Diethyl Ether → N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1(3-chloro-2-pyridinyl)-3-(2,2,2-trifluoroethoxy)-1H-pyrazole-5-carboxamide

HRID 1522752Notes

Reaction equation

HRID 1522752 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH3:31])[C:5]2[N:10]=[C:9]([C:11]3[N:15]([C:16]4[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][N:17]=4)[N:14]=[C:13]([O:23][CH2:24][C:25]([F:28])([F:27])[F:26])[CH:12]=3)[O:8][C:7](=[O:29])[C:6]=2[CH:30]=1.[CH3:32][NH2:33].C(OCC)C>O1CCCC1>[Cl:1][C:2]1[CH:30]=[C:6]([C:7]([NH:33][CH3:32])=[O:29])[C:5]([NH:10][C:9]([C:11]2[N:15]([C:16]3[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][N:17]=3)[N:14]=[C:13]([O:23][CH2:24][C:25]([F:28])([F:27])[F:26])[CH:12]=2)=[O:8])=[C:4]([CH3:31])[CH:3]=1

Participants

5

Reactant 3

HCID 3283Diethyl EtherHCID 6329MethylamineHCID 211133896-Chloro-2-[1-(3-chloro-2-pyridinyl)-3-(2,2,2-trifluoroethoxy)-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one2×

Product 1

HCID 11576978N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1(3-chloro-2-pyridinyl)-3-(2,2,2-trifluoroethoxy)-1H-pyrazole-5-carboxamideYield 21.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of the 6-chloro-2-[1-(3-chloro-2-pyridinyl)-3-(2,2,2-trifluoroethoxy)-1H-pyrazol-5-yl]-8-methyl-4H-3,1-benzoxazin-4-one (i.e. precipitate product of Step E) (3.53 g, 7.5 mmol) in tetrahydrofuran (15 mL), methylamine (2.0 M solution in THF, 11 mL, 22 mmol) was added dropwise, and the resulting solution was stirred at room temperature for 45 minutes. Thin layer chromatography then showed the reaction to be complete. Ethyl ether (100 mL) was added, and the reaction mixture was stirred for 2 hours while a precipitate formed. The precipitate was collected by filtration and then recrystallized from acetonitrile to yield a white solid (0.82 g). A second crop of white solid (0.35 g) precipitated from the acetonitrile mother liquor and was collected by filtration. The initial ether/tetrahydrofuran mother liquor was concentrated to dryness, and the residual solid was recrystallized from acetonitrile to yield a third crop of white solid (0.95 g). The three crops were combined, totaling 2.12 g (after drying) of the title compound, isolated as a white solid, melting at 207-208° C.

Workup

  1. additionwas added dropwise
  2. customthe reaction
  3. stirringthe reaction mixture was stirred for 2 hours while a precipitate
  4. customformed
  5. filtrationThe precipitate was collected by filtration
  6. customrecrystallized from acetonitrile

Sources & evidence

ORD record
ord-7fa361af9f5f433ebe3089a2ce5f18a6
Source dataset
uspto-grants-2015_07
Patent number
US09078437B2

Reaction notes

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