Triethylamine → HCID 58486421, compound

HRID 1890770Notes

Reaction equation

HRID 1890770 reaction equation
C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[F:41][C:42]1[CH:47]=[CH:46][C:45]([C:48]2[N:53]=[N:52][C:51]([N:54]3[CH2:59][CH2:58][CH:57]([NH:60][CH3:61])[CH2:56][CH2:55]3)=[C:50]([CH3:62])[C:49]=2[CH3:63])=[CH:44][CH:43]=1.[CH3:64][O:65][C:66]1[CH:84]=[CH:83][C:69]([CH2:70][N:71]2[CH:75]=[C:74]([C:76](O)=[O:77])[C:73]([C:79]([F:82])([F:81])[F:80])=[N:72]2)=[CH:68][CH:67]=1>CN(C=O)C>[F:41][C:42]1[CH:47]=[CH:46][C:45]([C:48]2[N:53]=[N:52][C:51]([N:54]3[CH2:59][CH2:58][CH:57]([N:60]([CH3:61])[C:76]([C:74]4[C:73]([C:79]([F:80])([F:81])[F:82])=[N:72][N:71]([CH2:70][C:69]5[CH:68]=[CH:67][C:66]([O:65][CH3:64])=[CH:84][CH:83]=5)[CH:75]=4)=[O:77])[CH2:56][CH2:55]3)=[C:50]([CH3:62])[C:49]=2[CH3:63])=[CH:44][CH:43]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 582442211-(4-Methoxybenzyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acidHCID 67368812HCID 67368812, compound

Product 1

HCID 58486421HCID 58486421, compoundYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Add PyBOP (343 mg, 0.65 mmol) and triethylamine (0.21 mL, 1.50 mmol) to a stirred solution of 1-(6-(4-fluorophenyl)-4,5-dimethylpyridazin-3-yl)-N-methylpiperidin-4-amine (157 mg, 0.50 mmol) and 1-(4-methoxybenzyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid (165 mg, 0.55 mmol) in anhydrous DMF (2.5 mL). Stir the resulting mixture at ambient temperature under N2 overnight. Concentrate, add MeOH, filter solids, and concentrate the filtrate. Dilute the residue with MeOH, and pour onto an SCX column (Thermo Scientific, 10 g). Wash with MeOH, and then elute the product with 2 M NH3/MeOH. Concentrate and purify by flash silica gel chromatography using a gradient of 0 to 10% (10% 2 M NH3/MeOH in EtOAc) in hexanes to obtain the title compound as a white solid (170 mg, 43%). ES/MS m/z 597.0 (M+1).

Workup

  1. concentrationConcentrate
  2. additionadd MeOH
  3. filtrationfilter solids
  4. concentrationconcentrate the filtrate
  5. additionDilute the residue with MeOH
  6. additionpour onto an SCX column (Thermo Scientific, 10 g)
  7. washWash with MeOH
  8. washelute the product with 2 M NH3/MeOH
  9. concentrationConcentrate
  10. custompurify by flash silica gel chromatography

Sources & evidence

ORD record
ord-ba5e918971504885b64f597e5cf52f6b
Source dataset
uspto-grants-2013_08
Patent number
US08507490B2

Reaction notes

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