Sodium Carbonate → 9-Benzyloxy-6-[[2-(3,4-difluorophenyl)phenyl]methyl]-2-isopropyl-3,4-dihydropyrazino[1,2-c]pyrimidine-1,8-dione

HRID 2169240Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2169240
[CH2:1]([O:8][C:9]1[C:14](=[O:15])[N:13]=[C:12]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2Br)[N:11]2[CH2:24][CH2:25][N:26]([CH:29]([CH3:31])[CH3:30])[C:27](=[O:28])[C:10]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:32][C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[CH:37][C:38]=1[F:39].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:8][C:9]1[C:14](=[O:15])[N:13]=[C:12]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[C:36]2[CH:35]=[CH:34][C:33]([F:32])=[C:38]([F:39])[CH:37]=2)[N:11]2[CH2:24][CH2:25][N:26]([CH:29]([CH3:31])[CH3:30])[C:27](=[O:28])[C:10]=12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 27343373,4-Difluorobenzeneboronic acidHCID 867258609-benzyloxy-6-(2-bromobenzyl)-2-isopropyl-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione

Produkt 1

HCID 867258909-Benzyloxy-6-[[2-(3,4-difluorophenyl)phenyl]methyl]-2-isopropyl-3,4-dihydropyrazino[1,2-c]pyrimidine-1,8-dioneAusbeute 99,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 21863594Toluene ethanolLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

9-Benzyloxy-6-[(2-bromophenyl)methyl]-2-isopropyl-3,4-dihydropyrazino[1,2-c]pyrimidine-1,8-dione (169) (150 mg, 0.311 mmol) and 3,4-difluorphenylboronic acid (56.5 mg, 0.358 mmol) were suspended in a mixture of toluene/ethanol (10 ml/1 ml), treated at room temperature under argon with tetrakis(triphenylphosphine)palladium(0) (14.4 mg, 12.4 μmol) and 2M sodium carbonate solution (342 μl, 684 μmol) and the reaction mixture was then heated at 90° C. for 7 h. The reaction was quenched with water and the mixture was extracted twice with ethyl acetate. The organic layers were combined, washed with brine, dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography over 25 g silica gel with methanol/dichloromethane (gradient: 0 to 10% methanol). All fractions containing product were combined and concentrated to afford 9-benzyloxy-6-[[2-(3,4-difluorophenyl)phenyl]methyl]-2-isopropyl-3,4-dihydropyrazino[1,2-c]pyrimidine-1,8-dione (160 mg) as a white solid.

Aufarbeitung

  1. customThe reaction was quenched with water
  2. extractionthe mixture was extracted twice with ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by chromatography over 25 g silica gel with methanol/dichloromethane (gradient: 0 to 10% methanol)
  8. additionAll fractions containing product
  9. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-73f4b1c1edb6403996d30d7f4073ddb6
Quelldatensatz
uspto-grants-2015_06
Patentnummer
US09045486B2

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