Sodium Hydroxide → 2-(2,6-dichloro-phenyl)-3H-benzoimidazole-5-carboxylic acid (3-chloro-phenyl)-methyl-amide

HRID 1514857Notes

Reaction equation

HRID 1514857 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[NH:10][C:11]2[CH:17]=[C:16]([C:18]([OH:20])=O)[CH:15]=[CH:14][C:12]=2[N:13]=1.[CH3:21][NH:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C.[OH-].[Na+]>CN(C=O)C>[Cl:29][C:25]1[CH:24]=[C:23]([N:22]([CH3:21])[C:18]([C:16]2[CH:15]=[CH:14][C:12]3[N:13]=[C:9]([C:3]4[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][C:4]=4[Cl:8])[NH:10][C:11]=3[CH:17]=2)=[O:20])[CH:28]=[CH:27][CH:26]=1

Participants

7

Reactant 5

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 1389003-chloro-N-methylanilineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 433492922-(2,6-Dichloro-phenyl)-3H-benzoimidazole-5-carboxylic acid

Product 1

HCID 581562662-(2,6-dichloro-phenyl)-3H-benzoimidazole-5-carboxylic acid (3-chloro-phenyl)-methyl-amide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 2-(2,6-dichloro-phenyl)-3H-benzoimidazole-5-carboxylic acid (107.5 mg, 0.35 mmol). N-methyl-3-chloroaniline (50 mg, 0.35 mmol), BOP (186 mg, 0.42 mmol) and DIEA (0.091 mL, 0.53 mmol) in DMF (1 mL) was stirred at room temperature for 60 h. Then 1N NaOH aqueous solution was added. The aqueous layer was extracted with EtOAc, and the organic extracts were dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography (SiO2, EtOAc:Hexane=20:80 to 80:10) and prep-HPLC later to give 2-(2,6-dichloro-phenyl)-3H-benzoimidazole-5-carboxylic acid (3-chloro-phenyl)-methyl-amide: MS (m/z) 432 (M+1); 1H NMR (CDCl3, 400 MHz) δ 9.86 (s, 1H), 7.87 (s, 1H), 7.59 (d, 1H), 7.28-7.42 (m, 4H), 7.18 (s, 1H), 7.13 (t, 2H), 6.93 (t, 1H), 3.51 (s, 3H) (major tautomer).

Workup

  1. extractionThe aqueous layer was extracted with EtOAc
  2. dry with materialthe organic extracts were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by column chromatography (SiO2, EtOAc:Hexane=20:80 to 80:10)

Sources & evidence

ORD record
ord-c8a56b9c20a847d0817b6a1089057d0c
Source dataset
uspto-grants-2012_07
Patent number
US08222248B2

Reaction notes

Loading…