PyBroP → Tert-butyl 3-(2-((2-cyano-6-(trifluoromethyl)quinolin-4-yl)amino)acetamido)azetidine-1-carboxylate

HRID 1896878Notes

Reaction equation

HRID 1896878 reaction equation
O[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([F:15])([F:14])[F:13])[CH:10]=2)[N:5]=[C:4]([C:16]#[N:17])[CH:3]=1.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.[NH2:42][CH2:43][C:44]([NH:46][CH:47]1[CH2:50][N:49]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:48]1)=[O:45]>O1CCOCC1>[C:16]([C:4]1[CH:3]=[C:2]([NH:42][CH2:43][C:44]([NH:46][CH:47]2[CH2:50][N:49]([C:51]([O:53][C:54]([CH3:57])([CH3:56])[CH3:55])=[O:52])[CH2:48]2)=[O:45])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]([F:15])([F:14])[F:13])[CH:10]=2)[N:5]=1)#[N:17]

Participants

5

Reactant 3

HCID 2733179PyBroPHCID 18699815Tert-butyl 3-(2-aminoacetamido)azetidine-1-carboxylateHCID 1785102352-Quinolinecarbonitrile, 4-hydroxy-6-(trifluoromethyl)-

Product 1

HCID 58562784Tert-butyl 3-(2-((2-cyano-6-(trifluoromethyl)quinolin-4-yl)amino)acetamido)azetidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 4-hydroxy-6-(trifluoromethyl)quinoline-2-carbonitrile (2 g, 8.4 mmol) from above step D, in dry dioxane was added TEA (2.9 mL, 21 mmol) and PyBroP (4.75 g, 10 mmol) and stirred at 50 C for 2 hour. To this solution tert-butyl 3-(2-aminoacetamido)azetidine-1-carboxylate (2.9 g, 12.45 mmol) from example 1, step E, was added and stirred at room temperature for 48 h. The solution was concentrated in vacuo. Water was added to the residue and extracted with EtOAc. The ethyl acetate was removed under vacuum and the residue was purified by flash chromatography (silica gel, 0 to 80% EtOAc in hexane) to give the title compound.

Workup

  1. stirringstirred at room temperature for 48 h
  2. concentrationThe solution was concentrated in vacuo
  3. additionWater was added to the residue
  4. extractionextracted with EtOAc
  5. customThe ethyl acetate was removed under vacuum
  6. customthe residue was purified by flash chromatography (silica gel, 0 to 80% EtOAc in hexane)

Sources & evidence

ORD record
ord-d3654a01b5e64755b1d04d86eaa6e5dd
Source dataset
uspto-grants-2013_08
Patent number
US08518969B2

Reaction notes

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