Triethylamine → Benzyl (2-fluoro-4-{2-[(4-pyrrolidin-1-ylpiperidine-1-carbonyl)amino]pyridin-4-yloxy}phenyl)carbamate

HRID 492764Notes

Reaction equation

HRID 492764 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.C(N(CC)CC)C.Cl[C:35](OC1C=CC=CC=1)=[O:36].[N:44]1([CH:49]2[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]2)[CH2:48][CH2:47][CH2:46][CH2:45]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:35]([N:52]3[CH2:53][CH2:54][CH:49]([N:44]4[CH2:48][CH2:47][CH2:46][CH2:45]4)[CH2:50][CH2:51]3)=[O:36])[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 787034-(1-Pyrrolidinyl)piperidineHCID 57470855Benzyl[4-(2-aminopyridin-4-yloxy)-2-fluorophenyl]carbamate

Product 1

HCID 23153372Benzyl (2-fluoro-4-{2-[(4-pyrrolidin-1-ylpiperidine-1-carbonyl)amino]pyridin-4-yloxy}phenyl)carbamateYield 47.5%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of benzyl [4-(2-aminopyridin-4-yloxy)-2-fluorophenyl]carbamate (230 mg) in tetrahydrofuran (6.50 ml) was added triethylamine (0.181 ml), and then phenyl chloroformate (0.123 ml) was added dropwise thereto while stirring in an ice bath, followed by stirring 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 4-(1-pyrrolidinyl)piperidine (301 mg) were then added, followed by stirring at room temperature for 11 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 under a reduced pressure to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; heptane:ethyl acetate=1:2, ethyl acetate, then ethyl acetate:methanol=10:1) to provide the titled compound (165 mg, 47.5%) as pale yellow powder.

Workup

  1. stirringby stirring for 10 min
  2. concentrationThe reaction mixture was concentrated under a reduced pressure
  3. customto give a residue
  4. stirringby stirring at room temperature for 11 hrs
  5. customto partition
  6. washThe organic layer was washed with brine (30 ml×3)
  7. dry with materialdried over anhydrous sodium sulfate
  8. customThe solvent was evaporated under a reduced pressure
  9. customto give a residue, which
  10. customwas then purified by silica gel column chromatography (FUJI Silysia NH, eluent

Sources & evidence

ORD record
ord-fed1a37c5c9b4576a98fdc64bc7f1f4c
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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