Dichloromethane → 4'-(5-Aminopyridin-2-yl)-N-tert-butyl-3'-fluorobiphenyl-2-sulfonamide

HRID 1523944Notes

Reaction equation

HRID 1523944 reaction equation
[C:1]([NH:5][S:6]([C:9]1[C:10]([C:15]2[CH:20]=[CH:19][C:18](B3OC(C)(C)C(C)(C)O3)=[C:17]([F:30])[CH:16]=2)=[CH:11][CH:12]=[CH:13][CH:14]=1)(=[O:8])=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:32]1[N:37]=[CH:36][C:35]([NH2:38])=[CH:34][CH:33]=1.C([O-])([O-])=O.[Na+].[Na+].C(Cl)Cl>C(OCC)(=O)C.O.O1CCOCC1>[NH2:38][C:35]1[CH:34]=[CH:33][C:32]([C:18]2[CH:19]=[CH:20][C:15]([C:10]3[C:9]([S:6]([NH:5][C:1]([CH3:4])([CH3:3])[CH3:2])(=[O:8])=[O:7])=[CH:14][CH:13]=[CH:12][CH:11]=3)=[CH:16][C:17]=2[F:30])=[N:37][CH:36]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 6428116-Bromopyridin-3-amineHCID 90313401N-(tert-butyl)-3'-fluoro-4'-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1'-biphenyl]-2-sulfonamide

Product 1

HCID 903139274'-(5-Aminopyridin-2-yl)-N-tert-butyl-3'-fluorobiphenyl-2-sulfonamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

N-(tert-Butyl)-3′-fluoro-4′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-[1,1′-biphenyl]-2-sulfonamide (37 mg, 0.085 mmol) and 6-bromopyridin-3-amine (22 mg, 0.13 mmol) were added to a 5 mL sealable vial equipped with a stir bar. 1,4-Dioxane (0.2 mL) and 2 M Na2CO3 (0.2 mL) were added. Argon was bubbled through the solvent while it was rapidly stirred for 10 min then Pd(dppf)Cl2.CH2Cl2 (3 mg, 0.004 mmol) was added, and the mixture stirred for 15 hours at 80° Celsius under an argon atmosphere. The reaction was diluted with 2 mL of ethyl acetate and 2 mL of water and the aqueous layer was extracted with 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 C21H22FN3O2S, 399.14; m/z found, 400.2 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.66 (s, 1H), 8.25-8.16 (dd, J=8.0, 1.4, 1H), 7.83-7.76 (dd, J=8.8, 1.7, 1H), 7.77-7.68 (m, 1H), 7.66-7.58 (m, 1H), 7.58-7.48 (m, 2H), 7.46-7.39 (m, 2H), 7.37-7.30 (dd, J=7.4, 1.5, 1H), 4.31 (s, 1H), 1.09 (s, 9H).

Workup

  1. customequipped with a stir bar
  2. customArgon was bubbled through the solvent while it
  3. stirringthe mixture stirred for 15 hours at 80° Celsius under an argon atmosphere
  4. extractionthe aqueous layer was extracted with ethyl acetate (3×10 mL)
  5. dry with materialThe combined organic extracts were then dried with Na2SO4
  6. concentrationconcentrated to dryness
  7. customThe crude product was purified by HPLC

Sources & evidence

ORD record
ord-b2c9bd5e1f0f4802875578a487a8c5d2
Source dataset
uspto-grants-2015_07
Patent number
US09079866B2

Reaction notes

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