1,4-Dioxane → HCID 86662053, compound

HRID 869250Notes

Reaction equation

HRID 869250 reaction equation
Cl[C:2]1[C:3]([C:13]([NH2:15])=[O:14])=[N:4][C:5]([C:9](O)([CH3:11])[CH3:10])=[C:6]([Cl:8])[N:7]=1.[CH3:16][N:17]1[CH2:22][CH2:21][N:20]([CH:23]2[CH2:28][CH2:27][N:26]([C:29]3[CH:35]=[CH:34][C:32]([NH2:33])=[CH:31][C:30]=3[C:36]([F:39])([F:38])[F:37])[CH2:25][CH2:24]2)[CH2:19][CH2:18]1.C(N(CC)C(C)C)(C)C.O1CCOCC1>C(O)(=O)C.O>[Cl:8][C:6]1[N:7]=[C:2]([NH:33][C:32]2[CH:34]=[CH:35][C:29]([N:26]3[CH2:25][CH2:24][CH:23]([N:20]4[CH2:19][CH2:18][N:17]([CH3:16])[CH2:22][CH2:21]4)[CH2:28][CH2:27]3)=[C:30]([C:36]([F:39])([F:38])[F:37])[CH:31]=2)[C:3]([C:13]([NH2:15])=[O:14])=[N:4][C:5]=1[C:9]([CH3:11])=[CH2:10]

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 66642957HCID 66642957, compoundHCID 86662050HCID 86662050, compound

Product 1

HCID 86662053HCID 86662053, compoundYield 41.8%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3,5-dichloro-6-(1-hydroxy-1-methylethyl)pyrazine-2-carboxamide (1.10 g), 4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]-3-(trifluoromethyl)aniline (Preparation Example 436) (1.58 g), N,N-diisopropylethylamine (0.80 mL) and dioxane (31 mL) was stirred at 100° C. for 135 hours. After cooling, water was added, followed by extraction with ethyl acetate. Further, insoluble materials were separated by filtration, and the insoluble materials were dissolved in methanol and thereafter mixed with the organic layer. The solvent was distilled off under reduced pressure, followed by drying to give a brown solid. A mixture of the brown solid and acetic acid (30 mL) was stirred at 120° C. for 5 hours. After the solvent was distilled off, saturated aqueous sodium hydrogen carbonate was added, and the precipitated solid was collected by filtration and washed with water. The resulting solid was purified by basic silica gel column chromatography (eluent: chloroform) to give 5-chloro-6-isopropenyl-3-({4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]-3-(trifluoromethyl)phenyl}amino)pyrazine-2-carboxamide (0.99 g) as a yellow solid.

Workup

  1. temperatureAfter cooling
  2. extractionfollowed by extraction with ethyl acetate
  3. customFurther, insoluble materials were separated by filtration
  4. dissolutionthe insoluble materials were dissolved in methanol
  5. additionmixed with the organic layer
  6. distillationThe solvent was distilled off under reduced pressure
  7. customby drying
  8. customto give a brown solid
  9. stirringwas stirred at 120° C. for 5 hours
  10. distillationAfter the solvent was distilled off
  11. additionsaturated aqueous sodium hydrogen carbonate was added
  12. filtrationthe precipitated solid was collected by filtration
  13. washwashed with water
  14. customThe resulting solid was purified by basic silica gel column chromatography (eluent: chloroform)

Sources & evidence

ORD record
ord-1f9be13702a64f219c592bd04cf541a2
Source dataset
uspto-grants-2015_03
Patent number
US08969336B2

Reaction notes

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