Triethylamine → (R)-1-(4-{5-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-pyridin-2-yl}-benzoyl)-pyrrolidine-2-carboxylic acid tert-butyl ester

HRID 1691924Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1691924
[C:1]1([C:7]2[O:8][C:9]([C:30]([F:33])([F:32])[F:31])=[C:10]([C:12]([NH:14][C:15]3[CH:16]=[CH:17][C:18]([C:21]4[CH:29]=[CH:28][C:24]([C:25](O)=[O:26])=[CH:23][CH:22]=4)=[N:19][CH:20]=3)=[O:13])[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[C:35]([O:39][C:40](=[O:46])[C@H:41]1[CH2:45][CH2:44][CH2:43][NH:42]1)([CH3:38])([CH3:37])[CH3:36].C(N(CC)CC)C.ON1C2N=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>ClCCl.CN(C)C=O>[C:35]([O:39][C:40]([C@H:41]1[CH2:45][CH2:44][CH2:43][N:42]1[C:25](=[O:26])[C:24]1[CH:28]=[CH:29][C:21]([C:18]2[CH:17]=[CH:16][C:15]([NH:14][C:12]([C:10]3[N:11]=[C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[O:8][C:9]=3[C:30]([F:33])([F:32])[F:31])=[O:13])=[CH:20][N:19]=2)=[CH:22][CH:23]=1)=[O:46])([CH3:38])([CH3:36])[CH3:37]

Komponenten

8

Edukt 5

HCID 8471TriethylamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 44629909tert-butyl (2R)-pyrrolidine-2-carboxylate hydrochlorideHCID 576519234-{5-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-pyridin-2-yl}-benzoic acid

Produkt 1

HCID 66738324(R)-1-(4-{5-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-pyridin-2-yl}-benzoyl)-pyrrolidine-2-carboxylic acid tert-butyl esterAusbeute 84,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A mixture of 4-{5-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-pyridin-2-yl}-benzoic acid (45 mg, 0.1 mmol), D-proline t-butyl ester hydrochloride (31 mg, 0.15 mmol), triethylamine (50 μL, 0.3 mmol), 1-hydroxy-7-azabenzotriazole (HOAT) (20 mg, 0.15 mmol), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (30 mg, 0.15 mmol) in anhydrous dichloromethane (5 mL) and N,N-dimethylformamide (1.5 mL) was stirred at room temperature overnight. The reaction mixture was concentrated and purified by flash chromatography (Merck silica gel 60, 230-400 mesh, 0%-100% ethyl acetate in hexane) to give (R)-1-(4-{5-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-pyridin-2-yl}-benzoyl)-pyrrolidine-2-carboxylic acid tert-butyl ester (51 mg, 84%) as a white solid.

Aufarbeitung

  1. concentrationThe reaction mixture was concentrated
  2. custompurified by flash chromatography (Merck silica gel 60, 230-400 mesh, 0%-100% ethyl acetate in hexane)

Quellen und Nachweise

ORD-Eintrag
ord-70b868e01a824935b572be4a1934e8f7
Quelldatensatz
uspto-grants-2012_04
Patentnummer
US08153644B2

Notizen zur Reaktion

Wird geladen…