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

HRID 1186826ノート

反応式

HRID 1186826 の反応式
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

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
105 °C

実験手順

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.

後処理

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

出典と根拠

ORDレコード
ord-54c4cdbb6f4245109fa8066ba567cee0
出典データセット
uspto-grants-2014_03
特許番号
US08673922B2

反応ノート

読み込み中…