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

HRID 81469

Reaction equation

HRID 81469 reaction equation
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

Participants

9

Reactant 6

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst2×HCID 80711,2-DimethoxyethaneSolvent2×

Procedure

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-6) 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]+

Workup

  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

Sources & evidence

ORD record
ord-14fc1a40cc2b431189450d9b558e3968
Source dataset
uspto-grants-2014_09
Patent number
US08846687B2

Linked notes

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