Cesium carbonate → N-(4-(1,2,4-oxadiazol-3-yl)benzyl)-4-chloro-N-(trans-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide

HRID 1011515Notes

Reaction equation

HRID 1011515 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C@@H:12]2[CH2:17][CH2:16][CH2:15][CH2:14][C@H:13]2[CH2:18][OH:19])(=[O:10])=[O:9])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:27][C:28]1[CH:33]=[CH:32][C:31]([C:34]2[N:38]=[CH:37][O:36][N:35]=2)=[CH:30][CH:29]=1>CN(C)C=O>[O:36]1[CH:37]=[N:38][C:34]([C:31]2[CH:32]=[CH:33][C:28]([CH2:27][N:11]([C@@H:12]3[CH2:17][CH2:16][CH2:15][CH2:14][C@H:13]3[CH2:18][OH:19])[S:8]([C:5]3[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=3)(=[O:9])=[O:10])=[CH:29][CH:30]=2)=[N:35]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 594977704-chloro-N-(trans-2-hydroxymethylcyclohexyl)benzenesulfonamideHCID 666700193-(4-(Bromomethyl)phenyl)-1,2,4-oxadiazole

Product 1

HCID 59497773N-(4-(1,2,4-oxadiazol-3-yl)benzyl)-4-chloro-N-(trans-2-(hydroxymethyl)cyclohexyl)benzenesulfonamideYield 15.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of 4-chloro-N-(trans-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide (300 mg, 1.0 mmol), cesium carbonate (390 mg, 1.2 mmol), and 3-(4-(bromomethyl)phenyl)-1,2,4-oxadiazole (280 mg, 1.2 mmol) in dimethylformamide (5 mL) was stirred for 2 h. The reaction was concentrated and purified by flash chromatography on a 40 g silica gel column using a gradient of 0 to 80% ethyl acetate in hexane, then by preparative HPLC to give N-(4-(1,2,4-oxadiazol-3-yl)benzyl)-4-chloro-N-(trans-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide (70 mg, 15%). 1H NMR (400 MHz, MeOD) δ ppm 9.23 (s, 1H), 8.00 (d, J=8.30 Hz, 2H), 7.75 (d, J=8.81 Hz, 2H), 7.54 (d, J=8.00 Hz, 2H), 7.51 (d, J=8.60 Hz, 2H), 4.55 (d, J=15.61 Hz, 1H), 4.36 (d, J=15.86 Hz, 1H), 3.52 (br. s., 1H), 3.31-3.38 (m, 1H), 3.14 (dd, J=11.08, 7.30 Hz, 1H), 1.87 (d, J=12.34 Hz, 1H), 1.53-1.75 (m, 2H), 1.30-1.53 (m, 3H), 0.98-1.22 (m, 3H). LC/MS R.T.=2.72 min; [M+H]+=462. HRMS [M+H]+ calc'd 462.1254, found 462.1241.

Workup

  1. concentrationThe reaction was concentrated
  2. custompurified by flash chromatography on a 40 g silica gel column

Sources & evidence

ORD record
ord-e925f7ef171c4a468c7459f1b7287386
Source dataset
uspto-grants-2011_07
Patent number
US07977362B2

Reaction notes

Loading…