Water → HCID 69935106, compound

HRID 341080Notes

Reaction equation

HRID 341080 reaction equation
[N:1]([CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[C:35](=[O:36])[C:14]2=[CH:15][N:16]([CH2:23][C:24]3[CH:29]=[CH:28][C:27]([N:30]4[CH:34]=[CH:33][CH:32]=[N:31]4)=[CH:26][CH:25]=3)[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:22]=3[C:13]2=[N:12]1)=[N+]=[N-].CP(C)C.[OH-].[Na+].O>O1CCCC1>[NH2:1][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[N:11]1[C:35](=[O:36])[C:14]2=[CH:15][N:16]([CH2:23][C:24]3[CH:29]=[CH:28][C:27]([N:30]4[CH:34]=[CH:33][CH:32]=[N:31]4)=[CH:26][CH:25]=3)[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][C:22]=3[C:13]2=[N:12]1

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 68983TrimethylphosphineHCID 86668681HCID 86668681, compound

Product 1

HCID 69935106HCID 69935106, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

2-[2-(Azidomethyl)phenyl]-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (Example 661, 92 mg, 0.19 mmol) was dissolved in tetrahydrofuran (6 mL) and cooled to 0° C. Trimethylphosphine (0.97 mL, 1 M tetrahydrofuran solution, 0.97 mmol, 5 equiv) was added, the ice bath removed and the mixture was warmed to ambient temperature and stirred for 2 hours. The mixture was treated with sodium hydroxide (1.9 mL, 1 M aqueous, 10 equiv) and stirred for an additional 1 hour. The mixture was poured into water and extracted with chloroform (4×150 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 85:15; dichloromethane:methanol containing 10% ammonium hydroxide), providing the titled compound: 1H-NMR (400 MHz, d6-DMSO, hydrochloride salt) δ 9.27 (1H, s), 8.47 (1H, d, J=2.6 Hz), 8.33 (1H, dd, J=7.9, 1.4 Hz), 8.36-8.27 (3H, br s), 7.86-7.82 (3H, m), 7.73 (1H, d, J=1.5 Hz), 7.70-7.64 (3H, m), 7.60-7.55 (2H, m), 7.52-7.47 (3H, m), 6.54 (1H, m), 5.83 (2H, s), 4.04 (2H, q, J=5.6 Hz) ppm; high resolution mass spectrometry (ES+) m/z 447.1911 [(M+H)+; calculated for C27H23N6O: 447.1928].

Workup

  1. customthe ice bath removed
  2. temperaturethe mixture was warmed to ambient temperature
  3. stirringstirred for an additional 1 hour
  4. extractionextracted with chloroform (4×150 mL)
  5. dry with materialThe combined organic extracts were dried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel gradient chromatography (100:0 to 85:15; dichloromethane:methanol containing 10% ammonium hydroxide)

Sources & evidence

ORD record
ord-ac4f955fdfde4d01866f505efde77257
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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