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

HRID 1186795Notes

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.I[C:21]1[CH:22]=[N:23][CH:24]=[CH:25][C:26]=1[O:27][CH3:28].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>[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:21]4[CH:22]=[N:23][CH:24]=[CH:25][C:26]=4[O:27][CH3:28])=[C:11]3[CH:10]=[N:9]2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 105 °C

Procedure

Example 6 was prepared according to the general procedure of Example 1, except that the reaction mixture was heated at 105° C. for 2.25 h and using the following materials: Intermediate 5A (38.0 mg, 0.148 mmol), 3-iodo-4-methoxypyridine (86.2 mg, 0.367 mmol), sodium carbonate (56.1 mg, 0.529 mmol), degassed EtOH:DME:H2O (1.2:2.5:1.0 ratio) (1.5 mL) and tetrakis(triphenylphosphine)palladium(0) (17 mg, 0.015 mmol). Example 6 was isolated as an off white solid (14.9 mg, 31.1%). Purification was done by preparative HPLC (Condition A) using a Phenomenex Luna Axia 30×100 mm S10 column from 10% Solvent B to 95% Solvent B over 12 min, ret. T=8.6 min. 1H NMR (500 MHz, DMSO-d6) δ ppm 8.75 (1 H, d, J=4.88 Hz), 8.64 (1 H, d, J=5.80 Hz), 8.59 (1 H, s), 8.27-8.36 (3 H, m), 7.42-7.51 (3 H, m), 7.35 (1 H, d, J=6.10 Hz), 3.93 (3 H, s). LC/MS (Condition B): ret. T=2.84 min, (M+H)+ 321.05. Analytical HPLC: (Condition A): >99%, ret. T=22.96 min, (Condition B): >99%, ret. T=23.17 min, (Condition C): >99%, ret. T=9.33 min, (Condition D): >99%, ret. T=9.91 min.

Workup

customExample 6 was prepared

Sources & evidence

ORD record: ord-6d1952700f29468fa35b7314a8e23cc9
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08673922B2

Reaction notes

Loading…