Water → HCID 68154200, compound

HRID 341074Notes

Reaction equation

HRID 341074 reaction equation
[O:1]=[C:2]1[C:6]2=[CH:7][N:8]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([N:22]4[CH:26]=[CH:25][CH:24]=[N:23]4)=[CH:18][CH:17]=3)[C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=3[C:5]2=[N:4][N:3]1[C:27]1[CH:34]=[CH:33][CH:32]=[CH:31][C:28]=1C=O.[CH2:35]([Mg]Br)[CH3:36].[C:39](=O)(O)[O-:40].[Na+].O>ClCCl>[OH:40][CH2:39][CH2:35][CH2:36][C:28]1[CH:31]=[CH:32][CH:33]=[CH:34][C:27]=1[N:3]1[C:2](=[O:1])[C:6]2=[CH:7][N:8]([CH2:15][C:16]3[CH:17]=[CH:18][C:19]([N:22]4[CH:26]=[CH:25][CH:24]=[N:23]4)=[CH:20][CH:21]=3)[C:9]3[CH:10]=[CH:11][CH:12]=[CH:13][C:14]=3[C:5]2=[N:4]1

Participants

6

Reactant 4

HCID 962WaterHCID 516892Sodium BicarbonateHCID 86668679HCID 86668679, compoundHCID 178418443HCID 178418443, compound2×

Product 1

HCID 68154200HCID 68154200, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

2-(3-oxo-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-3,5-dihydro-2H-pyrazolo[4,3-c]quinolin-2-yl)benzaldehyde (Example 529, 0.14 g, 0.32 mmol) was dissolved in dichloromethane (5 mL) and cooled to −78° C. Ethylmagnesium bromide (0.10 mL, 3 M diethyl ether solution, 0.32 mmol, equiv) was added dropwise and the mixture was stirred for 30 minutes at −78° C. Additional ethylmagnesium bromide (0.10 mL, 3 M diethyl ether solution, 0.32 mmol, 1 equiv) was added and the mixture was stirred for an additional 30 minutes at −78° C. The mixture was treated with sodium bicarbonate (3 mL, aqueous saturated) and warmed to ambient temperature, poured into water and extracted with dichloromethane (3×50 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified via silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate; then 100:0 to 0:100; ethyl acetate:ethyl acetate containing 5% methanol), providing the titled compound: 1H-NMR (400 MHz, d6-DMSO) δ 9.14 (1H, s), 8.46 (1H, d, J=2.4 Hz), 8.18 (1H, d, J=8.0 Hz), 7.84 (2H, d, J=8.7 Hz), 7.78 (1H, d, J=8.7 Hz), 7.73 (1H, m), 7.67-7.60 (2H, m), 7.53 (1H, t, J=7.7 Hz), 7.48 (2H, d, J=8.5 Hz), 7.43 (1H, br t, J=7.6 Hz), 7.38-7.33 (2H, m), 6.53 (1H, m), 5.78 (2H, s), 5.12 (1H, d, J=4.7 Hz), 4.73-4.68 (1H, m), 1.71-1.64 (1H, m), 1.5-1.43 (1H, m), 0.78 (3H, t, J=7.4 Hz) ppm; high resolution mass spectrometry (ES+) m/z 476.2061 [(M+H)+; calculated for C29H26N5O2: 476.2081].

Workup

  1. stirringthe mixture was stirred for an additional 30 minutes at −78° C
  2. temperaturewarmed to ambient temperature
  3. extractionextracted with dichloromethane (3×50 mL)
  4. dry with materialThe combined organic extracts were dried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified via silica gel gradient chromatography (100:0 to 0:100

Sources & evidence

ORD record
ord-07bb39b8e4654e009b47af67fb4eabcb
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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