Tin tetrachloride → HCID 90411447, compound

HRID 717348Notes

Reaction equation

HRID 717348 reaction equation
[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH2:13][C:14]([NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=O.P(Cl)(Cl)(Cl)(Cl)Cl.Cl[Sn](Cl)(Cl)Cl.[CH2:34]([O:36][C:37](=[O:40])[C:38]#[N:39])[CH3:35]>O=P(Cl)(Cl)Cl>[O:1]=[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[N:3]1[CH2:12][CH2:13][C:14]1[N:39]=[C:38]([C:37]([O:36][CH2:34][CH3:35])=[O:40])[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]=1

Participants

6

Reactant 4

HCID 24287Tin tetrachlorideHCID 24819Phosphorus pentachlorideHCID 69336Ethyl cyanoformateHCID 5647944443-34-9

Product 1

HCID 90411447HCID 90411447, compound

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Conditions

Temperature
65 °C

Procedure

Into a 2000-mL 4-necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 3-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)-N-phenylpropanamide (40 g, 135.91 mmol, 1.00 equiv) in POCl3 (300 mL). This was followed by the addition of PCl5 (30 g, 144.06 mmol, 1.06 equiv). The mixture was stirred for 2 h at 65° C. The resulting mixture was concentrated under vacuum. The residue was poured into chlorobenzene (500 mL). To this was added SnCl4 (53 g) and 2-ethoxy-2-oxoacetonitrile (26 g, 262.39 mmol, 1.93 equiv) dropwise with stirring. The resulting solution was stirred for 2 h at 120° C. in an oil bath. The reaction mixture was cooled to room temperature. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:5). This resulted in 7.0 g (14%) of ethyl 2-[2-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)ethyl]quinazoline-4-carboxylate as a white solid. MS (ESI) m/z 376 ([M+H]+).

Workup

  1. customInto a 2000-mL 4-necked round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. concentrationThe resulting mixture was concentrated under vacuum
  4. additionThe residue was poured into chlorobenzene (500 mL)
  5. stirringwith stirring
  6. stirringThe resulting solution was stirred for 2 h at 120° C. in an oil bath
  7. temperatureThe reaction mixture was cooled to room temperature
  8. concentrationThe resulting mixture was concentrated under vacuum
  9. customThis resulted in 7.0 g (14%) of ethyl 2-[2-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)ethyl]quinazoline-4-carboxylate as a white solid

Sources & evidence

ORD record
ord-9163db652b0d4a76b83b99c9d907c6e8
Source dataset
uspto-grants-2015_11
Patent number
US09193707B2

Reaction notes

Loading…