Morpholine → 1'-[(5-morpholin-4-ylpyridin-2-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3'-indol]-2'(1'H)-one

HRID 2385560Notes

Reaction equation

HRID 2385560 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(N1CC[C@@H](N)C1)(OC(C)(C)C)=O.Br[C:21]1[CH:22]=[CH:23][C:24]([CH2:27][N:28]2[C:36]3[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=3)[C:30]3([C:48]4[C:39](=[CH:40][C:41]5[O:46][CH2:45][CH2:44][O:43][C:42]=5[CH:47]=4)[O:38][CH2:37]3)[C:29]2=[O:49])=[N:25][CH:26]=1.BrC1C=CC(CN2C3C(=CC=CC=3)C3(C4C=C(F)C(F)=CC=4OC3)C2=O)=CC=1>>[N:1]1([C:21]2[CH:22]=[CH:23][C:24]([CH2:27][N:28]3[C:36]4[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=4)[C:30]4([C:48]5[C:39](=[CH:40][C:41]6[O:46][CH2:45][CH2:44][O:43][C:42]=6[CH:47]=5)[O:38][CH2:37]4)[C:29]3=[O:49])=[N:25][CH:26]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

5

Reactant 4

HCID 8083MorpholineHCID 854070(R)-(+)-1-Boc-3-aminopyrrolidineHCID 593524831'-(4-bromobenzyl)-5,6-difluorospiro[1-benzofuran-3,3'-indol]-2'(1'H)-oneHCID 59352743HCID 59352743, compound

Product 1

HCID 593522091'-[(5-morpholin-4-ylpyridin-2-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 33.1 and making non-critical variations using morpholine to replace (R)-(+)-1-Boc-3-aminopyrrolidine, and 1′-[(5-bromopyridin-2-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one to replace 1′-(4-bromobenzyl)-5,6-difluorospiro[1-benzofuran-3,3′-indol]-2′(1′H)-one, 1′-[(5-morpholin-4-ylpyridin-2-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one was obtained (60%) as a pale yellow solid: mp 204-206° C.; 1H NMR (300 MHz, CDCl3) δ8.23 (d, J=2.4 Hz, 1H), 7.23-7.11 (m, 4H), 7.01 (dd, J=7.5, 7.5 Hz, 1H), 6.95 (d, J=7.8 Hz, 1H), 6.50 (s, 1H), 6.27 (s, 1H), 5.13 (d, J=15.3 Hz, 1H), 4.94 (d, J=9.0 Hz, 1H), 4.89 (d, J=15.6 Hz, 1H), 4.66 (d, J=9.0 Hz, 1H), 4.21-4.11 (m, 4H), 3.87 (t, J=4.8 Hz, 4H), 3.17 (t, J=5.0 Hz, 4H); 13C NMR (75 MHz, CDCl3) δ 177.4, 155.3, 146.3, 146.2, 144.6, 142.2, 138.3, 137.3, 132.2, 128.8, 123.7, 123.4, 123.2, 122.0, 121.1, 111.7, 109.7, 99.4, 80.2, 66.6, 64.5, 63.9, 58.1, 48.5, 45.6; MS (ES+) m/z 472.2 (M+1).

Sources & evidence

ORD record
ord-6a4554bb2354427b8d9ee4a16d9669be
Source dataset
uspto-grants-2012_09
Patent number
US08263606B2

Reaction notes

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