Potassium bis(trimethylsilyl)amide → HCID 178518574, compound

HRID 1250177Notes

Reaction equation

HRID 1250177 reaction equation
C1(S([CH2:9][N:10]2[C:14]([NH:15][C:16](=[O:23])[CH:17](Cl)[CH:18]3[CH2:21][CH2:20][CH2:19]3)=[C:13]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[F:30])[N:12]=[N:11]2)=O)C=CC=CC=1.C[Si]([N-][Si](C)(C)C)(C)C.[K+]>O1CCCC1>[CH:18]1([C:17]2[C:16](=[O:23])[NH:15][C:14]3[N:10]([N:11]=[N:12][C:13]=3[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[F:30])[CH:9]=2)[CH2:21][CH2:20][CH2:19]1

Participants

4

Reactant 2

HCID 3251421Potassium bis(trimethylsilyl)amideHCID 18327314n-[3-Benzenesulfinylmethyl-5-(2-fluorophenyl)-3h-1,2,3-triazol-4-yl]-2-chloro-2-cyclobutylacetamide

Product 1

HCID 178518574HCID 178518574, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

To a cold (−78° C.), stirred solution of N-[3-benzenesulfinylmethyl-5-(2-fluorophenyl)-3H-1,2,3-triazol-4-yl]-2-chloro-2-cyclobutylacetamide (166 mg. 0.37 mmol) in dry tetrahydrofuran (20 ml) under nitrogen was added a solution of potassium bis(trimethylsilyl)amide (1.8 ml, 0.752 M in toluene, 1.3 mmol) and the reaction stirred for 2 hours. The reaction was allowed to warm to −20° C. and maintained at this temperature for 45 minutes before quenching by careful addition to water (100 ml). The aqueous mixture was stirred for 5 minutes and then acidified with citric acid solution (25 ml, 10% aqueous). The aqueous was extracted with ethyl acetate (2×70 ml) and the combined organic extracts were washed with water (50 l), brine (50 l), dried (Na2SO4) and evaporated in vacuo to approximately 2 ml total volume. The concentrated solution was allowed to stand at room temperature for 16 hours. The solid precipitate thus formed was collected by filtration and washed with diethyl ether to afford 6-cyclobutyl-3-(2-fluorophenyl)-4H-1,2,3-triazolo[1,5-α]pyrimidin-5-one (45 mg, 43%) as a pale solid which was used in subsequent reactions without further purification. δH (400 MHz, d6-DMSO) 1.78-1.89 (1H, m, CH(CH2)3), 1.93-2.0 4(1H, m, CH(CH2)3), 2.11-2.31 (4H, m, CH(CH2)3), 3.47 (1H, quintet, J=8.6 Hz, CH(CH2)3), 7.30-7.35 (2H, m, ArH, 7.44-7.50 (1H, m, ArH), 7.69 (1H, t, J=7.2 Hz, ArH), 8.82 (1H, s, CH═C.), 12.33 (1H, br s, NH); m/z (ES+) 285 (M+H+).

Workup

  1. temperaturemaintained at this temperature for 45 minutes
  2. custombefore quenching by careful addition to water (100 ml)
  3. stirringThe aqueous mixture was stirred for 5 minutes
  4. extractionThe aqueous was extracted with ethyl acetate (2×70 ml)
  5. washthe combined organic extracts were washed with water (50 l), brine (50 l)
  6. dry with materialdried (Na2SO4)
  7. customevaporated in vacuo to approximately 2 ml total volume
  8. waitto stand at room temperature for 16 hours
  9. customThe solid precipitate thus formed
  10. filtrationwas collected by filtration
  11. washwashed with diethyl ether

Sources & evidence

ORD record
ord-821aab2a122543cabd6a6202d47ab213
Source dataset
uspto-grants-2002_01
Patent number
US06337331B1

Reaction notes

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