Methanesulfonyl chloride → [4-(2,5-Dichloro-phenoxy)-pyridin-3-yl]-(4-methanesulfonyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanone

HRID 1966974Notes

Reaction equation

HRID 1966974 reaction equation
[Cl:1][C:2]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[CH:7][C:6]=1[C:11]([N:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[NH:16][CH2:15][CH2:14]1)=[O:12].C(N(CC)C(C)C)(C)C.[CH3:37][S:38](Cl)(=[O:40])=[O:39]>ClCCl>[Cl:1][C:2]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:3]=1[O:4][C:5]1[CH:10]=[CH:9][N:8]=[CH:7][C:6]=1[C:11]([N:13]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]([S:38]([CH3:37])(=[O:40])=[O:39])[CH2:15][CH2:14]1)=[O:12]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chloride2×HCID 81531Diisopropylethylamine2×HCID 53311864[4-(2,5-Dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone

Product 1

HCID 53311868[4-(2,5-Dichloro-phenoxy)-pyridin-3-yl]-(4-methanesulfonyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanoneYield 26%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 0.10 g (0.25 mmol) [4-(2,5-dichloro-phenoxy)-pyridin-3-yl]-(3,4-dihydro-2H-quinoxalin-1-yl)-methanone (Example 3) in 2 mL dichloromethane were added 0.08 mL (0.50 mmol) N,N-diisopropylethylamine followed by dropwise addition of 0.02 mL (0.27 mmol) methanesulfonylchloride. After 16 hours another 0.08 mL (0.50 mmol) N,N-diisopropylethylamine and 0.02 mL (0.27 mmol) methanesulfonylchloride were added. The reaction mixture was poured on water and was extracted three times with dichloromethane. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered, treated with silica gel and evaporated. The resulting powder was purified by silica gel chromatography using a MPLC system (10 g silical gel column, CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate (100:0 to 50:50) followed by a second chromatography on a 10 g silica gel column using a gradient from n-heptane: tert-butyl methyl ether (100:0 to 25:75) to give 31 mg (26%) of the desired compound as a light brown foam. MS (ESI): m/z=478.039 [M+H]+.

Workup

  1. additionThe reaction mixture was poured on water
  2. extractionwas extracted three times with dichloromethane
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. additiontreated with silica gel
  7. customevaporated
  8. customThe resulting powder was purified by silica gel chromatography
  9. washeluting with a gradient of n-heptane:ethyl acetate (100:0 to 50:50)

Sources & evidence

ORD record
ord-f8d0fc0ce3f54ca6a066bf12b56eadc7
Source dataset
uspto-grants-2013_04
Patent number
US08420647B2

Reaction notes

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