Hydrochloric Acid → HCID 46866166, compound

HRID 1970784Notes

Reaction equation

HRID 1970784 reaction equation
[NH2:1][C:2]1[C:7]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:6][C:5]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)=[CH:4][N:3]=1.[CH2:23]([S:30](Cl)(=[O:32])=[O:31])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.Cl>N1C=CC=CC=1>[CH2:8]([C:7]1[C:2]([NH:1][S:30]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)(=[O:32])=[O:31])=[N:3][CH:4]=[C:5]([C:15]2[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=2)[N:6]=1)[C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 74740Phenylmethanesulfonyl chloride4×HCID 113007862-Amino-3-benzyl-5-(4-methoxyphenyl)pyrazine

Product 1

HCID 46866166HCID 46866166, compoundYield 36.8%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

Under an argon atmosphere, 2-amino-3-benzyl-5-(4-methoxyphenyl)pyrazine (c-11) (prepared by the method described in Adamczyk M. et al., Org. Prep. Proced. Int., 33, 477-485 (2001)) (99.5 mg, 342 μmol) was dissolved in pyridine (1 mL) and cooled to 0° C. To this was added benzylsulfonyl chloride (84.7 mg, 444 μmol) and stirred for an hour after warming to room temperature. To this was added benzylsulfonyl chloride (13.8 mg, 72.3 μmol) and the mixture was stirred for 2.5 h. To this was further added benzylsulfonyl chloride (13.9 mg, 72.9 pimp and the mixture was stirred for 15 h. To this was further added benzylsulfonyl chloride (13.1 mg, 68.7 μmol) and the mixture was stirred for 5.5 h. To this was added 2 M hydrochloric acid to stop the reaction, and after separating the aqueous layer and organic layer, it was extracted 3 times with dichloromethane. The organic layer was washed with saturated aqueous solution of sodium sulfate and then dried over anhydrous sodium sulfate. After removing anhydrous sodium sulfate by filtration, the organic layer was concentrated under reduced pressure. The residue was purified by column chromatography (7 g, n-hexane/ethyl acetate=7/3→ethyl acetate). The resulting solid was recrystallized from ethyl acetate to give 3-benzyl-2-benzylsulfonylamino-5-(4-methoxyphenyl)pyrazine (c-18) as a colorless solid (56.0 mg, 36.8%). Rf=0.32 (n-hexane/ethyl acetate=7/3). Mp. 213-215° C. UV (MeOH, 0.3% DMSO) λmax (log ε) 334.5 (4.04), 290 (4.21), 276.5 (4.23). UV (pH 7.4 PB, 0.3% DMSO) λmax (log ε) 348.5 (3.90), 293 (3.95). 1H NMR (400 MHz, DMSO-d6) δ 3.80 (s, 3H), 4.22 (s, 2H), 4.91 (s, 2H), 7.02-7.07 (AA′BB′, 2H), 7.14-7.21 (m, 1H), 7.24-7.27 (m, 4H), 7.36 (s, 5H), 7.99 (d, J=7.3 Hz, 2H), 8.88 (s, 1H), 10.46 (s, 1H). 13C NMR (75.5 MHz, DMSO-d6) δ 38.0, 55.3, 59.6, 114.4 (2C), 126.3, 127.6 (2C), 128.1, 128.3 (2C), 128.4, 128.5 (2C), 129.0 (2C), 129.9, 130.9 (2C), 136.2, 138.1, 144.6, 145.8, 146.0, 160.3. IR (KBr, cm−1) 459, 538, 586, 698, 748, 785, 831, 893, 912, 926, 1032, 1121, 1132, 1177, 1215, 1256, 1287, 1319, 1395, 1452, 1495, 1516, 1609, 3231. HRMS (FAB+) m/z 446.1548 (M+H, C25H24N3O3S requires 446.1548).

Workup

  1. temperatureafter warming to room temperature
  2. stirringthe mixture was stirred for 2.5 h
  3. stirringthe mixture was stirred for 15 h
  4. stirringthe mixture was stirred for 5.5 h
  5. customthe reaction
  6. customafter separating the aqueous layer and organic layer, it
  7. extractionwas extracted 3 times with dichloromethane
  8. washThe organic layer was washed with saturated aqueous solution of sodium sulfate
  9. dry with materialdried over anhydrous sodium sulfate
  10. customAfter removing anhydrous sodium sulfate
  11. filtrationby filtration
  12. concentrationthe organic layer was concentrated under reduced pressure
  13. customThe residue was purified by column chromatography (7 g, n-hexane/ethyl acetate=7/3→ethyl acetate)
  14. customThe resulting solid was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-fb9d1b27ab20440bae6cf86bb8ae6923
Source dataset
uspto-grants-2013_04
Patent number
US08431525B2

Reaction notes

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