Benzenesulfonamide → N-(3-amino-6-(4-(methylsulfonyl)phenyl)pyrazin-2-yl)benzenesulfonamide

HRID 2174660Notes

Reaction equation

HRID 2174660 reaction equation
Br[C:2]1[C:3]([NH2:18])=[N:4][CH:5]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][CH:9]=2)[N:7]=1.[C:19]1([S:25]([NH2:28])(=[O:27])=[O:26])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[C@@H]1(N)CCCC[C@H]1N.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1>[NH2:18][C:3]1[C:2]([NH:28][S:25]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)(=[O:27])=[O:26])=[N:7][C:6]([C:8]2[CH:13]=[CH:12][C:11]([S:14]([CH3:17])(=[O:16])=[O:15])=[CH:10][CH:9]=2)=[CH:5][N:4]=1

Participants

6

Reactant 4

HCID 7370BenzenesulfonamideHCID 11430Potassium CarbonateHCID 438061,2-Diaminocyclohexane, trans-HCID 580843703-Bromo-5-(4-methylsulfonylphenyl)pyrazin-2-amine

Product 1

HCID 54597165N-(3-amino-6-(4-(methylsulfonyl)phenyl)pyrazin-2-yl)benzenesulfonamideYield 6.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

3-bromo-5-(4-methylsulfonylphenyl)pyrazin-2-amine (0.05 g, 0.152 mmol), benzene sulfonamide (0.12 g, 0.762 mmol), (1R,2R)-cyclohexane-1,2-diamine (0.017 g, 0.152 mmol), cuprous iodide (0.058 g, 0.305 mmol) and K2CO3 (0.042 g, 0.305 mmol) were combined together in dioxane (4 mL) and heated for 15 minutes under microwave conditions at 120° C. and then 140° C. for a further 20 minutes. The reaction mixture was concentrated in vacuo, and the residue was partitioned between DCM and water. The layers were separated and the aqueous further extracted with DCM. The combined organic extract was dried (MgSO4), filtered and concentrated in vacuo. This material was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, and freeze-dried to give the title compound (3.9 mg, 3.65% Yield). H1 NMR (400.0 MHz, DMSO) δ 8.34 (s, 1H), 8.04-8.01 (m, 2H), 7.88 (d, J=8.6 Hz, 2H), 7.81 (d, J=8.7 Hz, 2H), 7.67-7.64 (m, 3H) and 3.23 (s, 3H). MS (ES+) 405.0

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue was partitioned between DCM and water
  3. customThe layers were separated
  4. extractionthe aqueous further extracted with DCM
  5. extractionThe combined organic extract
  6. dry with materialwas dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThis material was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  10. customThe fractions were collected
  11. customfreeze-dried

Sources & evidence

ORD record
ord-724b464e68ab48f0b1f751bbea1c65a5
Source dataset
uspto-grants-2015_06
Patent number
US09062008B2

Reaction notes

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