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

HRID 1186826Notes

Reaction equation

HRID 1186826 reaction equation
I[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([C:11]3[CH:12]=[C:13]([S:17]([NH2:20])(=[O:19])=[O:18])[CH:14]=[CH:15][CH:16]=3)[N:9]=[CH:10][C:3]=12.C(=O)([O-])[O-].[K+].[K+].Cl.[CH3:28][C:29]1[C:34](B(O)O)=[CH:33][N:32]=[CH:31]N=1.[CH2:38](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>[CH3:28][C:29]1[CH:38]=[CH:31][N:32]=[CH:33][C:34]=1[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([C:11]3[CH:12]=[C:13]([S:17]([NH2:20])(=[O:19])=[O:18])[CH:14]=[CH:15][CH:16]=3)[N:9]=[CH:10][C:3]=12

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 66664699(4-Methylpyrimidin-5-yl)boronic acid hydrochlorideHCID 666648613-(4-iodo-1H-pyrazolo[3,4-b]pyridin-1-yl)benzenesulfonamide

Product 1

HCID 566027053-(4-(4-methylpyridin-3-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)benzenesulfonamideYield 125.4%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
105 °C

Procedure

Example 80 was prepared according to the general procedure in Example 2, except heating at 105° C. for 4 h followed by heating at 115° C. for 5.25 h, and using the following materials: Intermediate 1A (32.8 mg, 0.189 mmol), potassium carbonate (149.6 mg, 1.08 mmol), 4-methylpyrimidin-5-ylboronic acid hydrochloride salt (62.8 mg, 0.362 mmol), NMP (1.1 mL), deoxygenated water (100 μL), and PdCl2(dppf).CH2Cl2 (29.7 mg, 0.036 mmol). Example 80 was isolated as an off white solid (16.5 mg, 24.6%). Purification was done by preparative HPLC (Condition A) using a Phenomenex Luna Axia 30×100 mm S10 column from 5% Solvent B to 85% Solvent B over 12 min, ret. T=7.04 min, followed by purification by preparative HPLC (Condition B) using a Phenomenex Luna 30×100 mm S10 column from 15% Solvent B to 100% Solvent B over 12 min, ret. T=7.06 min. 1H NMR (500 MHz, METHANOL-d4) δ ppm 8.97-9.02 (1 H, m), 8.80 (1 H, d, J=4.58 Hz), 8.68 (1 H, ddd, J=8.09, 2.14, 1.07 Hz), 8.53-8.61 (2 H, m), 8.17 (1 H, s), 7.87-7.95 (1 H, m), 7.76 (1 H, t, J=7.93 Hz), 7.55 (1 H, d, J=5.19 Hz), 7.38 (1 H, d, J=4.58 Hz), 2.37 (3 H, s) LC/MS (Condition B): ret. T=2.20 min, (M+H)+ 366.01. Analytical HPLC: (Condition A): >98%, ret. T=18.43 min, (Condition B): >98%, ret. T=16.85 min, (Condition C): >97%, ret. T=5.64 min, (Condition D): >98%, ret. T=5.92 min.

Workup

  1. customExample 80 was prepared
  2. temperatureby heating at 115° C. for 5.25 h

Sources & evidence

ORD record
ord-54c4cdbb6f4245109fa8066ba567cee0
Source dataset
uspto-grants-2014_03
Patent number
US08673922B2

Reaction notes

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