Dichloromethane → 5-[2,3-Difluoro-2'-(methylsulfonyl)biphenyl-4-yl]pyrazin-2-amine

HRID 1523965Notes

Reaction equation

HRID 1523965 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])[C:3]=1[F:16].[CH3:17][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]>[F:16][C:3]1[C:4]([F:15])=[C:5]([C:8]2[N:9]=[CH:10][C:11]([NH2:14])=[N:12][CH:13]=2)[CH:6]=[CH:7][C:2]=1[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[S:18]([CH3:17])(=[O:20])=[O:19]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27735392-(Methylsulfonyl)phenylboronic AcidHCID 903145395-(4-Bromo-2,3-difluorophenyl)pyrazin-2-amine

Product 1

HCID 903143235-[2,3-Difluoro-2'-(methylsulfonyl)biphenyl-4-yl]pyrazin-2-amineYield 41%

Reagents, catalysts & solvents 1

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

Procedure

Nitrogen sparged DMSO (0.73 ml) was added to a mixture of 5-(4-bromo-2,3-difluorophenyl)pyrazin-2-amine (50 mg, 0.18 mmol), (2-(methylsulfonyl)phenyl)boronic acid (35 mg, 0.18 mmol), K2CO3 (73 mg, 0.532 mmol) and PdCl2(dppf).CH2Cl2 (13 mg, 0.018 mmol) and heated at 80° Celsius for 2.5 hours. The mixture was cooled to rt and partitioned between sat. NaHCO3 and EtOAc. The organic layer was isolated, dried over MgSO4, and concentrated to dryness. Purification by FCC afforded the title compound (26 mg, 41%). MS (ESI): mass calcd. for C17H13F2N3O2S, 361.07; m/z found, 362.0 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 8.44-8.41 (m, 1H), 8.14 (dd, J=7.9, 1.4, 1H), 8.04 (d, J=1.5, 1H), 7.84 (m, 1H), 7.78 (m, 1H), 7.75-7.66 (m, 1H), 7.53 (dd, J=7.5, 1.3, 1H), 7.30 (dd, J=11.6, 4.9, 1H), 6.85 (s, 2H), 3.06 (s, 3H).

Workup

  1. customNitrogen sparged DMSO (0.73 ml)
  2. custompartitioned between sat. NaHCO3 and EtOAc
  3. customThe organic layer was isolated
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated to dryness
  6. customPurification by FCC

Sources & evidence

ORD record
ord-ed3a668adfd948819e11d59cb8833af6
Source dataset
uspto-grants-2015_07
Patent number
US09079866B2

Reaction notes

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