Water → Methyl (2R)-4'-chloro-6'-oxo-1,3,6',7'-tetrahydrospiro[indene-2,5'-pyrrolo[2,3-d]pyrimidine]-5-carboxylate

HRID 334849Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 334849
Br[CH2:2][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[CH2:13]Br)[C:6]([O:8][CH3:9])=[O:7].[Cl:15][C:16]1[C:17]2[CH2:24][C:23](=[O:25])[NH:22][C:18]=2[N:19]=[CH:20][N:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C=O>[Cl:15][C:16]1[C:17]2[C@@:24]3([CH2:2][C:3]4[C:12](=[CH:11][CH:10]=[C:5]([C:6]([O:8][CH3:9])=[O:7])[CH:4]=4)[CH2:13]3)[C:23](=[O:25])[NH:22][C:18]=2[N:19]=[CH:20][N:21]=1

Komponenten

6

Edukt 4

HCID 962WaterHCID 10796Cesium carbonateHCID 2736819Methyl 3,4-bis(bromomethyl)benzoateHCID 120958704-chloro-5H,6H,7H-pyrrolo[2,3-d]pyrimidin-6-one

Produkt 1

HCID 86695346Methyl (2R)-4'-chloro-6'-oxo-1,3,6',7'-tetrahydrospiro[indene-2,5'-pyrrolo[2,3-d]pyrimidine]-5-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of methyl 3,4-bis(bromomethyl)benzoate (5.0 g, 15.5 mmol) and 4-chloro-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one (5.3 g, 31.1 mmol) in N,N-dimethylformamide (150 mL) was added cesium carbonate (10.1 g, 31.1 mmol). After 10 min, water was added and the mixture was extracted with ethyl acetate. The combined organic extracts were washed with water, brine, dried over magnesium sulfate, filtered and concentrated. Purification by silica gel chromatography (1% methanol/dichloromethane→5% methanol/dichloromethane) then a second silica gel purification (100% dichloromethane→>75% dichloromethane/EtOAc gave the title compound as a racemic mixture. Chiral separation of the individual enantiomers was accomplished by use of HPLC using a 10 cm ChiralPak® AD column (60% EtOH/hexanes with 0.1% diethylamine to give the title compound as the 1st eluting enantiomer. MS: m/z=330.1 (M+1).

Aufarbeitung

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe combined organic extracts were washed with water, brine
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography (1% methanol/dichloromethane→5% methanol/dichloromethane)
  7. customa second silica gel purification (100% dichloromethane→>75% dichloromethane/EtOAc

Quellen und Nachweise

ORD-Eintrag
ord-2f20aa8731d54de8b5b192b99b6c1fa7
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08883807B2

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