Phenyl 5-tert-butylisoxazol-3-ylcarbamate → 1-(5-Tert-butyl-isoxazol-3-yl)-3-{4-[7-(2-chloro-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea

HRID 1038326Notes

Reaction equation

HRID 1038326 reaction equation
[Cl:1][CH2:2][CH2:3][O:4][C:5]1[CH:23]=[CH:22][C:8]2[N:9]3[CH:14]=[C:13]([C:15]4[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=4)[N:12]=[C:10]3[S:11][C:7]=2[CH:6]=1.[C:24]([C:28]1[O:32][N:31]=[C:30]([NH:33][C:34](=O)[O:35]C2C=CC=CC=2)[CH:29]=1)([CH3:27])([CH3:26])[CH3:25]>C1COCC1>[C:24]([C:28]1[O:32][N:31]=[C:30]([NH:33][C:34]([NH:21][C:18]2[CH:19]=[CH:20][C:15]([C:13]3[N:12]=[C:10]4[N:9]([CH:14]=3)[C:8]3[CH:22]=[CH:23][C:5]([O:4][CH2:3][CH2:2][Cl:1])=[CH:6][C:7]=3[S:11]4)=[CH:16][CH:17]=2)=[O:35])[CH:29]=1)([CH3:27])([CH3:25])[CH3:26]

Participants

4

Reactant 2

HCID 13489605Phenyl 5-tert-butylisoxazol-3-ylcarbamateHCID 667940197-(2-Chloro-ethoxy)-2-(4-amino-phenyl)-benzo[d]imidazo[2,1-b]thiazole

Product 1

HCID 667941831-(5-Tert-butyl-isoxazol-3-yl)-3-{4-[7-(2-chloro-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of 7-(2-chloro-ethoxy)-2-(4-amino-phenyl)-benzo[d]imidazo[2,1-b]thiazole (1 equivalent) and phenyl 5-tert-butylisoxazol-3-ylcarbamate, prepared as described in WO 2006/082404 A1 (1 equivalent) in anhydrous THF is stirred at selected temperatures between rt and 50° C. until the reaction is substantially complete as monitored by LCMS or TLC. The mixture is concentrated under reduced pressure and the residue is partitioned between water and either dichloromethane or a mixture of dichloromethane and isopropanol. The separated aqueous layer is further extracted with dichloromethane or a mixture of isopropanol and dichloromethane, and the combined organic layers are dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by silica gel flash chromatography to afford 1-(5-tert-butyl-isoxazol-3-yl)-3-{4-[7-(2-chloro-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea.

Workup

  1. customprepared
  2. concentrationThe mixture is concentrated under reduced pressure
  3. customthe residue is partitioned between water
  4. additioneither dichloromethane or a mixture of dichloromethane and isopropanol
  5. extractionThe separated aqueous layer is further extracted with dichloromethane
  6. additiona mixture of isopropanol and dichloromethane
  7. dry with materialthe combined organic layers are dried 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-c921b3457f7e438b9c45bdbbe20e52ef
Source dataset
uspto-grants-2013_10
Patent number
US08551963B2

Reaction notes

Loading…