Ethyl orthoformate → 1-(2-fluoro-5-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-5-iodo-1H-benzo[d]imidazole

HRID 706466Notes

Reaction equation

HRID 706466 reaction equation
[F:1][C:2]1[CH:17]=[C:16]([O:18][CH2:19][C:20]2[CH:21]=[N:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=2)[C:15]([O:28][CH3:29])=[CH:14][C:3]=1[CH2:4][NH:5][C:6]1[C:7]([NH2:13])=[CH:8][C:9]([I:12])=[CH:10][CH:11]=1.[CH:30](OCC)(OCC)OCC>C(O)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>[F:1][C:2]1[CH:17]=[C:16]([O:18][CH2:19][C:20]2[CH:21]=[N:22][C:23]([O:26][CH3:27])=[CH:24][CH:25]=2)[C:15]([O:28][CH3:29])=[CH:14][C:3]=1[CH2:4][N:5]1[C:6]2[CH:11]=[CH:10][C:9]([I:12])=[CH:8][C:7]=2[N:13]=[CH:30]1

Participants

5

Reactant 2

HCID 31214Ethyl orthoformateHCID 118389318N1-(2-fluoro-5-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-4-iodobenzene-1,2-diamine

Product 1

HCID 1181140131-(2-fluoro-5-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-5-iodo-1H-benzo[d]imidazoleYield 68.8%

Reagents, catalysts & solvents 2

HCID 6101p-Toluenesulfonic acidCatalystHCID 702EthanolSolvent

Procedure

To a stirred solution of N1-(2-fluoro-5-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-4-iodobenzene-1,2-diamine (0.36 g, 0.70 mmol) in ethanol (10 mL) was added triethyl orthoformate (0.31 g, 2.11 mmol) and p-toluenesulfonic acid (0.007 g, 0.035 mmol). The reaction mixture was heated to reflux. After 30 min, the brown solution was allowed to cool to room temperature and was concentrated. The residue was partitioned between water and dichloromethane. The phases were separated, and the aqueous phase extracted with dichloromethane. The combined organic phases were washed with water and brine, dried over magnesium sulfate, filtered, and concentrated. Chromatographic purification (Combi-Flash, 12 g SiO2 column, 1-5% methanol/dichloromethane elute) afforded 0.25 g (68%) of 1-(2-fluoro-5-methoxy-4-((6-methoxypyridin-3-yl)methoxy)benzyl)-5-iodo-1H-benzo[d]imidazole as a tan solid.

Workup

  1. temperatureThe reaction mixture was heated to reflux
  2. concentrationwas concentrated
  3. customThe residue was partitioned between water and dichloromethane
  4. customThe phases were separated
  5. extractionthe aqueous phase extracted with dichloromethane
  6. washThe combined organic phases were washed with water and brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customChromatographic purification (Combi-Flash, 12 g SiO2 column, 1-5% methanol/dichloromethane elute)

Sources & evidence

ORD record
ord-037f71bf31784a92856bdd249024b50e
Source dataset
uspto-grants-2015_11
Patent number
US09174986B2

Reaction notes

Loading…