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

HRID 2387197

反応式

HRID 2387197 の反応式
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

参加物

9

反応物 6

HCID 6344Dichloromethane2 回HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 5995392-Amino-5-bromopyrazineHCID 2733548Bis(pinacolato)diboraneHCID 686319385-Bromo-2-chloro-N-(4-hydroxy-cyclohexyl)-benzenesulfonamide

生成物 1

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

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒2 回HCID 80711,2-Dimethoxyethane溶媒2 回

実験手順

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]+

後処理

  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

出典と根拠

ORDレコード
ord-e6b79e87a964465b966cdaee3de9307d
出典データセット
uspto-grants-2012_09
特許番号
US08268834B2

関連ノート

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