Sodium Hydroxide → n-(4-(6h-Pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)-3-chlorobenzenesulfonamide

HRID 1854343Notes

Reaction equation

HRID 1854343 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([S:8]([NH:11][C:12]23[CH2:19][CH2:18][C:15]([C:20]4[N:24]5[C:25]6[CH:31]=[CH:30][N:29](S(C7C=CC(C)=CC=7)(=O)=O)[C:26]=6[N:27]=[CH:28][C:23]5=[N:22][N:21]=4)([CH2:16][CH2:17]2)[CH2:14][CH2:13]3)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.C(OC(NC12CCC(C(O)=O)(CC1)CC2)=O)(C)(C)C.ClC1C=C(S(Cl)(=O)=O)C=CC=1.[OH-].[Na+]>O1CCOCC1>[C:20]1([C:15]23[CH2:16][CH2:17][C:12]([NH:11][S:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=4)(=[O:9])=[O:10])([CH2:19][CH2:18]2)[CH2:13][CH2:14]3)[N:24]2[C:25]3[CH:31]=[CH:30][NH:29][C:26]=3[N:27]=[CH:28][C:23]2=[N:22][N:21]=1

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 179093-Chlorobenzenesulphonyl chlorideHCID 231507384-{[(Tert-butoxy)carbonyl]amino}bicyclo[2.2.2]octane-1-carboxylic acidHCID 580097923-chloro-N-(4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)benzenesulfonamide

Product 1

HCID 136199053n-(4-(6h-Pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)-3-chlorobenzenesulfonamideYield 86%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

A 100 mL round-bottomed flask was charged with 3-chloro-N-(4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)benzenesulfonamide (0.14 g, 0.22 mmol, prepared using A from Preparation #9 and 4-(tert-butoxycarbonylamino)bicyclo-[2.2.2]octane-1-carboxylic acid [Prime Organics], C with TEA, I, and N from 3-chlorobenzenesulfonyl chloride) and 1,4-dioxane (5 mL) to give a tan suspension and then aqueous NaOH (1N, 0.45 mL, 0.45 mmol, J. T. Baker) was added. The suspension was heated at about 60° C. for about 3 h. The reaction mixture was cooled to ambient temperature and the solvents were removed under reduced pressure. Upon addition of NH4OAc (50 mM aqueous buffer solution), a solid precipitated that was collected by vacuum filtration, washed with water, and dried to give N-(4-(6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)bicyclo[2.2.2]octan-1-yl)-3-chlorobenzenesulfonamide as a white solid (0.088 g, 86%): LC/MS (Table 2, Method a) Rt=1.88 min; MS m/z: 457 (M+H)+.

Workup

  1. customprepared
  2. customto give a tan suspension
  3. temperatureThe reaction mixture was cooled to ambient temperature
  4. customthe solvents were removed under reduced pressure
  5. additionUpon addition of NH4OAc (50 mM aqueous buffer solution)
  6. customa solid precipitated that
  7. filtrationwas collected by vacuum filtration
  8. washwashed with water
  9. customdried

Sources & evidence

ORD record
ord-fde22530bb154e39aa156aa0f245f287
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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