Potassium Carbonate → HCID 59549920, compound

HRID 1810108Notes

Reaction equation

HRID 1810108 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH2:10][C:11]([O:13]C(C)(C)C)=[O:12])[CH:6]=[CH:7][C:8]=1F)#[N:2].[Cl:18][C:19]1[CH:39]=[CH:38][C:22]([CH2:23][CH2:24][NH:25][C:26]([C:28]2[CH:37]=[CH:36][C:31]3[NH:32][C:33]([CH3:35])=[N:34][C:30]=3[CH:29]=2)=[O:27])=[CH:21][CH:20]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[Cl:18][C:19]1[CH:20]=[CH:21][C:22]([CH2:23][CH2:24][NH:25][C:26]([C:28]2[CH:37]=[CH:36][C:31]3[N:32]([C:8]4[CH:7]=[CH:6][C:5]([CH2:10][C:11]([OH:13])=[O:12])=[CH:4][C:3]=4[C:1]#[N:2])[C:33]([CH3:35])=[N:34][C:30]=3[CH:29]=2)=[O:27])=[CH:38][CH:39]=1.[Cl:18][C:19]1[CH:20]=[CH:21][C:22]([CH2:23][CH2:24][NH:25][C:26]([C:28]2[CH:37]=[CH:36][C:31]3[N:32]=[C:33]([CH3:35])[N:34]([C:8]4[CH:7]=[CH:6][C:5]([CH2:10][C:11]([OH:13])=[O:12])=[CH:4][C:3]=4[C:1]#[N:2])[C:30]=3[CH:29]=2)=[O:27])=[CH:38][CH:39]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 45925946Tert-butyl 2-(3-cyano-4-fluorophenyl)acetateHCID 178432229HCID 178432229, compound

Product 2

HCID 59549920HCID 59549920, compoundYield 59.7%HCID 59549925HCID 59549925, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

A mixture of tert-butyl 2-(3-cyano-4fluorophenyl)acetate (0.0825 g, 0.351 mmol), N-(4-chlorophenethyl)-2-methyl-1H-benzo[d]imidazole-5carboxamide (0.100 g, 0.319 mmol) and potassium carbonate (0.0661 g, 0.478 mmol) was stirred together in 3 mL of DMSO at 85° C. After stirring for 4 hours, the reaction was loaded onto a silica gel samplet and the product eluted using a gradient of 5% ethyl acetate/hexanes to 100% ethyl acetate/hexanes. The resulting oil was dissolved in DCM (1 mL) and treated with TFA (1 mL). After 2 hours, the reaction was concentrated, and the residue was loaded onto silica gel. The product was eluted using a gradient of 0.5% MeOH/DCM containing 0.5% AcOH to 10% MeOH/DCM containing 0.5% AcOH to provide 2-(4-(5-(4-chlorophenethylcarbamoyl)-2-methyl-1H-benzo[d]imidazol-1yl)3-cyanophenyl)acetic acid and 2-(4-(6-(4-chlorophenethylcarbamoyl)-2-methyl-1H-benzo[d]imidazol-1-yl)-3-cyanophenyl)acetic acid (0.045 g, 29.9% yield) as a 2:1 mixture. 1H NMR (400 MHz, CD3OD) δ 8.49 (t, J=5.5 Hz, NH), 7.77-7.82 (m, 2H), 7.68 (s, 1H), 7.52-7.54 (m, 1H), 7.20-7.32 (m, 4H) 7.00-7.08 (m, 2H), 3.71 (s, 2H), 3.58 (q, J=6.8 Hz, 2H), 3.30 (s, 3H), 2.90 (t, J=7.3 Hz, 2H). MS(APCI)=473.5 (M+1).

Workup

  1. washthe product eluted
  2. dissolutionThe resulting oil was dissolved in DCM (1 mL)
  3. additiontreated with TFA (1 mL)
  4. waitAfter 2 hours
  5. concentrationthe reaction was concentrated
  6. washThe product was eluted

Sources & evidence

ORD record
ord-2d1eebf3b37d456593eddc86bb1cd71e
Source dataset
uspto-grants-2013_01
Patent number
US08362056B2

Reaction notes

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