Methyl iodide → 2-{[4-Chloro-3-(trifluoromethyl)phenylamino)-1-methylbenzimidazol-5-yloxy)pyridine-2-carboxylic acid

HRID 2070272Notes

Reaction equation

HRID 2070272 reaction equation
C([O:5][C:6]([C:8]1[CH:13]=[C:12](OC2C=CC(NC)=C(N)C=2)[CH:11]=[CH:10][N:9]=1)=[O:7])(C)(C)C.NC(N)=S.IC.C(OC(C1C=C([O:43][C:44]2[CH:65]=[CH:64][C:47]3[N:48]([CH3:63])[C:49]([NH:51][C:52]4[CH:57]=[CH:56][C:55]([Cl:58])=[C:54]([C:59]([F:62])([F:61])[F:60])[CH:53]=4)=[N:50][C:46]=3[CH:45]=2)C=CN=1)=O)(C)(C)C.FC(F)(F)C(O)=O>CO.C(Cl)Cl>[Cl:58][C:55]1[CH:56]=[CH:57][C:52]([NH:51][C:49]2[N:48]([CH3:63])[C:47]3[CH:64]=[CH:65][C:44]([O:43][C:8]4([C:6]([OH:7])=[O:5])[CH:13]=[CH:12][CH:11]=[CH:10][NH:9]4)=[CH:45][C:46]=3[N:50]=2)=[CH:53][C:54]=1[C:59]([F:62])([F:61])[F:60]

Participants

8

Reactant 5

HCID 6328Methyl iodideHCID 6422Trifluoroacetic acidHCID 2723790ThioureaHCID 22040526Tert-butyl4-[3-amino-4-(methylamino)phenoxy]pyridine-2-carboxylateHCID 86593095Tert-butyl4-(2-{[4-chloro-3-(trifluoromethyl)phenyl]amino)-1-methylbenzimidazol-5-yloxy)pyridine-2-carboxylate

Product 1

HCID 865930932-{[4-Chloro-3-(trifluoromethyl)phenylamino)-1-methylbenzimidazol-5-yloxy)pyridine-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To tert-butyl4-[3-amino-4-(methylamino)phenoxy]pyridine-2-carboxylate (1 eq) in methanol was added 4-chloro-3-(trifluoromethyl)benzeneisothiocyanate (1 eq) and stir at ambient temperature for 16 h. Formation of the corresponding thiourea was followed by LC/MS. To it was then added iodomethane (1 eq) and heated to 60° C. for 2 h. Formation of tert-butyl4-(2-{[4-chloro-3-(trifluoromethyl)phenyl]amino)-1-methylbenzimidazol-5-yloxy)pyridine-2-carboxylate was followed by LC/MS. To it in methylene chloride was added trifluoroacetic acid and stirred at ambient temperature overnight. Resulting 4-(2-{[4-chloro-3-(trifluoromethyl)phenylamino)-1-methylbenzimidazol-5-yloxy)pyridine-2-carboxylic acid was purified by preparative chromatography. MS: MH+=462.

Workup

  1. stirringstirred at ambient temperature overnight

Sources & evidence

ORD record
ord-f7347066e2264ca0a23e81eddc05ab49
Source dataset
uspto-grants-2012_10
Patent number
US08299108B2

Reaction notes

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