Methyl 4-(4-methylphenyl)-2,4-dioxobutanoate → methyl 1-(4-cyanopyridin-2-yl)-5-(4-methylphenyl)-1H-pyrazole-3-carboxylate

HRID 514393Notes

Reaction equation

HRID 514393 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][C:10](=O)[C:11]([O:13][CH3:14])=[O:12])=[CH:4][CH:3]=1.Cl.[NH:18]([C:20]1[CH:25]=[C:24]([C:26]#[N:27])[CH:23]=[CH:22][N:21]=1)[NH2:19]>CC(O)=O>[C:26]([C:24]1[CH:23]=[CH:22][N:21]=[C:20]([N:18]2[C:8]([C:5]3[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=3)=[CH:9][C:10]([C:11]([O:13][CH3:14])=[O:12])=[N:19]2)[CH:25]=1)#[N:27]

Participants

4

Reactant 2

HCID 308119Methyl 4-(4-methylphenyl)-2,4-dioxobutanoateHCID 867254842-Hydrazinylpyridine-4-carbonitrile hydrochloride salt

Product 1

HCID 86725519methyl 1-(4-cyanopyridin-2-yl)-5-(4-methylphenyl)-1H-pyrazole-3-carboxylateYield 85%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of methyl 4-(4-methylphenyl)-2,4-dioxobutanoate (500 mg, 22.7 mmol) and 2-hydrazinylpyridine-4-carbonitrile hydrochloride salt (500 mg, 24.2 mmol, PREPARATION 3) in AcOH (10 mL) was heated at 100° C. for 30 min and cooled to rt. The solution was concentrated to an oily residue which was partitioned between EtOAc (50 mL) and water (50 mL). The pH was adjusted to pH=8 using a saturated aq. Na2CO3 solution. The organics were dried (MgSO4), filtered, and concentrated to give a solid which was triturated with MTBE/hexanes (1:1) and filtered to give the title compound (613 mg, 85%) as a yellow solid. 1H NMR (400 MHz, CD3OD): δ 2.48 (3H, s), 3.92 (3H, s), 7.01 (1H, s), 7.08-7.21 (4H, m), 7.71 (1H, d, J=4.8 Hz), 8.12 (1H, s), 8.48 (1H, d, J=4.8 Hz), 8.00 (1H, s), 8.48 (1H, d, J=8 Hz).

Workup

  1. concentrationThe solution was concentrated to an oily residue which
  2. customwas partitioned between EtOAc (50 mL) and water (50 mL)
  3. dry with materialThe organics were dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give a solid which
  7. customwas triturated with MTBE/hexanes (1:1)
  8. filtrationfiltered

Sources & evidence

ORD record
ord-9200489db5bb4663af329ed15a58889a
Source dataset
uspto-grants-2015_08
Patent number
US09107916B2

Reaction notes

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