Cesium carbonate → 4-chloro-N-(2,5-difluoro-4-(oxazol-2-yl)benzyl)-N-((1R,2R)-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide

HRID 1011527Notes

Reaction equation

HRID 1011527 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[C:33]([F:34])=[CH:32][C:31]([C:35]2[O:36][CH:37]=[CH:38][N:39]=2)=[C:30]([F:40])[CH:29]=1.ClC1C=CC(S(N(CC2C=CC(C3OC=CN=3)=C(F)C=2F)[C@@H]2CCCC[C@H]2CO)(=O)=O)=CC=1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([N:11]([CH2:27][C:28]2[CH:29]=[C:30]([F:40])[C:31]([C:35]3[O:36][CH:37]=[CH:38][N:39]=3)=[CH:32][C:33]=2[F:34])[C@@H:12]2[CH2:17][CH2:16][CH2:15][CH2:14][C@H:13]2[CH2:18][OH:19])(=[O:9])=[O:10])=[CH:4][CH:3]=1

Participants

5

Reactant 4

HCID 10796Cesium carbonateHCID 594977704-chloro-N-(trans-2-hydroxymethylcyclohexyl)benzenesulfonamideHCID 594977804-chloro-N-(2,3-difluoro-4-(oxazol-2-yl)benzyl)-N-(trans-2-(hydroxymethyl)cyclohexyl)benzenesulfonamideHCID 666699622-(4-(Bromomethyl)-2,5-difluorophenyl)oxazole

Product 1

HCID 594978084-chloro-N-(2,5-difluoro-4-(oxazol-2-yl)benzyl)-N-((1R,2R)-2-(hydroxymethyl)cyclohexyl)benzenesulfonamideYield 31%

Procedure

The title compound was synthesized from 4-chloro-N-((1R,2R)-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide (90 mg, 0.30 mmol), cesium carbonate (117 mg, 0.36 mmol), and 2-(4-(bromomethyl)-2,5-difluorophenyl)oxazole (99 mg, 0.36 mmol) according to the procedure described for 4-chloro-N-(2,3-difluoro-4-(oxazol-2-yl)benzyl)-N-((1R,2R)-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide (Example 20) to give 4-chloro-N-(2,5-difluoro-4-(oxazol-2-yl)benzyl)-N-((1R,2R)-2-(hydroxymethyl)cyclohexyl)benzenesulfonamide (46 mg, 31%). 1H NMR (400 MHz, CDCl3) δ ppm 7.77 (s, 1H), 7.74 (d, J=8.56 Hz, 2H), 7.68 (dd, J=9.95, 5.67 Hz, 1H), 7.52 (dd, J=9.95, 5.67 Hz, 1H), 7.49 (d, J=8.56 Hz, 2H), 7.29 (s, 1H), 4.52 (d, J=16.00 Hz, 1H), 4.37 (d, J=16.00 Hz, 1H), 3.53-3.65 (m, 2H), 3.12 (d, J=11.08 Hz, 1H), 2.57 (d, J=1.01 Hz, 1H), 1.58-1.77 (m, 3H), 1.36-1.53 (m, 2H), 0.98-1.21 (m, 4H). Analytical HPLC R.T.=22.02 min. MS [M+H]+=497. HRMS [M+H]+ calc'd 497.1113, found 497.1100.

Sources & evidence

ORD record
ord-b667e459d0e247c688e16d833b2c318b
Source dataset
uspto-grants-2011_07
Patent number
US07977362B2

Reaction notes

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