Cesium carbonate → racemic 3-methyl-5-{[4-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]methyl}-1,3-oxazolidin-2-one

HRID 595277Notes

Reaction equation

HRID 595277 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:13][C:14]2[N:19]=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:17]=[CH:16][N:15]=2)[CH:5]=[C:6]([C:8]2[CH:9]=[N:10][NH:11][CH:12]=2)[CH:7]=1.Cl[CH2:25][CH:26]1[O:30][C:29](=[O:31])[N:28]([CH3:32])[CH2:27]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(N(C)C)=O.O.C(#N)C>[CH3:32][N:28]1[CH2:27][CH:26]([CH2:25][N:10]2[CH:9]=[C:8]([C:6]3[CH:5]=[C:4]([NH:13][C:14]4[N:19]=[C:18]([C:20]([F:21])([F:23])[F:22])[CH:17]=[CH:16][N:15]=4)[CH:3]=[C:2]([CH3:1])[CH:7]=3)[CH:12]=[N:11]2)[O:30][C:29]1=[O:31]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 128899255-(Chloromethyl)-3-methyl-2-oxazolidinone2×HCID 118208677N-(3-methyl-5-(1H-pyrazol-4-yl)phenyl)-4-(trifluoromethyl)pyrimidin-2-amine

Product 1

HCID 118208485racemic 3-methyl-5-{[4-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]methyl}-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
140 °C

Procedure

N-[3-Methyl-5-(1H-pyrazol-4-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (100 mg, 0.31 mmol), 5-(chloromethyl)-3-methyl-1,3-oxazolidin-2-one (56.2 mg, 0.38 mmol), and cesium carbonate (122 mg, 0.38 mmol) were dissolved in DMA (1 mL). The mixture was then heated by microwave irradiation to 140° C. for 1.5 hours. Additional 5-(chloromethyl)-3-methyl-1,3-oxazolidin-2-one (30 mg, 0.19 mmol) was added and the mixture heated by microwave irradiation to 140° C. for 30 minutes. The reaction was cooled to room temperature, diluted with water (3 mL) and ACN (3 mL) then filtered through a syringe filter and concentrated under reduced pressure. The residue was purified by reverse phase preparative HPLC (45 to 80% ACN/water with 0.1% TFA modifier). The free base was liberated using PL-HCO3 cartridges (Stratospheres™, 0.9 mmol) and lyophilized to afford racemic 3-methyl-5-{[4-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}phenyl)-1H-pyrazol-1-yl]methyl}-1,3-oxazolidin-2-one. MS ESI calcd. for C20H20F3N6O2 [M+H]+ 433. found 433. 1H NMR (500 MHz, DMSO-d6) δ 10.12 (s, 1H), 8.80 (d, J=3.9 Hz, 1H), 8.04 (s, 1H), 7.82 (s, 1H), 7.80 (s, 1H), 7.35 (s, 1H), 7.24 (d, J=3.4 Hz, 1H), 7.06 (s, 1H), 4.90-4.79 (m, 1H), 4.45-4.32 (m, 2H), 3.65 (t, J=8.9 Hz, 1H), 3.40 (dd, J=6.2, 9.0, 1H), 2.68 (s, 3H), 2.29 (s, 3H).

Workup

  1. temperaturethe mixture heated by microwave irradiation to 140° C. for 30 minutes
  2. temperatureThe reaction was cooled to room temperature
  3. filtrationthen filtered through a syringe
  4. filtrationfilter
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by reverse phase preparative HPLC (45 to 80% ACN/water with 0.1% TFA modifier)

Sources & evidence

ORD record
ord-045557a50dc4484fa4e6feb570049279
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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