Toluene → 5-(4-Bromo-2,3-difluorophenyl)pyrazin-2-amine

HRID 1523964Notes

Reaction equation

HRID 1523964 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[C:4]([F:11])[C:3]=1[F:12].Br[C:14]1[N:15]=[CH:16][C:17]([NH2:20])=[N:18][CH:19]=1.C1(C)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>CCO.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>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:14]2[N:15]=[CH:16][C:17]([NH2:20])=[N:18][CH:19]=2)=[C:4]([F:11])[C:3]=1[F:12]

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 5995392-Amino-5-bromopyrazineHCID 27732924-Bromo-2,3-difluorobenzeneboronic acid

Product 1

HCID 903145395-(4-Bromo-2,3-difluorophenyl)pyrazin-2-amineYield 33%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (4-bromo-2,3-difluorophenyl)boronic acid (400 mg, 1.69 mmol) and 5-bromopyrazin-2-amine (588 mg, 3.38 mmol was suspended in EtOH (5.6 ml) and toluene (5.7 mL) The resulting mixture was treated with aqueous Na2CO3 (2.0 N, 4.2 mL, 8.45 mmol). The resulting mixture was then sparged with nitrogen through the mixture for 10 min, and then Pd(PPh3)4 (98 mg, 0.085 mmol) was added. The reaction vessel was sealed and heated at 80° Celsius for 17 hours. The reaction mixture was cooled to rt and then partitioned between saturated aqueous NH4Cl and EtOAc. The organic layer was dried over MgSO4 and concentrated to dryness. The residue was suspended in DCM and the solid isolated by filtration to afford the title compound (160 mg, 33%), which was used without further purification. MS (ESI): mass calcd. for C10H6BrF2N3, 284.97; m/z found, 286.0 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 8.36 (s, 1H), 8.01 (d, J=1.2, 1H), 7.68-7.56 (m, 2H), 6.87 (s, 2H).

Workup

  1. customThe resulting mixture was then sparged with nitrogen through the mixture for 10 min
  2. customThe reaction vessel was sealed
  3. temperatureThe reaction mixture was cooled to rt
  4. custompartitioned between saturated aqueous NH4Cl and EtOAc
  5. dry with materialThe organic layer was dried over MgSO4
  6. concentrationconcentrated to dryness
  7. customthe solid isolated by filtration

Sources & evidence

ORD record
ord-c9ff847c0a10429a83780defe80b96f5
Source dataset
uspto-grants-2015_07
Patent number
US09079866B2

Reaction notes

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