Trifluoroacetic acid → 1-{2-[6-(3-Hydroxyazetidin-1-yl)pyrimidin-4-yl]-3-oxo-2,3-dihydro-1H-pyrazol-4-yl}-1H-imidazole-4-carbonitrile

HRID 562463Notes

Reaction equation

HRID 562463 reaction equation
FC(F)(F)C(O)=O.C[N:9]([CH:11]=[C:12]([N:18]1[CH:22]=[C:21]([C:23]#[N:24])[N:20]=[CH:19]1)[C:13]([O:15]CC)=O)C.[NH:25]([C:27]1[N:32]=[CH:31][N:30]=[C:29]([N:33]2[CH2:36][CH:35]([OH:37])[CH2:34]2)[CH:28]=1)N>C(OCC)(=O)C>[OH:37][CH:35]1[CH2:36][N:33]([C:29]2[N:30]=[CH:31][N:32]=[C:27]([N:25]3[C:13](=[O:15])[C:12]([N:18]4[CH:22]=[C:21]([C:23]#[N:24])[N:20]=[CH:19]4)=[CH:11][NH:9]3)[CH:28]=2)[CH2:34]1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 552790421-(6-Hydrazinopyrimidin-4-yl)azetidin-3-olHCID 66726020Ethyl 3-(N,N-dimethylamino)-2-(4-cyano-1H-imidazol-1-yl)acrylate

Product 1

HCID 444646081-{2-[6-(3-Hydroxyazetidin-1-yl)pyrimidin-4-yl]-3-oxo-2,3-dihydro-1H-pyrazol-4-yl}-1H-imidazole-4-carbonitrile

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

46 μl (68 mg, 0.6 mmol) of trifluoroacetic acid are added to a mixture of 700 mg (3.0 mmol) of the compound from Example 6A and 541 mg (3.0 mmol) of the compound from Example 10A in 10 ml of ethyl acetate, and the mixture is stirred at 100° C. for 10 h. The reaction mixture is concentrated under reduced pressure and taken up in 5 ml of ethanol, and the precipitate is filtered off. The solid is suspended in 10 ml of water, and 1 N aqueous sodium hydroxide solution (pH=9) is added until the solid is dissolved. The pH is then adjusted to 7 using 1 N hydrochloric acid, the mixture is concentrated to a volume of about 5 ml and the precipitate formed is filtered off. The residue is washed with water and diisopropyl ether and chromatographed by preparative HPLC (Method 8). The solid is then suspended in 10 ml of water, and 1 N aqueous sodium hydroxide solution (pH=9) is added until the solid is dissolved. The pH is then adjusted to 7 using 1 N hydrochloric acid, the mixture is concentrated to a volume of about 2.5 ml and the precipitate formed is filtered off. The filtrate is concentrated to about 2 ml and filtered again. Both residues are combined, washed with water and ethyl acetate and dried under reduced pressure. Yield: 78 mg (8% of theory)

Workup

  1. concentrationThe reaction mixture is concentrated under reduced pressure
  2. filtrationthe precipitate is filtered off
  3. addition1 N aqueous sodium hydroxide solution (pH=9) is added until the solid
  4. dissolutionis dissolved
  5. concentrationthe mixture is concentrated to a volume of about 5 ml
  6. customthe precipitate formed
  7. filtrationis filtered off
  8. washThe residue is washed with water and diisopropyl ether
  9. customchromatographed by preparative HPLC (Method 8)
  10. addition1 N aqueous sodium hydroxide solution (pH=9) is added until the solid
  11. dissolutionis dissolved
  12. concentrationthe mixture is concentrated to a volume of about 2.5 ml
  13. customthe precipitate formed
  14. filtrationis filtered off
  15. concentrationThe filtrate is concentrated to about 2 ml
  16. filtrationfiltered again
  17. washwashed with water and ethyl acetate
  18. customdried under reduced pressure

Sources & evidence

ORD record
ord-519be5fa90e3447286f89477898127be
Source dataset
uspto-grants-2011_11
Patent number
US08067407B2

Reaction notes

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