Sodium Iodide → [2-(2-{4-[3-(5-Tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yloxy)-ethylamino]-acetic acid methyl ester

HRID 1038328Notes

Reaction equation

HRID 1038328 reaction equation
[C:1]([C:5]1[O:9][N:8]=[C:7]([NH:10][C:11]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[N:21]=[C:22]4[N:26]([CH:27]=3)[C:25]3[CH:28]=[CH:29][C:30]([O:32][CH2:33][CH2:34]Cl)=[CH:31][C:24]=3[S:23]4)=[CH:16][CH:15]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[CH2:37]([O:39][C:40](=[O:43])[CH2:41][NH2:42])C.C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>CN(C=O)C>[CH3:37][O:39][C:40](=[O:43])[CH2:41][NH:42][CH2:34][CH2:33][O:32][C:30]1[CH:29]=[CH:28][C:25]2[N:26]3[CH:27]=[C:20]([C:17]4[CH:18]=[CH:19][C:14]([NH:13][C:11]([NH:10][C:7]5[CH:6]=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[O:9][N:8]=5)=[O:12])=[CH:15][CH:16]=4)[N:21]=[C:22]3[S:23][C:24]=2[CH:31]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 2723640Glycine ethyl ester, hydrochlorideHCID 667941831-(5-Tert-butyl-isoxazol-3-yl)-3-{4-[7-(2-chloro-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea

Product 1

HCID 66794279[2-(2-{4-[3-(5-Tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yloxy)-ethylamino]-acetic acid methyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(2-chloro-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea (1 equivalent), glycine ethyl ester hydrochloride (1-3 equivalents), potassium carbonate (2-6 equivalents), and sodium iodide (2-5 equivalents) in anhydrous DMF is stirred at selected temperatures between rt and 80° C. until the reaction is substantially complete as monitored by LCMS or TLC. The mixture is partitioned between water and either dichloromethane or a mixture of isopropanol and dichloromethane. The organic layer is separated and the aqueous layer is further extracted with dichloromethane or a mixture of isopropanol and dichloromethane. The combined extracts are washed with water or brine, then dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica gel flash chromatography to afford [2-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yloxy)-ethylamino]-acetic acid methyl ester.

Workup

  1. customThe mixture is partitioned between water
  2. additioneither dichloromethane or a mixture of isopropanol and dichloromethane
  3. customThe organic layer is separated
  4. extractionthe aqueous layer is further extracted with dichloromethane
  5. additiona mixture of isopropanol and dichloromethane
  6. washThe combined extracts are washed with water or brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue is purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-6dc2dd375d2943e7b9692ab9951e05b7
Source dataset
uspto-grants-2013_10
Patent number
US08551963B2

Reaction notes

Loading…