Ethanesulfonyl chloride → HCID 58115051, compound

HRID 1808704Notes

Reaction equation

HRID 1808704 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH3:14])[CH:10]([CH2:15][C:16]#[C:17][C:18]2[N:19]=[C:20]3[CH:26]=[CH:25][N:24]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[C:21]3=[N:22][CH:23]=2)[CH2:9]1)=O)(C)(C)C.C(N(C(C)C)C(C)C)C.[CH2:44]([S:46](Cl)(=[O:48])=[O:47])[CH3:45]>C(Cl)Cl.O1CCOCC1>[CH2:44]([S:46]([N:8]1[CH2:13][CH2:12][CH:11]([CH3:14])[CH:10]([CH2:15][C:16]#[C:17][C:18]2[N:19]=[C:20]3[CH:26]=[CH:25][N:24]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:32])[CH3:33])[C:21]3=[N:22][CH:23]=2)[CH2:9]1)(=[O:48])=[O:47])[CH3:45]

Participants

6

Reactant 3

HCID 11667Ethanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 66926038HCID 66926038, compound

Product 1

HCID 58115051HCID 58115051, compoundYield 79.7%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
0 °C

Procedure

To a flask containing a solution of (+/−)-4-methyl-3-{3-[5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-prop-2-ynyl}-piperidine-1-carboxylic acid tert-butyl ester (505 mg, 1.04 mmol) in methylene chloride (4 mL) was added a 25% solution of anhydrous HC1 in dioxane (3 mL). The mixture was lightly capped and stirred for 45 minutes. The solvent was stripped on the rotovap and the remainder was taken up in methylene chloride (15 mL) and stripped. This was repeated one more time to provide a yellow foamy solid. The crude material was taken up in dry methylene chloride and cooled to 0° C. (ice bath) under argon atmosphere. Ethyl diisopropyl amine was added and the material was stirred for 5 minutes. Ethane sulfonyl chloride (0.1 mL, 1.1 mmol) was slowly added via syringe and the material was stirred for 10 minutes. The cooling bath was removed and stirring continued for 1.5 hours. The crude mixture was taken up in water (40 mL) and methylene chloride (40 mL) and shaken in a reparatory funnel. The organic phase was collected and the aqueous phases were back extracted with methylene chloride (2×30 ml), the organics combined, dried (MgSO4), filtered and stripped. The remainder was purified by preparative TLC eluting with 50% ethyl acetate in hexanes. The product band was collected providing 395 mg of (+/−)-2-[3-(1-ethanesulfonyl-4-methyl-piperidin-3-yl)-prop-1-ynyl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine as a viscous yellow oil. MS (M+H)+=477.

Workup

  1. customThe mixture was lightly capped
  2. customto provide a yellow foamy solid
  3. stirringthe material was stirred for 5 minutes
  4. stirringthe material was stirred for 10 minutes
  5. customThe cooling bath was removed
  6. stirringstirring
  7. waitcontinued for 1.5 hours
  8. stirringmethylene chloride (40 mL) and shaken in a reparatory funnel
  9. customThe organic phase was collected
  10. extractionthe aqueous phases were back extracted with methylene chloride (2×30 ml)
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. customThe remainder was purified by preparative TLC
  14. washeluting with 50% ethyl acetate in hexanes
  15. customThe product band was collected

Sources & evidence

ORD record
ord-73404096aa7445c5990ba6e765bc36a5
Source dataset
uspto-grants-2013_01
Patent number
US08361962B2

Reaction notes

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