Phosphorus oxychloride → HCID 67453355, compound

HRID 2276763Notes

Reaction equation

HRID 2276763 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[NH:13][CH2:12][C:11](=O)[NH:10][N:9]=2)[CH:5]=[CH:6][CH:7]=1.O=P(Cl)(Cl)Cl.[F:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]([CH3:31])([CH3:30])[CH2:28][NH2:29])=[CH:23][CH:22]=1>O1CCOCC1.CCOC(C)=O.O=[Mn]=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[N:10][C:11]([NH:29][CH2:28][C:27]([C:24]3[CH:23]=[CH:22][C:21]([F:20])=[CH:26][CH:25]=3)([CH3:31])[CH3:30])=[CH:12][N:13]=2)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 212510232-(4-Fluorophenyl)-2-methylpropan-1-amineHCID 178516752HCID 178516752, compound

Product 1

HCID 67453355HCID 67453355, compoundYield 10%

Reagents, catalysts & solvents 3

HCID 14801Manganese dioxideCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 3-(3-chlorophenyl)-4,5-dihydro-1,2,4-triazin-6(1H)-one (6.0 g, 29 mmol) dissolved in dioxane (75 mL) was added MnO2 (10 g, 120 mmol). The mixture was stirred at 90° C. for 18 h. After filtering through diatomaceous earth and rinsing with hot dioxane, the combined organics were evaporated to dryness in vacuo. The crude residue (⅓ was used) was dissolved in POCl3 (10 mL, 108 mmol) and heated to 70° C. for 2.5 h. The mixture was allowed to cool to rt and evaporated to dryness in vacuo. The residue was dissolved in EtOAc/ether (1:1) and washed with 1 M NaOH. The organic phase was evaporated to dryness and dissolved in NMP (5.0 mL) in a microwave vial. Potassium carbonate (1.0 g) was added followed by (2-(4-fluorophenyl)-2-methylpropan-1-amine (2.0 g, 12 mmol), and the mixture was heated in a microwave reactor to 165° C. for 20 min. The solution was diluted with EtOAc and washed with saturated NaCl (4×), dried over Na2SO4, and evaporated to dryness. Purification using silica gel chromatography (0-35% EtOAc/hexanes) gave the desired product (430 mg) as an orange film.

Workup

  1. filtrationAfter filtering through diatomaceous earth
  2. washrinsing with hot dioxane
  3. customthe combined organics were evaporated to dryness in vacuo
  4. temperatureheated to 70° C. for 2.5 h
  5. temperatureto cool to rt
  6. customevaporated to dryness in vacuo
  7. dissolutionThe residue was dissolved in EtOAc/ether (1:1)
  8. washwashed with 1 M NaOH
  9. customThe organic phase was evaporated to dryness
  10. dissolutiondissolved in NMP (5.0 mL) in a microwave vial
  11. additionPotassium carbonate (1.0 g) was added
  12. temperaturethe mixture was heated in a microwave reactor to 165° C. for 20 min
  13. washwashed with saturated NaCl (4×)
  14. dry with materialdried over Na2SO4
  15. customevaporated to dryness
  16. customPurification

Sources & evidence

ORD record
ord-dc91f903a2004123bd988e4f53f3ecf3
Source dataset
uspto-grants-2015_09
Patent number
US09133123B2

Reaction notes

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