Triethylamine → HCID 136356802, compound

HRID 1255195Notes

Reaction equation

HRID 1255195 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[OH:14])[CH:5]=[N:4][CH:3]=1.O.NN.N1C=CN=CC=1[NH:24][NH2:25].C(N(CC)CC)C.C(O[CH:36]=[C:37]([C:43](=O)[C:44]([F:47])([F:46])[F:45])[C:38]([O:40][CH2:41][CH3:42])=[O:39])C>C(O)C.C(#N)C>[OH:14][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=1[C:6]1[N:7]=[C:2]([N:24]2[C:43]([C:44]([F:47])([F:46])[F:45])=[C:37]([C:38]([O:40][CH2:41][CH3:42])=[O:39])[CH:36]=[N:25]2)[CH:3]=[N:4][CH:5]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 24654Hydrazine hydrate (1:1)HCID 14878232-HydrazinopyrazineHCID 4685753Ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutanoateHCID 136284757HCID 136284757, compound

Product 1

HCID 136356802HCID 136356802, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of the title compound from Example 16 Step A (0.500 grams, 2.42 mmol) in ethanol (20 mL) was added hydrazine hydrate (3.25 mL, 35% v/v, 36.3 mmol). The reaction flask was equipped with a reflux condenser, and the reaction mixture was stirred at 80° C. After 12 h, the mixture was allowed to cool to room temperature, whereupon a yellow solid precipitated. The solid was triturated with hexanes, filtered, washed with water, and dried in vacuo: LCMS m/z 203.2 [M+H]+. To a solution of the crude pyrazinyl hydrazine in acetonitrile (10 mL) were added triethylamine (0.675 mL, 4.84 mmol) and ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutyrate (0.872 g, 3.63 mmol). After 40 min at ambient temperature, the reaction mixture was placed in a 60° C. bath and was stirred for 30 min, at which point the reaction mixture was allowed to cool to ambient temperature, then was concentrated in vacuo. Purification by flash chromatography on silica gel (0 to 60% EtOAc in hexanes, then 60 to 100% EtOAc in hexanes) provided the title compound: LCMS m/z 379.1 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 10.98 (s, 1H), 9.35 (s, 1H), 8.85 (s, 1H), 8.23 (s, 1H), 7.93 (dd, J=8.0, 1.5 Hz, 1H), 7.43 (t, J=8.0 Hz, 1H), 7.07 (d, J=8.5 Hz, 1H), 7.04 (t, J=8.0 Hz, 1H).

Workup

  1. customThe reaction flask was equipped with a reflux condenser
  2. temperatureto cool to room temperature, whereupon a yellow solid
  3. customprecipitated
  4. customThe solid was triturated with hexanes
  5. filtrationfiltered
  6. washwashed with water
  7. customdried in vacuo
  8. waitAfter 40 min at ambient temperature
  9. customwas placed in a 60° C.
  10. stirringwas stirred for 30 min, at which
  11. temperatureto cool to ambient temperature
  12. concentrationwas concentrated in vacuo
  13. customPurification by flash chromatography on silica gel (0 to 60% EtOAc in hexanes

Sources & evidence

ORD record
ord-ba8f193f0059420bbbb5d568866b5d47
Source dataset
uspto-grants-2013_06
Patent number
US08455638B2

Reaction notes

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