Triethylamine → HCID 90010990, compound

HRID 1481492Notes

Reaction equation

HRID 1481492 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([C:13]([F:16])([F:15])[F:14])=[CH:11][C:10]([CH:17]=[O:18])=[N:9]2)=[N:6][CH:7]=1.BrC1C=CC(N2C(C(F)(F)F)=CC(C(O)=O)=N2)=NC=1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.Cl.[CH3:61][NH:62][O:63][CH3:64].C(N(CC)CC)C>CN(C=O)C.C(OCC)(=O)C.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([C:13]([F:14])([F:16])[F:15])=[CH:11][C:10]([C:17]([N:62]([O:63][CH3:64])[CH3:61])=[O:18])=[N:9]2)=[N:6][CH:7]=1

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 90011004HCID 90011004, compoundHCID 90011172HCID 90011172, compound

Product 1

HCID 90010990HCID 90010990, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
65 °C

Procedure

Step-1: 1-(5-Bromopyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-3-carbaldehyde: To a stirred solution of 1-(5-bromopyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-3-carboxylic acid (6.20 g, 18.45 mmol), in DMF (50 mL) was successively added EDC.HCl (4.24 g, 22.14 mmol), HOBT (3.11 g, 20.29 mmol), N,O-dimethylhydroxylamine hydrochloride (2.70 g, 27.7 mmol) and triethylamine (5.14 mL, 36.9 mmol). After stirring the reaction mixture at 65° C. for 12 h, the reaction was cooled to RT. Water (60 mL) was added to the above reaction followed by ethyl acetate (100 mL). The layers were separated and aqueous layer was extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with water (100 mL), brine (100 mL), dried (Na2SO4) and filtered. The filtrate was rotary evaporated and the crude product was purified by flash column chromatography (silica gel, ethyl acetate-hexanes system as eluent) to afford 4.20 g (60%) of the 1-(5-bromopyridin-2-yl)-N-methoxy-N-methyl-5-(trifluoromethyl)-1H-pyrazole-3-carboxamide as white solid. 1HNMR (400 MHz, DMSO-d6) δ 8.74 (d, J=2.5 Hz, 1H), 8.37 (dd, J=2.5 & 8.5 Hz, 1H), 7.88 (d, J=8.5 Hz, 1H), 7.50 (s, 1H), 3.77 (s, 3H), 3.34 (s, 3H); ESI-MS (m/z) 379, 381 [(MH)+, Br79,81].

Workup

  1. temperaturethe reaction was cooled to RT
  2. customThe layers were separated
  3. extractionaqueous layer was extracted with ethyl acetate (3×100 mL)
  4. washThe combined organic layers were washed with water (100 mL), brine (100 mL)
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customThe filtrate was rotary evaporated
  8. customthe crude product was purified by flash column chromatography (silica gel, ethyl acetate-hexanes system as eluent)

Sources & evidence

ORD record
ord-f813827125264952ae6305200cdf5372
Source dataset
uspto-grants-2016_08
Patent number
US09409898B2

Reaction notes

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