Ethyl isocyanate → HCID 57722863, compound

HRID 222288Notes

Reaction equation

HRID 222288 reaction equation
[NH2:1][C:2]1[CH:23]=[CH:22][C:5]2[C:6](=[O:21])[C:7]3[C:8]([CH:19]=[CH:20][C:4]=2[CH:3]=1)=[N:9][CH:10]=[C:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH:12]=3.[CH2:24]([N:26]=[C:27]=[O:28])[CH3:25]>N1C=CC=CC=1>[CH2:24]([NH:26][C:27]([NH:1][C:2]1[CH:23]=[CH:22][C:5]2[C:6](=[O:21])[C:7]3[C:8]([CH:19]=[CH:20][C:4]=2[CH:3]=1)=[N:9][CH:10]=[C:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH:12]=3)=[O:28])[CH3:25]

Participants

4

Reactant 2

HCID 8022Ethyl isocyanate3×HCID 15980909HCID 15980909, compound

Product 1

HCID 57722863HCID 57722863, compound

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

To a 0° C. solution of 8-amino-3-phenyl-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one (6.4 mg, 0.021 mmol) in pyridine (0.3 mL) was ethyl isocyanate (0.1 mL, 0.38 M in CH2Cl2) The mixture was then stirred at room temperature for 4 hours followed by heating at 50° C. After 3 hours, more ethyl isocianate (3 μL, 0.038 mmol) was added and the mixture was heated at 70° C. After stirring for 14 hours, a new addition of ethyl isocyanate (9 μL, 0.114 mmol) was followed by heating at 80° C. More ethyl isocyanate (20 μL, 0.253 mmol) was added 2 hours later and heating was continued for 14 hours. The mixture was then concentrated to dryness. The crude residue was purified by flash chromatography (100-85% CH2Cl2/MeOH gradient) and reverse phase HPLC (30-100% acetonitrile/water gradient, 0.1% trifluoroacetic acid modifier) to afford the title compound. 1H NMR (600 MHz, DMSO-D6) δ 9.24 (d, 1H), 8.69 (d, 1H), 8.14 (d, 1H), 7.85 (d, 2H), 7.80 (d, 1H), 7.67 (dd, 1H), 7.53 (t, 2H), 7.45 (t, 2H), 7.31 (s, 2H), 2.95 (m, 2H), 0.93 (t, 3H). LRMS (APCI) calculated for C23H20N3O2 [M+H]+, 370.1; found 370.1.

Workup

  1. customTo a 0° C.
  2. temperatureby heating at 50° C
  3. waitAfter 3 hours
  4. additionwas added
  5. temperaturethe mixture was heated at 70° C
  6. stirringAfter stirring for 14 hours
  7. temperatureby heating at 80° C
  8. temperatureheating
  9. waitwas continued for 14 hours
  10. concentrationThe mixture was then concentrated to dryness
  11. customThe crude residue was purified by flash chromatography (100-85% CH2Cl2/MeOH gradient)

Sources & evidence

ORD record
ord-7fb6ea93971f45939ee89d2d049240b2
Source dataset
uspto-grants-2012_06
Patent number
US08207186B2

Reaction notes

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