Triethylamine → HCID 178481032, compound

HRID 42312Notes

Reaction equation

HRID 42312 reaction equation
[O:1]([C:8]1[N:13]=[CH:12][C:11]([C:14]2[NH:18][N:17]=[C:16]([C:19]([OH:21])=O)[CH:15]=2)=[CH:10][N:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:22][N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1.C(N(CC)CC)C>S(Cl)(Cl)=O.CN(C=O)C.ClCCl>[CH3:22][N:23]1[CH2:28][CH2:27][N:26]([C:19]([C:16]2[CH:15]=[C:14]([C:11]3[CH:12]=[N:13][C:8]([O:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)=[N:9][CH:10]=3)[NH:18][N:17]=2)=[O:21])[CH2:25][CH2:24]1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 531671-MethylpiperazineHCID 178524135HCID 178524135, compound

Product 1

HCID 178481032HCID 178481032, compoundYield 60.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 24386Thionyl ChlorideSolvent

Procedure

To a solution consisting of 5-(2-phenoxypyrimidin-5-yl)-1H-pyrazole-3-carboxylic acid (Example 56, 60 mg, 0.21 mmol) in thionyl chloride (10 mL) was added one drop of dry DMF. The solution was heated to reflux for four hours and was subsequently allowed to cool to room temperature. Thionyl chloride was evaporated under reduced pressure and to the residue was added toluene (2×30 mL), which was evaporated and the residue subjected to high vacuum to remove residual thionyl chloride. The residue and 1-methylpiperazine (25 mg, 0.028 mL, 0.25 mmol) were dissolved in dichloromethane (10 mL) followed by the addition of triethylamine (0.14 mL). The solution was stirred at room temperature for 18 hours. The solvent was evaporated and the residue was purified by silica gel flash chromatography using 0-10% methanol in dichloromethane gradient through a 25-g Silicycle® flash silica cartridge to afford the title compound as a white solid (46 mg, 60% yield); Rf 0.30 with 6% methanol in dichloromethane; 1H-NMR (300 MHz; CD3OD) δ 8.96 (s, 2H), 7.43 (m, 2H), 7.25 (m, 1H), 7.19 (d, 2H), 7.02 (s, 1H), 3.74-3.99 (br, 4H), 2.51 (br, 4H), 2.33 (s, 3H); MS (ESI−) m/z 363 (M−1); H-PGDS FPBA IC50: 0.65 μM; H-PGDS inhibitor EIA IC50: 0.42 μM.

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux for four hours
  3. customThionyl chloride was evaporated under reduced pressure and to the residue
  4. additionwas added toluene (2×30 mL), which
  5. customwas evaporated
  6. customto remove residual thionyl chloride
  7. customThe solvent was evaporated
  8. customthe residue was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-5536ad8a70794aa89c179d4751fb1418
Source dataset
uspto-grants-2013_09
Patent number
US08536185B2

Reaction notes

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