Urea → HCID 10346590, compound

HRID 895373Notes

Reaction equation

HRID 895373 reaction equation
[Na].[NH2:2][C:3]([NH2:5])=[O:4].C([O:8][C:9]([C:11]1([C:42](OCC)=[O:43])[CH2:15][CH2:14][CH2:13][N:12]1[C:16]1[CH:17]=[N:18][C:19]([O:22][C:23]2[CH:28]=[CH:27][C:26]([C:29]3[O:30][CH:31]=[C:32]([C:34]4[CH:39]=[CH:38][C:37]([C:40]#[N:41])=[CH:36][CH:35]=4)[N:33]=3)=[CH:25][CH:24]=2)=[CH:20][CH:21]=1)=O)C>C(O)C>[O:43]=[C:42]1[NH:5][C:3](=[O:4])[NH:2][C:9](=[O:8])[C:11]21[N:12]([C:16]1[CH:21]=[CH:20][C:19]([O:22][C:23]3[CH:28]=[CH:27][C:26]([C:29]4[O:30][CH:31]=[C:32]([C:34]5[CH:35]=[CH:36][C:37]([C:40]#[N:41])=[CH:38][CH:39]=5)[N:33]=4)=[CH:25][CH:24]=3)=[N:18][CH:17]=1)[CH2:13][CH2:14][CH2:15]2

Participants

5

Reactant 3

HCID 1176UreaHCID 5360545SodiumHCID 69702084HCID 69702084, compound

Product 1

HCID 10346590HCID 10346590, compoundYield 27.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a flame dried flask was added ethanol (6 mL) and freshly cut sodium metal (62.4 mg, 2.71 mmol). The solution was stirred until homogenous. Recrystallized urea (98 mg, 1.63 mmol) was added and the solution was stirred at room temperature for 5 minutes. 1-(6-{4-[4-(4-Cyano-phenyl)-oxazol-2-yl]-phenoxy}-pyridin-3-yl)-pyrrolidine-2,2-dicarboxylic acid diethyl ester (300 mg, 0.54 mmol) was added as a solid and the solution was heated to 80° C. for 30 minutes, then cooled to 50° C. and stirred for 16 hours. The reaction was then quenched by the addition of 10 mL water and 1N hydrochloric acid was added to adjust the pH to 5. The aqueous layer was extracted with ethyl acetate (3×20 mL). The combined ethyl acetate layers were washed with saturated sodium chloride, dried with magnesium sulfate, filtered, and concentrated under vacuum to produce 290 mg of crude product. This material was chromatographed on silica gel (ISCO MPLC purification, 30 minutes, 50-100% ethyl acetate gradient, Biotage flash 40 s column) to provide 78 mg of a product which required further purification. Reverse-phase HPLC on a portion of this material provided 15 mg of the title compound as a white solid. MS m/z: ESI+ 521.1 (M+H)+; ESI− 519.3 (M−H)−.

Workup

  1. customTo a flame dried flask
  2. stirringthe solution was stirred at room temperature for 5 minutes
  3. temperaturecooled to 50° C.
  4. stirringstirred for 16 hours
  5. customThe reaction was then quenched by the addition of 10 mL water and 1N hydrochloric acid
  6. additionwas added
  7. extractionThe aqueous layer was extracted with ethyl acetate (3×20 mL)
  8. washThe combined ethyl acetate layers were washed with saturated sodium chloride
  9. dry with materialdried with magnesium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under vacuum
  12. customto produce 290 mg of crude product
  13. customThis material was chromatographed on silica gel (ISCO MPLC purification, 30 minutes, 50-100% ethyl acetate gradient, Biotage flash 40 s column)

Sources & evidence

ORD record
ord-1665d6ad50b84576bb63ce436dfcaddc
Source dataset
uspto-grants-2005_07
Patent number
US06916807B2

Reaction notes

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