1-benzyl-1H-pyrazol-3-amine → N-(1-Benzyl-1H-pyrazol-3-yl)-3-isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzamide

HRID 883053

Reaction equation

HRID 883053 reaction equation
[CH:1]([O:4][C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([O:14][CH2:15][CH2:16][C:17]2[CH:21]=[CH:20][S:19][CH:18]=2)[CH:13]=1)[C:8]([OH:10])=O)([CH3:3])[CH3:2].[CH2:22]([N:29]1[CH:33]=[CH:32][C:31]([NH2:34])=[N:30]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>S(Cl)(Cl)=O>[CH2:22]([N:29]1[CH:33]=[CH:32][C:31]([NH:34][C:8](=[O:10])[C:7]2[CH:11]=[C:12]([O:14][CH2:15][CH2:16][C:17]3[CH:21]=[CH:20][S:19][CH:18]=3)[CH:13]=[C:5]([O:4][CH:1]([CH3:2])[CH3:3])[CH:6]=2)=[N:30]1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1

Participants

4

Reactant 2

HCID 15086161-benzyl-1H-pyrazol-3-amineHCID 585289133-Isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoic acid

Product 1

HCID 25261820N-(1-Benzyl-1H-pyrazol-3-yl)-3-isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzamideYield 45%

Reagents, catalysts & solvents 1

HCID 24386Thionyl ChlorideSolvent

Conditions

Temperature
70 °C

Procedure

3-Isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzoic acid (0.672 mmol) is dissolved in thionylchloride (1.2 ml) and heated to 70° C. for 1 hour. After cooling to room temperature, the solvent is removed in vacuo. The residue is dissolved in dichloromethane (1.2 ml) and ethyldiisopropyl-amine (167 μl) is added and 1-benzyl-1H-pyrazol-3-ylamine (1.2 eq) is added. The solution is stirred 21 hours at room temperature. The reaction solution is extracted with water. The organic layer is washed with brine and dried over MgSO4 and the solvent is removed in vacuo. N-(1-Benzyl-1H-pyrazol-3-yl)-3-isopropoxy-5-(2-thiophen-3-yl-ethoxy)-benzamide is isolated after column chromatography (heptan /ethylacetate) as yellow oil in a yield of 45%; HPLC (method B): 3.63 min; LC-MS (method B): 2.74 min, 462.2 (MH+); 1H-NMR (DMSO-d5, 500 MHz): δ [ppm] 10.78 (s, 1), 7.79 (d, 1H, J=2.2 Hz), 7.468 (dd, 1H, J=3 Hz, J=4.9 Hz), 7.359-7.269 (m, 4H), 7.245-7228 (m, 2H), 7.174-7.139 (m, 2H), 7.11 (dd, 1H, J=1.1 Hz, J=4.9 Hz), 6.648 (d, 1H, J=2.2 Hz), 5.256 (s, 2H), 4.678 (sep, 1H, J=6 Hz), 4.223 (t, 2H, J=6.9 Hz), 3.049 (t, 2H, J=6.9 Hz), 1.262 (d, 6H, J=6 Hz).

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe solvent is removed in vacuo
  3. dissolutionThe residue is dissolved in dichloromethane (1.2 ml)
  4. additionethyldiisopropyl-amine (167 μl) is added
  5. extractionThe reaction solution is extracted with water
  6. washThe organic layer is washed with brine
  7. dry with materialdried over MgSO4
  8. customthe solvent is removed in vacuo

Sources & evidence

ORD record
ord-9da74deedd434072b2758162eaa0882b
Source dataset
uspto-grants-2012_08
Patent number
US08236824B2

Linked notes

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