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N-(2,2-dimethoxyethyl)-2-Pyrazinamine → 2-{2-[7-Chloro-6-[3-(2,2-dimethoxyethyl)-3-pyrazin-2-yl-ureido]-3-(3,5-dimethylphenyl)-2-oxo-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid 2-trimethylsilanylethyl ester

HRID 1858080
Notes
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Reaction equation

HRID 1858080 reaction equation
[CH3:1][O:2][CH:3]([O:12][CH3:13])[CH2:4][NH:5][C:6]1[CH:11]=[N:10][CH:9]=[CH:8][N:7]=1.C([Li])CCC.[CH3:19][Si:20]([CH3:59])([CH3:58])[CH2:21][CH2:22][O:23][C:24]([N:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]1[CH2:32][CH2:33][O:34][C:35]1[C:44]2[C:39](=[CH:40][C:41]([Cl:48])=[C:42]([N:45]=[C:46]=[O:47])[CH:43]=2)[NH:38][C:37](=[O:49])[C:36]=1[C:50]1[CH:55]=[C:54]([CH3:56])[CH:53]=[C:52]([CH3:57])[CH:51]=1)=[O:25]>>[CH3:58][Si:20]([CH3:19])([CH3:59])[CH2:21][CH2:22][O:23][C:24]([N:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]1[CH2:32][CH2:33][O:34][C:35]1[C:44]2[C:39](=[CH:40][C:41]([Cl:48])=[C:42]([NH:45][C:46]([N:5]([CH2:4][CH:3]([O:2][CH3:1])[O:12][CH3:13])[C:6]3[CH:11]=[N:10][CH:9]=[CH:8][N:7]=3)=[O:47])[CH:43]=2)[NH:38][C:37](=[O:49])[C:36]=1[C:50]1[CH:55]=[C:54]([CH3:56])[CH:53]=[C:52]([CH3:57])[CH:51]=1)=[O:25]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

4

Reactant 3

HCID 22124488N-(2,2-dimethoxyethyl)-2-PyrazinamineHCID 539605652-{2-[7-Chloro-3-(3,5-dimethylphenyl)-6-isocyanato-2-oxo-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid 2-trimethylsilanylethyl esterHCID 178418339Butyllithium

Product 1

HCID 544133062-{2-[7-Chloro-6-[3-(2,2-dimethoxyethyl)-3-pyrazin-2-yl-ureido]-3-(3,5-dimethylphenyl)-2-oxo-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid 2-trimethylsilanylethyl ester
Yield 9%

Procedure

To a solution of (2,2-dimethoxyethyl)-pyrazin-2-yl-amine (103 mg in 3 mL dry tetrahydrofuran) at -78° C. was added 0.23 mL of a 2.5M solution of butyllithium and the mixture stirred for 30 minutes. At this time, a solution of 2-{2-[7-chloro-3-(3,5-dimethylphenyl)-6-isocyanato-2-oxo-1,2-dihydroquinolin-4-yloxy]-ethyl}-piperidine-1-carboxylic acid 2-trimethylsilanylethyl ester (94 mg in 2 mL tetrahydrofuran) was added via cannula and the mixture warmed to room temperature. After 20 hours, the reaction was quenched by the addition of saturated ammonium chloride and extracted with chloroform. The organic portion was washed with brine, dried over sodium sulfate and concentrated in vacuo. Purification of the residue by preparative tlc on silica gel (ethyl acetate) gave the title compound (11 mg).

Workup

  1. waitAfter 20 hours
  2. customthe reaction was quenched by the addition of saturated ammonium chloride
  3. extractionextracted with chloroform
  4. washThe organic portion was washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customPurification of the residue by preparative tlc on silica gel (ethyl acetate)

Sources & evidence

ORD record
ord-7da0a3eb687b4a18950504c3d7322933
Source dataset
uspto-grants-2000_11
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06150352

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes