Morpholine → 4-(4-Amino-3-chlorophenoxy)-2-[(morpholin-4-yl)carbonylamino]pyridine

HRID 492696Notes

Reaction equation

HRID 492696 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[C:11]([Cl:16])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.C(N(CC)CC)C.Cl[C:25](OC1C=CC=CC=1)=[O:26].[NH:34]1[CH2:39][CH2:38][O:37][CH2:36][CH2:35]1>O1CCCC1.C(OCC)C.CCCCCC.CN(C)C=O>[NH2:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:25]([N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[O:26])[CH:7]=2)=[CH:10][C:11]=1[Cl:16]

Participants

8

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 229367984-(4-Amino-3-chlorophenoxy)pyridin-2-ylamine

Product 1

HCID 231532884-(4-Amino-3-chlorophenoxy)-2-[(morpholin-4-yl)carbonylamino]pyridineYield 49%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 21584099Diethylether hexaneSolvent

Procedure

2-Amino-4-(4-amino-3-chlorophenoxy)pyridine (236 mg) as disclosed in WO 02/32872 was dissolved in tetrahydrofuran (10 ml) under a nitrogen atmosphere, and then triethylamine (0.21 ml) and phenyl chloroformate (0.188 ml) were added dropwise thereto while cooling in an ice bath, followed by raising the temperature gradually to room temperature and stirring overnight. To the reaction mixture were added N,N-dimethylformamide (2 ml) and morpholine (0.5 ml), followed by further stirring for 1 day. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (eluent; ethyl acetate). Fractions containing the target compound were concentrated to give a residue, to which diethyl ether-hexane was added to suspend, followed by evaporating the solvent. The residue was dried in vacuum to provide the titled compound (172 mg, 49%) as white powder.

Workup

  1. temperaturewhile cooling in an ice bath
  2. stirringby further stirring for 1 day
  3. customThe reaction mixture was partitioned between ethyl acetate and water
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was evaporated
  7. customto give a residue, which
  8. customwas then purified by silica gel column chromatography (eluent; ethyl acetate)
  9. additionFractions containing the target compound
  10. concentrationwere concentrated
  11. customto give a residue
  12. customby evaporating the solvent
  13. customThe residue was dried in vacuum

Sources & evidence

ORD record
ord-2a3b3273675247ad9d54972602ebfc15
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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