Triethylamine → Benzyl (2-fluoro-4-{2-[3-methyl-3-(1-methylpiperidin-4-yl)ureido]pyridin-4-yloxy}phenyl)carbamate

HRID 492743Notes

Reaction equation

HRID 492743 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.[CH2:27]([N:29]([CH2:32][CH3:33])[CH2:30][CH3:31])C.ClC([O:37][C:38]1C=CC=CC=1)=O.[CH3:44][N:45]1CCC(NC)C[CH2:46]1>O1CCCC1.O.C(OCC)(=O)C.CN(C)C=O>[F:26][C:11]1[CH:10]=[C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:1][C:38]([N:45]([CH3:46])[CH:44]3[CH2:33][CH2:32][N:29]([CH3:27])[CH2:30][CH2:31]3)=[O:37])[CH:7]=2)[CH:14]=[CH:13][C:12]=1[NH:15][C:16](=[O:25])[O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 5663231-Methyl-4-(methylamino)piperidineHCID 57470855Benzyl[4-(2-aminopyridin-4-yloxy)-2-fluorophenyl]carbamate

Product 1

HCID 57677492Benzyl (2-fluoro-4-{2-[3-methyl-3-(1-methylpiperidin-4-yl)ureido]pyridin-4-yloxy}phenyl)carbamateYield 40.7%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of Benzyl [4-(2-aminopyridin-4-yloxy)-2-fluorophenyl]carbamate (200 mg) in tetrahydrofuran (5.0 ml) was added triethylamine (0.197 ml), and then phenyl chloroformate (0.107 ml) 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) and 1-methyl-4-(methylamino)piperidine (0.329 ml) were then added, followed by stirring at room temperature for 18 hrs. To the reaction mixture was added ethyl acetate (50 ml) and water (30 ml) to partition. 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 (FUJI Silysia NH, heptane:ethyl acetate=1:2, ethyl acetate, then ethyl acetate:methanol=20:1 to 10:1) to provide the titled compound (117 mg, 40.7%) 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 18 hrs
  4. customto partition
  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 (FUJI Silysia NH, heptane

Sources & evidence

ORD record
ord-1abd45d560064c6ab67a5e2baa42825c
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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