Tetrahydrofuran → 4'-(6-Aminopyridin-3-yl)-N-cyclohexyl-3'-fluoro-[1,1'-biphenyl]-2-sulfonamide

HRID 1523902Notes

Reaction equation

HRID 1523902 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11](B(O)O)=[CH:10][C:9]=2[F:17])=[CH:4][CH:3]=1.Br[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[S:25]([NH:28][CH:29]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1)(=[O:27])=[O:26].C([O-])([O-])=O.[K+].[K+].C1COCC1>CCOC(C)=O.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2].[Pd](Cl)Cl>[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:19]3[C:20]([S:25]([NH:28][CH:29]4[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]4)(=[O:27])=[O:26])=[CH:21][CH:22]=[CH:23][CH:24]=3)=[CH:10][C:9]=2[F:17])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 11430Potassium CarbonateHCID 33149702-bromo-N-cyclohexylbenzenesulfonamideHCID 90313226(4-(6-Aminopyridin-3-yl)-3-fluorophenyl)boronic acid

Product 1

HCID 903128754'-(6-Aminopyridin-3-yl)-N-cyclohexyl-3'-fluoro-[1,1'-biphenyl]-2-sulfonamideYield 11%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 12976736Bis(ditert-butyl(cyclopenta-2,4-dien-1-yl)phosphane);iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (4-(6-aminopyridin-3-yl)-3-fluorophenyl)boronic acid (75 mg, 0.32 mmol), 2-bromo-N-cyclohexylbenzenesulfonamide (0.11 g, 0.36 mmol), 1,1′-bis[di-tert-butylphosphino)ferrocene]palladium(II) chloride (11 mg, 0.016 mmol), K2CO3 (2 M, 1.6 mL, sparged with nitrogen) and THF (2 mL, sparged with nitrogen) were combined in a sealed vessel under nitrogen. The mixture was vigorously stirred at rt for 16 hours, then diluted with EtOAc. The aqueous phase was removed and the organic layer was dried and concentrated. The residue was subjected to FCC to provide the title compound (15 mg, 11%). MS (CI): mass calcd. for C23H24FN3O2S, 425.16; m/z found, 426.1 [M+H]+. 1H NMR (500 MHz, DMSO-d6) δ 8.20-8.14 (s, 1H), 8.05-7.96 (m, 1H), 7.70-7.57 (m, 3H), 7.55-7.47 (m, 1H), 7.44-7.35 (m, 2H), 7.30-7.20 (m, 2H), 6.59-6.52 (d, J=8.6, 1H), 6.23-6.11 (s, 2H), 2.83-2.69 (d, J=7.4, 1H), 1.68-1.52 (m, 4H), 1.49-1.38 (s, 1H), 1.19-0.92 (m, 6H).

Workup

  1. customwere combined in a sealed vessel under nitrogen
  2. customThe aqueous phase was removed
  3. customthe organic layer was dried
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-47a8d384e45145b2a65ad6743576c93b
Source dataset
uspto-grants-2015_07
Patent number
US09079866B2

Reaction notes

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