Cesium carbonate → HCID 67296990, compound

HRID 1807237Notes

Reaction equation

HRID 1807237 reaction equation
[OH:1][C:2]1([CH2:8][N:9]2[CH:13]=[CH:12][C:11]([NH:14][C:15]([CH:17]3[CH:21]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[C:23]=4[F:29])[C:20]([C:32]4[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][C:33]=4[F:39])([C:30]#[N:31])[CH:19]([CH2:40][C:41]([CH3:44])([CH3:43])[CH3:42])[NH:18]3)=[O:16])=[N:10]2)[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:51]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])(=[O:53])[CH3:52]>CN(C=O)C.C(OCC)(=O)C>[C:55]([O:54][C:51](=[O:53])[CH2:52][N:5]1[CH2:4][CH2:3][C:2]([CH2:8][N:9]2[CH:13]=[CH:12][C:11]([NH:14][C:15]([C@H:17]3[C@H:21]([C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[C:23]=4[F:29])[C@:20]([C:32]4[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][C:33]=4[F:39])([C:30]#[N:31])[C@H:19]([CH2:40][C:41]([CH3:44])([CH3:43])[CH3:42])[NH:18]3)=[O:16])=[N:10]2)([OH:1])[CH2:7][CH2:6]1)([CH3:58])([CH3:57])[CH3:56]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 10908tert-Butyl acetateHCID 72244032HCID 72244032, compound

Product 1

HCID 67296990HCID 67296990, compoundYield 74.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid [1-(4-hydroxy-piperidin-4-ylmethyl)-1H-pyrazol-3-yl]-amide (80 mg, 0.12 mmol) was dissolved in DMF (3 mL) with cesium carbonate (100 mg, 0.31 mmol) then t-butyl acetate (0.1 mL, 0.677 mmol) was added stirred 16 hours at 25° C. The reaction mixture was diluted with ethyl acetate and separated with water (3×), the organic layer was dried with Na2SO4, filtered and concentrated under reduced pressure. The mixture was purified by reverse phase column chromatography (20-95% acetonitrile/water) to yield compound rac-[4-(3-{[(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carbonyl]-amino}-pyrazol-1-ylmethyl)-4-hydroxy-piperidin-1-yl]-acetic acid tert-butyl ester (68 mg, 74.7%).

Workup

  1. customseparated with water (3×)
  2. dry with materialthe organic layer was dried with Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe mixture was purified by reverse phase column chromatography (20-95% acetonitrile/water)

Sources & evidence

ORD record
ord-c528a7256d52441b9cddc17419554195
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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