Acetyl chloride → HCID 68154036, compound

HRID 341095Notes

Reaction equation

HRID 341095 reaction equation
[OH:1][C:2]1[C:3]2[C:4]3[C:5]([C:24](=[O:34])[N:25]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[CH3:33])[N:26]=3)=[CH:6][N:7]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([N:19]4[CH:23]=[CH:22][CH:21]=[N:20]4)=[CH:15][CH:14]=3)[C:8]=2[CH:9]=[CH:10][CH:11]=1.C(N(CC)C(C)C)(C)C.[C:44](Cl)(=[O:46])[CH3:45].C(=O)(O)[O-].[Na+]>ClCCl.CN(C1C=CN=CC=1)C>[C:44]([O:1][C:2]1[C:3]2[C:4]3[C:5]([C:24](=[O:34])[N:25]([C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=4[CH3:33])[N:26]=3)=[CH:6][N:7]([CH2:12][C:13]3[CH:18]=[CH:17][C:16]([N:19]4[CH:23]=[CH:22][CH:21]=[N:20]4)=[CH:15][CH:14]=3)[C:8]=2[CH:9]=[CH:10][CH:11]=1)(=[O:46])[CH3:45]

Participants

7

Reactant 4

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 178424336HCID 178424336, compound

Product 1

HCID 68154036HCID 68154036, compound

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

9-Hydroxy-2-(2-methylphenyl)-5-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one (Example 724, 56 mg, 0.12 mmol) was dissolved in dichloromethane (2.5 mL), treated with N,N-dimethyl-4-aminopyridine (1.5 mg, 0.013 mmol, 0.1 equiv) and N,N-diisopropylethylamine (0.033 mL, 0.19 mmol, 1.5 equiv) and cooled to 0° C. To the mixture was added acetyl chloride (0.012 mL, 0.17 mmol, 1.4 equiv), and after 15 minutes the mixture was warmed to ambient temperature. After 15 minutes at ambient temperature, the mixture was poured into sodium bicarbonate (5 mL, aqueous saturated) and extracted with dichloromethane (2×15 mL). The combined organic extracts were washed with hydrochloric acid (2×15 mL, 1 N aqueous) and brine (1×10 mL), dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate containing 5% methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.47 (1H, s), 7.91 (1H, d, J=2.6 Hz), 7.73 (1H, d, J=1.7 Hz), 7.72 (2H, d, J=8.6 Hz), 7.47 (1H, t, J=8.2 Hz), 7.44-7.42 (1H, m), 7.34-7.26 (6H, m), 7.17 (1H, d, J=7.9 Hz), 6.47 (1H, dd, J=2.3, 1.9 Hz), 5.45 (2H, s), 2.33 (3H, s), 2.32 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 490.1900 [(M+H)+; calculated for C29H24N5O3: 490.1874].

Workup

  1. temperatureafter 15 minutes the mixture was warmed to ambient temperature
  2. extractionextracted with dichloromethane (2×15 mL)
  3. washThe combined organic extracts were washed with hydrochloric acid (2×15 mL, 1 N aqueous) and brine (1×10 mL)
  4. dry with materialdried with sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel gradient chromatography (100:0 to 0:100; hexanes:ethyl acetate containing 5% methanol)

Sources & evidence

ORD record
ord-3ca1da19595b4dd2b73416e0288c1c7d
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

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