Potassium Carbonate → rac-tert-butyl 2-((4-(5-(m-tolyl)oxazole-4-carboxamido)-1H-pyrazol-1-yl)methyl)pyrrolidine-1-carboxylate

HRID 624079Notes

Reaction equation

HRID 624079 reaction equation
[NH:1]1[CH:5]=[C:4]([NH:6][C:7]([C:9]2[N:10]=[CH:11][O:12][C:13]=2[C:14]2[CH:15]=[C:16]([CH3:20])[CH:17]=[CH:18][CH:19]=2)=[O:8])[CH:3]=[N:2]1.Br[CH2:22][CH:23]1[CH2:27][CH2:26][CH2:25][N:24]1[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CCOC(C)=O>[C:16]1([CH3:20])[CH:17]=[CH:18][CH:19]=[C:14]([C:13]2[O:12][CH:11]=[N:10][C:9]=2[C:7]([NH:6][C:4]2[CH:5]=[N:1][N:2]([CH2:22][CH:23]3[CH2:27][CH2:26][CH2:25][N:24]3[C:28]([O:30][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:29])[CH:3]=2)=[O:8])[CH:15]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 14821711tert-Butyl 2-(bromomethyl)pyrrolidine-1-carboxylate2×HCID 68283740N-(1H-Pyrazol-4-yl)-5-(m-tolyl)oxazole-4-carboxamide

Product 1

HCID 131735188rac-tert-butyl 2-((4-(5-(m-tolyl)oxazole-4-carboxamido)-1H-pyrazol-1-yl)methyl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To N-(1H-pyrazol-4-yl)-5-(m-tolyl)oxazole-4-carboxamide (150 mg, 0.56 mmol) in DMF (1.5 mL), tert-butyl 2-(bromomethyl)pyrrolidine-1-carboxylate (148 mg, 0.56 mmol) was added and K2CO3 (309 mg, 2.24 mmol) followed by tetrabutylammoniumbromide (18 mg, 0.056 mmol). The reaction mixture was heated to 80° C. for 2 h, then tert-butyl 2-(bromomethyl)pyrrolidine-1-carboxylate (1 eq.) followed by heating to 90° C. for 6 h. The reaction mixture was diluted with EtOAc, washed with sat. aq. NaHCO3-solution (1×) and brine (1×). The aq. layers were reextracted with EtOAc (1×). The combined organic layers were dried (MgSO4), filtered and the solvent was removed under reduced pressure. Purification by FC (EtOAc/hex 9:1, Rf=0.45) yielded rac-tert-butyl 2-((4-(5-(m-tolyl)oxazole-4-carboxamido)-1H-pyrazol-1-yl)methyl)pyrrolidine-1-carboxylate as a yellow foam. LC-MS conditions A: tR=0.94 min, [M+H]+=452.23.

Workup

  1. temperatureby heating to 90° C. for 6 h
  2. washwashed with sat. aq. NaHCO3-solution (1×) and brine (1×)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. filtrationfiltered
  5. customthe solvent was removed under reduced pressure
  6. customPurification by FC (EtOAc/hex 9:1, Rf=0.45)

Sources & evidence

ORD record
ord-1536c0c5aabd47a4bb3e3bec14e5da47
Source dataset
uspto-grants-2016_04
Patent number
US09303023B2

Reaction notes

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