Réaction #661787

Équation de réaction

4-methyl-1-naphthoyl chloride

4-(2-(2-methyl-1H-pyrrolo[2,3-b]pyridin-1-yl)ethyl)morpholine

ethyl aluminum dichloride

→

(2-methyl-1-(2-morpholino ethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)(4-methylnaphthalen-1-yl)methanone

Solvants

CH2Cl2

Conditions de réaction

Traitement

1. 1
   AutreThe reaction mixture was then partitioned between ethyl acetate and cold H2O
2. 2
   Extractionthe aqueous layer extracted twice with ethyl acetate
3. 3
   ExtractionThe combined organic extract
4. 4
   Lavagewas washed successively with H2O, 10% K2CO3, and brine
5. 5
   Séchagedried over MgSO4
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated in vacuo
8. 8
   AutreThe crude product was purified via silica gel chromatography
9. 9
   Lavagewashed with a saturated solution of Na2CO3
10. 10
    Séchagedried over Na2SO4
11. 11
    Filtrationfiltered
12. 12
    Concentrationconcentrated in vacuo
13. 13
    Autreto give CBX003(32 mg, 0.077 mmol)

Mode opératoire

To a solution of 4-methyl-1-naphthoyl chloride (112 mg, 0.55 mmol) and 4-(2-(2-methyl-1H-pyrrolo[2,3-b]pyridin-1-yl)ethyl)morpholine (143 mg, 0.59 mmol) in 2.5 mL CH2Cl2 at −70° C. was added dropwise ethyl aluminum dichloride (0.67 mL, 1.21 mmol, 1.8 M in toluene). The reaction mixture was allowed to slowly warm to room temperature overnight. The reaction mixture was then partitioned between ethyl acetate and cold H2O, and the aqueous layer extracted twice with ethyl acetate. The combined organic extract was washed successively with H2O, 10% K2CO3, and brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified via silica gel chromatography using a gradient from 0 to 5% MeOH in CH2Cl2, then taken up in CHCl3 and washed with a saturated solution of Na2CO3, dried over Na2SO4, filtered, and concentrated in vacuo to give CBX003(32 mg, 0.077 mmol). 1H NMR (500 MHz, CDCl3, δ): 2.46-2.58 (m, 4H), 2.60 (s, 3H), 2.78 (t, J=6.8 Hz, 2H), 2.81 (s, 3H), 3.69 (t, J=4.5 Hz, 4H), 4.47 (t, J=6.8 Hz, 2H), 6.91-7.02 (m, 1H), 7.38 (d, J=7.2 Hz, 1H), 7.43 (dd, J=7.9 Hz, 1.4 Hz, 1H), 7.45-7.52 (m, 2H), 7.58 (td, J=7.6 Hz, 1.1 Hz, 1H), 8.11 (d, J=8.4 Hz, 1H), 8.16 (d, J=8.4 Hz, 1H), 8.26 (dd, J=4.7 Hz, 1.5 Hz, 1H). 13C NMR (500 MHz, CDCl3, δ): 12.83, 19.93, 39.55, 53.99, 57.68, 66.93, 113.29, 118.10, 119.85, 124.42, 125.76, 125.78, 126.06, 126.24, 126.66, 129.10, 130.36, 132.90, 137.15, 138.40, 143.02, 146.42, 147.59, 193.21. MS m/z 415.5 [M+H]+.

Source