Dichloromethane → N-[3'-Fluoro-4'-(5H-pyrrolo[2,3-b]pyrazin-2-yl)biphenyl-2-yl]methanesulfonamide

HRID 1523909Notes

Reaction equation

HRID 1523909 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:16]=[CH:15][NH:14][C:11]3=[N:12][CH:13]=2)=[C:4]([F:17])[CH:3]=1.CC1(C)C(C)(C)OB([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[NH:32][S:33]([CH3:36])(=[O:35])=[O:34])O1.C(Cl)Cl.C([O-])(O)=O.[Na+]>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].C(#N)C>[F:17][C:4]1[CH:3]=[C:2]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=2[NH:32][S:33]([CH3:36])(=[O:35])=[O:34])[CH:7]=[CH:6][C:5]=1[C:8]1[N:9]=[C:10]2[CH:16]=[CH:15][NH:14][C:11]2=[N:12][CH:13]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 43565252-(Methanesulfonylamino)phenylboronic acid pinacol esterHCID 90313071HCID 90313071, compound

Product 1

HCID 90313212N-[3'-Fluoro-4'-(5H-pyrrolo[2,3-b]pyrazin-2-yl)biphenyl-2-yl]methanesulfonamideYield 69.2%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
110 °C

Procedure

To a mixture of 2-(4-bromo-2-fluorophenyl)-5H-pyrrolo[2,3-b]pyrazine (50 mg, 0.17 mmol), N-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-methane-sulfonamide (61 mg, 0.21 mmol) and Pd(dppf)Cl2.CH2Cl2 (6.7 mg, 0.009 mmol) in a microwave vial were added acetonitrile (2.0 mL) and sat. NaHCO3 (2.0 mL). The vial was sparged with nitrogen for 5 min then heated at 110° Celsius for 90 min via microwave irradiation. After cooling to rt, the reaction mixture was diluted with ethyl acetate (50 mL), washed with water (25 mL) and brine (25 mL), dried (Na2SO4) and concentrated to dryness. The crude product was purified by HPLC giving the title compound (45 mg, 69%). MS (ESI): mass calcd. for C19H15FN4O2S, 382.09; m/z found, 383.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 10.38 (s, 1H), 8.78 (d, J=2.7, 1H), 8.20-8.12 (m, 1H), 7.71-7.64 (m, 2H), 7.48-7.39 (m, 1H), 7.37-7.31 (m, 2H), 7.28-7.21 (m, 2H), 6.91 (s, 1H), 6.81-6.75 (m, 1H), 2.93 (s, 3H).

Workup

  1. customThe vial was sparged with nitrogen for 5 min
  2. temperatureAfter cooling to rt
  3. additionthe reaction mixture was diluted with ethyl acetate (50 mL)
  4. washwashed with water (25 mL) and brine (25 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated to dryness
  7. customThe crude product was purified by HPLC

Sources & evidence

ORD record
ord-792a167526da449d84976ebdfd7f6d71
Source dataset
uspto-grants-2015_07
Patent number
US09079866B2

Reaction notes

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