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

HRID 423647Notes

Reaction equation

HRID 423647 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([S:8][CH3:9])[CH:5]=[CH:4][C:3]=1B(O)O.Br[C:14]1[N:15]=[CH:16][C:17]([NH2:20])=[N:18][CH:19]=1.C([O-])([O-])=O.[Na+].[Na+].O1CCOCC1>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.O.CO>[F:1][C:2]1[CH:7]=[C:6]([S:8][CH3:9])[CH:5]=[CH:4][C:3]=1[C:14]1[N:15]=[CH:16][C:17]([NH2:20])=[N:18][CH:19]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 5995392-Amino-5-bromopyrazineHCID 44717667[2-Fluoro-4-(methylsulfanyl)phenyl]boronic acid

Product 1

HCID 666733305-[2-Fluoro-4-(methylthio)phenyl]-2-pyrazinamineYield 54.2%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of [2-fluoro-4-(methylthio)phenyl]boronic acid (5 g, 26.9 mmol), 5-bromo-2-pyrazinamine (4.7 g, 26.9 mmol), Pd(PPh3)4 (0.62 g, 0.54 mmol), 2M Na2CO3 (25 mL), 1,4-dioxane (50 mL), and methanol (25 mL) was stirred and heated at 100° C. for 5 h, then at 25° C. overnight. The reaction was charged with water (300 mL) and extracted with EtOAc (100 mL). The organic extracts were dried over MgSO4, filtered, and concentrated to dryness to give a tan solid. The solid was triturated with CH2Cl2, filtered, and the solid air-dried to afford 5-[2-fluoro-4-(methylthio)phenyl]-2-pyrazinamine (3.43 g, 54% yield) as a tan solid. The filtrate was concentrated to dryness to give additional solid (2.5 g) that was purified by SiO2 chromatography (0-25% EtOAc/hexanes, 20 min. gradient; then 25% EtOAc/hexanes, 60 min.; 100 g column) to afford additional product (940 mg, 15% yield) as a tan solid. 1H NMR (400 MHz, CDCl3) δ 8.47 (s, 1H), 8.10 (d, 1H, J=1.4 Hz), 7.83 (t, 1H, J=8.3 Hz), 7.10 (dd, 1H, Ja=8.3 Hz, Jb=1.9 Hz), 7.00 (dd, 1H, Ja=12.1 Hz, Jb=1.9 Hz), 4.80 (bs, 2H), 2.50 (s, 3H).

Workup

  1. customat 25° C.
  2. customovernight
  3. extractionextracted with EtOAc (100 mL)
  4. dry with materialThe organic extracts were dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customto give a tan solid
  8. customThe solid was triturated with CH2Cl2
  9. filtrationfiltered
  10. customthe solid air-dried

Sources & evidence

ORD record
ord-ae8c044306b04e75be47058f25023242
Source dataset
uspto-grants-2012_01
Patent number
US08101634B2

Reaction notes

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