N-methyl-2-pyrrolidone → N-{4-bromo-2-[1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-5-yl]-5-(trifluoromethyl)phenyl}-2,2,2-trifluoroacetamide

HRID 69115

Reaction equation

HRID 69115 reaction equation
Cl.Cl.[O:3]1[CH2:8][CH2:7][CH:6]([NH:9][NH2:10])[CH2:5][CH2:4]1.CN1CCCC1=O.CCN(C(C)C)C(C)C.[Br:27][C:28]1[C:33]([C:34]([F:37])([F:36])[F:35])=[CH:32][C:31]([NH:38][C:39](=[O:44])[C:40]([F:43])([F:42])[F:41])=[C:30]([C:45](=O)/[CH:46]=[CH:47]/N(C)C)[CH:29]=1>O>[Br:27][C:28]1[C:33]([C:34]([F:37])([F:35])[F:36])=[CH:32][C:31]([NH:38][C:39](=[O:44])[C:40]([F:41])([F:42])[F:43])=[C:30]([C:45]2[N:9]([CH:6]3[CH2:7][CH2:8][O:3][CH2:4][CH2:5]3)[N:10]=[CH:47][CH:46]=2)[CH:29]=1

Participants

6

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 50988431Oxan-4-ylhydrazine dihydrochlorideHCID 86694320HCID 86694320, compound

Product 1

HCID 86694319N-{4-bromo-2-[1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-5-yl]-5-(trifluoromethyl)phenyl}-2,2,2-trifluoroacetamideYield 42.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of 6.0 g of tetrahydro-2H-pyran-4-ylhydrazine dihydrochloride and 175 mL of N-methylpyrrolidone was added 11 mL of DIPEA, followed by stirring at room temperature for 20 minutes. To the reaction mixture was added 8.86 g of N-{4-bromo-2-[(2E)-3-(dimethylamino)prop-2-enoyl]-5-(trifluoromethyl)phenyl}-2,2,2-trifluoroacetamide, followed by stirring at 110° C. for 1 hour. To the reaction mixture was added water, followed by extraction with isopropyl acetate, and the organic layer was washed with saturated brine. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (chloroform/methanol). The obtained oil was triturated with diethyl ether/n-hexane to obtain 4.19 g of N-{4-bromo-2-[1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-5-yl]-5-(trifluoromethyl)phenyl}-2,2,2-trifluoroacetamide.

Workup

  1. stirringby stirring at 110° C. for 1 hour
  2. extractionfollowed by extraction with isopropyl acetate
  3. washthe organic layer was washed with saturated brine
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (chloroform/methanol)
  6. customThe obtained oil was triturated with diethyl ether/n-hexane

Sources & evidence

ORD record
ord-827bb13d420d45d79a6d08b3559fd55b
Source dataset
uspto-grants-2014_09
Patent number
US08822448B2

Linked notes

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