Dichloromethane → 5-(5-Amino-pyrazin-2-yl)-2-chloro-N-(4-hydroxy-cyclohexyl)-benzenesulfonamide

HRID 2387197

반응식

HRID 2387197 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]([Cl:19])=[C:6]([S:8]([NH:11][CH:12]2[CH2:17][CH2:16][CH:15]([OH:18])[CH2:14][CH2:13]2)(=[O:10])=[O:9])[CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C(Cl)Cl.C([O-])(=O)C.[K+].[NH2:46][C:47]1[CH:52]=[N:51][C:50](Br)=[CH:49][N:48]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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]>[NH2:46][C:47]1[N:48]=[CH:49][C:50]([C:2]2[CH:3]=[CH:4][C:5]([Cl:19])=[C:6]([S:8]([NH:11][CH:12]3[CH2:17][CH2:16][CH:15]([OH:18])[CH2:14][CH2:13]3)(=[O:10])=[O:9])[CH:7]=2)=[N:51][CH:52]=1

참가 물질

9

반응물 6

HCID 6344Dichloromethane2회HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 5995392-Amino-5-bromopyrazineHCID 2733548Bis(pinacolato)diboraneHCID 686319385-Bromo-2-chloro-N-(4-hydroxy-cyclohexyl)-benzenesulfonamide

생성물 1

HCID 442363995-(5-Amino-pyrazin-2-yl)-2-chloro-N-(4-hydroxy-cyclohexyl)-benzenesulfonamide

시약·촉매·용매 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매2회HCID 80711,2-Dimethoxyethane용매2회

실험 절차

A suspension of 5-bromo-2-chloro-N-(4-hydroxy-cyclohexyl)-benzenesulfonamide (Intermediate DJ) (0.1 g, 0.27 mmol), bis(pinacolato)diboron (0.07 g, 0.29 mmol), Pd(dppf)Cl2.DCM (0.011 g, 0.014 mmol) and potassium acetate (0.04 g, 0.40 mmol) in DME (3 ml) is heated at reflux for 1.5 hours. Pd(dppf)Cl2.DCM (0.011 g, 0.014 mmol), 2-amino-5-bromopyrazine (0.05 g, 0.29 mmol), 2M Na2CO3 (1.5 ml) and DME (1 ml) are added and the reaction heated at reflux for 1 hour. The reaction mixture is purified by reverse phase column chromatography (C18, 0-100% MeCN in water −0.1% TFA) to yield a solid which was dried in vacuo at 45° C. overnight to yield the title compound. 1H NMR (400 MHz, DMSO-d6) δ 8.60 (1H, d), 8.55 (1H, d), 8.14 (1H, dd), 8.00 (1H, d), 7.85 (1H, d), 7.67 (1H, d), 7.14-6.45 (2H, br hump), 3.30-3.24 (1H, m), 3.02-2.93 (1H, m), 1.73-1.68 (2H, m), 1.64-1.60 (2H, m), 1.33-1.23 (2H, m) 1.10-1.00 (2H, m); MS m/z 383 [M+H]+

후처리

  1. temperatureat reflux for 1.5 hours
  2. temperaturethe reaction heated
  3. temperatureat reflux for 1 hour
  4. customThe reaction mixture is purified by reverse phase column chromatography (C18, 0-100% MeCN in water −0.1% TFA)
  5. customto yield a solid which
  6. customwas dried in vacuo at 45° C. overnight

출처 및 근거

ORD 기록
ord-e6b79e87a964465b966cdaee3de9307d
출처 데이터셋
uspto-grants-2012_09
특허 번호
US08268834B2

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