반응 #1017402

반응 방정식

(E)-3-(2-(4-methoxybenzylamino)-6-bromoquinolin-3-yl)-N-(cyclohexylmethyl)acrylamide

compound 10

(E)-3-(2-(4-methoxybenzylamino)-6-bromoquinolin-3-yl)-N-(cyclohexylmethyl)acrylamide

4-methylbenzenesulfonohydrazide

sodium acetate

→

compound 11

3-(2-(4-methoxybenzylamino)-6-bromoquinolin-3-yl)-N-(cyclohexylmethyl)propanamide

용매

DME

water

반응 조건

후처리

1. 1
   workup.ADDITIONvia addition funnel
2. 2
   workup.ADDITIONOnce the addition
3. 3
   온도the reaction was refluxed for an additional 30 min
4. 4
   온도cooled to RT
5. 5
   농축concentrated
6. 6
   기타to remove organic solvent
7. 7
   workup.DISSOLUTIONThe crude material was dissolved in DCM (150 mL)
8. 8
   세척washed sequentially with 1N NaOH, 1N HCl
9. 9
   건조The organic layer was dried over MgSO4
10. 10
    여과filtered
11. 11
    농축concentrated
12. 12
    기타to give a yellow oil
13. 13
    기타Purification via flash chromatography (5% EtOAc/dichloromethane)

실험 절차

To a stirred solution of (E)-3-(2-(4-methoxybenzylamino)-6-bromoquinolin-3-yl)-N-(cyclohexylmethyl)acrylamide (representative compound 10; 3.7 g, 7.3 mmol) in DME (100 mL) was added 4-methylbenzenesulfonohydrazide (13.6 g, 72.8 mmol). The mixture was brought to reflux at 86° C. and then via addition funnel was added dropwise a solution of sodium acetate (10.4 g, 127 mmol) in water (60 mL) over 1.5 h. Once the addition was complete, the reaction was refluxed for an additional 30 min, and then cooled to RT and concentrated to remove organic solvent. The crude material was dissolved in DCM (150 mL) and washed sequentially with 1N NaOH, 1N HCl, and then water. The organic layer was dried over MgSO4, filtered and concentrated to give a yellow oil. Purification via flash chromatography (5% EtOAc/dichloromethane) afforded 3-(2-(4-methoxybenzylamino)-6-bromoquinolin-3-yl)-N-(cyclohexylmethyl)propanamide (representative compound 11). Step 2 In a sealed tube was combined 3-(2-(4-methoxybenzylamino)-6-bromoquinolin-3-yl)-N-(cyclohexylmethyl)propanamide (0.16 g, 0.31 mmol), 2-chlorophenylboronic acid (0.074 g, 0.47 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (0.0044 g, 0.0063 mmol), potassium acetate (0.062 g, 0.63 mmol), EtOH (6.0 ml) and water (0.41 mL). The flask was sealed and heated in an oil bath at 85° C. for 16 h. The reaction mixture was cooled to RT, adsorbed onto silica and purified by flash chromatography (5% MeOH/dichloromethane) to afford 3-(2-(4-methoxybenzylamino)-6-(2-chlorophenyl)quinolin-3-yl)-N-(cyclohexylmethyl)propanamide. Step: 3 Following the same procedure as in Step 9 of Scheme II, 3-(2-amino-6-(2-chlorophenyl)quinolin-3-yl)-N-(cyclohexylmethyl)propanamide (representative compound 6) was obtained after 3 hours of refluxing in TFA. MS (ESI, pos. ion) m/z: 422 (M+1).

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