2-(Bromomethyl)tetrahydro-2H-pyran → 4'-[6-(dimethylamino)pyridin-3-yl]-1'-{[2-(1-methylethyl)-1,3-thiazol-4-yl]methyl}spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-one

HRID 1965538Notes

Reaction equation

HRID 1965538 reaction equation
Cl[CH2:2][C:3]1[N:4]=[C:5]([CH:8]([CH3:10])[CH3:9])[S:6][CH:7]=1.BrCC1CCCCO1.[CH3:19][N:20]([CH3:48])[C:21]1[N:26]=[CH:25][C:24]([C:27]2[CH:35]=[CH:34][CH:33]=[C:32]3[C:28]=2[C:29]2([C:40]4=[CH:41][C:42]5[O:46][CH2:45][O:44][C:43]=5[CH:47]=[C:39]4[O:38][CH2:37]2)[C:30](=[O:36])[NH:31]3)=[CH:23][CH:22]=1>>[CH3:19][N:20]([CH3:48])[C:21]1[N:26]=[CH:25][C:24]([C:27]2[CH:35]=[CH:34][CH:33]=[C:32]3[C:28]=2[C:29]2([C:40]4=[CH:41][C:42]5[O:46][CH2:45][O:44][C:43]=5[CH:47]=[C:39]4[O:38][CH2:37]2)[C:30](=[O:36])[N:31]3[CH2:2][C:3]2[N:4]=[C:5]([CH:8]([CH3:10])[CH3:9])[S:6][CH:7]=2)=[CH:23][CH:22]=1

Participants

4

Reactant 3

HCID 1419172-(Bromomethyl)tetrahydro-2H-pyranHCID 27631934-(Chloromethyl)-2-isopropyl-1,3-thiazoleHCID 593521484'-[6-(dimethylamino)pyridin-3-yl]spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-one

Product 1

HCID 593522144'-[6-(dimethylamino)pyridin-3-yl]-1'-{[2-(1-methylethyl)-1,3-thiazol-4-yl]methyl}spiro[furo[2,3-f][1,3]benzodioxole-7,3'-indol]-2'(1'H)-one

Procedure

Following the procedure as described in EXAMPLE 4 and making non-critical variations using 4-(chloromethyl)-2-isopropylthiazole to replace 2-(bromomethyl)tetrahydro-2H-pyran, and 4′-[6-(dimethylamino)pyridin-3-yl]spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one to replace 5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2″(1H)-one, 4′-[6-(dimethylamino)pyridin-3-yl]-1′-{[2-(1-methylethyl)-1,3-thiazol-4-yl]methyl}spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one was obtained (73%) as a colorless solid: mp 164-165° C. (diethyl ether); 1H NMR (300 MHz, DMSO-d6) δ7.58 (d, J=2.3 Hz, 1H), 7.49 (s, 1H), 7.32 (dd, J=7.8, 7.8 Hz, 1H), 7.06 (d, J=7.9 Hz, 1H), 6.82-6.76 (m, 2H), 6.42-6.37 (m, 3H), 5.96 (d, J=19.0 Hz, 2H), 5.11 (d, J=16.0 Hz, 1H), 4.89 (d, J=16.0 Hz, 1H), 4.57 (d, J=9.4 Hz, 1H), 4.42 (d, J=9.4 Hz, 1H), 3.29-3.20 (m, 1H), 2.99 (s, 6H), 1.31 (d, J=6.9 Hz, 6H); 13C NMR (75 MHz, DMSO-d6) δ 177.5, 176.9, 157.9, 155.4, 149.9, 148.3, 146.6, 142.6, 141.5, 136.8 (2C), 129.2, 128.8, 125.2, 121.7, 121.1, 115.3, 108.6, 104.3, 102.6, 101.3, 93.2, 77.2, 57.8, 37.6, 32.4, 22.8, 22.7; MS (ES+) m/z 541.3 (M+1).

Sources & evidence

ORD record
ord-0f6654ca75264744b953217ab0dd61e1
Source dataset
uspto-grants-2013_04
Patent number
US08415370B2

Reaction notes

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