1-Ethylpyrazole-5-boronic Acid

To the crude 3-(5-amino-8-bromo-2-(hydroxymethyl)-[l, 2, 4]triazolo[L5- c]pyrimidin-7-yl)benzonitrile from previous step was added (1-ethyl- l//-pyrazol-5-yl)boronic acid (47 mg, 0.34 mmol), XPhos Pd G2 (13 mg, 0.017 mmol), K3PO4 (71 mg, 0.34 mmol), dioxane (3 mL) and water (0.6 mL). The reaction mixture was heated and stirred at 90 C for 1 h, cooled to r.t, diluted with saturated NH4CI solution (3 mL), and extracted with EtOAc (15 mL). The organic phase was separated, dried over Na2S04, concentrated, and purified by flash chromatography (0 to 70% EtOAc in diehloromethane) to give the desired product (40 mg, 55%). LCMS calculated for CI8HI7N80 (M+H)+: 361.1. Found: 361.1.A vial was charged with 3-(5-amino-2-(benzo[i/|isoxazol-3-yhnethyl)-8-bromo- [l , 2, 4jtriazolo[l , 5-cjpyrimidin-7-yl)benzonitrile (24 mg, 0.054 mmol), (1 -ethyl- LH-pyrazol- 5-yl)boronic acid (17 mg, 0.12 mmol), XPhos Pd G2 (4 3 mg, 0.0054 mmol), K3PO4 (23 mg, 0.11 mmol), dioxane (1 mL) and water (0.2 mL). The reaction mixture was then heated and stirred at 80 C for 1 h, cooled to r.t, diluted with saturated NH4CI solution (1 mL), and extracted with EtOAc (5 mL). The organic phase was separated, dried over NaiSCL, concentrated, and purified by preparative LC-MS (pH 2, acetonitrile/water with TFA) to afford the product as a TFA salt. LCMS calculated for C25H20N9O (M+H)1 : 462.2. Found; 462.2.3- bromo-4-(2, 6-difluoro-4-nitrophenoxy)-1 -{[2-(trimeth^ H-pyrrolo[2, 3- b]pyridine (1.00 g, 2.00 mmol, intermediate 16), [1 , 1 '-Bis(diphenylphosphino)- ferrocene]dichloropalladium(ll) (146 mg, 0.20 mmol), (1 -ethyl-1 H-pyrazol-5-yl)boronic acid (559 mg, 4.00 mmol, CAS No. [1095080-54-8]), and potassium carbonate (1 .38 g, 9.99 mmol), were dissolved in a mixture of 1 , 4-dioxane (20 ml_), and water (10 ml_). The resulting mixture was degassed with argon for 10 min, after which time it was heated to 100C for 3h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate and water was added. The layers were separated, and the aqueous phase was extracted two times with ethyl acetate. The combined organic phases were washed with brine, dried over sodium sulfate, filtered and concentrated to dryness to give the crude product. The crude produt was purified by flash column chromatography to afford 4-(2, 6-difluoro-4-nitrophenoxy)-3-(1 -ethyl-1 H- pyrazol-5-yl)-1 -{[2-(trimethylsilyl)ethoxy]methyl}-1 H-pyrrolo[2, 3-b]pyridine (260 mg, 20% Yield). LC-MS (Method 2): Rt = 1 .52 min; MS (ESIpos): m/z = 516 [M+H]+ 1H NMR (400 MHz, DMSO-d6) delta ppm -0.10 (s, 9 H), 0.80 - 0.88 (m, 2 H), 1 .25 (t, 3 H), 3.56 - 3.65 (m, 2 H), 4.10 (q, 2 H), 5.71 (s, 2 H), 6.30 (d, 1 H), 6.66 (d, 1 H), 7.45 (d, 1 H), 7.90 (s, 1 H), 8.25 (d, 1 H), 8.32 - 8.38 (m, 2 H)A suspension of 100 mg (0.19 mmol) of 2-[(3R)-3-methylmorpholin-4-yl]-8-[1-(tetrahydro-2H- pyran-2-yl)-1H-pyrazol-5-yl]-1, 7-naphthyridin-4-yl trifluoromethanesulfonate, 53 mg (0.38 mmol)

Molecular Weight:139.95
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:2
Exact Mass:140.0757077
Monoisotopic Mass:140.0757077
Topological Polar Surface Area:58.3
Heavy Atom Count:10
Complexity:112
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes