1,1,1-Trifluoro-2,4-pentanedione → 2-[3-(4-Chlorophenoxy)propyl]-5-methyl-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidine

HRID 1752811Notes

Reaction equation

HRID 1752811 reaction equation
[F:1][C:2]([F:10])([F:9])[C:3](=O)[CH2:4][C:5](=O)[CH3:6].[Cl:11][C:12]1[CH:27]=[CH:26][C:15]([O:16][CH2:17][CH2:18][CH2:19][C:20]2[N:24]=[C:23]([NH2:25])[NH:22][N:21]=2)=[CH:14][CH:13]=1>C(O)(=O)C>[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([O:16][CH2:17][CH2:18][CH2:19][C:20]2[N:24]=[C:23]3[N:25]=[C:5]([CH3:6])[CH:4]=[C:3]([C:2]([F:10])([F:9])[F:1])[N:22]3[N:21]=2)=[CH:26][CH:27]=1

Participants

4

Reactant 2

HCID 739431,1,1-Trifluoro-2,4-pentanedioneHCID 178508402HCID 178508402, compound

Product 1

HCID 766849232-[3-(4-Chlorophenoxy)propyl]-5-methyl-7-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidineYield 41.8%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
135 °C

Procedure

A mixture of 1,1,1-trifluoro-2,4-pentanedione (91 mg, 0.594 mmol), 3-[3-(4-chlorophenoxy)propyl]-1H-1,2,4-triazol-5-amine (150 mg, 0.594 mmol), and glacial acetic acid (2.0 mL) was added to a 50 mL RBF with a magnetic stirring bar. The flask was fitted with a condenser, and warmed in an oil bath to a gentle reflux at 135° C. Progress of the reaction was monitored by analytical HPLC with UV detection at 215 nm. The starting material elutes with retention time of 5.1 min, and the product elutes with retention time of 6.89 min. After 15 h, the solution was allowed to cool to room temperature and added to stirring ice/water (17 mL). Solid material was isolated by filtration, rinsed with 15 mL of water, and then dried under reduced pressure. The solid was dissolved in ethanol (3 mL) and water (1 mL) with gentle warming and allowed to cool. The needles that formed were isolated by filtration, washed with 3 mL of cold ethanol, and allowed to dry to afford the title compound (92 mg, 41% yield). 1H NMR (DMSO-d6, 400 MHz) δ ppm: 7.83 (s, 1H), 7.31 (d, 2H), 6.95 (d, 2H), 4.09 (t, 2H), 3.03 (t, 2H), 2.70 (s, 3H), 2.21 (m, 2H).

Workup

  1. additionwas added to a 50 mL RBF with a magnetic stirring bar
  2. customThe flask was fitted with a condenser
  3. temperaturewarmed in an oil bath to
  4. temperatureto cool to room temperature
  5. additionadded
  6. customSolid material was isolated by filtration
  7. washrinsed with 15 mL of water
  8. customdried under reduced pressure
  9. dissolutionThe solid was dissolved in ethanol (3 mL)
  10. temperaturewater (1 mL) with gentle warming
  11. temperatureto cool
  12. customThe needles that formed
  13. customwere isolated by filtration
  14. washwashed with 3 mL of cold ethanol
  15. customto dry

Sources & evidence

ORD record
ord-31ab08d234304e859124f77adc84b7cb
Source dataset
uspto-grants-2015_10
Patent number
US09163027B2

Reaction notes

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