Nintedanib Impurity31

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Prepared according to the procedure described by Hubschwerlen, C. and Schmid, G. Helv. Chim. Acta 1983, 66, 2206-2209 with the addition of MgSO4. To a suspension of (S)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde (Carbosynth LLC, 346 g, 43% in DCM, 1.143 mol) and MgSO4 (278 g) in DCM (1.5 L) at 0° C. was added 2,4-dimethoxybenzylamine (193 g, 1.154 mol) over 20 min. After stirring at rt for 2 h it was filtered, washing the filter cake with DCM (2×250 mL). The mother liquor was used directly in step 2. Prepared was filtered washing the filter cake with DCM (2×250 mL)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: The preparation is carried out starting from 1-[4-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)thiazol-2-yl]piperidin-4-ylamine hydrobromide and (S)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde. The protecting group is cleaved off by means of a 1.25 N HCl/methanol solution: The reaction mixture was stirred at room temperature for 5 h, evaporated to dryness and dried under a high vacuum. The product was converted into the hydrochloride by treatment with methanolic HCl. evaporated to dryness dried under a high vacuum

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Prepared according to the procedure described by Hubschwerlen, C. and Schmid, G. Helv. Chim. Acta 1983, 66, 2206-2209 with the addition of MgSO4. To a suspension of (S)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde (Carbosynth LLC, 346 g, 43% in DCM, 1.143 mol) and MgSO4 (278 g) in DCM (1.5 L) at 0° C. was added 2,4-dimethoxybenzylamine (193 g, 1.154 mol) over 20 min. After stirring at rt for 2 h it was filtered, washing the filter cake with DCM (2×250 mL). The mother liquor was used directly in step 2. Prepared was filtered washing the filter cake with DCM (2×250 mL)