Citric Acid → HCID 58920342, compound

HRID 1365509Notes

Reaction equation

HRID 1365509 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:27][S@](C(C)(C)C)=O)([C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])[CH:19]=[C:18]([F:26])[CH:17]=2)[CH2:9][C:10]2[S:11][CH:12]=[C:13]([CH3:15])[N:14]=2)=[N:6][CH:7]=1.Cl.[CH:35]1([N:40]=[C:41]=[O:42])[CH2:39][CH2:38][CH2:37][CH2:36]1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C@@:8]([NH:27][C:41]([NH:40][CH:35]2[CH2:39][CH2:38][CH2:37][CH2:36]2)=[O:42])([C:16]2[CH:21]=[C:20]([C:22]([F:24])([F:23])[F:25])[CH:19]=[C:18]([F:26])[CH:17]=2)[CH2:9][C:10]2[S:11][CH:12]=[C:13]([CH3:15])[N:14]=2)=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 313Hydrochloric AcidHCID 643500Cyclopentyl IsocyanateHCID 58920827HCID 58920827, compound

Product 1

HCID 58920342HCID 58920342, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

(S)-N-((S)-1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-(4-methylthiazol-2-yl)ethyl)-2-methylpropane-2-sulfinamide (29 mg, 0.058 mmol) in MeOH (1.0 mL) was added HCl (0.5 mL, 2 mmol, 4N solution in dioxane) and the reaction was stirred at room temperature for 0.5 h. The mixture was concentrated, diluted with EtOAc (20 mL), washed with sat. NaHCO3 (20 mL), dried over Na2SO4, filtered and concentrated. The residue was dissolved in DCM (1 mL) and cyclopentyl isocyanate (9 mg, 0.083 mmol) was added followed by two crystals of citric acid. The reaction was stirred overnight, concentrated and purified by Prep TLC (Uniplate, Silica Gel GF, 20×20 cm, 1000 Microns) using Hexane/EtOAc (1/1) to yield (S)-1-(1-(5-chloropyridin-2-yl)-1-(3-fluoro-5-(trifluoromethyl)phenyl)-2-(4-methylthiazol-2-yl)ethyl)-3 -cyclopentylurea as a clear oil (10 mg, 70% yield) LCMS: 1.91 min [M+1] 527.2 (2 min gradient, MeOH/H2O 0.1% TFA); HPLC: 3.91 min (4 min gradient, MeOH/H2O 0.2% PPA); Purity 100%; NMR: 400 MHz 1H (CDCl3) 8.29 ppm, 1 H, d, J=2.64 Hz; 7.54 ppm, 1 H, dd, J=8.57, 2.42 Hz; 7.40 ppm, 1 H, s; 7.32 ppm, 1 H, s; 7.26 ppm, 1 H, d, J=9.67 Hz; 7.12 ppm, 2 H, d, J=8.35 Hz; 6.60 ppm, 1 H, s; 4.58 ppm, 1 H, d, J=13.62 Hz; 4.43 ppm, 1 H, d, J=7.03 Hz; 4.08 ppm, 1 H, d, J=13.62 Hz; 3.92 ppm, 1 H, m; 2.20 ppm, 3 H, s; 1.93 ppm, 2 H, m; 1.61 ppm, 2 H, m; 1.53 ppm, 2 H, m; 1.40 ppm, 1 H, m; 1.32 ppm, 1 H, dd, J=13.18, 7.03 Hz.

Workup

  1. concentrationThe mixture was concentrated
  2. additiondiluted with EtOAc (20 mL)
  3. washwashed with sat. NaHCO3 (20 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in DCM (1 mL)
  8. stirringThe reaction was stirred overnight
  9. concentrationconcentrated
  10. custompurified by Prep TLC (Uniplate, Silica Gel GF, 20×20 cm, 1000 Microns)

Sources & evidence

ORD record
ord-6222bae668b741d89708d69d4e1ecb4a
Source dataset
uspto-grants-2011_02
Patent number
US07888376B2

Reaction notes

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