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

HRID 1186826노트

반응식

HRID 1186826 반응식
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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
105 °C

실험 절차

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.

후처리

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

출처 및 근거

ORD 기록
ord-54c4cdbb6f4245109fa8066ba567cee0
출처 데이터셋
uspto-grants-2014_03
특허 번호
US08673922B2

반응 노트

불러오는 중…