Hydrochloric Acid → 3-(4-((5-(2-(3,4-Dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzamido)propanoic acid

HRID 1627261Notes

Reaction equation

HRID 1627261 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]([C:12]2[N:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[C:19]([O:24][CH3:25])[CH:18]=3)[C:15]([S:26][CH2:27][C:28]3[C:42]([F:43])=[CH:41][C:31]([C:32]([NH:34][CH2:35][CH2:36][C:37]([O:39]C)=[O:38])=[O:33])=[CH:30][C:29]=3[F:44])=[N:14][CH:13]=2)([CH3:11])[CH3:10])[CH:5]=[CH:6][C:7]=1[Cl:8].[OH-].[Na+].Cl>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]([C:12]2[N:16]([C:17]3[CH:22]=[CH:21][C:20]([F:23])=[C:19]([O:24][CH3:25])[CH:18]=3)[C:15]([S:26][CH2:27][C:28]3[C:42]([F:43])=[CH:41][C:31]([C:32]([NH:34][CH2:35][CH2:36][C:37]([OH:39])=[O:38])=[O:33])=[CH:30][C:29]=3[F:44])=[N:14][CH:13]=2)([CH3:10])[CH3:11])[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66741184methyl 3-(4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzamido)propanoate

Product 1

HCID 667399793-(4-((5-(2-(3,4-Dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzamido)propanoic acidYield 40%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of methyl 3-(4-((5-(2-(3,4-dichlorophenyl)propan-2-yl)-1-(4-fluoro-3-methoxyphenyl)-1H-imidazol-2-ylthio)methyl)-3,5-difluorobenzamido)propanoate (0.85 mmol from previous step) in MeOH (10 mL) was treated with a solution of NaOH (0.6 mL of a 5M aqueous solution, 3 mmol) at ambient temperature. After stirring for 100 min, the reaction mixture was added dropwise to 1N HCl. The addition afforded a thick, white oil that separated from the aqueous acid. The aqueous mixture was extracted with EtOAc. The combined extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure to afford crude product. This material was purified by flash chromatography (silica gel, MeOH/DCM, 0:100 to 10:90) to afford the title compound (220 mg, 40% yield over three steps) as a white powder. 1H NMR (400 MHz, CDCl3) δ 7.29 (dt, J=9.4, 6.0 Hz, 5H), 7.07 (d, J=2.2 Hz, 1H), 6.95 (dd, J=10.5, 8.6 Hz, 1H), 6.82 (dd, J=8.4, 2.2 Hz, 1H), 6.34-6.25 (m, 1H), 5.94 (dd, J=7.4, 2.4 Hz, 1H), 3.96 (s, 2H), 3.76-3.67 (m, 2H), 3.53 (s, 3H), 2.65 (s, 2H), 1.54 (s, 3H), 1.48 (s, 3H); MS (EI) m/z 652 (MH+).

Workup

  1. additionThe addition
  2. customafforded a thick, white oil
  3. customthat separated from the aqueous acid
  4. extractionThe aqueous mixture was extracted with EtOAc
  5. washThe combined extracts were washed with brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated under reduced pressure
  8. customto afford crude product
  9. customThis material was purified by flash chromatography (silica gel, MeOH/DCM, 0:100 to 10:90)

Sources & evidence

ORD record
ord-ae60364e31b949948ebc8369513da710
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

Loading…