Phosgene → 3-[3-(cyclopentyloxy)-4-methoxyphenyl]-2,5-dihydro-2-methyl-5-oxo-1H-pyrazole-1-carboxamide

HRID 1655627Notes

Reaction equation

HRID 1655627 reaction equation
[C:1](Cl)(Cl)=[O:2].[CH:5]1([O:10][C:11]2[CH:12]=[C:13]([C:19]3[N:23]([CH3:24])[NH:22][C:21](=[O:25])[CH:20]=3)[CH:14]=[CH:15][C:16]=2[O:17][CH3:18])[CH2:9][CH2:8][CH2:7][CH2:6]1.C[Si](C)(C)[NH:28][Si](C)(C)C>O1CCCC1.O1C=CC=C1.O1CCCC1>[CH:5]1([O:10][C:11]2[CH:12]=[C:13]([C:19]3[N:23]([CH3:24])[N:22]([C:1]([NH2:28])=[O:2])[C:21](=[O:25])[CH:20]=3)[CH:14]=[CH:15][C:16]=2[O:17][CH3:18])[CH2:6][CH2:7][CH2:8][CH2:9]1

Participants

6

Reactant 3

HCID 6371PhosgeneHCID 13838HexamethyldisilazaneHCID 197927825-[3-(cyclopentyloxy)-4-methoxyphenyl]-1,2-dihydro-1-methyl-3H-pyrazol-3-one

Product 1

HCID 197927913-[3-(cyclopentyloxy)-4-methoxyphenyl]-2,5-dihydro-2-methyl-5-oxo-1H-pyrazole-1-carboxamideYield 78%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 22709418Tetrahydrofuran furanSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of phosgene (8.75 mmol, 4.61 mL; 1.9 M solution in toluene) in dry tetrahydrofuran (30 mi) is added 5-[3-(cyclopentyloxy)-4-methoxyphenyl]-1,2-dihydro-1-methyl-3H-pyrazol-3-one (7.0 mmol, 2.02 g) in dry tetrahydrofuran furan (15 mL) dropwise over 20 minutes. The resulting cloudy solution is stirred at 0° C. for 10 minutes and at room temperature for 1 hour after which a homogenous solution is obtained. The reaction mixture is cooled to 0° C. and hexamethyldisilazane (17.5 mmol, 2.82 g; 3.64 mi) in dry tetrahydrofuran (15 mL) is added in one portion. The resulting suspension is stirred at room temperature for 1 hour and then the volatiles are removed in vacuo. The residue is partitioned between 2% aqueous acetic acid (200 mi) and ethyl acetate (200 mi) and the aqueous phase is extracted with ethyl acetate (150 mL). The combined organic layers are washed with H2O (100 mL), dried (Na2SO4), and concentrated in vacuo to afford a tan solid. This material is triturated with ether and dried in vacuo for 1 hour at 60° C. to give the title compound as a white solid (1.80 g; 78%). 1H NMR (DMSO-d6 400 MHz) δ 7.23 (br s, 1H); 7.02 (m, 3H); 6.92 (br s, 1H); 6.08 (s, 1H); 4.86 (m, 1H); 3.78 (s, 3H); 3.72 (s, 3H); 1.88 (m, 2H); 1.70 (m, 4H); 1.56 (m, 2H). IR (KBr, cm-1) 3400, 3300, 3200, 2950, 1760, 1500,1330,1250,1130.

Workup

  1. customis obtained
  2. temperatureThe reaction mixture is cooled to 0° C.
  3. stirringThe resulting suspension is stirred at room temperature for 1 hour
  4. customthe volatiles are removed in vacuo
  5. customThe residue is partitioned between 2% aqueous acetic acid (200 mi) and ethyl acetate (200 mi)
  6. extractionthe aqueous phase is extracted with ethyl acetate (150 mL)
  7. washThe combined organic layers are washed with H2O (100 mL)
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated in vacuo
  10. customto afford a tan solid
  11. customThis material is triturated with ether
  12. customdried in vacuo for 1 hour at 60° C.

Sources & evidence

ORD record
ord-2379be1d94854a009dfa63efd244cc5a
Source dataset
uspto-grants-1993_10
Patent number
US05250700

Reaction notes

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