Sodium bis(trimethylsilyl)amide → 3-(6-Chloro-5-fluoro-pyrimidin-4-yl)-2-[(1R)-1-(4-methoxyphenyl)ethyl]-3-methyl-6-(1-tetrahydropyran-2-ylpyrazol-4-yl)isoindolin-1-one

HRID 1749380Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1749380
C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([C@H:19]([N:21]2[CH:29]([CH3:30])[C:28]3[C:23](=[CH:24][C:25]([C:31]4[CH:32]=[N:33][N:34]([CH:36]5[CH2:41][CH2:40][CH2:39][CH2:38][O:37]5)[CH:35]=4)=[CH:26][CH:27]=3)[C:22]2=[O:42])[CH3:20])=[CH:15][CH:14]=1.Cl[C:44]1[C:49]([F:50])=[C:48]([Cl:51])[N:47]=[CH:46][N:45]=1>O1CCCC1.C(OCC)(=O)C.O>[Cl:51][C:48]1[N:47]=[CH:46][N:45]=[C:44]([C:29]2([CH3:30])[C:28]3[C:23](=[CH:24][C:25]([C:31]4[CH:32]=[N:33][N:34]([CH:36]5[CH2:41][CH2:40][CH2:39][CH2:38][O:37]5)[CH:35]=4)=[CH:26][CH:27]=3)[C:22](=[O:42])[N:21]2[C@@H:19]([C:16]2[CH:15]=[CH:14][C:13]([O:12][CH3:11])=[CH:18][CH:17]=2)[CH3:20])[C:49]=1[F:50]

Komponenten

7

Edukt 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 112866754,6-Dichloro-5-fluoropyrimidineHCID 904082912-[(1R)-1-(4-Methoxyphenyl)ethyl]-3-methyl-6-(1-tetrahydropyran-2-ylpyrazol-4-yl)isoindolin-1-one

Produkt 1

HCID 904080383-(6-Chloro-5-fluoro-pyrimidin-4-yl)-2-[(1R)-1-(4-methoxyphenyl)ethyl]-3-methyl-6-(1-tetrahydropyran-2-ylpyrazol-4-yl)isoindolin-1-oneAusbeute 103 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Add sodium bis(trimethylsilyl)amide (210 mL, 210 mmol, 1 M THF) drop wise over 60 minutes to an ice cold suspension of 2-[(1R)-1-(4-methoxyphenyl)ethyl]-3-methyl-6-(1-tetrahydropyran-2-ylpyrazol-4-yl)isoindolin-1-one (62 g, 144 mmol) and 4,6-dichloro-5-fluoropyrimidine (31 g, 186 mmol) in tetrahydrofuran (620 mL). Stir the solution 60 minutes at 0° C. and then dilute the mixture with ethyl acetate (1 L) and water (1 L). Wash the organic phase with saturated aqueous sodium chloride and evaporate under reduced pressure. Dissolve the residue in 1:1 petroleum ether/ethyl acetate, filter through a pad of silica gel, and evaporate to give the title compound as a yellow foam (83 g, 103%). ES/MS m/z: 562 (M+H).

Aufarbeitung

  1. washWash the organic phase with saturated aqueous sodium chloride
  2. customevaporate under reduced pressure
  3. dissolutionDissolve the residue in 1:1 petroleum ether/ethyl acetate
  4. filtrationfilter through a pad of silica gel
  5. customevaporate

Quellen und Nachweise

ORD-Eintrag
ord-247e438b108e466dae7d5cb2d45e977b
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09156824B2

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