Diisopropylethylamine → tert-Butyl {4-[({4-[4-(3-chlorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)carbonyl]benzyl}carbamate

HRID 1663476

Reaktionsgleichung

Reaktionsgleichung von HRID 1663476
[NH2:1][C:2]1[C:3]([C:7]2[N:11]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[CH:13]=3)[C:10](=[O:19])[O:9][N:8]=2)=[N:4][O:5][N:6]=1.[C:20]([O:24][C:25]([NH:27][CH2:28][C:29]1[CH:37]=[CH:36][C:32]([C:33](O)=[O:34])=[CH:31][CH:30]=1)=[O:26])([CH3:23])([CH3:22])[CH3:21].C(N(CC)C(C)C)(C)C>ClCCl.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[Cl:18][C:14]1[CH:13]=[C:12]([N:11]2[C:10](=[O:19])[O:9][N:8]=[C:7]2[C:3]2[C:2]([NH:1][C:33]([C:32]3[CH:31]=[CH:30][C:29]([CH2:28][NH:27][C:25](=[O:26])[O:24][C:20]([CH3:21])([CH3:22])[CH3:23])=[CH:37][CH:36]=3)=[O:34])=[N:6][O:5][N:4]=2)[CH:17]=[CH:16][CH:15]=1

Komponenten

7

Edukt 3

HCID 81531Diisopropylethylamine2×HCID 8536054-(((tert-Butoxycarbonyl)amino)methyl)benzoic acidHCID 585582673-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-chlorophenyl)-1,2,4-oxadiazol-5(4H)-one

Produkt 1

HCID 58558288tert-Butyl {4-[({4-[4-(3-chlorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)carbonyl]benzyl}carbamate

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 6344DichloromethaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A solution of 3-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-chlorophenyl)-1,2,4-oxadiazol-5(4H)-one (0.5 g, 1.8 mmol) and 4-{[(tert-butoxycarbonyl)amino]methyl}benzoic acid (0.67 g, 2.7 mmol) in dichloromethane (35 mL) was treated with 4-dimethylaminopyridine (0.13 g, 1.1 mmol) and N,N-diisopropylethylamine (0.93 mL, 5.4 mmol) followed by bromotris(pyrrolydino)phosphonium hexafluorophosphate (1.3 g, 2.7 mmol) and additional N,N-diisopropylethylamine (0.93 mL, 5.4 mmol). The reaction mixture was stirred for 16 h, diluted with ethyl acetate (˜200 mL) and washed with 0.1 M HCl (2×100 mL) and brine (25 mL), dried with sodium sulfate, filtered, and concentrated. Purification of the crude reaction mixture on silica gel gave the intermediate tert-butyl {4-[({4-[4-(3-chlorophenyl)-5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl]-1,2,5-oxadiazol-3-yl}amino)carbonyl]benzyl}carbamate. This material was diluted with dichloromethane (30 mL), treated with 4.0 M HCl in 1,4-dioxane (4.5 mL), and stirred for 1 h. The reaction mixture was concentrated and purified by preparative LCMS to give the desired product (542 mg, 58%). LCMS for C18H14ClN6O4 (M+H)+: m/z=413.0.

Aufarbeitung

  1. washwashed with 0.1 M HCl (2×100 mL) and brine (25 mL)
  2. dry with materialdried with sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification of the crude
  6. customreaction mixture on silica gel

Quellen und Nachweise

ORD-Eintrag
ord-d2022448a87f4ba4b7e64ff61a32bac0
Quelldatensatz
uspto-grants-2011_10
Patentnummer
US08034953B2

Verknüpfte Notizen

Wird geladen…