tert-Butyl piperazine-1-carboxylate → Tert-butyl 4-(3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)piperazine-1-carboxylate

HRID 1674766

Reaction equation

HRID 1674766 reaction equation
[N:1]1([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Br[C:15]1[CH:16]=[CH:17][C:18]2[N:19]([C:21]([C:24]([F:27])([F:26])[F:25])=[N:22][N:23]=2)[CH:20]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[F:27][C:24]([F:25])([F:26])[C:21]1[N:19]2[CH:20]=[C:15]([N:4]3[CH2:5][CH2:6][N:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:2][CH2:3]3)[CH:16]=[CH:17][C:18]2=[N:23][N:22]=1

Participants

6

Reactant 4

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 581189066-Bromo-3-(trifluoromethyl)-(1,2,4)triazolo(4,3-a)pyridine

Product 1

HCID 67341427Tert-butyl 4-(3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)piperazine-1-carboxylateYield 66.2%

Reagents, catalysts & solvents 1

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

A solution of tert-butyl piperazine-1-carboxylate (1.30 g, 6.99 mmol)], 6-bromo-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine (0.93 g, 3.50 mmol), bis(dibenzylideneacetone)palladium (0.101 g, 0.17 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (0.163 g, 0.26 mmol) and sodium tert-butoxide (0.84 g, 8.74 mmol) in xylenes (30 mL) was sealed into a microwave tube and degassed for 10 minutes. The reaction mixture was heated at 100° C. for 30 minutes and then cooled to ambient temperature. The reaction mixture was diluted with water (20 mL) and then extracted with ethyl acetate (2×40 mL). The organic phases were combined, dried over Na2SO4, filtered, and evaporated to give an involatile residue. The residue was purified by flash chromatography on silica-gel using an increasing gradient of ethyl acetate in isohexane as eluant to give tert-butyl 4-(3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yl)piperazine-1-carboxylate (0.86 g, 66.2%) as a yellow solid.

Workup

  1. customdegassed for 10 minutes
  2. temperaturecooled to ambient temperature
  3. additionThe reaction mixture was diluted with water (20 mL)
  4. extractionextracted with ethyl acetate (2×40 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customto give an involatile residue
  9. customThe residue was purified by flash chromatography on silica-gel

Sources & evidence

ORD record
ord-9b99dc86ca844e108e401908c69c3ad5
Source dataset
uspto-grants-2011_08
Patent number
US08003649B2

Linked notes

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