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

HRID 2175559Notes

Reaction equation

HRID 2175559 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-ef1c89fd16cf4e718ad764314bd012e9
Source dataset
uspto-grants-2015_06
Patent number
US09062048B2

Reaction notes

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