Pyridine → HCID 67202244, compound

HRID 387906Notes

Reaction equation

HRID 387906 reaction equation
[NH2:1][C:2]1[CH:30]=[CH:29][C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:20][C@H:21]([OH:28])[CH2:22][N:23]([CH2:26][CH3:27])[CH2:24][CH3:25])=[C:14]([C:17]#[N:18])[CH:15]=3)[N:10]=[CH:9][CH:8]=2)=[CH:4][C:3]=1[Cl:31].[N:32]1[CH:37]=C[CH:35]=[CH:34][CH:33]=1.ClC(OC1C=CC=CC=1)=[O:40].C1(N)CC1.C(=O)(O)[O-].[Na+]>CN(C)C=O.C(OCC)(=O)C>[Cl:31][C:3]1[CH:4]=[C:5]([O:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:20][C@H:21]([OH:28])[CH2:22][N:23]([CH2:26][CH3:27])[CH2:24][CH3:25])=[C:14]([C:17]#[N:18])[CH:15]=3)[N:10]=[CH:9][CH:8]=2)[CH:29]=[CH:30][C:2]=1[NH:1][C:37]([NH:32][CH:33]1[CH2:35][CH2:34]1)=[O:40]

Participants

8

Reactant 5

HCID 1049PyridineHCID 15891Phenyl chloroformateHCID 69828CyclopropylamineHCID 516892Sodium BicarbonateHCID 67201998HCID 67201998, compound

Product 1

HCID 67202244HCID 67202244, compoundYield 53.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

After dissolving (4-(4-amino-3-chlorophenoxy)-6-cyano-7-(((2R)-3-(diethylamino)-2-hydroxypropyl)oxy)quinoline) (96.9 mg, 0.22 mmol) in dimethylformamide (1 ml) under a nitrogen atmosphere, pyridine (0.027 ml, 0.33 mmol) and phenyl chloroformate (0.035 ml, 0.28 mmol) were added dropwise at room temperature, and the mixture was stirred for 1 hour. Cyclopropylamine (0.10 ml) 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 saline 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 (61.6 mg, 0.118 mmol, 53.5%) as light yellow crystals.

Workup

  1. waitthe mixture was further stirred overnight
  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. additiondiluted with hexane
  8. filtrationthe crystals were filtered out and
  9. customblow-dried

Sources & evidence

ORD record
ord-ac9f9705fc354b179f02ef7f9e0f1923
Source dataset
uspto-grants-2013_02
Patent number
US08372981B2

Reaction notes

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