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

HRID 1038330Notes

Reaction equation

HRID 1038330 reaction equation
C[O:2][C:3](=[O:40])[CH2:4][NH:5][CH2:6][CH2:7][O:8][C:9]1[CH:39]=[CH:38][C:12]2[N:13]3[CH:18]=[C:17]([C:19]4[CH:24]=[CH:23][C:22]([NH:25][C:26]([NH:28][C:29]5[CH:33]=[C:32]([C:34]([CH3:37])([CH3:36])[CH3:35])[O:31][N:30]=5)=[O:27])=[CH:21][CH:20]=4)[N:16]=[C:14]3[S:15][C:11]=2[CH:10]=1.O.[OH-].[Li+].Cl>C1COCC1>[C:34]([C:32]1[O:31][N:30]=[C:29]([NH:28][C:26](=[O:27])[NH:25][C:22]2[CH:21]=[CH:20][C:19]([C:17]3[N:16]=[C:14]4[N:13]([CH:18]=3)[C:12]3[CH:38]=[CH:39][C:9]([O:8][CH2:7][CH2:6][NH:5][CH2:4][C:3]([OH:40])=[O:2])=[CH:10][C:11]=3[S:15]4)=[CH:24][CH:23]=2)[CH:33]=1)([CH3:37])([CH3:35])[CH3:36]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 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

Product 1

HCID 46214311[2-(2-{4-[3-(5-Tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yloxy)-ethylamino]-acetic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture of [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 (1 equivalent) and lithium hydroxide monohydrate (3-6 equivalents) in 50% aq THF is stirred at selected temperatures between rt and 60° C. until the reaction is substantially complete as monitored by LCMS or TLC. The reaction mixture is neutralized with aq hydrochloric acid and 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 organic layers are 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 [2-(2-{4-[3-(5-tert-butyl-isoxazol-3-yl)-ureido]-phenyl}-benzo[d]imidazo[2,1-b]thiazol-7-yloxy)-ethylamino]-acetic acid (I-3).

Workup

  1. custompartitioned 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. dry with materialThe combined organic layers are dried 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-97fdd80cfda54ef1bc9adfd683692c4f
Source dataset
uspto-grants-2013_10
Patent number
US08551963B2

Reaction notes

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