Sodium Carbonate → 5-[4-(Methylsulfonyl)phenyl]-2-pyrazinamine

HRID 423605Notes

Reaction equation

HRID 423605 reaction equation
[NH2:1][C:2]1[CH:7]=[N:6][C:5](Br)=[CH:4][N:3]=1.[CH3:9][S:10]([C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1)(=[O:12])=[O:11].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.CO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:9][S:10]([C:13]1[CH:18]=[CH:17][C:16]([C:5]2[N:6]=[CH:7][C:2]([NH2:1])=[N:3][CH:4]=2)=[CH:15][CH:14]=1)(=[O:12])=[O:11]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 5995392-Amino-5-bromopyrazineHCID 27343644-(Methanesulfonyl)phenylboronic acid

Product 1

HCID 580843845-[4-(Methylsulfonyl)phenyl]-2-pyrazinamineYield 67%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2-amino-5-bromopyrazine (0.5 g, 2.79 mmol) and [4-(methylsulfonyl)phenyl]boronic acid (0.57 g, 2.79 mmol) in 1,4-dioxane (10 mL) and MeOH (4 mL) was treated with 2M Na2CO3 (4 mL) and Pd(PPh3)4 (65 mg, 0.06 mmol). The reaction mixture was degassed with N2 and heated at 100° C. for 3 h. Most of 1,4-dioxane and MeOH was removed under reduced pressure. Water was added, and the mixture was extracted with EtOAc (50 mL×4). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and the filtrate was concentrated to a brown solid, which was triturated with CH2Cl2 to give 0.465 g (67%) of 5-[4-(methylsulfonyl)phenyl]-2-pyrazinamine as a yellow solid. The filtrate was washed with 1 N HCl (25 mL), and the aqueous layer was separated and basified with 4N NaOH. The mixture was extracted with EtOAc (50 mL×2) and the combined organic extracts were washed with brine, dried over Na2SO4, filtered, and the filtrate was concentrated to give additional 0.045 g (7%) of 5-[4-(methylsulfonyl)phenyl]-2-pyrazinamine as a yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 8.63 (s, 1H), 8.15 (d, 2H, J=8.5 Hz), 7.97 (s, 1H), 7.91 (d, 2H, J=8.5 Hz), 6.81 (s, 2H), 3.20 (s, 3H); LRMS (ESI), m/z 250 (M+H).

Workup

  1. customThe reaction mixture was degassed with N2
  2. customMost of 1,4-dioxane and MeOH was removed under reduced pressure
  3. additionWater was added
  4. extractionthe mixture was extracted with EtOAc (50 mL×4)
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated to a brown solid, which
  9. customwas triturated with CH2Cl2

Sources & evidence

ORD record
ord-17119b30468c41959ff345644b9a1e5a
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

Loading…