HCID 59743357, compound → HCID 178472431, compound

HRID 1946999Notes

Reaction equation

HRID 1946999 reaction equation
CS([C:5]1[N:10]=[C:9]([N:11]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[N:12]2)[CH:8]=[CH:7][N:6]=1)(=O)=O.[CH2:20]([O:22][C:23]([C@H:25]1[CH2:30][CH2:29][C@H:28]([NH2:31])[CH2:27][CH2:26]1)=[O:24])[CH3:21]>C1COCC1>[CH2:20]([O:22][C:23]([C@H:25]1[CH2:30][CH2:29][C@H:28]([NH:31][C:5]2[N:10]=[C:9]([N:11]3[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[CH:13]=[N:12]3)[CH:8]=[CH:7][N:6]=2)[CH2:27][CH2:26]1)=[O:24])[CH3:21]

Participants

4

Reactant 2

HCID 59743357HCID 59743357, compoundHCID 178472434HCID 178472434, compound

Product 1

HCID 178472431HCID 178472431, compoundYield 33.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

1-(2-Methanesulfonylpyrimidin-4-yl)-1H-indazole (6.4 g) was suspended in THF and the mixture heated to 60° C. until complete dissolution of the solids. trans-4-Amino-cyclohexane-carboxylic acid ethyl ester (7.99 g, 46.6 mmol) was added, followed by TEA (9.7 mL, 69.9 mmol), and the resulting mixture stirred overnight. The reaction mixture was concentrated under reduced pressure until solids started to precipitate, and was then heated to 60° C. for 24 h. THF (4 mL) was added, and the reaction mixture stirred for 64 h at 60° C. The resulting mixture was extracted with EtOAc, the combined organic extracts washed with water, dried over MgSO4, filtered, and evaporated under reduced pressure. The crude residue was purified by flash chromatography (DCM/MeOH, 98:2) and the brown solid obtained was triturated with Et2O to give trans-4-(4-indazol-1-ylpyrimidin-2-ylamino)-cyclohexanecarboxylic acid ethyl ester (2.883 g) as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure until solids
  2. customto precipitate
  3. temperaturewas then heated to 60° C. for 24 h
  4. additionTHF (4 mL) was added
  5. stirringthe reaction mixture stirred for 64 h at 60° C
  6. extractionThe resulting mixture was extracted with EtOAc
  7. washthe combined organic extracts washed with water
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customevaporated under reduced pressure
  11. customThe crude residue was purified by flash chromatography (DCM/MeOH, 98:2)
  12. customthe brown solid obtained
  13. customwas triturated with Et2O

Sources & evidence

ORD record
ord-c7ece807f54746e4bb896f07308da206
Source dataset
uspto-grants-2013_03
Patent number
US08399462B2

Reaction notes

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