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Sulfamic Acid → 2-Methyl-2-[3-(3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-ureido)-isoxazol-5-yl]-propionic acid

HRID 1038334
Notes
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Reaction equation

HRID 1038334 reaction equation
[CH3:1][C:2]([C:6]1[O:10][N:9]=[C:8]([NH:11][C:12]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[N:22]=[C:23]4[N:27]([CH:28]=3)[C:26]3[CH:29]=[CH:30][C:31]([O:33][CH2:34][CH2:35][N:36]5[CH2:41][CH2:40][O:39][CH2:38][CH2:37]5)=[CH:32][C:25]=3[S:24]4)=[CH:17][CH:16]=2)=[O:13])[CH:7]=1)([CH3:5])[CH:3]=[O:4].S(N)(=O)(=O)[OH:43].Cl([O-])=O.[Na+].[OH-].[Na+]>C(O)(=O)C.O>[CH3:5][C:2]([C:6]1[O:10][N:9]=[C:8]([NH:11][C:12]([NH:14][C:15]2[CH:16]=[CH:17][C:18]([C:21]3[N:22]=[C:23]4[N:27]([CH:28]=3)[C:26]3[CH:29]=[CH:30][C:31]([O:33][CH2:34][CH2:35][N:36]5[CH2:37][CH2:38][O:39][CH2:40][CH2:41]5)=[CH:32][C:25]=3[S:24]4)=[CH:19][CH:20]=2)=[O:13])[CH:7]=1)([CH3:1])[C:3]([OH:43])=[O:4]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 5987Sulfamic AcidHCID 14798Sodium HydroxideHCID 23668197Sodium ChloriteHCID 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

Product 1

HCID 462144722-Methyl-2-[3-(3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-ureido)-isoxazol-5-yl]-propionic acid

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×

Procedure

Alternatively final compound 2-methyl-2-[3-(3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-ureido)-isoxazol-5-yl]-propionic acid (I-5) is prepared by following a general procedure given in US 2005/0070549 A1. To a stirred solution of 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) (1 equivalent) in a mixture of acetic acid and water at rt is added a solution of amidosulfuric acid (1.5 equivalents) and sodium chlorite (1.5 equivalents) in water, and the mixture is stirred at rt until the reaction is substantially complete as monitored by LCMS or TLC. The mixture is neutralized with 30% aq sodium hydroxide and 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 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-methyl-2-[3-(3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-ureido)-isoxazol-5-yl]-propionic acid (I-5).

Workup

  1. customAlternatively final compound 2-methyl-2-[3-(3-{4-[7-(2-morpholin-4-yl-ethoxy)-benzo[d]imidazo[2,1-b]thiazol-2-yl]-phenyl}-ureido)-isoxazol-5-yl]-propionic acid (I-5) is prepared
  2. custompartitioned between water
  3. additioneither dichloromethane or a mixture of isopropanol and dichloromethane
  4. extractionThe separated aqueous layer is further extracted with dichloromethane
  5. additiona mixture of isopropanol and dichloromethane
  6. washthe combined organic layers 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 preparative reverse-phase HPLC or silica gel flash chromatography

Sources & evidence

ORD record
ord-8337ec81c84a49e69951aca43f11ee7c
Source dataset
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08551963B2

Reaction notes

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