3-(4-{3-[2-(4-Chloro-phenyl)-2H-indazol-3-yl]-3-cyclohexyl-ureido}-3-fluoro-phenyl)-propionic acid tert-butyl ester → 3-(4-{3-[2-(4-Chloro-phenyl)-2H-indazol-3-yl]-3-cyclohexyl-ureido}-3-fluoro-phenyl)-propionic acid

HRID 1690566Notes

Reaction equation

HRID 1690566 reaction equation
C([O:5][C:6](=[O:42])[CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16]([N:18]([C:25]2[N:26]([C:34]3[CH:39]=[CH:38][C:37]([Cl:40])=[CH:36][CH:35]=3)[N:27]=[C:28]3[C:33]=2[CH:32]=[CH:31][CH:30]=[CH:29]3)[CH:19]2[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)=[O:17])=[C:11]([F:41])[CH:10]=1)(C)(C)C>Cl.O1CCOCC1>[Cl:40][C:37]1[CH:38]=[CH:39][C:34]([N:26]2[C:25]([N:18]([CH:19]3[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]3)[C:16](=[O:17])[NH:15][C:12]3[CH:13]=[CH:14][C:9]([CH2:8][CH2:7][C:6]([OH:42])=[O:5])=[CH:10][C:11]=3[F:41])=[C:33]3[C:28]([CH:29]=[CH:30][CH:31]=[CH:32]3)=[N:27]2)=[CH:35][CH:36]=1

Participants

4

Reactant 1

HCID 669053413-(4-{3-[2-(4-Chloro-phenyl)-2H-indazol-3-yl]-3-cyclohexyl-ureido}-3-fluoro-phenyl)-propionic acid tert-butyl ester

Product 1

HCID 451111783-(4-{3-[2-(4-Chloro-phenyl)-2H-indazol-3-yl]-3-cyclohexyl-ureido}-3-fluoro-phenyl)-propionic acidYield 12%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

3-(4-{3-[2-(4-Chloro-phenyl)-2H-indazol-3-yl]-3-cyclohexyl-ureido}-3-fluoro-phenyl)-propionic acid tert-butyl ester (20 mg, 34 μmol) was dissolved in a 4 M solution of HCl in dioxane (190 μl) under an argon atmosphere. The solution was stirred for 14 h at ambient temperature, poured onto ice water/1 N aqueous NaOH solution 1/1 and extracted two times with TBME. The aqueous layer was acidified with 1 N HCl and extracted two times with iPrOAc. The extracts were washed with ice water/brine 1/1 and dried over Na2SO4. The solvent was removed under reduced pressure and the residue was purified by preparative thin layer chromatography (silica gel, CH2Cl2/MeOH) to give the title compound (2 mg, 3.7 μmol; 12%) as yellow foam. MS: m/e=535.3 [M+H+].

Workup

  1. additionpoured onto ice water/1 N aqueous NaOH solution 1/1
  2. extractionextracted two times with TBME
  3. extractionextracted two times with iPrOAc
  4. washThe extracts were washed with ice water/brine 1/1
  5. dry with materialdried over Na2SO4
  6. customThe solvent was removed under reduced pressure
  7. customthe residue was purified by preparative thin layer chromatography (silica gel, CH2Cl2/MeOH)

Sources & evidence

ORD record
ord-333540bf0b754125b9b1476c5dd743d6
Source dataset
uspto-grants-2012_04
Patent number
US08153663B2

Reaction notes

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