Réaction #88653

Équation de réaction

4-bromo-benzoyl chloride

(3R,4R)-1-(2-hydroxy-ethyl)-4-{3-methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-3-ol

(3R,4R)-1-(2-Hydroxy-ethyl)-4-{3-methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-3-ol

triethylamine

methylene chloride

→

4-bromo-benzoic acid 2-((3R,4R)-3-hydroxy-4-{3-methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-1-yl)-ethyl ester

Rendement 60.0%

Conditions de réaction

Traitement

1. 1
   Autrethe cooling bath/reaction
2. 2
   AutreThe volatile were evaporated
3. 3
   Séchagethe crude residue was further dried on high vacuum
4. 4
   AutreThe product was isolated by preparative reverse phase hplc (Gilson)

Mode opératoire

To a mixture of (3R,4R)-1-(2-hydroxy-ethyl)-4-{3-methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-3-ol (Example 16b; 40.00 mg, 0.082 mmol) and triethylamine (12 uL, 0.09 mmol) in methylene chloride (0.400 mL, 6.24 mmol) was added 4-bromo-benzoyl chloride, (19 mg, 0.086 mmol) at 0° C. The reaction was stirred overnight allowing the cooling bath/reaction to slowly warm to room temperature. The volatile were evaporated and the crude residue was further dried on high vacuum, The product was isolated by preparative reverse phase hplc (Gilson) and the free base was released by using a strong cation exchange resin column (Strata, from Phenomenex) to give 33 mg (60% yield) of 4-bromo-benzoic acid 2-((3R,4R)-3-hydroxy-4-{3-methoxy-4-[7-(2-methoxy-phenyl)-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino]-phenyl}-piperidin-1-yl)-ethyl ester. 1H NMR (CDCl3): 8.70 (br s, 1H), 8.35 (d, J=8.1 Hz, 1H), 7.96 (d, J=7.6 Hz, 1H), 7.92 (d, J=8.4 Hz, 2H), 7.60 (d, J=8.4 Hz, 2H), 7.47 (br s, 1H), 7.46-7.40 (m, 1H), 7.12 (app t, J=7.5 Hz, 1H), 7.07 (d, J=8.3 Hz, 1H), 7.02 (d, J=4.7 Hz, 1H), 6.85 (d, J=4.7 Hz, 1H), 6.78 (d, J=8.7 Hz, 1H), 6.76 (br s, 1H), 4.50 (app t, J=5.8 Hz, 2H), 3.89 (s, 3H), 3.84 (s, 3H), 3.80 (m, 1H), 3.31 (m, 1H), 3.04 (br d, J=11.3 Hz, 1H), 2.90 (app t, J=5.8 Hz, 2H), 2.35 (m, 1H), 2.26 (m, 1H), 2.15 (app t, J=10.2 Hz, 1H), 1.86 (m, 2H), 1.67 (br s, 1H).

Source