Sodium Carbonate → 4-(4-chloropyridin-3-yl)-1-(4-fluorophenyl)-1H-pyrazolo[3,4-b]pyridine

HRID 1186799Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16](B(O)O)=[C:11]3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.Br[C:21]1[CH:22]=[N:23][CH:24]=[CH:25][C:26]=1[Cl:27].C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCO.COCCOC.O>[Cl:27][C:26]1[CH:25]=[CH:24][N:23]=[CH:22][C:21]=1[C:16]1[CH:15]=[CH:14][N:13]=[C:12]2[N:8]([C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)[N:9]=[CH:10][C:11]=12

Participants

Conditions

Temperature: 105 °C

Procedure

Example 10 was prepared according to the general procedure of Example 1, except that the reaction mixture was heated at 105° C. for 2 h, and using the following materials: Intermediate 5A (40 mg, 0.156 mmol), 3-bromo-4-chloropyridine (53.6 mg, 0.279 mmol), sodium carbonate (61.3 mg, 0.578 mmol), degassed EtOH:DME:H2O (1.2:2.5:1.0 ratio) (1.5 mL) and tetrakis(triphenylphosphine)palladium(0) (25.3 mg, 0.022 mmol). Example 10 was isolated as an off-white solid (5.7 mg, 11%). Purification was done by preparative HPLC (Condition A) using a Phenomenex Luna Axia 30×100 mm S10 column from 35% Solvent B to 100% Solvent B over 12 min, ret. T=11.8 min. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.78-8.86 (2 H, m), 8.74 (1 H, d, J=5.19 Hz), 8.37 (1 H, s), 8.26-8.34 (2 H, m), 7.86 (1 H, d, J=5.19 Hz), 7.43-7.55 (3 H, m). LC/MS (Condition B): ret. T=3.8 min, (M+H)+ 325.00, 326.98. Analytical HPLC: (Condition A): >98%, ret. T=24.69 min, (Condition B): >98%, ret. T=24.45 min, (Condition C): >98%, ret. T=18.88 min, (Condition D): >98%, ret. T=15.00 min.

Workup

customExample 10 was prepared

Sources & evidence

ORD record: ord-bfa496694b124c1dab644c96909d8525
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08673922B2

Reaction notes

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