1-(1-Methyl-1H-pyrazol-3-yl)ethan-1-one → HCID 178517415, compound
Reaction equation
C[N:2]1C=CC(C(=O)C)=N1.Cl.FC1C=CC=CC=1CNN.C([O:24][C:25]1[C:30]([F:31])=[CH:29]C=[C:27]([C:32]2[CH:36]=[C:35]([C:37]3[CH:41]=[CH:40][O:39][N:38]=3)[N:34]([CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=3[F:49])[N:33]=2)[N:26]=1)(=O)C.C(OC(=O)C(F)=C[O-])C.[Na+]>N1C=CC=N1.C(O)C>[F:31][C:30]1[C:25]([OH:24])=[N:26][C:27]([C:32]2[CH:36]=[C:35]([C:37]3[CH:41]=[CH:40][O:39][N:38]=3)[N:34]([CH2:42][C:43]3[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=3[F:49])[N:33]=2)=[N:2][CH:29]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
This compound was generated exploiting General Procedure A-I from 1-(1-methyl-1H-pyrazol-3-yl)ethanone (1.67 g, 13.45 mmol) in the initial Claisen condensation, and using (2-fluorobenzyl)hydrazine hydrochloride (2.38 g, 13.45 mmol) in the pyrazole formation step (72%, two steps). The ester was then carried on to the corresponding amidine, again, as outlined in General Procedure A-I. The amidine (213 mg, 0.714 mmol) was cyclized via treatment with sodium 3-ethoxy-2-fluoro-3-oxoprop-1-en-1-olate (446 mg, 2.86 mmol) in ethanol (5.0 mL)—stirring at 90° C. for 14 hour. The solvent was removed in vacuo, and purification by silica gel chromatography (0-10% methanol in DCM) provided a mixture of the desired compound and a side-product. The mixture was then subjected to reverse-phase preparative HPLC which afforded Compound 92 (20 mg, 7.6% yield) as a white solid.
Workup
- customClaisen condensation
- customThe solvent was removed in vacuo, and purification by silica gel chromatography (0-10% methanol in DCM)
- customprovided
Sources & evidence
- ORD record
- ord-2748e533de3f4b1bb283f512ce01631d
- Source dataset
- uspto-grants-2015_09
- Patent number
- US09139564B2
Reaction notes
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