Dimethylamine, hydrochloride → Benzyl {4-[2-(3,3-dimethylureido)pyridin-4-yloxy]-2-fluorophenyl}carbamate

HRID 492741Notes

Reaction equation

HRID 492741 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:25])[O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[C:11]([F:26])[CH:10]=2)[CH:5]=[CH:4][N:3]=1.ClC([O:30][C:31]1C=CC=CC=1)=O.Cl.[CH3:38][NH:39][CH3:40]>O1CCCC1.C(N(CC)CC)C.CN(C)C=O>[CH3:38][N:39]([CH3:40])[C:31](=[O:30])[NH:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:25])[O:17][CH2:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[C:11]([F:26])[CH:10]=2)[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 3

HCID 10473Dimethylamine, hydrochlorideHCID 15891Phenyl chloroformateHCID 57470855Benzyl[4-(2-aminopyridin-4-yloxy)-2-fluorophenyl]carbamate

Product 1

HCID 57677734Benzyl {4-[2-(3,3-dimethylureido)pyridin-4-yloxy]-2-fluorophenyl}carbamateYield 84.3%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolvent2×

Procedure

To a solution of benzyl [4-(2-aminopyridin-4-yloxy)-2-fluorophenyl]carbamate (163 mg, 0.461 mmol) in tetrahydrofuran (4.50 ml) was added triethylamine (0.128 ml, 0.918 mmol), and then phenyl chloroformate (0.0872 ml, 0.695 mmol) was added dropwise thereto, followed by stirring at room temperature for 10 min. The reaction mixture was concentrated under a reduced pressure to give a residue, to which N,N-dimethylformamide (2.0 ml), dimethylamine hydrochloride (188 mg, 2.31 mmol) and triethylamine (0.386 ml) were then added, followed by stirring at room temperature for 8 hrs. The reaction mixture was partitioned between ethyl acetate (50 ml) and water (30 ml). The organic layer was washed with brine (30 ml×3), 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, then ethyl acetate:methanol=20:1) to provide the titled compound (165 mg, 47.5%) as pale yellow powder.

Workup

  1. concentrationThe reaction mixture was concentrated under a reduced pressure
  2. customto give a residue
  3. stirringby stirring at room temperature for 8 hrs
  4. customThe reaction mixture was partitioned between ethyl acetate (50 ml) and water (30 ml)
  5. washThe organic layer was washed with brine (30 ml×3)
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated
  8. customto give a residue, which
  9. customwas then purified by silica gel column chromatography (eluent

Sources & evidence

ORD record
ord-afe4c793e111489d9b3d763a0dd6b6fb
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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