 1′-[(5-fluoropyridin-3-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one was obtained (71%) as a colorless solid: 1H NMR (300 MHz, CDCl3) δ 8.45-8.38 (m, 2H), 7.37-7.34 (m, 1H), 7.24-7.14 (m, 2H), 7.04-7.00 (m, 1H), 6.78-6.75 (m, 1H), 6.46 (s, 1H), 6.17 (s, 1H), 5.03-4.85 (m, 3H), 4.64-4.61 (m, 1H), 4.16-4.04 (m, 4H); 13C NMR (75 MHz, CDCl3) δ 177.6, 155.3, 144.7, 144.6, 141.4, 138.4, 138.1, 137.8, 132.1, 129.0, 124.3, 123.9, 122.1, 121.9, 120.6, 111.4, 108.8, 99.5, 80.1, 64.5, 63.9, 58.0, 41.1; MS (ES+) m/z 405.0 (M+1).

Sources & evidence

ORD record
ord-505e35ade99f4296b4541047a70c02ee
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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