Sulfuric Acid → 2-(3-Difluoromethyl-5-phenyl-pyrazol-1-yl)-5-methanesulfonyl-pyridine

HRID 479863Notes

Reaction equation

HRID 479863 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([NH:11][NH2:12])=[N:9][CH:10]=1)(=[O:4])=[O:3].C(O)(C)C.[F:17][CH:18]([F:30])[C:19](=O)[CH2:20][C:21]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=O.S(=O)(=O)(O)O>O>[CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([N:11]2[C:21]([C:23]3[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=3)=[CH:20][C:19]([CH:18]([F:17])[F:30])=[N:12]2)=[N:9][CH:10]=1)(=[O:3])=[O:4]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 3776Isopropanol3×HCID 27742054,4-Difluoro-1-phenylbutane-1,3-dioneHCID 99642932-Hydrazino-5-(methanesulfonyl)-pyridine

Product 1

HCID 99682152-(3-Difluoromethyl-5-phenyl-pyrazol-1-yl)-5-methanesulfonyl-pyridine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To 120 g of 5-(methylsulfonyl)-2-hydrazinyl-pyridine [CP-675,775] (0.641 moles) was charged isopropanol (900 mL) followed by 4,4-difluoro-1-phenyl-1,3-butanedione (122 g, 0.615 moles, 0.96 eq.) as a melt, followed by 900 mL of isopropanol. The slurry was stirred for 15 minutes, then 36 mL of concentrated sulfuric acid was added (slight exotherm) (15 volumes of isopropanol total). The reaction was stirred for 6 hours at 20-30° C., 2.4 L (20 volumes) of water was added (slight exotherm, reaction temperature kept below 45° C.) and the reaction was granulated for 2 days. The product was filtered and was rinsed with water. The product contained less than 0.5% of compound 6 (retention time 5.1 minutes). Analytical data: HPLC retention time (title compound) 8.4 minutes; MS: 349.36 (calc), M+1=350.1; 1H NMR in CDCl3: 8.75 doublet, (1H), 8.26 Quartet (1H), 7.38 multiplet (3H), 7.36 doublet (2H), 6.70 multiplet (2H), 3.08, Singlet, (3H); 13C NMR in CDCl3: 15.3, 149.3, 147.9, 146.6, 138.1, 130.27, 133.5, 130.0, 129.1, 128.7, 117.9, 113.4, 111.1, 108.1, 107.7, 45.

Workup

  1. stirringThe reaction was stirred for 6 hours at 20-30° C.
  2. custom(slight exotherm, reaction temperature kept below 45° C.)
  3. waitthe reaction was granulated for 2 days
  4. filtrationThe product was filtered
  5. washwas rinsed with water
  6. customHPLC retention time (title compound) 8.4 minutes

Sources & evidence

ORD record
ord-ac23f77a5a874f7098015a5e5ab85165
Source dataset
uspto-grants-2003_11
Patent number
US06646128B2

Reaction notes

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