Reaktion #329121

Reaktionsgleichung

chloride

2-isopropylaniline

chloro-actyl chloride

adenine

K2CO3

Thionyl chloride

2-amino-6-methylbenzoic acid

→

2-(6-Aminopurin-9-ylmethyl)-3-(2-isopropylphenyl)-5-methyl-3H-quinazolin-4-one

Lösungsmittel

EtOAc hexane

DMF

water

benzene

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe mixture was heated
2. 2
   Temperaturat reflux for 18 h
3. 3
   TemperaturOnce cooled
4. 4
   Sonstigethe solvent was removed in vacuo
5. 5
   workup.DISSOLUTIONThe residue was dissolved in CHCl3 (50 mL)
6. 6
   TemperaturThe slurry was then heated
7. 7
   Temperaturat reflux for 3 h
8. 8
   workup.ADDITIONthe reaction mixture was poured atop a 4 cm plug of silica gel
9. 9
   Sonstigeflushed through with 20% EtOAc/hexane
10. 10
    workup.ADDITIONThe product containing fractions
11. 11
    Einengenconcentrated in vacuo
12. 12
    workup.DISSOLUTIONThe residue was dissolved in HOAc (50 mL)
13. 13
    Temperaturthe mixture was heated
14. 14
    Temperaturat reflux for 18 h
15. 15
    TemperaturThe reaction was cooled
16. 16
    Einengenconcentrated in vacuo
17. 17
    SonstigeThe remaining HOAc was removed
18. 18
    Sonstigeby azeotroping with toluene (25 mL) three times
19. 19
    workup.DISSOLUTIONThe residue was dissolved in toluene (10 mL)
20. 20
    workup.ADDITIONpoured through a 4 cm plug of silica gel
21. 21
    Sonstigeflushing through with 20% EtOAc/hexane
22. 22
    workup.ADDITIONThe product containing fractions
23. 23
    Einengenconcentrated in vacuo
24. 24
    Sonstigeto afford 975 mg (30%) as a white foam
25. 25
    workup.STIRRINGstirred at room temperature for 30 min
26. 26
    Temperaturthen chilled in the refrigerator for 30 min
27. 27
    FiltrationThe resultant solid was collected by vacuum filtration
28. 28
    Sonstigerecrystallized from EtOH
29. 29
    Sonstigeto afford 285 mg (49%) of an off white solid

Vorschrift

Thionyl chloride (2.2 mL, 30 mmol) was added to a stirred solution of 2-amino-6-methylbenzoic acid (1.51 g, 10 mmol) in benzene (50 mL) and the mixture was heated at reflux for 18 h. Once cooled, the solvent was removed in vacuo and stripped down twice with benzene (25 mL). The residue was dissolved in CHCl3 (50 mL) and treated with 2-isopropylaniline (2.83 mL, 20 mmol). The slurry was then heated at reflux for 3 h. At that time TLC (50% EtOAc/hexane) indicated that the reaction was complete. After cooling to room temperature, the reaction mixture was poured atop a 4 cm plug of silica gel and flushed through with 20% EtOAc/hexane. The product containing fractions were combined and concentrated in vacuo. The residue was dissolved in HOAc (50 mL) and treated with chloro-actyl chloride (1.6 mL, 20 mmol) and the mixture was heated at reflux for 18 h. The reaction was cooled and concentrated in vacuo. The remaining HOAc was removed by azeotroping with toluene (25 mL) three times. The residue was dissolved in toluene (10 mL) and poured through a 4 cm plug of silica gel, flushing through with 20% EtOAc/hexane. The product containing fractions were identified by LCMS (MS (ES): m/z 327 (M+)), and concentrated in vacuo to afford 975 mg (30%) as a white foam. The white foam chloride (450 mg, 1.36 mmol) was dissolved in DMF (10 mL) and treated with adenine (275 mg, 2.04 mmol) and K2CO3 (281 mg, 2.04 mmol) and the mixture was stirred overnight at room temperature. The suspension was then poured into 200 mL of water, stirred at room temperature for 30 min then chilled in the refrigerator for 30 min. The resultant solid was collected by vacuum filtration and recrystallized from EtOH to afford 285 mg (49%) of an off white solid. mp 258.0-258.2° C. 1H NMR (DMSO-d6) δ: 8.19 (s, 1H), 8.09 (s, 1H), 7.60 (m, 3H), 7.45 (m, 2H), 7.23 (m, 3H), 5.11 (d, J=17.5 Hz, 1H), 4.71 (d, J=17.5 Hz, 1H), 2.68 (s, 3H), 2.73 (q, J=6.9 Hz, 1H), 1.34 (d, J=6.8 Hz, 3H), 1.13 (d, J=6.8 Hz, 3H). 13C NMR (DMSO-d6) ppm: 161.9, 156.2, 152.8, 151.6, 150.1, 148.4, 146.1, 142.2, 140.8, 134.3, 133.7, 130.6, 130.0, 129.0, 127.7, 127.6, 125.8, 119.2, 118.4, 44.8, 28.3, 24.4, 23.3, 22.9. MS (ES): m/z 426.4 (M+). Anal. calcd. for C24H23N7O: C, 67.75; H, 5.45; N, 23.04. Found: C, 67.60; H, 5.45; N, 22.82.

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