Lithium Chloride → HCID 178422947, compound

HRID 526547Notes

Reaction equation

HRID 526547 reaction equation
C[O:2][C:3]1[N:7]([C:8]2[CH:23]=[CH:22][C:11]([C:12]([NH:14][CH2:15][CH:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[O:13])=[CH:10][N:9]=2)[N:6]=[CH:5][C:4]=1[C:24]1[CH:29]=[CH:28][N:27]=[C:26]([CH3:30])[CH:25]=1.[Cl-].[Li+]>CC(N(C)C)=O.CS(C)=O>[OH:2][C:3]1[N:7]([C:8]2[CH:23]=[CH:22][C:11]([C:12]([NH:14][CH2:15][CH:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[O:13])=[CH:10][N:9]=2)[N:6]=[CH:5][C:4]=1[C:24]1[CH:29]=[CH:28][N:27]=[C:26]([CH3:30])[CH:25]=1

Participants

5

Reactant 2

HCID 433294Lithium Chloride2×HCID 1176010586-(5-methoxy-4-(2-methylpyridin-4-yl)-1H-pyrazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)nicotinamide

Product 1

HCID 178422947HCID 178422947, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
100 °C

Procedure

Combined 6-(5-methoxy-4-(2-methylpyridin-4-yl)-1H-pyrazol-1-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)nicotinamide (25.8 mg, 0.063 mmol) and lithium chloride (13.42 mg, 0.317 mmol) in DMA (0.5 mL) and then heated at 50° C. using a heating block for 2 days. Additional portion of lithium chloride (13.42 mg, 0.317 mmol) was added and the reaction mixture was stirred at 100° C. for 17 hours. The reaction mixture was cooled to 23° C., filtered through a Hydrophilic PTFE 0.45 um filter (Millipore Millex™-LCR), rinsed with DMSO (2×0.5 mL), and purified via preparative HPLC (SunFire™ C18, 5 μm, ID 30 mm×75 mm) using a gradient of 10-40% ACN (with 0.035% TFA) in water (with 0.05% TFA) to give a residue. The residue was dissolved in DMSO, filtered through a Hydrophilic PTFE 0.45 um filter (Millipore Millex™-LCR), rinsed with DMSO, and purified again via preparative HPLC (SunFire™ C18, 5 μm, ID 30 mm×75 mm) using an isocratic method of 17% ACN (with 0.05% TFA) in water (with 0.05% TFA) to give the title compound, as a TFA salt, (6.2 mg, 19.30% yield) as a green oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.16-1.26 (m, 2H) 1.55-1.67 (m, 2H) 1.77-1.84 (m, 1H) 2.51 (br. s., 3H) 3.17-3.24 (m, 2H) 3.24-3.32 (m, 2H) 3.83-3.88 (m, 2H) 7.77-8.07 (m, 2H) 8.07-8.22 (m, 1H) 8.22-8.30 (m, 1H) 8.36-8.44 (m, 1H) 8.58-8.67 (m, 1H) 8.67-8.81 (m, 1H) 8.81-8.92 (m, 1H) 13.58 (br. s., 1H). MS m/z [M+H]+ 394.5.

Workup

  1. customfor 2 days
  2. temperatureThe reaction mixture was cooled to 23° C.
  3. filtrationfiltered through a Hydrophilic PTFE 0.45 um
  4. filtrationfilter (Millipore Millex™-LCR)
  5. washrinsed with DMSO (2×0.5 mL)
  6. custompurified via preparative HPLC (SunFire™ C18, 5 μm, ID 30 mm×75 mm)
  7. customto give a residue
  8. filtrationfiltered through a Hydrophilic PTFE 0.45 um
  9. filtrationfilter (Millipore Millex™-LCR)
  10. washrinsed with DMSO
  11. custompurified again via preparative HPLC (SunFire™ C18, 5 μm, ID 30 mm×75 mm)

Sources & evidence

ORD record
ord-134b17090d794cf0b1f320f6b00cd715
Source dataset
uspto-grants-2016_05
Patent number
US09345713B2

Reaction notes

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