3-Aminopyridine → 1-pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[3-(3-fluoro-5-trifluoromethyl-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide

HRID 1093878Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1093878
CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[N:31]1[CH:36]=[CH:35][CH:34]=[C:33]([N:37]2[CH:41]=[C:40]([C:42]([NH:44][CH2:45][C:46]([OH:48])=O)=[O:43])[N:39]=[N:38]2)[CH:32]=1.NC1C=NC=CC=1.Cl.[F:57][C:58]1[CH:59]=[C:60]([CH:66]=[C:67]([C:69]([F:72])([F:71])[F:70])[CH:68]=1)[O:61][CH:62]1[CH2:65][NH:64][CH2:63]1>CN(C=O)C>[F:57][C:58]1[CH:59]=[C:60]([CH:66]=[C:67]([C:69]([F:71])([F:70])[F:72])[CH:68]=1)[O:61][CH:62]1[CH2:65][N:64]([C:46](=[O:48])[CH2:45][NH:44][C:42]([C:40]2[N:39]=[N:38][N:37]([C:33]3[CH:32]=[N:31][CH:36]=[CH:35][CH:34]=3)[CH:41]=2)=[O:43])[CH2:63]1

Komponenten

8

Edukt 6

HCID 100093-AminopyridineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 66592012[(1-pyridin-3-yl-1H-[1,2,3]triazole-4-carbonyl)-amino]-acetic acidHCID 665922143-(3-Fluoro-5-trifluoromethyl-phenoxy)-azetidine hydrochloride

Produkt 1

HCID 578744501-pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[3-(3-fluoro-5-trifluoromethyl-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amideAusbeute 16,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

DIPEA (143 mg, 1.1 mmol) followed by HOBt (39 mg, 0.29 mmol) and EDCI (56 mg, 0.29 mmol) was added to a stirred solution of [(1-pyridin-3-yl-1H-[1,2,3]triazole-4-carbonyl)-amino]-acetic acid (prepared by the method used for the synthesis of Intermediate 64, starting from 3-aminopyridine, and subsequently, application of Step 3 of the General Scheme) (68.3 mg, 0.27 mmol) in DMF (2 mL). After 2 minutes of stirring, 3-(3-fluoro-5-trifluoromethyl-phenoxy)-azetidine hydrochloride (prepared by the method used for the synthesis of Intermediate 71) (75 mg, 0.27 mmol) was added and the resulting mixture was stirred at room temperature overnight. The reaction mixture was partitioned between cold water and ethyl acetate. The organic layer was, dried over sodium sulfate and concentrated under reduced pressure. Purification by preparative HPLC afforded 21 mg (16.4% Yield) of 1-pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[3-(3-fluoro-5-trifluoromethyl-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide. LC/MS [M+H]+: 465, 93.03%. 1H NMR (300 MHz, DMSO-d6): δ 9.5 (s, 1H), 9.2 (d, 1H), 8.7 (m, 2H), 8.4 (m, 1H), 8.3 (s, 1H), 7.65 (m, 1H), 7.3 (d, 1H), 7.1 (m, 2H), 5.2 (m, 1H), 4.7 (m, 1H), 4.4 (m, 1H), 4.2 (m, 1H), 3.8 (m, 3H).

Aufarbeitung

  1. customprepared by the method
  2. additionwas added
  3. stirringthe resulting mixture was stirred at room temperature overnight
  4. customThe reaction mixture was partitioned between cold water and ethyl acetate
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customPurification by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-84a2c17416874d5e83cf0d54fdda988e
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08129376B2

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