Pyridine → HCID 22936999, compound

HRID 1433559Notes

Reaction equation

HRID 1433559 reaction equation
[NH2:1][C:2]1[CH:36]=[CH:35][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:20][CH2:21][CH:22]4[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]4)=[C:14]([C:17]#[N:18])[CH:15]=3)[N:10]=[CH:9][CH:8]=2)=[CH:4][C:3]=1[Cl:37].[N:38]1[CH:43]=C[CH:41]=[CH:40][CH:39]=1.ClC(OC1C=CC=CC=1)=[O:46].C1(N)CC1.C(=O)(O)[O-].[Na+]>CN(C)C=O.C(OCC)(=O)C>[Cl:37][C:3]1[CH:4]=[C:5]([CH:35]=[CH:36][C:2]=1[NH:1][C:43]([NH:38][CH:39]1[CH2:41][CH2:40]1)=[O:46])[O:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([O:19][CH2:20][CH2:21][CH:22]3[CH2:23][CH2:24][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:32])[CH3:33])=[O:29])[CH2:26][CH2:27]3)=[C:14]([C:17]#[N:18])[CH:15]=2)[N:10]=[CH:9][CH:8]=1

Participants

8

Reactant 5

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 69828CyclopropylamineHCID 516892Sodium BicarbonateHCID 22936784HCID 22936784, compound

Product 1

HCID 22936999HCID 22936999, compoundYield 60.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

After dissolving tert-butyl 4-(((4-(4-amino-3-chlorophenoxy)-6-cyano-7-quinolyl)oxy)ethyl)-1-piperidine carboxylate (486.5 mg, 0.930 mmol) in dimethylformamide (5 ml) under a nitrogen atmosphere, pyridine (0.170 ml, 2.09 mmol) and phenyl chloroformate (0.175 ml, 1.34 mmol) were added dropwise at room temperature, and the mixture was stirred for 1 hour. Cyclopropylamine (0.322 ml, 4.65 mmol) was added dropwise, and the mixture was further stirred overnight. The reaction solution was distributed between ethyl acetate and saturated aqueous sodium bicarbonate, and the organic layer was washed with water and saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off, the residue was subjected to silica gel column chromatography (eluent—ethyl acetate), the fraction containing the target substance was concentrated, suspended in ethyl acetate and diluted with hexane, and the crystals were filtered out and blow-dried to obtain the title compound (343 mg, 0.566 mmol, 60.8%) as light yellow crystals.

Workup

  1. waitthe mixture was further stirred overnight
  2. washthe organic layer was washed with water and saturated brine
  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. additiondiluted with hexane
  8. filtrationthe crystals were filtered out and
  9. customblow-dried

Sources & evidence

ORD record
ord-ed398927fbeb48c1b49957c6e87b2606
Source dataset
uspto-grants-2009_11
Patent number
US07612092B2

Reaction notes

Loading…