Methyl iodide → 4-{2-[(4-Bromo-3-methylphenyl)amino]-6-methoxy-1-methylbenzimidazol-5-yloxy)pyridine-2-carboxylic acid

HRID 13495Notes

Reaction equation

HRID 13495 reaction equation
C([O:5][C:6]([C:8]1[CH:13]=[C:12]([O:14][C:15]2[C:20]([O:21][CH3:22])=[CH:19][C:18]([NH:23][CH3:24])=[C:17]([NH2:25])[CH:16]=2)[CH:11]=[CH:10][N:9]=1)=[O:7])(C)(C)C.NC(N)=S.IC.C(OC(C1C=C(OC2C=CC3N(C)[C:51]([NH:53][C:54]4[CH:59]=[CH:58][C:57]([Br:60])=[C:56]([CH3:61])[CH:55]=4)=NC=3C=2)C=CN=1)=O)(C)(C)C.FC(F)(F)C(O)=O>CO.C(Cl)Cl>[Br:60][C:57]1[CH:58]=[CH:59][C:54]([NH:53][C:51]2[N:23]([CH3:24])[C:18]3[CH:19]=[C:20]([O:21][CH3:22])[C:15]([O:14][C:12]4[CH:11]=[CH:10][N:9]=[C:8]([C:6]([OH:5])=[O:7])[CH:13]=4)=[CH:16][C:17]=3[N:25]=2)=[CH:55][C:56]=1[CH3:61]

Participants

8

Reactant 5

HCID 6328Methyl iodideHCID 6422Trifluoroacetic acidHCID 2723790ThioureaHCID 68430819Tert-butyl4-[3-amino-6-methoxy-4-(methylamino)phenoxy]pyridine-2-carboxylateHCID 86592198Tert-butyl4-(2-{[4-bromo-3-methylphenyl]amino)-1-methylbenzimidazol-5-yloxy)pyridine-2-carboxylate

Product 1

HCID 220407544-{2-[(4-Bromo-3-methylphenyl)amino]-6-methoxy-1-methylbenzimidazol-5-yloxy)pyridine-2-carboxylic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To tert-butyl4-[3-amino-6-methoxy-4-(methylamino)phenoxy]pyridine-2-carboxylate (1 eq) in methanol was added 4-bromo-3-methylbenzeneisothiocyanate (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-bromo-3-methylphenyl]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-bromo-3-methylphenyl]amino)-6-methoxy-1-methylbenzimidazol-5-yloxy)pyridine-2-carboxylic acid was purified by preparative chromatography. MS: MH+=482.

Workup

  1. stirringstirred at ambient temperature overnight
  2. customResulting 4-(2-{[4-bromo-3-methylphenyl]amino)-6-methoxy-1-methylbenzimidazol-5-yloxy)pyridine-2-carboxylic acid was purified by preparative chromatography

Sources & evidence

ORD record
ord-0f88705bc4954343b67c1e6be598d7cd
Source dataset
uspto-grants-2010_06
Patent number
US07728010B2

Reaction notes

Loading…