Water → HCID 86587186, compound

HRID 2414509Notes

Reaction equation

HRID 2414509 reaction equation
[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[NH:17][C:18]4[C:23]([C:24](=[O:26])[CH:25]=3)=[CH:22][C:21]([O:27][CH3:28])=[CH:20][C:19]=4[Br:29])=[O:15])=[CH:9][CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[H-].[Na+].[CH3:32][Si:33]([CH3:40])([CH3:39])[CH2:34][CH2:35][O:36][CH2:37]Cl.O>CN1CCCC1=O.CO>[N:1]1([C:7]2[CH:12]=[CH:11][C:10]([NH:13][C:14]([C:16]3[CH:25]=[C:24]([O:26][CH2:37][O:36][CH2:35][CH2:34][Si:33]([CH3:40])([CH3:39])[CH3:32])[C:23]4[C:18](=[C:19]([Br:29])[CH:20]=[C:21]([O:27][CH3:28])[CH:22]=4)[N:17]=3)=[O:15])=[CH:9][CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 86587185HCID 86587185, compound

Product 1

HCID 86587186HCID 86587186, compoundYield 80.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A yellow suspension of 8-bromo-6-methoxy-4-oxo-1,4-dihydro-quinoline-2-carboxylic acid (4-morpholin-4-yl-phenyl)-amide (Reference Example 27b) (3.092 g, 6.75 mmol) in 40 mL N-methylpyrolidinone was treated with sodium hydride (60% dispersion in oil, 0.410 g, 10.24 mmol). Gas evolution and warming were observed and the suspension became light brown and almost clear. The reaction was stirred for 10 minutes at room temperature under nitrogen. Addition of the 2-(trimethylsilyl)ethoxymethyl chloride (1.6 mL, 9.1 mmol) resulted in a slightly cloudy, lighter brown solution. After 4.5 hours at room temperature, the reaction mixture was poured into 300 mL water, stirred for 15 minutes and then stored at 0° C. overnight. The solids were isolated by filtration, suspended in methanol, filtered again, and dried under high vacuum to afford the product as a yellow solid (3.190 g, 80%). 1H NMR (300 MHz, DMSO, d6) δ 10.18 (s, 1H, C(O)NH), 7.95 (d, 1H, Jm=2.4 Hz, ArH7), 7.83 (s, 1H, ArH3), 7.69 (d, 2H, Jo=9.0 Hz, ArH2′ & H6′), 7.51 (d, 1H, Jm=2.7 Hz, ArH5), 7.00 (d, 2H, Jo=9.0 Hz, ArH3′ & H5′), 5.69 (s, 2H, OCH2O), 3.95 (s, 3H, OCH3), 3.85 (t, 2H, J=8.0 Hz, OCH2CH2Si), 3.75 (t, 4H, J=4.7 Hz, OCH2CH2N), 3.10 (t, 4H, J=4.7 Hz, OCH2CH2N), 0.94 (t, 2H, J=8.0 Hz, OCH2CH2Si), −0.04 (s, 9H, Si(CH3)3; Mass Spec.: calc. for [C27H34BrN3O5Si+H]+ Theor. m/z=588, 590; Obs.=588, 590.

Workup

  1. temperatureGas evolution and warming
  2. customresulted in a slightly cloudy, lighter brown solution
  3. waitAfter 4.5 hours at room temperature
  4. stirringstirred for 15 minutes
  5. waitstored at 0° C. overnight
  6. customThe solids were isolated by filtration
  7. filtrationfiltered again
  8. customdried under high vacuum

Sources & evidence

ORD record
ord-ba7edcf726b749aa986fd46d3ec12a2e
Source dataset
uspto-grants-2004_11
Patent number
US06812225B2

Reaction notes

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