Pyrazole → HCID 24969552, compound

HRID 1508596Notes

Reaction equation

HRID 1508596 reaction equation
[Cl-].[F:2][C:3]([F:42])([F:41])[C:4]1[CH:5]=[C:6]([C@H:14]2[O:18][C:17](=[O:19])[N:16]([CH2:20][C:21]3[C:26]([C:27]4[CH:32]=[C:31]([CH:33]([CH3:35])[CH3:34])[C:30]([F:36])=[CH:29][C:28]=4[O:37][CH3:38])=[CH:25][CH:24]=[C:23]([Cl:39])[N:22]=3)[C@H:15]2[CH3:40])[CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1.N1C=CC=N1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)CCN>O1CCOCC1.[Cu]I>[F:13][C:10]([F:11])([F:12])[C:8]1[CH:7]=[C:6]([C@H:14]2[O:18][C:17](=[O:19])[N:16]([CH2:20][C:21]3[C:26]([C:27]4[CH:32]=[C:31]([CH:33]([CH3:35])[CH3:34])[C:30]([F:36])=[CH:29][C:28]=4[O:37][CH3:38])=[CH:25][CH:24]=[C:23]([Cl:39])[N:22]=3)[C@H:15]2[CH3:40])[CH:5]=[C:4]([C:3]([F:2])([F:42])[F:41])[CH:9]=1

Participants

7

Reactant 4

HCID 1048PyrazoleHCID 10796Cesium carbonateHCID 66053N,N-DimethylethylenediamineHCID 86704644HCID 86704644, compound

Product 1

HCID 24969552HCID 24969552, compoundYield 13.1%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-({6-chloro-3-[4-fluoro-2-methoxy-5-(propan-2-yl)phenyl]pyridin-2-yl}methyl)-4-methyl-1,3-oxazolidin-2-one chloride (40 mg, 0.066 mmol) and pyrazole (5.40 mg, 0.079 mmol) were dissolved in dioxane (0.7 mL) in a 2-5 mL microwave vial. Cesium carbonate (43.1 mg, 0.132 mmol) and copper(I) iodide (12.6 mg, 0.066 mmol) were added and the mixture was degassed. N,N-dimethylethylenediamine (23.3 mg, 0.264 mmol) was added before sealing the system and heating (thermally) to 110° C. overnight. The reaction was cooled and filtered over Celite® (ethyl acetate wash) and the filtrate was concentrated and was purified by reverse phase HPLC to yield (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-({6-chloro-3-[4-fluoro-2-methoxy-5-(propan-2-yl)phenyl]pyridin-2-yl}methyl)-4-methyl-1,3-oxazolidin-2-one (5.5 mg, 8.64 μmol). 1H NMR (CD3OD, 500 MHz) δ 8.63 (s, 1H), 7.99 (s, 1H), 7.93 (m, 3H), 7.79 (s, 1H), 7.75 (d, J=8.2 Hz, 1H), 7.17 (br s, 1H), 6.88 (d, J=12.3 Hz, 1H), 6.57 (s, 1H), 5.84 (m, 1H), 4.85 (m, 1H), 4.21 (m, 2H), 3.81 (s, 3H), 3.21 (m, 1H), 1.29 (m, 6H), 0.64 (d, J=41.1 Hz, 3H). SPA=55.8 nM

Workup

  1. customthe mixture was degassed
  2. temperatureThe reaction was cooled
  3. filtrationfiltered over Celite® (ethyl acetate wash)
  4. concentrationthe filtrate was concentrated
  5. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-8d81fc5c909f4ea6b2edbff1e205d480
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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