Triethylamine → HCID 25115011, compound

HRID 2194623Notes

Reaction equation

HRID 2194623 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:18]2[C:13](=[C:14]([C:19]3[C:24]([F:25])=[CH:23][CH:22]=[CH:21][C:20]=3[F:26])[N:15]=[CH:16][CH:17]=2)[N:12]=[C:11](C(O)=O)[CH:10]=1.C1(P([N:44]=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1.C(N(CC)CC)C>C(O)(C)(C)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:18]2[C:13](=[C:14]([C:19]3[C:20]([F:26])=[CH:21][CH:22]=[CH:23][C:24]=3[F:25])[N:15]=[CH:16][CH:17]=2)[N:12]=[C:11]([NH2:44])[CH:10]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 25114770HCID 25114770, compound

Product 1

HCID 25115011HCID 25115011, compoundYield 114.8%

Reagents, catalysts & solvents 1

HCID 6386tert-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

To a suspension of the title compound from Example 1 (100 mg, 0.25 mmol) in tert-butanol (2.4 mL) were added diphenylphosphoryl azide (DPPA) (0.07 mL, 0.32 mmol) and triethylamine (0.045 mL, 0.32 mmol). The mixture was heated at 100° C. for 75 minutes. The solvent was evaporated and the mixture redissolved in HCl (4M in dioxane, 2 mL) and stirred at room temperature for 2.5 hours. Subsequently, 4% aqueous sodium bicarbonate (40 mL) was added to the mixture and the reaction was extracted with ethyl acetate (3×25 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulphate and the solvent was removed under reduced pressure to give 106 mg of a yellowish oil. The mixture was purified by column chromatography (C-18 silica from Waters©, reverse phase water/(acetonitrile/methanol 50:50) as eluent [0.1% v/v ammonium formate buffered] 0% to 100%). The organic solvent from the appropriate fractions was evaporated and the aqueous phase basified to pH 10 with ammonium hydroxide. This was extracted with ethyl acetate, dried over sodium sulphate and the solvent removed under reduced pressure to give the title compound as a white solid (55 mg, 60%).

Workup

  1. customThe solvent was evaporated
  2. dissolutionthe mixture redissolved in HCl (4M in dioxane, 2 mL)
  3. additionSubsequently, 4% aqueous sodium bicarbonate (40 mL) was added to the mixture
  4. extractionthe reaction was extracted with ethyl acetate (3×25 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over anhydrous sodium sulphate
  7. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-72839b29db664eb38dc6dc8ce7081188
Source dataset
uspto-grants-2012_12
Patent number
US08334294B2

Reaction notes

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