Potassium Carbonate → 4-{3-[1-(2,2-dimethylpropyl)-4-fluoro-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl]phenoxy}nicotinonitrile

HRID 882209Notes

Reaction equation

HRID 882209 reaction equation
[CH3:1][C:2]([CH3:24])([CH3:23])[CH2:3][N:4]1[C:8]2[CH:9]=[CH:10][C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([OH:20])[CH:15]=3)=[C:12]([F:13])[C:7]=2[N:6]([CH3:21])[C:5]1=[O:22].C(=O)([O-])[O-].[K+].[K+].Cl[C:32]1[CH:37]=[CH:36][N:35]=[CH:34][C:33]=1[C:38]#[N:39]>CS(C)=O>[CH3:1][C:2]([CH3:24])([CH3:23])[CH2:3][N:4]1[C:8]2[CH:9]=[CH:10][C:11]([C:14]3[CH:15]=[C:16]([CH:17]=[CH:18][CH:19]=3)[O:20][C:32]3[C:33]([C:38]#[N:39])=[CH:34][N:35]=[CH:36][CH:37]=3)=[C:12]([F:13])[C:7]=2[N:6]([CH3:21])[C:5]1=[O:22]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 134111124-Chloro-nicotinonitrileHCID 667491271-(2,2-dimethylpropyl)-4-fluoro-5-(3-hydroxyphenyl)-3-methyl-1,3-dihydro-2H-benzimidazol-2-one

Product 1

HCID 667502474-{3-[1-(2,2-dimethylpropyl)-4-fluoro-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl]phenoxy}nicotinonitrile

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A solution of 1-(2,2-dimethylpropyl)-4-fluoro-5-(3-hydroxyphenyl)-3-methyl-1,3-dihydro-2H-benzimidazol-2-one (7-15, 55 mg, 0.17 mmol) in DMSO (1 ml) was charged with Potassium carbonate (46.3 mg, 0.34 mmol, 2.0 eq) and 4-Chloro-3-cyanopyridine (34.8 mg, 0.25 mmol, 1.5 eq). The mixture was irradiated in a microwave at 160 deg C. for 20 min, then purified via reverse-phase HPLC (Acetonitrile/Water gradient with 0.1% TFA present) providing 4-{3-[1-(2,2-dimethylpropyl)-4-fluoro-3-methyl-2-oxo-2,3-dihydro-1H-benzimidazol-5-yl]phenoxy}nicotinonitrile (8-1) as a tan solid-oil. 1H NMR (400 MHz, CDCl3) δ 8.81 (bs, 1H), 7.60-7.53 (m, 2H), 7.35 (s, 1H), 7.27 (s, 1H), 7.17-7.14 (m, 1H), 7.11-7.07 (m, 1H), 6.91 (d, 2H, J=8.24 Hz), 3.69 (s, 2H), 3.66 (s, 3H), 1.10 (s, 9H). LRMS m/z: Calc'd for C25H23FN4O2(M+H) 431.4, found 431.5.

Workup

  1. customThe mixture was irradiated in a microwave at 160 deg C
  2. custompurified via reverse-phase HPLC (Acetonitrile/Water gradient with 0.1% TFA present)

Sources & evidence

ORD record
ord-c3b6d0c21faa4033ae79e8b432413354
Source dataset
uspto-grants-2015_03
Patent number
US08993779B2

Reaction notes

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