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

HRID 492764Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 492764
[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

Komponenten

9

Edukt 4

HCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 787034-(1-Pyrrolidinyl)piperidineHCID 57470855Benzyl[4-(2-aminopyridin-4-yloxy)-2-fluorophenyl]carbamate

Produkt 1

HCID 23153372Benzyl (2-fluoro-4-{2-[(4-pyrrolidin-1-ylpiperidine-1-carbonyl)amino]pyridin-4-yloxy}phenyl)carbamateAusbeute 47,5 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-fed1a37c5c9b4576a98fdc64bc7f1f4c
Quelldatensatz
uspto-grants-2009_05
Patentnummer
US07531532B2

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