Imidazole → 5-(t-Butyldimethylsilanyloxy)-3-(1-methylpiperidin-4-yl)-1H-indol

HRID 1766230Notes

Reaction equation

[CH3:1][N:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([OH:17])[CH:15]=3)[NH:10][CH:9]=2)=[CH:4][CH2:3]1.CN1CCCC1=O.[Si:25](Cl)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26].N1C=CN=C1>ClCCl>[Si:25]([O:17][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[C:8]2[CH:5]1[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]1)([C:28]([CH3:31])([CH3:30])[CH3:29])([CH3:27])[CH3:26]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 3-(1-methyl-pyridin-4-yl)-5-hydroxy-1H-indole (8.0 g, 34.7 mmol) and 1-methyl-2-pyrrolidinone (10 mL) in dichloromethane (90 mL) stirring at 0° C., was added tert-butyldimethylsilyl chloride in small portions (5.50 g, 36.5 mmol), followed by imidazole also in small portions (2.48 g, 36.5 mmol). The reaction mixture was stirred for 1 hour at 0° C., then overnight at room temperature. The mixture was concentrated in vacuo to a solid residue, which was directly purified on silica gel. Elution with a 9:1 mixture of dichloromethane and methanol provided 7.60 g (63%) of the title compound as a white solid: mp=191-195° C.; 1H NMR (400 MHz, dmso-d6): 10.46 (s, 1H), 7.02 (d, 1H, J=8.4 Hz), 6.87 (d, 1H, J=2.4 Hz), 6.74 (d, 1H, J=2.4 Hz), 6.45 (dd, 1H, J=8.6, 2.6 Hz), 2.69 (br d, 2H, J=11.2 Hz), 2.46 (tt, 1H, J=11.8, 3.6 Hz), 2.04 (s, 3H), 1.92-1.80 (m, 2H), 1.75-1.67 (m, 2H), 1.50 (qd, 2H, J=12.4, 3.6 Hz), 0.81 (s, 9H), 0.00 (s, 6H); MS (APCI): m/e 345 0.2 (M+1).

Workup

customovernight
customat room temperature
concentrationThe mixture was concentrated in vacuo to a solid residue, which
customwas directly purified on silica gel
washElution
additionwith a 9:1 mixture of dichloromethane and methanol

Sources & evidence

ORD record: ord-41ae64e5498f44fabd09799c3a520656
Source dataset: uspto-grants-2007_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07230011B2

Reaction notes

Loading…