HCID 18980957, compound → HCID 19786522, compound

HRID 1031240Notes

Reaction equation

HRID 1031240 reaction equation
[F:1][C:2]([F:35])([F:34])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]([N:13]2[CH2:17][CH:16]([N:18]([CH3:23])[C:19]([O:21][CH3:22])=[O:20])[C:15]([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH2:31][CH2:32][CH3:33])=[CH:26][CH:25]=3)=[N:14]2)=[O:12])=[CH:6][CH:5]=1.[H-].C([Al+]CC(C)C)C(C)C>O1CCCC1>[F:35][C:2]([F:1])([F:34])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11]([N:13]2[CH2:17][CH:16]([N:18]([CH3:23])[C:19]([O:21][CH3:22])=[O:20])[CH:15]([C:24]3[CH:29]=[CH:28][C:27]([O:30][CH2:31][CH2:32][CH3:33])=[CH:26][CH:25]=3)[NH:14]2)=[O:12])=[CH:6][CH:5]=1

Participants

4

Reactant 2

HCID 18980957HCID 18980957, compoundHCID 21225700Diisobutylaluminumhydride2×

Product 1

HCID 19786522HCID 19786522, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
20 °C

Procedure

To 5.2 grams (g) (10.6 mmole) of N-(4-trifluoromethoxyphenyl)-3-(4-propoxyphenyl)-4-(N-methyl-N-(methoxycarbonyl)amino)-4,5-dihydro-1H-pyrazole-1-carboxamide in 50 ml of tetrahydrofuran (THF) that had been cooled under a nitrogen atmosphere to -75° C. was added 28 ml of 1.0M diisobutylaluminum hydride (DIBAL-H) in THF. The reaction mixture was warmed to 20° C. and stirred for 5 hours. An additional 6 ml of the 1.0M DIBAL-H solution was added. After stirring at 20° C. overnight, the mixture was cooled to 0° C. and carefully quenched with 10 ml of methanol, a solid forms. Into this mixture was poured a mixture of 20 g of water and 10 ml of 12M aqueous hydrochloric acid. After the solid dissolved, the mixture was concentrated in vacuo and partitioned between diethyl ether and water. The organic layer was washed with dilute aqueous sodium hydroxide and brine and then dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The resulting oil was chromatographed on silica gel using diethyl ether and hexanes to give the expected compound, an oil. NMR (200 MHz, CDCl3) 1.1 t 3H, 1.8 sextet 2H, 2.6 s 3H, 3.6 s 3H, 4.0 t 2H, 4.1-4.6 m 3H, 5.5 bd 1H, 6.9 d 2H, 7.1 m 5H, 7.5 d 2H, 8.5 s 1H. Peaks exibit satellites due to hindered rotation.

Workup

  1. stirringAfter stirring at 20° C. overnight
  2. temperaturethe mixture was cooled to 0° C.
  3. customcarefully quenched with 10 ml of methanol
  4. additionInto this mixture was poured
  5. additiona mixture of 20 g of water and 10 ml of 12M aqueous hydrochloric acid
  6. dissolutionAfter the solid dissolved
  7. concentrationthe mixture was concentrated in vacuo
  8. custompartitioned between diethyl ether and water
  9. washThe organic layer was washed with dilute aqueous sodium hydroxide and brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe resulting oil was chromatographed on silica gel

Sources & evidence

ORD record
ord-9cae1897ba09474ca0fb39a210040dc0
Source dataset
uspto-grants-1992_04
Patent number
US05109014

Reaction notes

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