Triethylamine → 1-{1-[3-(4-fluorophenyl)-2,2-dimethylpropionyl]-piperidin-3-ylmethyl}-3-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-urea

HRID 896520Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 896520
Cl.[CH3:2][N:3]1[C:7]([C:8]2[CH:9]=[C:10]([NH:14][C:15]([NH:17][CH2:18][CH:19]3[CH2:24][CH2:23][CH2:22][NH:21][CH2:20]3)=[O:16])[CH:11]=[CH:12][CH:13]=2)=[N:6][N:5]=[N:4]1.[F:25][C:26]1[CH:31]=[CH:30][C:29]([CH2:32][C:33]([CH3:38])([CH3:37])[C:34](O)=[O:35])=[CH:28][CH:27]=1.C(N(CC)CC)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>ClCCl>[F:25][C:26]1[CH:27]=[CH:28][C:29]([CH2:32][C:33]([CH3:38])([CH3:37])[C:34]([N:21]2[CH2:22][CH2:23][CH2:24][CH:19]([CH2:18][NH:17][C:15]([NH:14][C:10]3[CH:11]=[CH:12][CH:13]=[C:8]([C:7]4[N:3]([CH3:2])[N:4]=[N:5][N:6]=4)[CH:9]=3)=[O:16])[CH2:20]2)=[O:35])=[CH:30][CH:31]=1

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 2724699PyBOPHCID 223502093-(4-Fluorophenyl)-2,2-dimethylpropanoic acidHCID 223502531-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-3-piperidin-3-ylmethylurea hydrochloride

Produkt 1

HCID 697363521-{1-[3-(4-fluorophenyl)-2,2-dimethylpropionyl]-piperidin-3-ylmethyl}-3-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-urea

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

A solution of 1-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-3-piperidin-3-ylmethylurea hydrochloride (100 mg, 284 μmol), 3-(4-fluorophenyl)-2,2-dimethylpropionic acid (56 mg, 284 μmol) and triethylamine (158 μL, 1.14 mmol) in dichloromethane (2 mL) was treated with benzotriazol-1-yloxy-tripyrrolidinophosphonium hexafluorophosphate (177 mg, 341 μmol) and the mixture was stirred at room temperature for 17 hours. The mixture was diluted with dichloromethane, washed with saturated aqueous sodium hydrogen carbonate and then with 1.0 N aqueous hydrochloric acid, dried (sodium sulfate) and concentrated under vacuum. The residue was purified by flash chromatography, eluting with 25% hexane in ethyl acetate, to provide an amorphous white solid. 1H NMR (300 MHz, CDCl3) δ7.83 (s, 1H), 7.58 (d, J=7 Hz, 1H), 7.38 (t, J=8 Hz, 1H), 7.28 (m, 1H), 7.05 (m, 2H), 6.90 (t, J=9 Hz, 2H), 4.18 (s, 3H), 4.10 (m, 2H), 3.31 (m, 2H), 3.00 (m, 2H), 2.90 (s, 2H), 1.90 (m, 1H), 1.77 (m, 2H), 1.56 (m, 1H), 1.40 (m, 1H), 1.23 (s, 6H). Mass spec (AP+) m/z 494.2 (M+H+).

Aufarbeitung

  1. washwashed with saturated aqueous sodium hydrogen carbonate
  2. dry with materialwith 1.0 N aqueous hydrochloric acid, dried (sodium sulfate)
  3. concentrationconcentrated under vacuum
  4. customThe residue was purified by flash chromatography
  5. washeluting with 25% hexane in ethyl acetate
  6. customto provide an amorphous white solid

Quellen und Nachweise

ORD-Eintrag
ord-c54c2198d38d4fd4943afcd80f11665d
Quelldatensatz
uspto-grants-2005_07
Patentnummer
US06919356B2

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