Diethylamine → HCID 11685165, compound

HRID 388038Notes

Reaction equation

HRID 388038 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+].[CH3:22][NH:23][C:24]([C:26]1[CH:27]=[C:28]2[C:33](=[CH:34][C:35]=1[OH:36])[N:32]=[CH:31][CH:30]=[C:29]2[O:37][C:38]1[CH:43]=[CH:42][C:41]([NH:44][C:45]([NH:47][CH3:48])=[O:46])=[C:40]([Cl:49])[CH:39]=1)=[O:25].[CH2:50]([NH:52][CH2:53][CH3:54])[CH3:51]>O.C(OCC)(=O)C.O1CCCC1.CN(C)C=O>[CH3:22][NH:23][C:24]([C:26]1[CH:27]=[C:28]2[C:33](=[CH:34][C:35]=1[O:36][CH2:15][C@H:13]([OH:14])[CH2:12][N:52]([CH2:53][CH3:54])[CH2:50][CH3:51])[N:32]=[CH:31][CH:30]=[C:29]2[O:37][C:38]1[CH:43]=[CH:42][C:41]([NH:44][C:45]([NH:47][CH3:48])=[O:46])=[C:40]([Cl:49])[CH:39]=1)=[O:25]

Participants

8

Reactant 4

HCID 8021DiethylamineHCID 11430Potassium CarbonateHCID 154187Glycidyl tosylate, (R)-HCID 135829386HCID 135829386, compound

Product 1

HCID 11685165HCID 11685165, compoundYield 45.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 21939870Tetrahydrofuran ethyl acetateSolvent

Conditions

Temperature
60 °C

Procedure

After adding (2R)oxiran-2-ylmethyl 4-methyl-1-benzenesulfonate (103 mg, 0.499 mmol), potassium carbonate (50 mg, 0.359 mmol) and dimethylformamide (3 ml) to N6-methyl-4-(3-chloro-4-(((methylamino)carbonyl)amino)phenoxy)-7-hydroxy-6-quinolinecarboxamide (120 mg, 0.299 mmol), the mixture was stirred at 60° C. for 7 hours. Next, diethylamine (1.5 ml) was added and the mixture was further stirred overnight at 60° C. The reaction solution was distributed between ethyl acetate-tetrahydrofuran (1:1) 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 ethyl acetate-hexane (1:1), filtered out and blow-dried to obtain the title compound (71.8 mg, 0.135 mmol, 45.2%) as white crystals.

Workup

  1. waitthe mixture was further stirred overnight at 60° 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 ethyl acetate-hexane (1:1)
  8. filtrationfiltered out and
  9. customblow-dried

Sources & evidence

ORD record
ord-b54ed955de4d48bf8e1e63f4bcd7f080
Source dataset
uspto-grants-2013_02
Patent number
US08372981B2

Reaction notes

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