1-Hydroxybenzotriazole → 3-cylcopentyl-2-(4-ethoxymethylsulfonyl-phenyl)-N-(5-methoxythiazolo[5,4-b]pyridin-2yl)-propionamide

HRID 505585Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 505585
[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH2:20][O:21][CH2:22][CH3:23])(=[O:19])=[O:18])=[CH:13][CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[CH3:47][O:48][C:49]1[N:54]=[C:53]2[S:55][C:56]([NH2:58])=[N:57][C:52]2=[CH:51][CH:50]=1.CCN(C(C)C)C(C)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH2:20][O:21][CH2:22][CH3:23])(=[O:18])=[O:19])=[CH:13][CH:12]=2)[C:8]([NH:58][C:56]2[S:55][C:53]3[C:52]([N:57]=2)=[CH:51][CH:50]=[C:49]([O:48][CH3:47])[N:54]=3)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1

Komponenten

8

Edukt 6

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 28015575-Methoxy[1,3]thiazolo[5,4-b]pyridin-2-amineHCID 221413011-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride hydrochlorideHCID 674860323-Cyclopentyl-2-(4-ethoxymethylsulfonyl-phenyl)-propionic acid

Produkt 1

HCID 114207133-cylcopentyl-2-(4-ethoxymethylsulfonyl-phenyl)-N-(5-methoxythiazolo[5,4-b]pyridin-2yl)-propionamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

A solution of the title D compound, 3-cyclopentyl-2-(4-ethoxymethylsulfonyl-phenyl)-propionic acid (1 g, 0.0029 mol), HOBt (596 mg, 0.0044 mol), EDCl hydrochloride (846 mg, 0.0044 mol) and 583 mg (0.0032 mol) of the title E compound, 5-methoxy-thiazolo[5,4-b]pyridin-2-ylamine in DCM is treated with DIEA (2 mL, 0.011 mol). The reaction is stirred at 25° C. for 24 h. The reaction mixture is treated with saturated aqueous sodium bicarbonate solution and washed with water. The resulting organic layer is then washed with 1 N aqueous hydrochloric acid solution followed by water and brine. The organic layer is dried over sodium sulfate, filtered and evaporated under vacuum. The crude product is purified by column chromatography over Silica gel (60-120 mesh) using 80/20—hexane/ethyl acetate to give 3-cylcopentyl-2-(4-ethoxymethylsulfonyl-phenyl)-N-(5-methoxythiazolo[5,4-b]pyridin-2yl)-propionamide as a white solid: MS e/z (ES) 502.13 (M−1−, 100%); m.p. 158-160° C.; 1H NMR δ 12.7 (s, 1H), 8.02 (d, J=8.4, 1H), 7.88 (d, J=7.2, 2H), 7.69 (d, J=7.6, 2H), 6.91 (d, J=8.8, 1H), 4.81 (s, 2H), 4.10 (m, 1H), 3.90 (s, 3H), 3.73 (m, 2H), 2.14-2.17 (m, 1H), 1.83-1.85 (m, 1H), 1.60-1.73 (m, 2H), 1.50-1.59 (m, 3H), 1.40-1.52 (m, 2H), 1.10-1.15 (m, 2H), 1.02-1.12 (m, 3H).

Aufarbeitung

  1. washwashed with water
  2. washThe resulting organic layer is then washed with 1 N aqueous hydrochloric acid solution
  3. dry with materialThe organic layer is dried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated under vacuum
  6. customThe crude product is purified by column chromatography over Silica gel (60-120 mesh)

Quellen und Nachweise

ORD-Eintrag
ord-4ab1cdc339984879b34e08c1e663d866
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07781451B2

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