Dichloromethane → 4'-(5-Aminopyrazin-2-yl)-3'-fluoro-N-(2-hydroxyethyl)biphenyl-2-sulfonamide

HRID 1523828Notes

Reaction equation

HRID 1523828 reaction equation
[F:1][C:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[CH:4][C:3]=1[C:17]1[N:18]=[CH:19][C:20]([NH2:23])=[N:21][CH:22]=1.Br[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[S:31]([NH:34][CH2:35][CH2:36][OH:37])(=[O:33])=[O:32].C([O-])([O-])=O.[Na+].[Na+].C(Cl)Cl>C(OC(=O)C)C.O.O1CCOCC1>[NH2:23][C:20]1[N:21]=[CH:22][C:17]([C:3]2[CH:4]=[CH:5][C:6]([C:25]3[C:26]([S:31]([NH:34][CH2:35][CH2:36][OH:37])(=[O:33])=[O:32])=[CH:27][CH:28]=[CH:29][CH:30]=3)=[CH:7][C:2]=2[F:1])=[N:18][CH:19]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 435020592-bromo-N-(2-hydroxyethyl)benzenesulfonamideHCID 903122765-(2-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl)-pyrazin-2-amine

Product 1

HCID 903126564'-(5-Aminopyrazin-2-yl)-3'-fluoro-N-(2-hydroxyethyl)biphenyl-2-sulfonamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

5-(2-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine (40 mg, 0.13 mmol) and 2-bromo-N-(2-hydroxyethyl)benzenesulfonamide (53 mg, 0.19 mmol) were added to a 5 mL sealable vial equipped with a stir bar. 1,4-Dioxane (0.7 mL) and Na2CO3 (0.3 mL, 2 M) were added. Argon was bubbled through the solvent while it was rapidly stirred for 10 min before adding Pd(dppf)Cl2.CH2Cl2 (5 mg, 0.006 mmol) and heating the mixture heated 15 hours at 80° Celsius. The reaction was cooled to rt, diluted with 2 mL of ethylacetate, 2 mL of water and extracted with of ethyl acetate (3×10 mL). The combined organic extracts were then dried with Na2SO4 and concentrated to dryness. The crude product was purified by HPLC to give the title compound. MS (ESI): mass calcd. for C18H17FN4O3S, 388.10; m/z found, 389.1 [M+H]+. 1H NMR (500 MHz, CD3OD) δ 8.43-8.37 (dd, J=2.2, 1.5, 1H), 8.11-8.06 (m, 2H), 7.93-7.86 (m, 1H), 7.70-7.64 (m, 1H), 7.62-7.56 (m, 1H), 7.44-7.38 (dd, J=7.6, 1.3, 1H), 7.35-7.27 (m, 2H), 3.49-3.44 (t, J=5.9, 2H), 2.90-2.84 (t, J=5.9, 2H).

Workup

  1. customequipped with a stir bar
  2. customArgon was bubbled through the solvent while it
  3. additionbefore adding Pd(dppf)Cl2
  4. temperatureThe reaction was cooled to rt
  5. extractionextracted with of ethyl acetate (3×10 mL)
  6. dry with materialThe combined organic extracts were then dried with Na2SO4
  7. concentrationconcentrated to dryness
  8. customThe crude product was purified by HPLC

Sources & evidence

ORD record
ord-018ff6471be64b05a67a5c07c4caa5dd
Source dataset
uspto-grants-2015_07
Patent number
US09079866B2

Reaction notes

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