Dichloromethane → 4'-(5-Aminopyrazin-2-yl)-3'-fluoro-N,N-dimethylbiphenyl-2-sulfonamide

HRID 1523782Notes

Reaction equation

HRID 1523782 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[CH:10][C:11]([NH2:14])=[N:12][CH:13]=2)=[C:4]([F:15])[CH:3]=1.[CH3:16][N:17]([CH3:30])[S:18]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1B(O)O)(=[O:20])=[O:19].C([O-])([O-])=O.[K+].[K+].C(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]>[NH2:14][C:11]1[N:12]=[CH:13][C:8]([C:5]2[CH:6]=[CH:7][C:2]([C:22]3[C:21]([S:18]([N:17]([CH3:30])[CH3:16])(=[O:19])=[O:20])=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:3][C:4]=2[F:15])=[N:9][CH:10]=1

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 41973482-(N,N-dimethylsulphamoyl)benzeneboronic acidHCID 903128885-(4-Bromo-2-fluorophenyl)pyrazin-2-amine

Product 1

HCID 778441314'-(5-Aminopyrazin-2-yl)-3'-fluoro-N,N-dimethylbiphenyl-2-sulfonamideYield 40%

Reagents, catalysts & solvents 1

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

Conditions

Temperature
80 °C

Procedure

To a 20 mL vial were 5-(4-bromo-2-fluorophenyl)pyrazin-2-amine (50 mg, 0.19 mmol), (2-(N,N-dimethylsulfamoyl)phenyl)boronic acid, K2CO3 (43 mg, 0.19 mmol), and Pd(dppf)Cl2.CH2Cl2 (8 mg, 0.009 mmol), and a stir-bar. The vial was sealed with a teflon lined cap and sparged with N2. The vial was then charged with freshly sparged DMSO (2 mL) and then stirred 16 hours at 80° Celsius. The reaction mixture was then cooled to rt, filtered, and purified by HPLC to give the title compound (36 mg, 40%). MS (ESI): mass calcd. for C18H17FN4O2S, 372.11; m/z found, 373.2 [M+H]+. 1H NMR (400 MHz, CD3OD) δ 8.33 (s, 2H), 8.06-7.96 (m, 2H), 7.72-7.67 (m, 1H), 7.64-7.59 (m, 1H), 7.43-7.39 (m, 1H), 7.32-7.26 (m, 2H), 2.49 (s, 6H).

Workup

  1. customlined cap
  2. customsparged with N2
  3. additionThe vial was then charged with freshly sparged DMSO (2 mL)
  4. temperatureThe reaction mixture was then cooled to rt
  5. filtrationfiltered
  6. custompurified by HPLC

Sources & evidence

ORD record
ord-2e602a67476a40a490887aa319e788c3
Source dataset
uspto-grants-2015_07
Patent number
US09079866B2

Reaction notes

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