O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate → methyl 6-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinecarboxylate

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Reaction Steps

To a suspension of 6-[(methyloxy)carbonyl]-2-pyridinecarboxylate potassium salt (39.5 g, 180 mmol) in a 500 mL 3-neck flask was added N,N-dimethylformamide (DMF) (1,700 mL) followed by TBTU (60.4 g, 188 mmol) [still a suspension]. After 2 min the 5-(aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine (55.6 g, 164 mmol) was added as a solid and after 15 min nearly all the material had gone into solution. After 2.5 h the slightly cloudy mixture was evaporated off to remove as much DMF as possible using high vacuum and this gave a beige oily solid which was partitioned between saturated sodium bicarbonate and ethyl acetate. Solid started to come out of solution from the organics so they it was filtered off dried under high vacuum. This gave 29.56 g (39%) of the above named compound as a white solid. Lab HPLC of this material showed 95.8% of desired product (ret time 1.87 min) contaminated with 3.4% of HOBt. (ret time 1.16 min). LC-MS m/z 467 (M+H)+, 0.78 min (ret time).

Provenance & Evidence