Dimethyl Sulfoxide → 1-[5-(1,1-Dimethyl-2-oxo-ethyl)-isoxazol-3-yl]-3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea

HRID 1038332Notes

Reaction equation

HRID 1038332 reaction equation
CS(C)=O.C(Cl)(=O)C(Cl)=O.[OH:11][CH2:12][C:13]([C:16]1[O:20][N:19]=[C:18]([NH:21][C:22]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]3[N:32]=[C:33]4[N:37]([CH:38]=3)[C:36]3[CH:39]=[CH:40][C:41]([O:43][CH2:44][CH2:45][N:46]5[CH2:51][CH2:50][O:49][CH2:48][CH2:47]5)=[CH:42][C:35]=3[S:34]4)=[CH:27][CH:26]=2)=[O:23])[CH:17]=1)([CH3:15])[CH3:14].C(N(CC)CC)C>ClCCl>[CH3:15][C:13]([C:16]1[O:20][N:19]=[C:18]([NH:21][C:22]([NH:24][C:25]2[CH:26]=[CH:27][C:28]([C:31]3[N:32]=[C:33]4[N:37]([CH:38]=3)[C:36]3[CH:39]=[CH:40][C:41]([O:43][CH2:44][CH2:45][N:46]5[CH2:47][CH2:48][O:49][CH2:50][CH2:51]5)=[CH:42][C:35]=3[S:34]4)=[CH:29][CH:30]=2)=[O:23])[CH:17]=1)([CH3:14])[CH:12]=[O:11]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 461867861-[5-(2-Hydroxy-1,1-dimethyl-ethyl)-isoxazol-3-yl]-3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea

Product 1

HCID 462144741-[5-(1,1-Dimethyl-2-oxo-ethyl)-isoxazol-3-yl]-3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Alternatively, 1-[5-(1,1-dimethyl-2-oxo-ethyl)-isoxazol-3-yl]-3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea (I-4a) is prepared in the following manner. To a stirred mixture of dimethyl sulfoxide (1 equivalent) in anhydrous dichloromethane at −78° C. under an argon atmosphere is added dropwise oxalyl chloride (0.5 equivalents). After stirring for a further 20 to 40 min, compound 1-[5-(2-hydroxy-1,1-dimethyl-ethyl)-isoxazol-3-yl]-3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea (I-1) (0.3 equivalents) is added and the mixture is stirred at −78° C. Triethylamine (1-2 equivalents) is added, and the mixture is allowed to warm to rt, then the mixture is filtered through Celite and concentrated under reduced pressure. The residue is purified by silica gel flash chromatography to afford 1-[5-(1,1-dimethyl-2-oxo-ethyl)-isoxazol-3-yl]-3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea (I-4a).

Workup

  1. customAlternatively, 1-[5-(1,1-dimethyl-2-oxo-ethyl)-isoxazol-3-yl]-3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-urea (I-4a) is prepared in the following manner
  2. stirringthe mixture is stirred at −78° C
  3. filtrationthe mixture is filtered through Celite
  4. concentrationconcentrated under reduced pressure
  5. customThe residue is purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-1f369c10ceee4c628d7acaf761c7a118
Source dataset
uspto-grants-2013_10
Patent number
US08551963B2

Reaction notes

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