Cesium carbonate → Tert-butyl 4-((4-(4-cyano-2-(2,6-difluorophenyl)oxazol-5-ylamino)benzamido)methyl)piperidine-1-carboxylate

HRID 714989Notes

Reaction equation

HRID 714989 reaction equation
CC1(C)C2C=CC=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=2OC2C1=CC=CC=2P(C1C=CC=CC=1)C1C=CC=CC=1.Br[C:44]1[O:48][C:47]([C:49]2[C:54]([F:55])=[CH:53][CH:52]=[CH:51][C:50]=2[F:56])=[N:46][C:45]=1[C:57]#[N:58].[NH2:59][C:60]1[CH:82]=[CH:81][C:63]([C:64]([NH:66][CH2:67][CH:68]2[CH2:73][CH2:72][N:71]([C:74]([O:76][C:77]([CH3:80])([CH3:79])[CH3:78])=[O:75])[CH2:70][CH2:69]2)=[O:65])=[CH:62][CH:61]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(O)CCC.O1CCOCC1.CCOC(C)=O.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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:57]([C:45]1[N:46]=[C:47]([C:49]2[C:54]([F:55])=[CH:53][CH:52]=[CH:51][C:50]=2[F:56])[O:48][C:44]=1[NH:59][C:60]1[CH:82]=[CH:81][C:63]([C:64]([NH:66][CH2:67][CH:68]2[CH2:69][CH2:70][N:71]([C:74]([O:76][C:77]([CH3:78])([CH3:79])[CH3:80])=[O:75])[CH2:72][CH2:73]2)=[O:65])=[CH:62][CH:61]=1)#[N:58]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 595875125-Bromo-2-(2,6-difluorophenyl)oxazole-4-carbonitrileHCID 59587665Tert-butyl 4-((4-aminobenzamido)methyl)piperidine-1-carboxylate

Product 1

HCID 59587428Tert-butyl 4-((4-(4-cyano-2-(2,6-difluorophenyl)oxazol-5-ylamino)benzamido)methyl)piperidine-1-carboxylateYield 32%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 67780350nBuOH dioxaneSolvent

Conditions

Temperature
140 °C

Procedure

A solution of tris(dibenzylideneacetone)dipalladium(0) (0.019 g, 0.021 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.011 g, 0.021 mmol) in nBuOH:dioxane (1:1) (5 mL) was stirred at room temperature for 3 minutes. Then 5-bromo-2-(2,6-difluorophenyl)oxazole-4-carbonitrile (0.080 g, 0.281 mmol), tert-butyl 4-((4-aminobenzamido)methyl)piperidine-1-carboxylate (0.250 g, 1.40 mmol) and cesium carbonate (0.108 g, 0.561 mmol) were added and the mixture heated in the microwave for 3 minutes at 140° C. The reaction was diluted with EtOAc and washed with water. The organic phase was passed through a thiol resin cartridge, dried over MgSO4 and the solvent removed in vacuo. The residue was purified by preparative HPLC to afford tert-butyl 4-((4-(4-cyano-2-(2,6-difluorophenyl)oxazol-5-ylamino)benzamido)methyl)piperidine-1-carboxylate (0.035 g, 0.09 mmol, 26%) as a light yellow solid. LCMS (2) Rt: 3.09 min; m/z (ES+) 538.

Workup

  1. washwashed with water
  2. dry with materialdried over MgSO4
  3. customthe solvent removed in vacuo
  4. customThe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-cc55643d62d3412885f89f629c808e33
Source dataset
uspto-grants-2015_11
Patent number
US09187465B2

Reaction notes

Loading…