Diisopropylethylamine → tert-Butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamate

HRID 1774943Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1774943
[Br:1][CH:2]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)[C:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:14][CH2:13][CH2:12]2)=[CH:7][CH:6]=1)=[O:4].[NH2:29][C:30]1[N:31]=[CH:32][C:33]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[N:34][CH:35]=1.C(N(C(C)C)CC)(C)C>C(#N)CCC>[Br:1][CH:2]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[C:3]([C:5]1[CH:6]=[CH:7][C:8]([C:11]2([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])[CH2:14][CH2:13][CH2:12]2)=[CH:9][CH:10]=1)=[O:4].[C:18]([O:17][C:16]([NH:15][C:11]1([C:8]2[CH:7]=[CH:6][C:5]([C:3]3[N:29]=[C:30]4[CH:35]=[N:34][C:33]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:32][N:31]4[C:2]=3[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[CH:10][CH:9]=2)[CH2:14][CH2:13][CH2:12]1)=[O:22])([CH3:20])([CH3:19])[CH3:21]

Komponenten

6

Edukt 3

HCID 81531DiisopropylethylamineHCID 22271413Ethyl 5-Aminopyrazine-2-carboxylateHCID 86691038tert-Butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamate

Produkt 2

HCID 86691038tert-Butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamateHCID 89691425Ethyl 2-(4-{1-[(tert-butoxycarbonyl)amino]cyclobutyl}phenyl)-3-phenylimidazo[1,2-a]pyrazine-6-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8008ButyronitrileLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a mixture of crude tert-butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamate [Int-1-A] (213 mg, 0.38 mmol, 1.0 eq), ethyl 5-aminopyrazine-2-carboxylate (CAS-Nr. 54013-06-8, 70.5 mg, 0.42 mmol, 1.1 eq.) and diisopropylethylamine (0.055 mL, 0.42 mmol, 1.1 eq) in 2.3 mL butyronitrile was added predried 3 Å mol sieves. The mixture was heated overnight at 120° C. The reaction mixture was partitioned between DCM/water and was filtered through a phase separator. The remaining volatile organic components were removed by the use of a rotary evaporator. In parallel we conducted the same experiment in the absence of diisopropylethylamine following the same protocol. The crude materials of both experiments were combined and purified via MPLC (Biotage Isolera, 25 g Snap-cartridge; eluent: hexane/ethyl acetate (1/1)→ethyl acetate) to deliver 69 mg (14%, yield based on combined amount of tert-butyl (1-{4-[bromo(phenyl)acetyl]-phenyl}cyclobutyl)carbamate) of the title compound.

Aufarbeitung

  1. additionwas added
  2. customThe reaction mixture was partitioned between DCM/water
  3. filtrationwas filtered through a phase separator
  4. customThe remaining volatile organic components were removed by the use of a rotary evaporator
  5. custompurified via MPLC (Biotage Isolera, 25 g Snap-cartridge; eluent: hexane/ethyl acetate (1/1)→ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-9c127fc3192e41b290bc6e63be7810f1
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09260435B2

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