Diethyl Ether → 3-(5-(1-(4-cyanophenyl)-1H-pyrazol-5-yl)-6-methyl-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxamido)-N,N,N-trimethylpropan-1-aminium benzene sulfonate

HRID 2089255Notes

Reaction equation

HRID 2089255 reaction equation
C([O-])(O)=O.[Na+].C([O-])(=O)C.[C:10]([C:12]1[CH:17]=[CH:16][C:15]([N:18]2[C:22]([C:23]3[CH:24]=[C:25]([C:41]([NH:43][CH2:44][CH2:45][CH2:46][N+:47]([CH3:50])([CH3:49])[CH3:48])=[O:42])[C:26](=[O:40])[N:27]([C:30]4[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[CH:31]=4)[C:28]=3[CH3:29])=[CH:21][CH:20]=[N:19]2)=[CH:14][CH:13]=1)#[N:11].[C:51]1([S:57]([OH:60])(=[O:59])=[O:58])[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1.C(OCC)C>CO>[C:51]1([S:57]([O-:60])(=[O:59])=[O:58])[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1.[C:10]([C:12]1[CH:13]=[CH:14][C:15]([N:18]2[C:22]([C:23]3[CH:24]=[C:25]([C:41]([NH:43][CH2:44][CH2:45][CH2:46][N+:47]([CH3:49])([CH3:48])[CH3:50])=[O:42])[C:26](=[O:40])[N:27]([C:30]4[CH:35]=[CH:34][CH:33]=[C:32]([C:36]([F:39])([F:38])[F:37])[CH:31]=4)[C:28]=3[CH3:29])=[CH:21][CH:20]=[N:19]2)=[CH:16][CH:17]=1)#[N:11]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 7371Benzenesulfonic AcidHCID 516892Sodium BicarbonateHCID 670927683-(5-(1-(4-cyanophenyl)-1H-pyrazol-5-yl)-6-methyl-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxamido)-N,N,N-trimethylpropan-1-aminium acetate

Product 1

HCID 866523733-(5-(1-(4-cyanophenyl)-1H-pyrazol-5-yl)-6-methyl-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxamido)-N,N,N-trimethylpropan-1-aminium benzene sulfonateYield 86.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Conditions

Temperature
50 °C

Procedure

A column of DOWEX 1×8 (50-100 mesh, Cl−) (approximately 10 g) was activated by passing through a aqueous saturated NaHCO3-solution (approximately 70 mL), followed by washing with H2O (100 mL) (until the pH of the eluent was neutral) and MeOH (40 mL). 3-(5-(1-(4-cyanophenyl)-1H-pyrazol-5-yl)-6-methyl-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2-dihydropyridine-3-carboxamido)-N,N,N-trimethylpropan-1-aminium acetate (300 mg, 0.48 mmol, Example 8) was dissolved in MeOH (2 mL) and the solution was allowed to pass slowly through the column followed by about 20 mL of MeOH. Benzenesulfonic acid (76 mg, 0.48 mmol) was added to the filtrate and the solution was evaporated, the residue was co-evaporated with EtOH and then dissolved in EtOH (0.5 mL) and THF (3.5 mL). The mixture was heated at 50° C. for 0.5 hr and was then stirred at room temperature over the weekend. No precipitate had formed over this time. Diethylether (3 mL) was added and the mixture was stirred at room temperature. After 1 hr a solid had started to precipitate and the slurry was stirred overnight. The precipitate was filtered off, washed with heptane and dried to afford the title compound as an off-white solid (300 mg, 86%); 1H NMR (400 MHz, dmso) δ 1.81 (3H, s), 1.90 (2H, m), 3.01 (9H, s), 3.27 (4H, m), 6.72 (1H, d), 7.30 (3H, m), 7.59 (2H, m), 7.67 (2H, d), 7.71 (1H, d), 7.85 (2H, m), 7.94 (4H, m), 8.04 (1H, s), 9.41 (1H, t). APCI-MSm/z: 563 [M+]

Workup

  1. washby washing with H2O (100 mL) (until the pH of the eluent
  2. customthe solution was evaporated
  3. dissolutiondissolved in EtOH (0.5 mL)
  4. customNo precipitate had formed over this time
  5. stirringthe mixture was stirred at room temperature
  6. customto precipitate
  7. stirringthe slurry was stirred overnight
  8. filtrationThe precipitate was filtered off
  9. washwashed with heptane
  10. customdried

Sources & evidence

ORD record
ord-fe15a9208c2946d293c83ebbd2ebea41
Source dataset
uspto-grants-2013_05
Patent number
US08436024B2

Reaction notes

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