Diethylamine → HCID 58930988, compound

HRID 388034Notes

Reaction equation

HRID 388034 reaction equation
CC1C=CC(S(O[CH2:12][C@H:13]2[CH2:15][O:14]2)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+].[Cl:22][C:23]1[CH:24]=[C:25]([CH:41]=[CH:42][C:43]=1[NH:44][C:45]([NH:47][CH:48]1[CH2:50][CH2:49]1)=[O:46])[O:26][C:27]1[C:36]2[C:31](=[CH:32][C:33]([OH:40])=[C:34]([C:37]([NH2:39])=[O:38])[CH:35]=2)[N:30]=[CH:29][CH:28]=1.[CH2:51]([NH:53][CH2:54][CH3:55])[CH3:52]>O.C(OCC)(=O)C.CN(C)C=O>[Cl:22][C:23]1[CH:24]=[C:25]([CH:41]=[CH:42][C:43]=1[NH:44][C:45]([NH:47][CH:48]1[CH2:50][CH2:49]1)=[O:46])[O:26][C:27]1[C:36]2[C:31](=[CH:32][C:33]([O:40][CH2:15][C@H:13]([OH:14])[CH2:12][N:53]([CH2:54][CH3:55])[CH2:51][CH3:52])=[C:34]([C:37]([NH2:39])=[O:38])[CH:35]=2)[N:30]=[CH:29][CH:28]=1

Participants

8

Reactant 4

HCID 8021DiethylamineHCID 11430Potassium CarbonateHCID 154187Glycidyl tosylate, (R)-HCID 1355660464-[3-Chloro-4-(cyclopropylcarbamamido)phenoxy]-7-hydroxy-6-quinolinecarboxamide

Product 1

HCID 58930988HCID 58930988, compoundYield 36.3%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

After adding (2R)oxiran-2-ylmethyl 4-methyl-1-benzenesulfonate (308 mg, 1.35 mmol), potassium carbonate (149 mg, 1.08 mmol) and dimethylformamide (9 ml) to 4-(3-chloro-4-(((cyclopropylamino)carbonyl)amino)phenoxy)-7-hydroxy-6-quinolinecarboxamide (372.0 mg, 0.90 mmol), the mixture was stirred at 60° C. for 6 hours. Next, diethylamine (2 ml) was added and the mixture was further stirred overnight at 50° C. The reaction solution was distributed between ethyl acetate and water, and the organic layer was washed with water and saturated saline and then dried over anhydrous sodium sulfate. The solvent was distilled off, the residue was subjected to silica gel column chromatography (eluent-ethyl acetate:methanol=95:5), the fraction containing the target substance was concentrated, and crystals were precipitated from diethyl ether, filtered out and blow-dried to obtain the title compound (177.5 mg, 0.327 mmol, 36.3%) as white crystals.

Workup

  1. waitthe mixture was further stirred overnight at 50° C
  2. washthe organic layer was washed with water and saturated saline
  3. dry with materialdried over anhydrous sodium sulfate
  4. distillationThe solvent was distilled off
  5. additionthe fraction containing the target substance
  6. concentrationwas concentrated
  7. customcrystals were precipitated from diethyl ether
  8. filtrationfiltered out
  9. customblow-dried

Sources & evidence

ORD record
ord-2d8d18369a044aae961892793e5ed572
Source dataset
uspto-grants-2013_02
Patent number
US08372981B2

Reaction notes

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