Dichloromethane → 3-Chloro-4-{2-[2-(6-chloro-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-acetylamino}-benzoic acid

HRID 1161302Notes

Reaction equation

HRID 1161302 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]3)[C:14](O)=[O:15])[C:11]3[CH:23]=[C:24]([F:28])[C:25]([F:27])=[CH:26][C:10]=3[N:9]=2)=[CH:4][CH:3]=1.C[O:30][C:31](=[O:40])[C:32]1[CH:37]=[CH:36][C:35]([NH2:38])=[C:34]([Cl:39])[CH:33]=1.C([O-])(O)=O.[Na+].ClCCl>S(Cl)(Cl)=O>[Cl:39][C:34]1[CH:33]=[C:32]([CH:37]=[CH:36][C:35]=1[NH:38][C:14](=[O:15])[CH:13]([N:12]1[C:11]2[CH:23]=[C:24]([F:28])[C:25]([F:27])=[CH:26][C:10]=2[N:9]=[C:8]1[C:5]1[CH:6]=[N:7][C:2]([Cl:1])=[CH:3][CH:4]=1)[CH:17]1[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]1)[C:31]([OH:40])=[O:30]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 516892Sodium BicarbonateHCID 1515284Methyl 4-Amino-3-chlorobenzoateHCID 86632022[2-(6-Chloro-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-cyclohexylacetic acid

Product 1

HCID 441976913-Chloro-4-{2-[2-(6-chloro-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-acetylamino}-benzoic acid

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Procedure

The title compound was prepared by heating [2-(6-chloro-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-cyclohexylacetic acid (200 mg, 0.46 mmol) in 5 ml thionylchloride to 80° C. for 4 h. The solvent was evaporated and the residue taken up in dichloromethane. 4-Amino-3-chloro-benzoic acid methyl ester (85 mg, 0.46 mmol) were added and the reaction mixture stirred at rt overnight. The crude product was worked up by addition of a solution of 1 M NaHCO3 and extraction of the aqueous layer with dichloromethane. Organic layers were combined, dried over MgSO4 and evaporated to dryness. The residue was taken up in methanol (3 ml) and 1N NaOH (1 ml) added. The mixture was stirred at rt overnight, the solvent evaporated and the product isolated via preparative HPLC. MS (ES+): 560 (M+H).

Workup

  1. customThe solvent was evaporated
  2. dry with materialdried over MgSO4
  3. customevaporated to dryness
  4. addition1N NaOH (1 ml) added
  5. stirringThe mixture was stirred at rt overnight
  6. customthe solvent evaporated
  7. customthe product isolated via preparative HPLC

Sources & evidence

ORD record
ord-d9c84aa98f984483a388e061efb6dcc9
Source dataset
uspto-grants-2010_10
Patent number
US07816540B2

Reaction notes

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