Acetonitrile → HCID 86732656, compound

HRID 1056661Notes

Reaction equation

HRID 1056661 reaction equation
[CH2:1]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH:11]1[C:20]2[CH:19]=[C:18]3[O:21][CH2:22][O:23][C:17]3=[CH:16][C:15]=2[NH:14][C:13](=O)[CH2:12]1)[CH2:2][CH3:3].C(OC1C=CC=CC=1C=CC(O)=O)CC.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=S.[CH:54]([NH:56]N)=O.C(#[N:60])C>C(O)(=O)C.C(N(CC)CC)C>[CH2:1]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[CH:11]1[C:20]2[C:15](=[CH:16][C:17]3[O:23][CH2:22][O:21][C:18]=3[CH:19]=2)[N:14]2[N:60]=[CH:54][N:56]=[C:13]2[CH2:12]1)[CH2:2][CH3:3]

Participants

8

Reactant 5

HCID 6342AcetonitrileHCID 12229HydrazinecarboxaldehydeHCID 14817Phosphorus sulfide (P2S5)HCID 3245942HCID 3245942, compoundHCID 47153793-(2-Propoxyphenyl)-2-propenoic acid

Product 1

HCID 86732656HCID 86732656, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
100 °C

Procedure

8-(2-propoxyphenyl)-7,8-dihydro-[1,3]dioxolo[4,5-g]quinolin-6(5H)-one (175 mg, 1.0 equiv—prepared essentially as described in Example 1 using 2-propoxycinnamic acid as the starting material) was dissolved in 0.8 mL dry acetonitrile and 0.54 mL triethylamine under an atmosphere of nitrogen. Phosphorus pentasulfide (179 mg, 1.5 equiv) was added in one portion and the reaction was heated to 100° C. for six hours. The solvent was removed in vacuo and the residue was partitioned between 20 mL DCM and 10 mL brine. The layers were separated and the organic portion was washed with two additional portions of brine, dried over sodium sulfate, and reduced in vacuo. The resultant crude orange foam was dissolved in 1.0 mL n-butanol in a vial under an atmosphere of nitrogen. Acetic acid (6 uL) and formohydrazide (31 mg, 1.0 equiv) were added and the vial was tightly capped and heated to 130° C. for 24 hours. The solvent was removed in vacuo and the residue was suspended in DCM and washed with three portions of brine. The organic layer was dried over sodium sulfate and condensed to give a crude oil that was purified by flash column chromatography (2% to 5% methanol in chloroform). Fractions containing product were pooled to give 125 mg of a brown oil that was recrystallized from chloroform/hexanes to give triazole compound IX as a yellow solid (31 mg, 17%) that was >99% pure by UPLC-MS (ELSD). 1H NMR (400 MHz, CDCl3) δ=8.54 (s, 1 H), 7.19 (dt, J=2.0, 8.2 Hz, 1 H), 6.99-6.92 (m, 1 H), 6.88 (d, J=8.2 Hz, 1 H), 6.76 (t, J=7.4 Hz, 1 H), 6.65 (dd, J=1.6, 7.8 Hz, 1 H), 6.59-6.54 (m, 1 H), 6.03-5.96 (m, 2 H), 4.67 (dd, J=6.4, 7.4 Hz, 1 H), 4.03-3.88 (m, 2 H), 3.55 (dd, J=7.4, 16.2 Hz, 1 H), 3.33 (dd, J=6.4, 16.2 Hz, 1 H), 1.78 (qd, J=7.1, 13.9 Hz, 2 H), 0.98 (t, J=7.4 Hz, 3 H). ESI-MS (M+H+) m/z=350.

Workup

  1. customThe solvent was removed in vacuo
  2. customthe residue was partitioned between 20 mL DCM and 10 mL brine
  3. customThe layers were separated
  4. washthe organic portion was washed with two additional portions of brine
  5. dry with materialdried over sodium sulfate
  6. dissolutionThe resultant crude orange foam was dissolved in 1.0 mL n-butanol in a vial under an atmosphere of nitrogen
  7. customthe vial was tightly capped
  8. temperatureheated to 130° C. for 24 hours
  9. customThe solvent was removed in vacuo
  10. washwashed with three portions of brine
  11. dry with materialThe organic layer was dried over sodium sulfate and condensed
  12. customto give a crude oil that
  13. customwas purified by flash column chromatography (2% to 5% methanol in chloroform)
  14. additionFractions containing product

Sources & evidence

ORD record
ord-4e57441364374e6b934d98505742f33f
Source dataset
uspto-grants-2016_07
Patent number
US09399644B2

Reaction notes

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