Nitrogen → 5-(2-fluoro-3-methoxyphenyl)-1-[2,6-difluorobenzyl]-3-{3-hydroxy-2(R)-phenylpropyl}-6-methylpyrimidine-2,4(1H,3H)-dione

HRID 1744306

Reaktionsgleichung

Reaktionsgleichung von HRID 1744306
Br[C:2]1[C:3](=[O:32])[N:4]([CH2:19][C@@H:20]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:21][O:22]C(=O)C)[C:5](=[O:18])[N:6]([CH2:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[F:17])[C:7]=1[CH3:8].[F:33][C:34]1[C:39]([O:40][CH3:41])=[CH:38][CH:37]=[CH:36][C:35]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+].N#N>O1CCOCC1.O>[F:33][C:34]1[C:39]([O:40][CH3:41])=[CH:38][CH:37]=[CH:36][C:35]=1[C:2]1[C:3](=[O:32])[N:4]([CH2:19][C@@H:20]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH2:21][OH:22])[C:5](=[O:18])[N:6]([CH2:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[F:17])[C:7]=1[CH3:8]

Komponenten

6

Edukt 4

HCID 947NitrogenHCID 10340Sodium CarbonateHCID 49857442-Fluoro-3-methoxyphenylboronic acidHCID 210183995-bromo-1-[2, 6-difluorobenzyl]-3-{3-acetoxy-2(R)-phenylpropyl}-6-methylpyrimidine-2,4(1H,3H)-dione

Produkt 1

HCID 210183965-(2-fluoro-3-methoxyphenyl)-1-[2,6-difluorobenzyl]-3-{3-hydroxy-2(R)-phenylpropyl}-6-methylpyrimidine-2,4(1H,3H)-dioneAusbeute 66,9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 218864351,4-Dioxane--water (1/1)Lösungsmittel

Versuchsvorschrift

To compound 8a (4.05 g, 8 mmol) in dioxane/water (100/50 mL) was added 2-fluoro-3-methoxyphenylboronic acid (2.04 g, 12 mmol) and Na2CO3 (5.08 g, 48 mmol). The reaction mixture was deoxygenated with N2 for 10 min, tetrakis(triphenylphosine) palladium (0) (924 mg, 0.8 mmol) was added and the reaction mixture was heated at 100° C. overnight under the protection of N2. The reaction mixture was partitioned between brine and EtOAc. The organic layer was dried (sodium sulfate), evaporated and purified by flash chromatography (silica, 50% EtOAc/hexanes) to give compound 8b (2.73 g, 66.9%). MS (CI) m/z 511.1 (MH+).

Aufarbeitung

  1. customThe reaction mixture was deoxygenated with N2 for 10 min
  2. customThe reaction mixture was partitioned between brine and EtOAc
  3. dry with materialThe organic layer was dried (sodium sulfate)
  4. customevaporated
  5. custompurified by flash chromatography (silica, 50% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-b9f8959cfd4c47879a75b453e4ca3bfb
Quelldatensatz
uspto-grants-2006_03
Patentnummer
US07015226B2

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