Water → Tyclopyrazoflor

HRID 1746027Notes

Reaction equation

HRID 1746027 reaction equation
[Cl:1][C:2]1[C:6]([NH:7][CH2:8][CH3:9])=[CH:5][N:4]([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[N:3]=1.N1C=CC=CC=1.[F:22][C:23]([F:33])([F:32])[CH2:24][CH2:25][S:26][CH2:27][CH2:28][C:29](Cl)=[O:30].O>C(Cl)Cl.CN(C)C1C=CN=CC=1>[Cl:1][C:2]1[C:6]([N:7]([CH2:8][CH3:9])[C:29](=[O:30])[CH2:28][CH2:27][S:26][CH2:25][CH2:24][C:23]([F:33])([F:32])[F:22])=[CH:5][N:4]([C:10]2[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=2)[N:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 1049PyridineHCID 674989573-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amineHCID 867006283-((3,3,3-Trifluoropropyl)thio)propanoyl chloride

Product 1

HCID 86700627TyclopyrazoflorYield 89%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 3-chloro-N-ethyl-1-(pyridin-3-yl)-1H-pyrazol-4-amine (prepared as described in the U.S. Publication No. 2012/0110702 to Yap et al.) (10 g, 44.9 mmol) in CH2Cl2 (100 mL) at a temperature of about 0° C. and under N2 was added pyridine (5.45 mL, 67.4 mmol), 4-dimethylaminopyridine (DMAP) (2.74 g, 22.45 mmol), and 3-((3,3,3-trifluoropropyl)thio) propanoyl chloride (9.91 g, 44.9 mmol), sequentially. The reaction was warmed to room temperature and stirred for one hour. The reaction mixture was poured into water (100 mL), and the resulting mixture was stirred for five minutes. The mixture was transferred to a separatory funnel, and the layers were separated. The aqueous phase was extracted with CH2Cl2 (3×50 mL), and the combined organic extracts were dried over sodium sulfate (Na2SO4), filtered, and concentrated in vacuo. The crude product was purified via normal phase flash chromatography (0% to 100% EtOAc/CH2Cl2) to provide the desired product as a pale yellow solid (17.21 g, 89%): IR (thin film) 1659 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.95 (d, J=2.6 Hz, 1H), 8.63 (dd, J=4.7, 1.3 Hz, 1H), 8.05 (ddd, J=8.3, 2.7, 1.4 Hz, 1H), 7.96 (s, 1H), 7.47 (dd, J=8.3, 4.8 Hz, 1H), 3.72 (q, J=7.1 Hz, 2H), 2.84 (t, J=7.2 Hz, 2H), 2.66 (m, 2H), 237 (t, J=7.2 Hz, 2H), 2.44 (m, 2H), 1.17 (t, J=7.2 Hz, 3H); ESIMS m/z 409 ([M+2H]+).

Workup

  1. stirringthe resulting mixture was stirred for five minutes
  2. customThe mixture was transferred to a separatory funnel
  3. customthe layers were separated
  4. extractionThe aqueous phase was extracted with CH2Cl2 (3×50 mL)
  5. dry with materialthe combined organic extracts were dried over sodium sulfate (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified via normal phase flash chromatography (0% to 100% EtOAc/CH2Cl2)

Sources & evidence

ORD record
ord-52e8303b8fb146bc8cb094e232da1752
Source dataset
uspto-grants-2015_10
Patent number
US09149040B2

Reaction notes

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