Urea → HCID 10480845, compound

HRID 2183729Notes

Reaction equation

HRID 2183729 reaction equation
[Na].[NH2:2][C:3]([NH2:5])=[O:4].C([O:8][C:9]([C:11]1([C:40](OCC)=[O:41])[CH2:15][CH2:14][CH2:13][N:12]1[C:16]1[CH:17]=[N:18][C:19]([O:22][C:23]2[CH:24]=[C:25]3[C:29](=[CH:30][CH:31]=2)[N:28]([C:32]2[CH:37]=[CH:36][C:35]([C:38]#[N:39])=[CH:34][CH:33]=2)[N:27]=[CH:26]3)=[CH:20][CH:21]=1)=O)C>C(O)C>[C:38]([C:35]1[CH:36]=[CH:37][C:32]([N:28]2[C:29]3[C:25](=[CH:24][C:23]([O:22][C:19]4[N:18]=[CH:17][C:16]([N:12]5[C:11]6([C:40](=[O:41])[NH:5][C:3](=[O:4])[NH:2][C:9]6=[O:8])[CH2:15][CH2:14][CH2:13]5)=[CH:21][CH:20]=4)=[CH:31][CH:30]=3)[CH:26]=[N:27]2)=[CH:33][CH:34]=1)#[N:39]

Participants

5

Reactant 3

HCID 1176UreaHCID 5360545SodiumHCID 69704582HCID 69704582, compound

Product 1

HCID 10480845HCID 10480845, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a flame dried flask is added ethanol (6 mL) and freshly cut sodium metal (62.4 mg, 2.71 mmol). The solution is stirred until homogenous. Recrystallized urea (98 mg, 1.63 mmol) is added and the solution is stirred at room temperature for 5 minutes. 1-{6-[1-(4-Cyano-phenyl)-1H-indazol-5-yloxy]-pyridin-3-yl}-pyrrolidine-2,2-dicarboxylic acid diethyl ester (0.54 mmol) is added, and the solution is heated to 80° C. for 30 minutes, then cooled to 50° C. and stirred for 16 hours. The reaction is then quenched by the addition of 10 mL water, and 1N hydrochloric acid is added to adjust the pH to 5. The aqueous layer is extracted with ethyl acetate (3×20 mL). The combined ethyl acetate layers are washed with saturated sodium chloride, dried with magnesium sulfate, filtered, and concentrated under vacuum to produce crude product. This material is chromatographed on silica gel (ISCO MPLC purification, 30 minutes, 50-100% ethyl acetate gradient, Biotage flash 40s column) to provide 1-{6-[1-(4-Cyano-phenyl)-1H-indazol-5-yloxy]-pyridin-3-yl}-1,7,9-triaza-spiro[4.5]decane-6,8,10-trione.

Workup

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

Sources & evidence

ORD record
ord-07377825803c4e3aa9af565c0ce81fde
Source dataset
uspto-grants-2005_05
Patent number
US06900201B2

Reaction notes

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