p-Toluenesulfonic acid → HCID 66780099, compound

HRID 1854802Notes

Reaction equation

HRID 1854802 reaction equation
C(OC([NH:8][NH:9][C:10]([CH3:24])([CH3:23])[CH2:11][NH:12][C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14])=O)(C)(C)C.CC1C=CC(S(O)(=O)=O)=CC=1.C(N(CC)CC)C.CO[C:45]([C:51]1[CH:56]=[CH:55][C:54](C)=[CH:53][CH:52]=1)=[C:46]([C:49]#[N:50])[C:47]#[N:48]>C(#N)C.C(O)C>[CH2:16]([O:15][C:13](=[O:14])[NH:12][CH2:11][C:10]([N:9]1[C:49]([NH2:50])=[C:46]([C:47]#[N:48])[C:45]([C:51]2[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=2)=[N:8]1)([CH3:24])[CH3:23])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

7

Reactant 4

HCID 6101p-Toluenesulfonic acid2×HCID 8471TriethylamineHCID 122908442-[Methoxy(4-methylphenyl)methylene]propanedinitrileHCID 66780909HCID 66780909, compound

Product 1

HCID 66780099HCID 66780099, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6342AcetonitrileSolvent2×

Procedure

Compound 1B (310 mg, 0.92 mmol) was dissolved in 1 mL of dry acetonitrile. Tosic acid (875 mg, 4.6 mmol) was dissolved in 3 mL of dry acetonitrile. Molecular sieves were added to both solutions and stood for 30 minutes. The solution of tosic acid was then added the other mixture and the reaction was stirred at room temperature for 3 hours. After that time the reaction was filtered and the solid washed with acetonitrile and CH2Cl2). The filtrate was concentrated to afford a thick colourless oil. It was dissolved in 2 mL of ethanol. Triethylamine (640 μL, 1.48 mmol) and 2-(Methoxy-p-tolyl-methylene)-malononitrile (182 mg, 0.92 mmol) were successively added. The reaction was then heated at 60° C. for 3 hours. After cooling down, the reaction was concentrated. Water and EtOAc were then added and the aqueous phase was extracted three times with EtOAc. The combined organic layers were dried over Na2SO4 and concentrated. The oily residue obtained was purified by flash chromatography on SiO2 using 100% CH2Cl2 then CH2Cl2/MeOH 99:1. A colourless oil that solidifies slowly overnight was obtained (m=270 mg, 73%). NMR (ppm, CDCl3): δ 1.58 (s, 6H), 2.36 (s, 3H), 3.77 (d, J=6.63 Hz, 2H), 4.40 (br s, 2H), 5.08 (s, 2H), 5.59 (br t, J=5.94 Hz, 1H), 7.20 (d, J=8.55 Hz, 2H), 7.31 (m, 5H), 7.74 (d, J=8.13 Hz, 2H). 13C NMR (ppm, CDCl3): δ 21.35, 24.18, 50.56, 63.17, 66.99, 76.34, 115.22, 126.09, 128.15, 128.22, 128.33, 128.55, 129.42, 136.34, 139.11, 149.13, 151.57, 156.96. LCMS (+esi): 404.3 (M+H+).

Workup

  1. additionMolecular sieves were added to both solutions
  2. filtrationAfter that time the reaction was filtered
  3. washthe solid washed with acetonitrile and CH2Cl2)
  4. concentrationThe filtrate was concentrated
  5. customto afford a thick colourless oil
  6. temperatureThe reaction was then heated at 60° C. for 3 hours
  7. temperatureAfter cooling down
  8. concentrationthe reaction was concentrated
  9. additionWater and EtOAc were then added
  10. extractionthe aqueous phase was extracted three times with EtOAc
  11. dry with materialThe combined organic layers were dried over Na2SO4
  12. concentrationconcentrated
  13. customThe oily residue obtained
  14. customwas purified by flash chromatography on SiO2 using 100% CH2Cl2
  15. waitA colourless oil that solidifies slowly overnight
  16. customwas obtained (m=270 mg, 73%)

Sources & evidence

ORD record
ord-71dea4c6113f47e1a8a3ee4d6a314d17
Source dataset
uspto-grants-2015_02
Patent number
US08962830B2

Reaction notes

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