تفاعل #72965

معادلة التفاعل

p-toluenesulfonyl chloride

1-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}cyclohexanol

m-chloroperoxybenzoic acid

ammonium hydroxide

m-CPBA

→

1-{[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}cyclohexanol

المذيبات

dichloromethane

Water

CHCl3

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONwas added over 1 h until the starting material
2. 2
   أخرىwas consumed
3. 3
   workup.ADDITIONWater (40 mL) and solid K2CO3 were added to the reaction mixture until the pH=10
4. 4
   workup.ADDITIONThe mixture was poured into a separatory funnel
5. 5
   استخلاصextracted with chloroform
6. 6
   أخرىresulting in an emulsion
7. 7
   استخلاصThe aqueous layer was extracted with chloroform three times
8. 8
   غسيلThe combined organic layers were washed with water and brine
9. 9
   تجفيفdried over MgSO4
10. 10
    ترشيحfiltered
11. 11
    تركيزconcentrated
12. 12
    أخرىto yield a crude white solid (1.51 g)
13. 13
    استخلاصthe aqueous layer was extracted with dichloromethane (2×30 mL)
14. 14
    غسيلThe combined organic layers were washed with brine (25 mL)
15. 15
    تجفيفwere dried over MgSO4
16. 16
    ترشيحfiltered
17. 17
    تركيزconcentrated
18. 18
    أخرىThe crude product was purified by flash chromatography (silica gel, gradient elution with 98:1:1 CH2Cl2/MeOH/NH4OH to 94:5:1 CH2Cl2/MeOH/NH4OH)
19. 19
    أخرىthen crystallized from acetonitrile

الإجراء التجريبي

To a solution of 1-{[2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}cyclohexanol (1.90 g, 5.60 mmol) in CHCl3 (43 mL) was added m-chloroperoxybenzoic acid (m-CPBA, 77% w/w, 1.26 g, 5.60 mmol) over 15 min. The reaction was monitored by thin layer chromatography (TLC) and more m-CPBA was added over 1 h until the starting material was consumed. Water (40 mL) and solid K2CO3 were added to the reaction mixture until the pH=10. The mixture was poured into a separatory funnel and extracted with chloroform, resulting in an emulsion. The aqueous layer was extracted with chloroform three times. The combined organic layers were washed with water and brine, dried over MgSO4, filtered, and concentrated to yield a crude white solid (1.51 g). The white solid (1.51 g, 4.24 mmol) was dissolved in dichloromethane (25 mL) at rt and concentrated ammonium hydroxide (16 mL) was added, followed by p-toluenesulfonyl chloride (TsCl, 0.81 g, 4.24 mmol). The mixture was stirred 1 day (d). Water (25 mL) was added and the aqueous layer was extracted with dichloromethane (2×30 mL). The combined organic layers were washed with brine (25 mL) and were dried over MgSO4, filtered, and concentrated. The crude product was purified by flash chromatography (silica gel, gradient elution with 98:1:1 CH2Cl2/MeOH/NH4OH to 94:5:1 CH2Cl2/MeOH/NH4OH) then crystallized from acetonitrile to yield 1-{[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}cyclohexanol as pale orange crystals that were dried under high vacuum (0.32 g, 16% over two steps), mp 186-188° C. 1H NMR (300 MHz, CDCl3) δ 8.15 (dm, J=8.4 Hz, 1H), 7.81 (dm, J=8.4 Hz, 1H), 7.52 (m, 1H), 7.32 (m, 1H), 5.38 (br s, 2H), 4.90 (br s, 2H), 4.74 (br s, 2H), 3.66 (q, J=7.0 Hz, 2H), 3.00 (s, 1H), 1.71-1.52 (m, 10), 1.25 (t, J=7.0 Hz, 3H). MS (APCI) m/z 355 (M+H+). Anal. calcd for C20H26O2N4: C, 67.77; H, 7.39; N, 15.81. Found: C, 67.52; H, 7.57; N, 15.78

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