Cesium carbonate → rac-N-(1-((1-(4,6-dimethoxypyrimidin-2-yl)pyrrolidin-2-yl)methyl)-1H-pyrazol-4-yl)-5-(m-tolyl)oxazole-4-carboxamide

HRID 624088Notes

Reaction equation

HRID 624088 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][CH:2]1[CH2:6][N:7]1[CH:11]=[C:10]([NH:12][C:13]([C:15]2[N:16]=[CH:17][O:18][C:19]=2[C:20]2[CH:21]=[C:22]([CH3:26])[CH:23]=[CH:24][CH:25]=2)=[O:14])[CH:9]=[N:8]1.Cl[C:28]1[N:33]=[C:32]([O:34][CH3:35])[CH:31]=[C:30]([O:36][CH3:37])[N:29]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CC#N.C(Cl)Cl>[CH3:37][O:36][C:30]1[CH:31]=[C:32]([O:34][CH3:35])[N:33]=[C:28]([N:1]2[CH2:5][CH2:4][CH2:3][CH:2]2[CH2:6][N:7]2[CH:11]=[C:10]([NH:12][C:13]([C:15]3[N:16]=[CH:17][O:18][C:19]=3[C:20]3[CH:21]=[C:22]([CH3:26])[CH:23]=[CH:24][CH:25]=3)=[O:14])[CH:9]=[N:8]2)[N:29]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 51523232-Chloro-4,6-dimethoxypyrimidineHCID 123442042rac-N-(1-(pyrrolidin-2-ylmethyl)-1H-pyrazol-4-yl)-5-(m-tolyl)oxazole-4-carboxamide

Product 1

HCID 123783876rac-N-(1-((1-(4,6-dimethoxypyrimidin-2-yl)pyrrolidin-2-yl)methyl)-1H-pyrazol-4-yl)-5-(m-tolyl)oxazole-4-carboxamideYield 55.2%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

To a microwave tube was added rac-N-(1-(pyrrolidin-2-ylmethyl)-1H-pyrazol-4-yl)-5-(m-tolyl)oxazole-4-carboxamide (40 mg, 0.11 mmol), 2-chloro-4,6-dimethoxypyrimidine (18 mg, 0.10 mmol) and Cs2CO3 (175 mg, 0.228 mmol) in MeCN (0.8 mL). The reaction mixture was irradiated at 180° C. for 30 min in the microwave, then the reaction mixture was diluted with DCM (30 mL). The organic layer was separated and washed with H2O (5 mL) and brine (5 mL). The combined organic layers were dried (MgSO4), filtered and the solvent was removed under reduced pressure. Purification by FC (hex/EtOAc 3:7) Rf=0.4) yielded the title compound (27 mg) as a yellowish solid. LC-MS conditions D: tR=1.16 min, [M+H]+=490.3.

Workup

  1. customThe reaction mixture was irradiated at 180° C. for 30 min in the microwave
  2. customThe organic layer was separated
  3. washwashed with H2O (5 mL) and brine (5 mL)
  4. dry with materialThe combined organic layers were dried (MgSO4)
  5. filtrationfiltered
  6. customthe solvent was removed under reduced pressure
  7. customPurification by FC (hex/EtOAc 3:7) Rf=0.4)

Sources & evidence

ORD record
ord-dd4ff556e7f74b27ae596296574fe87e
Source dataset
uspto-grants-2016_04
Patent number
US09303023B2

Reaction notes

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