Dimethylformamide → 5-[({1-[3-(1-Methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylthio)phenyl]pyridine

HRID 423668Notes

Reaction equation

[CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.CS(O[CH2:21][CH:22]1[CH2:27][CH2:26][N:25]([C:28]2[O:32][N:31]=[C:30]([CH:33]([CH3:35])[CH3:34])[N:29]=2)[CH2:24][CH2:23]1)(=O)=O.C([O-])([O-])=O.[K+].[K+].CN(C=O)C>O>[CH3:35][CH:33]([C:30]1[N:29]=[C:28]([N:25]2[CH2:24][CH2:23][CH:22]([CH2:21][O:15][C:12]3[CH:11]=[CH:10][C:9]([C:6]4[CH:5]=[CH:4][C:3]([S:2][CH3:1])=[CH:8][CH:7]=4)=[N:14][CH:13]=3)[CH2:27][CH2:26]2)[O:32][N:31]=1)[CH3:34]

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of 6-[4-(methylthio)phenyl]-3-pyridinol (53.2 g, 245 mmol), {1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl methanesulfonate (prepared as in Example 100, Step 4, 74.3 g, 735 mmol), K2CO3 (101.5 g, 735 mmol) and DMF (500 mL) was stirred at 80° C. for 2 h. The mixture was charged with water, allowed to stand for 30 min, and the resulting precipitate was filtered, washed with water, heptane, and air dried to give 5-[({1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}methyl)oxy]-2-[4-(methylthio)phenyl]pyridine (93.7 g, 90%) as a tan solid. 1H NMR (400 MHz, CDCl3): δ 8.32 (d, 1H, J=2.8 Hz), 7.83 (d, 2H, J=8.5 Hz), 7.61 (d, 1H, J=8.7 Hz), 7.30 (d, 2H, J=8.5 Hz), 7.22 (d, 1H, J=3.0 Hz), 4.30-4.10 (m, 2H), 3.90 (d, 2H, J=6.2 Hz), 3.15-3.05 (m, 2H), 2.92-2.82 (m, 1H), 2.50 (s, 3H), 2.14-1.99 (m, 1H), 2.00-1.90 (m, 2H), 1.55-1.40 (m, 2H), 1.27 (d, 6H, J=6.3 Hz); LRMS (ESI), m/z 425 (M+H).

Workup

waitto stand for 30 min
filtrationthe resulting precipitate was filtered
washwashed with water, heptane, and air
customdried

Sources & evidence

ORD record: ord-64cd7635af9a4ae3badf7cd5e912b56e
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08101634B2

Reaction notes

Loading…