Ethanolamine → 1-(5-Tert-butyl-isoxazol-3-yl)-3-(4-{7-[2-(2-hydroxy-ethylamino)-ethoxy]-benzo[d]imidazo[2,1-b]thiazol-2-yl}-phenyl)-urea

HRID 1038327Notes

Reaction equation

HRID 1038327 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].[CH2:36]([CH2:38][NH2:39])[OH:37].C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>CN(C=O)C>[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][NH:39][CH2:38][CH2:36][OH:37])=[CH:31][C:24]=3[S:23]4)=[CH:16][CH:15]=2)=[O:12])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 700EthanolamineHCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 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 462143101-(5-Tert-butyl-isoxazol-3-yl)-3-(4-{7-[2-(2-hydroxy-ethylamino)-ethoxy]-benzo[d]imidazo[2,1-b]thiazol-2-yl}-phenyl)-urea

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), ethanolamine (1-3 equivalents), potassium carbonate (2-5 equivalents) and sodium iodide (2-5 equivalents) in anhydrous DMF is stirred at 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 separated aqueous layer is further extracted with dichloromethane or a mixture of isopropanol and dichloromethane, and the combined organic layers are washed with water or brine, then dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue is purified by preparative reverse-phase HPLC or silica gel flash chromatography to afford 1-(5-tert-butyl-isoxazol-3-yl)-3-(4-{7-[2-(2-hydroxy-ethylamino)-ethoxy]-benzo[d]imidazo[2,1-b]thiazol-2-yl}-phenyl)-urea (I-2).

Workup

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

Sources & evidence

ORD record
ord-a7e61d0b322d484d90ac3a2e89fc6fff
Source dataset
uspto-grants-2013_10
Patent number
US08551963B2

Reaction notes

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