Sodium Carbonate → 1-(2,4-difluorophenyl)-4-(4-methylpyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridine

HRID 1186804Notes

Reaction equation

HRID 1186804 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]2=[N:14][CH:15]=[CH:16][C:17](B(O)O)=[C:12]2[CH:11]=[N:10]1.Br[C:22]1[C:23]([CH3:28])=[N:24][CH:25]=[N:26][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCO.COCCOC.O>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]2=[N:14][CH:15]=[CH:16][C:17]([C:22]3[C:23]([CH3:28])=[N:24][CH:25]=[N:26][CH:27]=3)=[C:12]2[CH:11]=[N:10]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 124618635-Bromo-4-methylpyrimidineHCID 666681771-(2,4-difluorophenyl)-1H-pyrazolo[3,4-b]pyridin-4-ylboronic acid

Product 1

HCID 566025401-(2,4-difluorophenyl)-4-(4-methylpyrimidin-5-yl)-1H-pyrazolo[3,4-b]pyridineYield 61.1%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 86587095Dimethoxyethane ethanol waterSolvent

Conditions

Temperature
90 °C

Procedure

Example 64 was prepared according to the general procedure in Example 1, except heating at 90° C. for 18 h, and using the following materials: Intermediate 63A (35.0 mg, 0.127 mmol), 5-bromo-4-methylpyrimidine (41.2 mg, 0.238 mmol), sodium carbonate (58.9 mg, 0.556 mmol), EtOH:DME:H2O (1.2:2.5:1.0 ratio) (1.0 mL) and tetrakis(triphenylphosphine) palladium(0) (17.5 mg, 0.0151 mmol). Example 64 was isolated as a white solid (25.1 mg, 60.7%). Purification was done by preparative HPLC (Condition A) using a Phenomenex Luna Axia 30×100 mm S10 column from 18% Solvent B to 100% Solvent B over 12 min, ret. T=9.2 min, followed by Biotage Silica gel chromatography on a 4 g Thompson Single Step™ silica cartridge using a linear gradient from 100% hexanes to 100% (1:1 acetone/hexanes) over 10 column volumes. 1H NMR (500 MHz, CCl3D) δ ppm 9.27 (1 H, s), 8.68-8.79 (2 H, m), 8.09 (1 H, s), 7.71 (1 H, td, J=8.62, 5.95 Hz), 7.21 (1 H, d, J=4.58 Hz), 7.13 (2 H, td, J=7.86, 5.65 Hz), 2.58 (3 H, s). LC/MS (Condition B): ret. T=3.22 min, (M+H)+ 324.13. Analytical HPLC: (Condition A): >99%, ret. T=18.26 min, (Condition B): >99%, ret. T=18.09 min, (Condition C): >99%, ret. T=12.33 min, (Condition D): >99%, ret. T=10.15 min.

Workup

  1. customExample 64 was prepared

Sources & evidence

ORD record
ord-b2e4af70d7f342a09ec6f63d89f6b6c2
Source dataset
uspto-grants-2014_03
Patent number
US08673922B2

Reaction notes

Loading…