tert-Butanol → HCID 118094192, compound

HRID 522796Notes

Reaction equation

HRID 522796 reaction equation
[Cl:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([C:6]([S:22][C:23]3[C:24]([F:32])=[C:25]([CH:29]=[CH:30][CH:31]=3)C(O)=O)=[C:7]([CH:19]3[CH2:21][CH2:20]3)[N:8]2[C:12]2[CH:13]=[N:14][N:15]([CH2:17][CH3:18])[CH:16]=2)=[CH:4][CH:3]=1.S(Cl)(Cl)=[O:34].C[Si](C=[N+]=[N-])(C)C.[C:44]([OH:48])([CH3:47])(C)C>C1(C)C=CC=CC=1>[Cl:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([C:6]([S:22][C:23]3[C:24]([F:32])=[C:25]([CH2:47][C:44]([OH:48])=[O:34])[CH:29]=[CH:30][CH:31]=3)=[C:7]([CH:19]3[CH2:21][CH2:20]3)[N:8]2[C:12]2[CH:13]=[N:14][N:15]([CH2:17][CH3:18])[CH:16]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 6386tert-ButanolHCID 24386Thionyl ChlorideHCID 167693TrimethylsilyldiazomethaneHCID 118094189PAT-505

Product 1

HCID 118094192HCID 118094192, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
85 °C

Procedure

To a stirred solution of 3-((6-chloro-2-cyclopropyl-1-(1-ethyl-1H-pyrazol-4-yl)-7-fluoro-1H-indol-3-yl)thio)-2-fluorobenzoic acid compound 1-34 (Example 9; 30 mg, 0.058 mmol) in toluene (2.0 mL) under inert atmosphere was added thionyl chloride (0.22 mL, 3.0 mmol) and the mixture was heated at 85° C. for 2 h. The volatiles were removed under reduced pressure and the residue was resuspended in toluene (2.0 mL) and (trimethylsilyl)diazomethane solution (2.0 M in hexanes, 0.88 mL, 0.88 mmol). After evolution of gas, t-butylalcohol (2.0 mL) was added and the mixture was heated for 0.5 hr at 50° C. The residue was purified by silica gel chromatography (0-20% Hx/EtOAC). After evaporation of the fractions, the residue was dissolved in 4.0 M HCl in 1,4-dioxane (0.5 mL) and the solution was stirred at RT for 2 hr. The solvent was removed and the residue was purified by HPLC to give the target compound as a clear film. MS (ESI): m/z 488.0 (M+H+).

Workup

  1. customThe volatiles were removed under reduced pressure
  2. temperaturethe mixture was heated for 0.5 hr at 50° C
  3. customThe residue was purified by silica gel chromatography (0-20% Hx/EtOAC)
  4. customAfter evaporation of the fractions
  5. dissolutionthe residue was dissolved in 4.0 M HCl in 1,4-dioxane (0.5 mL)
  6. customThe solvent was removed
  7. customthe residue was purified by HPLC
  8. customto give the target compound as a clear film

Sources & evidence

ORD record
ord-483f4be2d9ac4b628cc117ae45b29f24
Source dataset
uspto-grants-2016_05
Patent number
US09334261B2

Reaction notes

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