Nitrogen → N-(2',4'-difluoro-5-(5-(5-fluoropyridin-2-yl)-1H-benzo[d]imidazol-1-yl)-[1,1'-biphenyl]-3-yl)cyclopropanesulfonamide

HRID 64173Notes

Reaction equation

HRID 64173 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[C:13]([N:15]2[C:19]3[CH:20]=[CH:21][C:22](B4OC(C)(C)C(C)(C)O4)=[CH:23][C:18]=3[N:17]=[CH:16]2)[CH:12]=[C:11]([NH:33][S:34]([CH:37]2[CH2:39][CH2:38]2)(=[O:36])=[O:35])[CH:10]=1.N#N.Br[C:43]1[CH:48]=[CH:47][C:46]([F:49])=[CH:45][N:44]=1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.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:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:14]=[C:13]([N:15]2[C:19]3[CH:20]=[CH:21][C:22]([C:43]4[CH:48]=[CH:47][C:46]([F:49])=[CH:45][N:44]=4)=[CH:23][C:18]=3[N:17]=[CH:16]2)[CH:12]=[C:11]([NH:33][S:34]([CH:37]2[CH2:38][CH2:39]2)(=[O:35])=[O:36])[CH:10]=1

Participants

7

Reactant 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 27831712-Bromo-5-fluoropyridineHCID 89501185N-(2',4'-difluoro-5-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-1-yl)-[1,1'-biphenyl]-3-yl)cyclopropanesulfonamide

Product 1

HCID 117777778N-(2',4'-difluoro-5-(5-(5-fluoropyridin-2-yl)-1H-benzo[d]imidazol-1-yl)-[1,1'-biphenyl]-3-yl)cyclopropanesulfonamideYield 14.1%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of N-(2′,4′-difluoro-5-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-1-yl)-[1,1′-biphenyl]-3-yl)cyclopropanesulfonamide (0.15 g, 0.272 mmol) in 1,2-dimethoxyethane (5 ml) was degassed by N2 bubbling for 5 min. 2-Bromo-5-fluoropyridine (0.057 g, 0.326 mmol, 1.2 eq.) was added and the mixture was degassed for another 5 min. Pd(dppf)Cl2 (0.011, 0.013 mmol, 0.05 eq.) and aqueous sodium carbonate (0.072, 0.680 mmol, 2.5 eq.) were added and the procedure of Example 1(d) was followed. The crude residue of the product was purified by column chromatography (60-120 silica gel, 80% ethyl acetate in hexane) to yield the title product in 14.1% yield (0.02 g). 1H NMR (400 MHz, DMSO-d6): δ 10.23 (s, 1H), 8.75 (s, 1H), 8.68-8.67 (d, 1H), 8.48 (d, 1H), 8.20-8.13 (m, 2H), 7.86-7.743 (m, 3H), 7.61-7.60 (d, 2H), 7.51-7.43 (m, 2H), 7.30-7.25 (m, 1H), 2.89-2.86 (t, 1H), 1.03-1.02 (d, 4H); LC-MS (ESI): Calculated mass: 520.53; Observed mass: 521.2 [M+H]+ (rt: 1.64 min).

Workup

  1. customthe mixture was degassed for another 5 min
  2. customThe crude residue of the product was purified by column chromatography (60-120 silica gel, 80% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-cddba55b3e7244ad819db9e858738851
Source dataset
uspto-grants-2016_09
Patent number
US09447091B2

Reaction notes

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