Water → HCID 10254648, compound

HRID 719932Notes

Reaction equation

HRID 719932 reaction equation
C([O:3][C:4](=O)[CH:5]([C:11]1[CH:16]=[N:15][C:14]([NH:17][C:18](=[O:37])[C@@H:19]([C:26]2[CH:31]=[CH:30][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[C:28]([Cl:36])[CH:27]=2)[CH2:20][CH:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)=[CH:13][N:12]=1)[C:6](OCC)=[O:7])C.[H-].C([Al+]CC(C)C)C(C)C.O.C(OCC)(=O)C>O1CCCC1>[Cl:36][C:28]1[CH:27]=[C:26]([C@@H:19]([CH2:20][CH:21]2[CH2:25][CH2:24][CH2:23][CH2:22]2)[C:18]([NH:17][C:14]2[CH:13]=[N:12][C:11]([CH:5]([CH2:6][OH:7])[CH2:4][OH:3])=[CH:16][N:15]=2)=[O:37])[CH:31]=[CH:30][C:29]=1[S:32]([CH3:35])(=[O:34])=[O:33]

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 21225700Diisobutylaluminumhydride2×HCID 67482886HCID 67482886, compound

Product 1

HCID 10254648HCID 10254648, compoundYield 11.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 2(R)-{5-[2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazin-2-yl}-malonic acid diethyl ester (189 mg, 0.33 mmol) in tetrahydrofuran (5.0 mL) cooled to 0° C. was treated with a 1.0M solution of diisobutylaluminum hydride in hexanes (1.84 mL, 1.84 mmol). The reaction mixture was stirred at 0° C. for 1.25 h and then at 25° C. for 2 h. At this time, the reaction was re-cooled to 0° C. and was treated with an additional amount of a 1.0M solution of diisobutylaluminum hydride in hexanes (0.92 mL, 0.92 mmol). The reaction was stirred at 0° C. for 15 min and then at 25° C. for 1 h. At this time, the reaction mixture was poured onto a mixture of ice, water, and ethyl acetate. The aqueous layer was extracted with ethyl acetate and diethyl ether. The combined organic layers were washed with a 1N aqueous citric acid solution, a cold saturated aqueous sodium bicarbonate solution, a saturated aqueous sodium chloride solution, dried over magnesium sulfate and sodium sulfate, treated with charcoal, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40M, Silica, 9/1 ethyl acetate/acetonitrile) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-[5-(2-hydroxy-1-hydroxymethyl-ethyl)-pyrazin-2-yl]-propionamide (17.9 mg, 11%) as a pale yellow foam: mp 110–120° C.; (ES)+-HRMS m/e calcd for C22H28N3O5 (M+H)+ 482.1511, found 482.1512.

Workup

  1. waitat 25° C. for 2 h
  2. temperatureAt this time, the reaction was re-cooled to 0° C.
  3. stirringThe reaction was stirred at 0° C. for 15 min
  4. waitat 25° C. for 1 h
  5. extractionThe aqueous layer was extracted with ethyl acetate and diethyl ether
  6. washThe combined organic layers were washed with a 1N aqueous citric acid solution
  7. dry with materiala cold saturated aqueous sodium bicarbonate solution, a saturated aqueous sodium chloride solution, dried over magnesium sulfate and sodium sulfate
  8. additiontreated with charcoal
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-28fa14c1161b4a31ae561ee308f1c20d
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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