Dichloromethane → HCID 86634552, compound

HRID 2387209Notes

Reaction equation

HRID 2387209 reaction equation
Br[C:2]1[C:3]([F:20])=[CH:4][C:5]([F: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:23](C)(C)O1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+].[CH3:48][O:49][N:50]([CH3:61])[C:51]([C:53]1[C:58]([NH2:59])=[N:57][CH:56]=[C:55](Br)N=1)=[O:52]>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]>[NH2:59][C:58]1[N:57]=[CH:56][C:55]([C:2]2[CH:7]=[C:6]([S:8](=[O:10])(=[O:9])[NH:11][CH:12]3[CH2:17][CH2:16][CH:15]([OH:18])[CH2:14][CH2:13]3)[C:5]([F:19])=[CH:4][C:3]=2[F:20])=[CH:23][C:53]=1[C:51]([N:50]([O:49][CH3:48])[CH3:61])=[O:52]

Participants

8

Reactant 5

HCID 6344Dichloromethane2×HCID 10340Sodium CarbonateHCID 2733548Bis(pinacolato)diboraneHCID 686296535-bromo-2,4-difluoro-N-(4-hydroxy-cyclohexyl)-benzenesulfonamideHCID 86634551HCID 86634551, compound

Product 1

HCID 86634552HCID 86634552, compound

Reagents, catalysts & solvents 2

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

Procedure

A suspension of 5-bromo-2,4-difluoro-N-(4-hydroxy-cyclohexyl)-benzenesulfonamide-intermediate DX (300 mg, 0.81 mmol), BIS(pinacolato)diboron (222 mg, 0.88 mmol) and Pd(dppf)Cl2.DCM (0.066 g, 0.08 mmol) in DME (12 ml) is heated at reflux for 4 hours. 2M Na2CO3 (4 ml) is added to the reaction mixture followed by 3-amino-6-bromo-pyrazine-2-carboxylic acid methoxy-methyl-amide (0.211 g, 0.81 mmol) and Pd(dppf)Cl2.DCM (0.066 g, 0.08 mmol). The reaction mixture is refluxed for 30 minutes. The crude reaction mixture is purified by normal phase chromatography (30-100% EtOAc/iso-hexane) to afford a white solid as the titled compound. [M+H]+ 472

Workup

  1. temperatureat reflux for 4 hours
  2. temperatureThe reaction mixture is refluxed for 30 minutes
  3. customThe crude reaction mixture
  4. customis purified by normal phase chromatography (30-100% EtOAc/iso-hexane)

Sources & evidence

ORD record
ord-167d8b3514244d87bef80cecb6de6f72
Source dataset
uspto-grants-2012_09
Patent number
US08268834B2

Reaction notes

Loading…