Acetic Anhydride → HCID 46866374, compound

HRID 1970791Notes

Reaction equation

HRID 1970791 reaction equation
[CH2:1]([C:8]1[C:9]([NH:21][C:22](=[S:30])[CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[N:10][CH:11]=[C:12]([C:14]2[CH:19]=[CH:18][C:17]([OH:20])=[CH:16][CH:15]=2)[N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:31](OC(=O)C)(=[O:33])[CH3:32].C(=O)(O)[O-].[Na+].C(OCC)(=O)C>N1C=CC=CC=1>[C:31]([O:20][C:17]1[CH:18]=[CH:19][C:14]([C:12]2[N:13]=[C:8]([CH2:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[C:9]([NH:21][C:22](=[S:30])[CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[N:10][CH:11]=2)=[CH:15][CH:16]=1)(=[O:33])[CH3:32]

Participants

6

Reactant 4

HCID 7918Acetic Anhydride2×HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 135934896HCID 135934896, compound

Product 1

HCID 46866374HCID 46866374, compoundYield 47.8%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
0 °C

Procedure

Under an argon atmosphere, 3-benzyl-5-(4-hydroxyphenyl)-2-(phenylthioacetyl amino)pyrazine (h-coelenterathioamide) (c-14) (183 mg, 444 μmol) was dissolved in pyridine (2 mL) and cooled to 0° C. To this was added acetic anhydride (55 μL, 0.58 mmol) and stirred for 2 h after warming to room temperature. To this was further added acetic anhydride (25 μL, 0.26 mmol) and stirred at room temperature for 2.5 h. To this was added saturated aqueous solution of sodium bicarbonate and ethyl acetate to stop the reaction, and after separating the aqueous layer and organic layer, the organic layer was washed 3 times with water and once with 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. After purifying the residue by silica gel column chromatography (22 g, n-hexane/ethyl acetate=2/1), the obtained solid was further purified by silica gel column chromatography (7 g, n-hexane/ethyl acetate=2/1) to give 5-(4-acetoxyphenyl)-3-benzyl-2-(phenylthioacetylamino)pyrazine (c-31) as a pale yellow solid (96.3 mg, 47.8%). Rf=0.36 (n-hexane/ethyl acetate=2/1). Mp. 143-145° C. UV (MeOH) λmax (log ε) 320 (4.30), 258 (4.41). UV (pH 7.4 PB) λmax (log ε) 346 (4.36), 274 (4.35). 1H NMR (400 MHz, DMSO-d6) δ 2.29 (s, 3H), 3.95 (s, 2H), 4.14 (s, 2H), 7.00 (d, J=6.6 Hz, 2H), 7.12-7.24 (m, 3H), 7.26-7.32 (AA′BB′, 3H), 7.36 (t, J=7.3 Hz, 2H), 7.51 (d, J=7.5 Hz, 2H), 8.12-8.18 (AA′BB′, 2H), 9.04 (s, 1H), 12.23 (s, 1H). 13C NMR (75.5 MHz, DMSO-d6) δ 20.9, 39.4, 51.6, 122.6 (2C), 126.4, 127.0, 128.0 (2C), 128.3 (2C), 128.4 (2C), 128.9 (2C), 129.0 (2C), 132.8, 136.8, 137.9, 138.6, 145.9, 149.0, 151.9, 152.4, 169.1, 204.7. IR (KBr, cm−1) 700, 1128, 1165, 1179, 1200, 1238, 1368, 1389, 1416, 1441, 1493, 1508, 1730, 3265. HRMS (FAB+) m/z 454.1583 (M+H, C27H24N3O2S requires 454.1589).

Workup

  1. temperatureafter warming to room temperature
  2. stirringstirred at room temperature for 2.5 h
  3. customthe reaction
  4. customafter separating the aqueous layer and organic layer
  5. washthe organic layer was washed 3 times with water
  6. dry with materialonce with brine and dried 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. customAfter purifying the residue by silica gel column chromatography (22 g, n-hexane/ethyl acetate=2/1)
  11. customthe obtained solid was further purified by silica gel column chromatography (7 g, n-hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-e4432ac1b914482295d15980df9bc515
Source dataset
uspto-grants-2013_04
Patent number
US08431525B2

Reaction notes

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