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

HRID 1970797Notes

Reaction equation

HRID 1970797 reaction equation
C([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]=[C:13]([CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:14]([N:17](S(C)(=O)=O)[S:18]([CH3:21])(=[O:20])=[O:19])=[N:15][CH:16]=2)=[CH:7][CH:6]=1)(=O)C.[OH-].[Na+].Cl>CO>[CH2:26]([C:13]1[C:14]([NH:17][S:18]([CH3:21])(=[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:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 468661705-(4-Acetoxyphenyl)-3-benzyl-2-bis(methanesulfonyl)aminopyrazine

Product 1

HCID 1359348913-Benzyl-5-(4-hydroxyphenyl)2-(methanesulfonylamino)pyrazineYield 92.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

5-(4-Acetoxyphenyl)-3-benzyl-2-bis(methanesulfonyl)aminopyrazine (c-39) (239 mg, 503 μmol) was suspended in methanol (5 mL) and to this was added 10% (w/v) aqueous solution of sodium hydroxide (1.2 mL) while stirring at room temperature and then stirred at 65° C. for 30 min. 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 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 (23 g, n-hexane/ethyl acetate=1/1) to give 3-benzyl-5-(4-hydroxyphenyl)2-(methanesulfonylamino)pyrazine (coelenteramesylamide) (c-34) as a pale yellow solid (166 mg, 92.6%). Rf=0.30 (n-hexane/ethyl acetate=1/1). Mp. 208-209° C. (dec.). UV (MeOH) λmax (log ε) 335 (4.12), 290 (4.25), 276 (4.27). UV (pH 7.4 PB) λmax (log ε) 349 (4.14), 281 (4.38). 1H NMR (400 MHz, DMSO-d6) δ 3.36 (s, 3H), 4.25 (s, 2H), 6.82-6.87 (AA′BB′, 2H), 7.15-7.23 (m, 1H), 7.29 (d, J=5.0 Hz, 4H), 7.83-7.88 (AA′BB′, 2H), 8.73 (s, 1H), 9.80 (s, 1H), 10.41 (s, 1H). 13C NMR (75.5 MHz, DMSO-d6) δ 38.2, 42.7, 115.8 (2C), 126.4, 126.6, 127.7 (2C), 128.4 (2C), 129.0 (2C), 135.9, 138.1, 144.3, 146.0, 146.4, 158.8. IR (KBr, cm−1) 521, 538, 588, 606, 700, 750, 827, 841, 889, 916, 939, 970, 1118, 1138, 1153, 1175, 1213, 1273, 1314, 1400, 1456, 1495, 1609, 3206. HRMS (FAB+) m/z 356.1060 (M+H, C18H18N3O3S requires 356.1069).

Workup

  1. stirringstirred at 65° C. for 30 min
  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 (23 g, n-hexane/ethyl acetate=1/1)

Sources & evidence

ORD record
ord-f1a2f266e00741a0a6cd7aa3737a5424
Source dataset
uspto-grants-2013_04
Patent number
US08431525B2

Reaction notes

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