6-CHLORO-1,3-DIMETHYL-1H-PYRAZOLO[3,4-B]PYRIDINE-5-CARBALDEHYDE synthesis

Yield:898911-34-7 43%

Reaction Conditions:

Stage #1: N-(1,3-dimethyl-1H-pyrazol-5-yl)acetamidewith trichlorophosphate at 90 - 95; for 2 h;
Stage #2: with N,N-dimethyl-formamide at 90 - 95; for 3.3 h;Product distribution / selectivity;

Steps:

16.ii

Step (ii): Synthesis of 6-chloro-l,3-dimethyl-lH-pyrazolo[3,4-&]pyridine-5-carbaldehyde; A mixture of N-(2,5-dimethyl-2H-pyrazol-3-yl)-acetamide (13.7 g, 89 mmol) and phosphorus oxychloride (68.4 mL, 44.5 mmol, distilled prior to use) was heated to 90-95 °C with stirring under nitrogen atmosphere for 2 h followed by the slow addition of DMF (19.6 mL, 26.7 mmol) at the same temperature for 20 min. After stirring for 3 h, the reaction was cooled to 0 ⁰C and crushed ice was slowly added and continued stirring for EPO 30 min. The resultant solid was filtered off, washed with water and petroleum ether to yield a light yellow solid (7.8 g), yield: 43%.¹H NMR(400 MHz, CDC1₃₎: δ 10.48 (s, IH), 8.60 (s,lH), 4.07 (s, 3H), 2.59 (s, 3H).CI-MS m/z 210 (M⁺+ 1, 100%).

References:

WO2006/73973,2006,A2 Location in patent:Page/Page column 172-173