2-BOC-AMINO PYRIDINE-5-BORONIC ACID

General procedure: To a solution of compound 3(4.18 g, 10 mmol) in 1, 4-dioxane at room temperature, we subsequentlyadded Pd(PPh3)4 (1.16 g, 1 mmol), K2CO3 (2.76 g, 20 mmol), and (2-oxoindolin-5 -yl)boronic acid (2.12 g, 12 mmol). Afterdegassing, the resulting mixture was heated to 80 C for 4 h beforecooling to room temperature. The solution was extracted withEtOAc. The organic layer was washed with water and brine, dried(MgSO4), filtered, and evaporated to dryness as a yellow solid. (3.89 g, 82.6% yield)To a solution of I -?[2-[4?-(dimethyiamino)-1 -piperidyl jethyij-3-iodo-pyrazoic[3 4- d)pyrimidhm'4-amine (50 mg, 0.1205 mmcl) in dioxane/water (45/0.5 n'D was added (6-? ((tert?-Butoxycarbonyflamino)pyridin-?3-yflboronic acid (1.5 eq., 43.1 mq, 0181 mmcl), potassftJrn carbonate (1.5 eq., 25.0 mg, 0.181 rnmol) and tdphenylphosphine (20 mci %.9.5 mg) followed by r;aKaoam acetate (5 mol %) and the mixture heated m Ihe microwave at 120 C for 30 mins. The mixture was concentrated in vacua and purified by column chromatography, MeOH/OCM (10 % then 10-30 drops of NEt per 100 mU to qve a white soid, (23.8 mq, 0 0495 mmoL 41.0 %). 1H NMR (500 MHz, MeOD) 5 8.55- 8.51 Km. iH'j, 8.26 (a. 1K), 8.06 -. 8.01 (rn, 2H). 4.55 (t, J 6.5. 2H), 3.14 (d, J 12.0.2K). 2.94 (t: J 6.5. 2K), 2.68 (111, 1K), 2.55 (a, 6K), 2.14 (t. J 0, 2K), 1.92. (d. J =12 7, 2K). 1.55 (a, 9K). 1.53-S 1.46 (m. 2K); C NMR (126 MHz. MeOD) 5158.58(C).155.47 (CH), 154.40 (C), 153 05 (C). 152 96 (C). 147.13 (CH), 141.83 (C), 137.78 (CH), 123.46 (C)% 112.28 (CH), 97.92 (C), 80.49 (C), 62.79 (CH). 56.00 517 (2x CH7).44.12 (CH2), 39.64 (2x CH:J, 27. 6 (3x CH), 26.76 (2x CH2); MS (ES +ve) fM+HJ:481.8, HRMS (ES +ve), C24K:, N, O2 [M+Hf: caiculateci 482 29865, found 462.3004.Argon was bubbled through a suspension of intermediate 12 (150 mg, 317 imol), {6-[(tert- butoxycarbonyl)amino]pyridin-3-yl}boronic acid (113 mg, 476 imol) and potassium carbonate (87.7 mg, 634 imol) in 1, 2-dimethoxyethane (2.47 mL) and water (429 iL) for several minutes. Afterwards1, 1-bis(diphenylphosphino)ferrocene-palladium(ll)dichloride (116 mg, 159 imol) was added to the mixture, the tube was sealed and the reaction mixture was stirred over night at 90 C. After cooling to room temperature, the mixture was filtered over a pad of celite. The filtrate was concentrated under reduced pressure and the residue was purified by preparative HPLC (method 5) to yield the title compound 13 (52.4 mg, 26%).LC-MS (Method 4): R = 1.19 mm; MS (ESIneg): m/z = 629 [M-HrStep 1. Methyl 2-(6-(ieri-butoxycarbonylamino)pyridin-3-yl)-3- (isopropyl(methyl)amino)quinoxaline-6-carboxylateTo a solution of 6-(ieri-butoxycarbonylamino)pyridin-3-ylboronic acid (316.0 mg, 1.33 mmol) in dioxane (5 mL) was added methyl 2-chloro-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylate (130.0 mg, 0.44 mmol), K3PO4 (280.0 mg, 1.33 mmol) and Pd(PPh3)4 (25.6 mg, 0.02 mmol) and three drops water. The reaction mixture was stirred for 1 h at 90C in an oil bath with an inert atmosphere of nitrogen and concentrated under vacuum to give a residue, which was purified by a silica gel column with 1 % ethyl acetate in petroleum ether to afford methyl 2-(6-(ieri-butoxycarbonylamino)pyridin- 3-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylate as a light yellow solid (160 mg, 80%).'H-NMR (300 MHz, CDCI3) delta 8.95 (d, / = 2.4 Hz, 1H), 8.52 - 8.60 (m, 2H), 8.29 - 8.45 (m, 1H), 8.06 - 8.17 (m, 2H), 7.53 - 7.74 (m, 1H), 4.21 - 4.28 (m, 1H), 4.00 (s, 3H), 1.58 (s, 9H), 1.14 (d, 7 = 6.6 Hz, 6H)Methyl 2-(6-(tert-butoxycarbonylamino)pyridin-3-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylate To a solution of To the compound (360 mg) obtained from the step b above in 1-prorhoanol (40 mL) was added N-{[(5To the compound (2.0 g) obtained from the step a above in tetrahydrofuran (40 mL) was added triisopropylborate (4.25 mL) and the reaction mixture was stirred under argon atmosphere. The reaction mixture was cooled to -78 0C and to it butyl lithium was added dropwise. The reaction mixture was stirred at -78 0C for 4 hours and quenched with water (10 mL) and concentrated. The residue was washed with ether and acidified with 30 % aqueous hydrochloride to pH 5. The solid was filtered to yield the title product (1.05 g).; To the compound (2.0 g) obtained from the step a above in tetrahydrofuran (40 mL) was added triisopropylborate (4.25 mL) and the reaction mixture was stirred under argon atmosphere. The reaction mixture was cooled to -78 0C and to it was added butyl lithium dropwise. The reaction mixture was stirred at -78 0C for 4 hours and quenched with water (10 mL) and concentrated. The residue was washed with ether and acidified with 30 % aqueous hydrochloride to pEta 5. The solid was filtered to yield the title product (1.05 g).To the compound (360 mg) obtained from the step b above in 1-propanol (40 mL) was added (S)-[N-3- (4-iodo-3, 5-difluorophenyl)-2-oxo-5-oxazolidinyl]methyl acetamide (600 mg) obtained from step b of Example 1, Scheme I. The reaction mixture was stirred under argon temperature for 10 minutes, followed by the addition of palladium diacteate (56.6 mg) and triphenylphosphine (198.7 mg) and then stirred for an additional 10 minutes. To this was added sodium carbonate (133.8 mg) (dissolved in water) and the reaction mixture was degassed. The reaction mixture was heated for 1 hour at 100-110 0C and quenched with wate'ethyl acetate (15:100 mL). The organic layer was washed with a EPO

Molecular Weight:238.05
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:5
Rotatable Bond Count:4
Exact Mass:238.1124871
Monoisotopic Mass:238.1124871
Topological Polar Surface Area:91.7
Heavy Atom Count:17
Complexity:268
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes