Potassium Hydroxide → 1,1-Dimethylethyl 4-[6-[(ethylamino)carbonyl]-2-fluoro-3-pyridinyl]-1-piperazinecarboxylate

HRID 2182153Notes

Reaction equation

HRID 2182153 reaction equation
[CH3:1][C:2]1[S:3][CH:4]=[C:5]([CH2:7]O)[N:6]=1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:27]=[N:26][CH:25]=[C:24](Cl)[N:23]=2)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].[OH-].[K+].C1OCCOCCOCCOCCOCC[O:33]C1>C1(C)C=CC=CC=1>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:27]=[N:26][CH:25]=[C:24]([O:33][CH2:1][C:2]3[S:3][CH:4]=[C:5]([CH3:7])[N:6]=3)[N:23]=2)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10]

Participants

6

Reactant 4

HCID 14797Potassium HydroxideHCID 2855718-Crown-6HCID 10582809(2-Methyl-1,3-thiazol-4-yl)methanolHCID 18186946Tert-butyl 4-(6-chloropyrazin-2-YL)piperazine-1-carboxylate

Product 1

HCID 697329301,1-Dimethylethyl 4-[6-[(ethylamino)carbonyl]-2-fluoro-3-pyridinyl]-1-piperazinecarboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

(2-Methyl-thiazol-4-yl)-methanol I-3t (155 mg, 1.2 mmol) was dissolved in dry toluene (5 mL) under dry nitrogen and 6′-chloro-2,3,5,6-tetrahydro-[1,2′]-bipyrazinyl-4-carboxylic acid tert-butyl ester (I-1a) (299 mg, 1.00 mmol), powdered KOH (191 mg, 3.4 mmol), and 18-crown-6 (13.2 mg, 50 μmol) were added with stirring. The mixture was heated at reflux with vigorous stirring. The mixture was stirred at reflux for 3 h then cooled to room temperature. The toluene was removed in vacuo. The residue was purified by preparative thin layer chromatography (10% methanol/90% CH2Cl2) to give the title compound I-3u as a viscous amber oil (375 mg, 96% yield).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux with vigorous stirring
  3. stirringThe mixture was stirred
  4. temperatureat reflux for 3 h
  5. customThe toluene was removed in vacuo
  6. customThe residue was purified by preparative thin layer chromatography (10% methanol/90% CH2Cl2)

Sources & evidence

ORD record
ord-6dd884266060440686270685e91e3d01
Source dataset
uspto-grants-2005_05
Patent number
US06894050B2

Reaction notes

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