Potassium Carbonate → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(2(S),3-dihydroxy-propyl)-pyrazin-2-yl]-propionamide

HRID 720010Notes

Reaction equation

HRID 720010 reaction equation
[C:1](=[O:4])([O-])[O-].[K+].[K+].[CH2:7]([C:10]1[N:11]=[CH:12][C:13]([NH:16][C:17](=[O:36])[C@@H:18]([C:25]2[CH:30]=[CH:29][C:28]([S:31]([CH3:34])(=[O:33])=[O:32])=[C:27]([Cl:35])[CH:26]=2)[CH2:19][CH:20]2[CH2:24][CH2:23][CH2:22][CH2:21]2)=[N:14][CH:15]=1)C=C.S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+].[C:46]([OH:50])(C)(C)C.O>C(OCC)(=O)C.[Cl-].[Na+].O.[Fe-3](C#N)(C#N)(C#N)(C#N)(C#N)C#N.[K+].[K+].[K+].[Os](=O)(=O)(=O)=O.CC[C@H]1[C@H]2C[C@H]([C@H](OC3C4C(=CC=CC=4)C(O[C@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3C=C(OC)C=C4)N(CC2)C1.C1(C)C=CC=CC=1>[Cl:35][C:27]1[CH:26]=[C:25]([C@@H:18]([CH2:19][CH:20]2[CH2:24][CH2:23][CH2:22][CH2:21]2)[C:17]([NH:16][C:13]2[CH:12]=[N:11][C:10]([CH2:7][C@H:1]([OH:4])[CH2:46][OH:50])=[CH:15][N:14]=2)=[O:36])[CH:30]=[CH:29][C:28]=1[S:31]([CH3:34])(=[O:33])=[O:32]

Participants

12

Reactant 4

HCID 11430Potassium CarbonateHCID 656671Sodium PyrosulfiteHCID 67482647N-(5-allyl-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentylpropionamideHCID 714019492-Methylpropan-2-ol--water (1/1)

Product 1

HCID 104803772(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(2(S),3-dihydroxy-propyl)-pyrazin-2-yl]-propionamideYield 77.1%

Reagents, catalysts & solvents 7

HCID 1140TolueneCatalystHCID 30318Osmium TetroxideCatalystHCID 510036741-((1R)-((2R,4R,5S)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)-4-((1R)-((2R,4S,5R)-5-ethylquinuclidin-2-yl)(6-methoxyquinolin-4-yl)methoxy)phthalazineCatalystHCID 178511488HCID 178511488, compoundCatalystHCID 962WaterSolventHCID 5234Sodium ChlorideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A yellow solution of potassium ferricyanide (1.00 g, 3.037 mmol), potassium carbonate (430.0 mg, 3.111 mmol), and (DHQ)2PHAL (19.0 mg, 0.0244 mmol) in tert-butyl alcohol/water (16.0 mL, 1:1) was cooled to 0° C. and then treated with a 0.2M solution of osmium tetroxide in toluene (0.048 mL, 0.0096 mmol) followed by the N-(5-allyl-pyrazin-2-yl)-2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentylpropionamide (446.0 mg, 0.996 mmol). The reaction mixture was stirred at 0° C. for 4 h. The reaction mixture was then diluted with ethyl acetate and sodium metabisulfite (0.45 g, 2.37 mmol) and allowed to warm to 25° C. where it was stirred for 15 min. The mixture was then diluted with a saturated aqueous sodium chloride solution and water and extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 2/3 hexanes/ethyl acetate to ethyl acetate) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(2(S),3-dihydroxy-propyl)-pyrazin-2-yl]-propionamide (370.2 mg, 77.1%) as a white foam: mp 61–65° C. (foam to gel); (ES)+-HRMS m/e calcd for C22H28ClN3O5S (M+H)+ 482.1511, found 482.1516.

Workup

  1. temperatureto warm to 25° C. where it
  2. stirringwas stirred for 15 min
  3. extractionextracted with ethyl acetate
  4. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-c0d19ccf414043939db52726d227956a
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

Loading…