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

HRID 64195

Reaction equation

HRID 64195 reaction equation
Br[C:2]1[CH:31]=[CH:30][C:5]2[N:6]([C:9]3[CH:10]=[C:11]([NH:23][S:24]([CH:27]4[CH2:29][CH2:28]4)(=[O:26])=[O:25])[CH:12]=[C:13]([C:15]4[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:16]=4[F:22])[CH:14]=3)[CH:7]=[N:8][C:4]=2[CH:3]=1.C([O-])([O-])=O.[K+].[K+].Cl.CN(C)CC(O)=O.[NH:46]1[CH2:50][CH2:49][CH2:48][C:47]1=[O:51]>CS(C)=O.[Cu]I>[F:22][C:16]1[CH:17]=[C:18]([F:21])[CH:19]=[CH:20][C:15]=1[C:13]1[CH:14]=[C:9]([N:6]2[C:5]3[CH:30]=[CH:31][C:2]([N:46]4[CH2:50][CH2:49][CH2:48][C:47]4=[O:51])=[CH:3][C:4]=3[N:8]=[CH:7]2)[CH:10]=[C:11]([NH:23][S:24]([CH:27]2[CH2:29][CH2:28]2)(=[O:25])=[O:26])[CH:12]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 120252-PyrrolidoneHCID 75605N,N-Dimethylglycine hydrochlorideHCID 89501045N-(5-(5-bromo-1H-benzo[d]imidazol-1-yl)-2',4'-difluoro-[1,1'-biphenyl]-3-yl)cyclopropanesulfonamide

Product 1

HCID 117777859N-(2',4'-difluoro-5-(5-(2-oxopyrrolidin-1-yl)-1H-benzo[d]imidazol-1-yl)-[1,1'-biphenyl]-3-yl)cyclopropanesulfonamideYield 90%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
110 °C

Procedure

A solution of N-(5-(5-bromo-1H-benzo[d]imidazol-1-yl)-2′,4′-difluoro-[1,1′-biphenyl]-3-yl)cyclopropanesulfonamide (50 mg, 0.099 mmol, 1 eq.) in DMSO (2 ml) was degassed by nitrogen bubbling for 10 min. Copper(I)iodide (11.3 mg, 0.059 mmol, 0.6 eq.), K2CO3 (42 mg, 0.298 mmol, 3 eq.), N,N-dimethyl glycine HCl (11 mg, 0.079 mmol) and 2-pyrrolidone (42 mg, 0.49 mmol, 5 eq.) were added and the mixture was further degassed for 10 min and then heated to 110° C. for 16 h. The mixture was cooled to RT and diluted with ethyl acetate, filtered through a celite bed and washed with water and brine solution. The ethyl acetate layer was dried over sodium sulphate. The solvent was distilled off to afford the crude residue which was purified by preparative HPLC to afford the product in 90% yield (45 mg). 1H NMR (400 MHz, DMSO-d6): δ 8.65 (s, 1H), 7.96 (d, 1H), 7.78-7.65 (m, 3H), 7.54 (m, 2H), 7.45-7.42 (m, 2H), 7.28-7.24 (dt, 1H), 3.9 (t, 2H), 2.88-2.8 (m, 1H), 2.12-2.02 (m, 2H), 1.0 (m, 4H): LC-MS (ESI): Calculated mass: 508.54; Observed mass: 508.7 [M+H]+ (rt: 1.46 min).

Workup

  1. customthe mixture was further degassed for 10 min
  2. temperatureThe mixture was cooled to RT
  3. additiondiluted with ethyl acetate
  4. filtrationfiltered through a celite bed
  5. washwashed with water and brine solution
  6. dry with materialThe ethyl acetate layer was dried over sodium sulphate
  7. distillationThe solvent was distilled off

Sources & evidence

ORD record
ord-6c861e289c1e4bed9b8c97ea5f6c1e64
Source dataset
uspto-grants-2016_09
Patent number
US09447091B2

Linked notes

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