Carbon Dioxide → HCID 59252976, compound

HRID 884746Notes

Reaction equation

HRID 884746 reaction equation
C(C1C2C=CC=CC=2C(=O)OC=1N[C@H](C1C=CC=CC=1)CC)(=O)C.C(OC(C)(C)C)(=O)NN.C(OC(=O)[NH:40][N:41]1[C:50]([CH3:51])=[C:49]([C:52](=[O:63])[NH:53][C@H:54]([C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)[CH2:55][CH3:56])[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[C:42]1=[O:64])(C)(C)C.C(=O)=O>C(#N)C>[C:57]1([C@@H:54]([NH:53][C:52]([C:49]2[C:48]3[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=3)[C:42](=[O:64])[N:41]([NH2:40])[C:50]=2[CH3:51])=[O:63])[CH2:55][CH3:56])[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=1

Participants

6

Reactant 4

HCID 280Carbon Dioxide2×HCID 70091tert-Butyl carbazateHCID 57733336HCID 57733336, compoundHCID 67298343HCID 67298343, compound

Product 1

HCID 59252976HCID 59252976, compoundYield 67.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
180 °C

Procedure

A solution of 4-acetyl-3-((S)-1-phenyl-propylamino)-2-benzopyran-1-one (4.330 g, 13.47 mmol) and tert-butyl carbazate (1.959 g, 14.82 mmol) in acetonitrile (20 mL) was heated under microwave irradiation at 140° C. for 30 min. LC-MS the formation of the intermediate [3-methyl-1-oxo-4-((S)-1-phenyl-propylcarbamoyl)-1H-isoquinolin-2-yl]-carbamic acid tert-butyl ester as a major component (tR=1.36, UV 60%, ELSD 95%.). Then it was heated under microwave irradiation at 180° C. for total of 30 min (caution: CO2 gas formation; the reaction mixture was cooled automatically three times then the excess CO2 was released by puncture before heating continued to keep the pressure below the maximum limit of 20 bar). After cooling, the excess CO2 was carefully removed by puncture with needle, then by gentle shaking, then with stirring, then under sonication (caution: very intensive gas evolution). White precipitate formed, which was filtered, washed with acetonitrile and water to give pure title compound (3.07 g; Yield=67.9%). LC-MS (m/z) 336.6 (MH+); tR=1.04. 1H NMR (250 MHz, 70° C., DMSO-d6, DMSO-d5=2.5 ppm): 0.96 (t, J=7.3 Hz, Me of Et), 1.7-1.96 (m, 2H, diastereotopic CH2 of Et), 2.38 (s, 3H, Me), 5.0 (q (unres. dt), J (d)=6.8, J (t)=8.1, 1H, CH—NH), 5.82 (br. s, 2H, NH2), 7.27 (tm, J (t)=6.7 Hz, J (m)=ca 1.5 Hz, 1H), 7.32-7.49 (m, 6H), 7.61 (t (unresolved tdd), J (t)=8.1 Hz, J (d)=1 Hz, J (d)<1 Hz, 1H), 8.25 (dd, J=8 Hz, J=0.8 Hz, 1H), 8.68 (br. d, J=8.1 Hz, 1H, NHCO).

Workup

  1. temperaturethe reaction mixture was cooled automatically three times
  2. temperaturebefore heating
  3. temperatureAfter cooling
  4. customthe excess CO2 was carefully removed by puncture with needle
  5. customunder sonication (caution
  6. customWhite precipitate
  7. customformed
  8. filtrationwhich was filtered
  9. washwashed with acetonitrile and water

Sources & evidence

ORD record
ord-1d6dfd476b1545279c4b308286a377f1
Source dataset
uspto-grants-2012_08
Patent number
US08242134B2

Reaction notes

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