Hydrochloric Acid → 3-Benzyl-2-benzylsulfonylamino-5-(4-hydroxyphenyl)pyrazine

HRID 1970787Notes

Reaction equation

HRID 1970787 reaction equation
C([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[C:13]([CH2:38][C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[C:14]([N:17](S(CC3C=CC=CC=3)(=O)=O)[S:18]([CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)(=[O:20])=[O:19])=[N:15][CH:16]=2)=[CH:7][CH:6]=1)(=O)C.[OH-].[Na+].Cl>CO>[CH2:38]([C:13]1[C:14]([NH:17][S:18]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)(=[O:20])=[O:19])=[N:15][CH:16]=[C:11]([C:8]2[CH:9]=[CH:10][C:5]([OH:4])=[CH:6][CH:7]=2)[N:12]=1)[C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 468661695-(4-Acetoxyphenyl)-3-benzyl-2-bis(benzylsulfonyl)aminopyrazine

Product 1

HCID 1359348893-Benzyl-2-benzylsulfonylamino-5-(4-hydroxyphenyl)pyrazineYield 95.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

5-(4-Acetoxyphenyl)-3-benzyl-2-bis(benzylsulfonyl)aminopyrazine (c-20) (435 mg, 694 μmol) was dissolved in methanol (8 mL) and to this was added 10% (w/v) aqueous solution of sodium hydroxide (1.9 mL) while stirring at room temperature, and stirred at 65° C. for 9.5 h. After cooling to room temperature, to this was added 2 M hydrochloric acid to stop the reaction and extracted twice with ethyl acetate. The organic layer was washed with saturated brine and then dried over anhydrous sodium sulfate. After removing anhydrous sodium sulfate by filtration, the filtrate was concentrated under reduced pressure with a rotary evaporator. The residue was purified by column chromatography (35 g, n-hexane/ethyl acetate=3/1→2/1) to give 3-benzyl-2-benzylsulfonylamino-5-(4-hydroxyphenyl)pyrazine (h-coelenterasulfonamide) (c-15) as a pale yellow solid (286 mg, 95.6%). Rf=0.27 (n-hexane/ethyl acetate=3/2). Mp. 144-147° C. (dec.). UV (MeOH) λmax (log ε) 336 (4.06), 290 (4.23), 277.5 (4.25). UV (pH 7.4 PB) λmax (log ε) 351.5 (4.09), 283 (4.34). 1H NMR (400 MHz, DMSO-d6) δ 4.22 (s, 2H), 4.91 (s, 2H), 6.83-6.88 (AA′BB′, 2H), 7.14-7.20 (m, 1H), 7.22-7.29 (m, 4H), 7.36 (s, 5H), 7.86-7.93 (AA′BB′, 2H), 8.83 (s, 1H), 9.81 (s, 1H), 10.40 (s, 1H). 13C NMR (75.5 MHz, DMSO-d6) δ 38.0, 59.6, 115.8 (2C), 126.2, 126.5, 127.7, 128.28 (2C), 128.33 (2C), 128.5 (2C), 128.9 (2C), 129.9, 130.9 (2C), 136.0, 138.2, 144.2, 145.8, 146.5, 158.8. IR (KBr, cm−1) 527, 542, 604, 698, 835, 893, 912, 926, 935, 1117, 1130, 1188, 1213, 1244, 1267, 1321, 1402, 1452, 1495, 1516, 1595, 1609, 3055, 3221, 3522. HRMS (FAB+) m/z 432.1385 (M+H, C24H22N3O3S requires 432.1382).

Workup

  1. stirringstirred at 65° C. for 9.5 h
  2. temperatureAfter cooling to room temperature
  3. customthe reaction
  4. extractionextracted twice with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customAfter removing anhydrous sodium sulfate
  8. filtrationby filtration
  9. concentrationthe filtrate was concentrated under reduced pressure with a rotary evaporator
  10. customThe residue was purified by column chromatography (35 g, n-hexane/ethyl acetate=3/1→2/1)

Sources & evidence

ORD record
ord-cf423f8a3d6c4e9f822ae28443b11f3b
Source dataset
uspto-grants-2013_04
Patent number
US08431525B2

Reaction notes

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