4-(4-Bromobenzyl)piperazine, N1-BOC protected → Tert-butyl 4-{4-[4-(1-methyl-6-oxo-1,6-dihydro-[4,4']bipyrimidinyl-2-yloxy)piperidin-1-yl]benzyl}piperazine-1-carboxylate

HRID 1468776

Reaktionsgleichung

Reaktionsgleichung von HRID 1468776
Br[C:2]1[CH:21]=[CH:20][C:5]([CH2:6][N:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]2)=[CH:4][CH:3]=1.[CH3:22][N:23]1[C:28](=[O:29])[CH:27]=[C:26]([C:30]2[CH:35]=[CH:34][N:33]=[CH:32][N:31]=2)[N:25]=[C:24]1[O:36][CH:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd]>[CH3:22][N:23]1[C:28](=[O:29])[CH:27]=[C:26]([C:30]2[CH:35]=[CH:34][N:33]=[CH:32][N:31]=2)[N:25]=[C:24]1[O:36][CH:37]1[CH2:42][CH2:41][N:40]([C:2]2[CH:21]=[CH:20][C:5]([CH2:6][N:7]3[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH2:8]3)=[CH:4][CH:3]=2)[CH2:39][CH2:38]1

Komponenten

7

Edukt 4

HCID 27955194-(4-Bromobenzyl)piperazine, N1-BOC protectedHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 679776501-methyl-2-(piperidin-4-yloxy)-1H-[4,4']bipyrimidinyl-6-one

Produkt 1

HCID 50939811Tert-butyl 4-{4-[4-(1-methyl-6-oxo-1,6-dihydro-[4,4']bipyrimidinyl-2-yloxy)piperidin-1-yl]benzyl}piperazine-1-carboxylateAusbeute 40,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)KatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
150 °C

Versuchsvorschrift

To a mixture of tert-butyl 4-(4-bromo-benzyl)piperazine-1-carboxylate (371 mg, 1.04 mmol), 1-methyl-2-(piperidin-4-yloxy)-1H-[4,4′]bipyrimidinyl-6-one (300 mg, 1.04 mmol), tris(dibenzylideneacetone)dipalladium(0)-chloroform adduct (43.2 mg, 41.8 μmol) and 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (79.6 mg, 0.167 mmol) in toluene (2.09 ml) was added sodium tert-butoxide (151 mg, 1.57 mmol) under nitrogen atmosphere. The mixture was stirred at 150° C. for 30 minutes in Biotage Microwave reactor. The mixture was filtered through a pad of Celite, and concentrated in vacuo. The residue was purified by NH-silica gel column chromatography (eluent; hexane/ethyl acetate=1/1) to afford tert-butyl 4-{4-[4-(1-methyl-6-oxo-1,6-dihydro-[4,4′]bipyrimidinyl-2-yloxy)piperidin-1-yl]benzyl}piperazine-1-carboxylate as a pale yellow solid (236 mg, 0.420 mmol, 40%).

Aufarbeitung

  1. filtrationThe mixture was filtered through a pad of Celite
  2. concentrationconcentrated in vacuo
  3. customThe residue was purified by NH-silica gel column chromatography (eluent; hexane/ethyl acetate=1/1)

Quellen und Nachweise

ORD-Eintrag
ord-5b00b3b7a9b3403c8c0b3c197f0e0f3b
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09006232B2

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