2-Bromobenzonitrile → 2-[(3R)-3-methyl-4-(1-methyl-6-oxo-1,6-dihydro-[4,4']bipyrimidinyl-2-yl)-piperazin-1-yl]-benzonitrile

HRID 1045694Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1045694
[CH3:1][N:2]1[C:7](=[O:8])[CH:6]=[C:5]([C:9]2[CH:14]=[CH:13][N:12]=[CH:11][N:10]=2)[N:4]=[C:3]1[N:15]1[CH2:20][CH2:19][NH:18][CH2:17][C@H:16]1[CH3:21].Br[C:23]1[CH:30]=[CH:29][CH:28]=[CH:27][C:24]=1[C:25]#[N:26].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.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.[Pd].[Pd]>[CH3:21][C@H:16]1[N:15]([C:3]2[N:2]([CH3:1])[C:7](=[O:8])[CH:6]=[C:5]([C:9]3[CH:14]=[CH:13][N:12]=[CH:11][N:10]=3)[N:4]=2)[CH2:20][CH2:19][N:18]([C:23]2[CH:30]=[CH:29][CH:28]=[CH:27][C:24]=2[C:25]#[N:26])[CH2:17]1

Komponenten

7

Edukt 4

HCID 162722-BromobenzonitrileHCID 62657Potassium Phosphate, TribasicHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 250045961-methyl-2-((2R)-2-methyl-piperazin-1-yl)-1H-[4,4']bipyrimidinyl-6-one

Produkt 1

HCID 578699162-[(3R)-3-methyl-4-(1-methyl-6-oxo-1,6-dihydro-[4,4']bipyrimidinyl-2-yl)-piperazin-1-yl]-benzonitrileAusbeute 59,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a stirred solution of 1-methyl-2-((2R)-2-methyl-piperazin-1-yl)-1H-[4,4′]bipyrimidinyl-6-one (150 mg, 0.524 mmol) in ethylene glycol dimethyl ether (2.0 ml) was added 2-bromobenzonitrile (143 mg, 0.786 mmol), tris(dibenzylideneacetone)dipalladium (24 mg, 0.026 mmol), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (25 mg, 0.052 mmol) and tripotassium phosphate (167 mg, 0.786 mmol), and the reaction mixture was stirred for 12 hours at 80° C. The reaction was quenched with water, the aqueous layer was extracted with ether. The extract was washed with water and brine, dried over magnesium sulfate, and concentrated in vacuo. The resulting residue was purified with HPLC to afford 2-[(3R)-3-methyl-4-(1-methyl-6-oxo-1,6-dihydro-[4,4′]bipyrimidinyl-2-yl)-piperazin-1-yl]-benzonitrile (120 mg, 0.310 mmol, 59%) as pale yellow crystals.

Aufarbeitung

  1. customThe reaction was quenched with water
  2. extractionthe aqueous layer was extracted with ether
  3. washThe extract was washed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified with HPLC

Quellen und Nachweise

ORD-Eintrag
ord-fd8104571a644170bb759cbfa76a05d7
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08569294B2

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