Dichloromethane → 1-(4-fluorophenyl)-4-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyridine

HRID 1186792Notes

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](I)=[C:11]3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Cl.[CH3:25][C:26]1[C:31](B(O)O)=[CH:30][N:29]=[CH:28]N=1.[CH2:35](Cl)Cl>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O.CN1C(=O)CCC1>[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]([C:25]4[CH:28]=[N:29][CH:30]=[CH:31][C:26]=4[CH3:35])=[C:11]3[CH:10]=[N:9]2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 100 °C

Procedure

Example 3 was prepared according to the general procedure of Example 2. Intermediate 2A (0.32 mmol), potassium carbonate (140 mg, 1.01 mmol), 4-methylpyrimidin-5-ylboronic acid hydrochloride salt (78 mg, 0.45 mmol), NMP (1.0 mL), PdCl2(dppf).CH2Cl2 (45 mg, 0.056 mmol), and deoxygenated water (50 μL) were heated at 100° C. for 4 h to give 37.5 mg (63%) of the title compound as an off white solid. Purification was done by preparative HPLC (Condition A) using a Phenomenex Luna Axia 30×100 mm S10 column from 15% Solvent B to 85% Solvent B over 12 min, ret. T=9.3 min. 1H NMR (500 MHz, MeOD) δ ppm 2.36 (s, 3 H) 7.29-7.35 (m, 3 H) 7.54 (d, J=5.19 Hz, 1 H) 8.10 (s, 1 H) 8.26-8.32 (m, 2 H) 8.55 (s, 1 H) 8.57 (d, J=5.19 Hz, 1 H) 8.74 (d, J=4.58 Hz, 1 H). LC/MS (Condition B): ret. T=1.82 min, (M+H)+ 305.09. Analytical HPLC: (Condition A): >99%, ret. T=23.46 min, (Condition B): >99%, ret. T=23.49 min, (Condition C): >98%, ret. T=10.4 min, (Condition D): >98%, ret. T=10.6 min.

Workup

customExample 3 was prepared

Sources & evidence

ORD record: ord-503e296b619741fba9d63374147aea48
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08673922B2

Reaction notes

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