Ozone → HCID 5288259, compound

HRID 1180756Notes

Reaction equation

HRID 1180756 reaction equation
C([C:3](=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[C:4]([C@@H:6]([NH:11][C:12](=[O:27])[O:13][CH2:14][C:15]1([CH2:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[CH2:18][CH2:17][CH2:16]1)[CH2:7][CH2:8][CH2:9][CH3:10])=[O:5])#N.[O:47]=[O+][O-].[NH2:50][C:51]1[CH:55]=[CH:54][NH:53][N:52]=1>ClCCl>[O:47]=[C:3]([NH:50][C:51]1[NH:52][N:53]=[CH:54][CH:55]=1)[C:4]([C@@H:6]([NH:11][C:12](=[O:27])[O:13][CH2:14][C:15]1([CH2:19][C:20]2[CH:21]=[CH:22][C:23]([F:26])=[CH:24][CH:25]=2)[CH2:18][CH2:17][CH2:16]1)[CH2:7][CH2:8][CH2:9][CH3:10])=[O:5]

Participants

5

Reactant 3

HCID 24823OzoneHCID 58979664HCID 58979664, compoundHCID 178418806HCID 178418806, compound

Product 1

HCID 5288259HCID 5288259, compoundYield 21%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A −78° C. solution of 200 mg (0.32 mmol) of [1-(4-fluorobenzyl)cyclobutyl]methyl(1S)-1-[cyano(triphenylphosphoranylidene)acetyl]pentylcarbamate in 10 mL of dichloromethane was treated with a stream of ozone for 15 min before being purged with a stream of nitrogen for 5 min. To the reaction was added a solution of 26 mg (0.32 mmol) of 3-aminopyrazole in 1 mL of dichloromethane. The reaction was stirred for 30 min and concentrated under reduced pressure. The residue was dissolved in 5 mL of a 1M solution of silver nitrate in 4:1 tetrahydrofuran:water. The reacton was stirred at room temperature for 18 h and diluted with water. The mixture was extracted with dichloromethane, dried over magnesium sulfate, and concentrated. The residue was purified by silica gel chromatography eluting with 3.5:6.5 acetone:hexanes to afford 30 mg (21%) of [1-(4-fluorobenzyl)cyclobutyl]methyl(1S)-1-[oxo(1H-pyrazol-5-ylamino)acetyl]pentylcarbamate. 1H NMR (300 MHz, 80° C., DMSO-d6) δ 7.65 (s, 1H), 7.42 (s, 1H), 7.22 (t, J=6 Hz, 2H), 7.08 (t, J=9 Hz, 2H), 6.54 (s, 1H), 4.93 (m, 1H), 3.82 (s, 2H), 2.78 (s, 2H), 1.70-1.95 (m, 2H), 1.61 (m, 2H), 1.38 (m, 4H), 0.91 (t, J=7 Hz, 3H). ES-LCMS m/z 467 (M+Na). HRMS C23H29N4O4F1 m/z 467.2071 (M+Na)Cal; 467.2073 (M+Na)Obs.

Workup

  1. custombefore being purged with a stream of nitrogen for 5 min
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue was dissolved in 5 mL of a 1M solution of silver nitrate in 4:1 tetrahydrofuran
  4. stirringThe reacton was stirred at room temperature for 18 h
  5. additiondiluted with water
  6. extractionThe mixture was extracted with dichloromethane
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with 3.5:6.5 acetone

Sources & evidence

ORD record
ord-7ec0bca25b0147f7a9c23c44dbee36cf
Source dataset
uspto-grants-2007_10
Patent number
US07282512B2

Reaction notes

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