Tin tetrachloride → ethyl 2-[4-[(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)methyl]phenyl]quinazoline-4-carboxylate

HRID 717340Notes

Reaction equation

HRID 717340 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][C:13]1[CH:27]=[CH:26][C:16]([C:17]([NH:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=O)=[CH:15][CH:14]=1.P(Cl)(Cl)(Cl)(Cl)Cl.[CH2:34]([O:36][C:37](=[O:40])[C:38]#[N:39])[CH3:35].Cl[Sn](Cl)(Cl)Cl>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][C:13]1[CH:14]=[CH:15][C:16]([C:17]2[N:39]=[C:38]([C:37]([O:36][CH2:34][CH3:35])=[O:40])[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:19]=2)=[CH:26][CH:27]=1

Participants

6

Reactant 4

HCID 24287Tin tetrachlorideHCID 24819Phosphorus pentachlorideHCID 69336Ethyl cyanoformateHCID 2995396HCID 2995396, compound

Product 1

HCID 90411437ethyl 2-[4-[(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)methyl]phenyl]quinazoline-4-carboxylate

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Conditions

Temperature
65 °C

Procedure

Into a 500-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed 4-[(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)methyl]-N-phenylbenzamide (14 g, 39.28 mmol, 1.00 equiv), POCl3 (140 mL) and PCl5 (8.96 g, 43.03 mmol, 1.10 equiv). The resulting solution was stirred for 2 h at 65° C. in an oil bath. The resulting mixture was concentrated under vacuum. The residue was diluted with chlorobenzene (300 mL). To this was added 2-ethoxy-2-oxoacetonitrile (7.7 mL, 2.00 equiv), tetrachlorostannane (15 mL, 1.50 equiv). The resulting solution was allowed to react, with stirring, for an additional 2 h while the temperature was maintained at 120° C. in an oil bath. The resulting mixture was concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate:petroleum ether:tetrahydrofuran (30:6:1). This resulted in 4 g (23%) of ethyl 2-[4-[(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)methyl]phenyl]quinazoline-4-carboxylate as a light yellow solid. MS (ESI) m/z 438 ([M+H]+).

Workup

  1. customInto a 500-mL round-bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. concentrationThe resulting mixture was concentrated under vacuum
  4. additionThe residue was diluted with chlorobenzene (300 mL)
  5. customto react
  6. stirringwith stirring, for an additional 2 h while the temperature
  7. temperaturewas maintained at 120° C. in an oil bath
  8. concentrationThe resulting mixture was concentrated under vacuum
  9. customThis resulted in 4 g (23%) of ethyl 2-[4-[(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)methyl]phenyl]quinazoline-4-carboxylate as a light yellow solid

Sources & evidence

ORD record
ord-a25153ee691c4f9095593d68a675f961
Source dataset
uspto-grants-2015_11
Patent number
US09193707B2

Reaction notes

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