Ammonium Chloride → 5-methyl-1-(5-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo-[3.1.0]hex-3-yl}pentyl)-2,4(1H,3H)-pyrimidinedione hydrochloride

HRID 12751

Reaktionsgleichung

Reaktionsgleichung von HRID 12751
[F:1][C:2]([F:16])([F:15])[C:3]1[CH:8]=[CH:7][C:6]([C@:9]23[CH2:14][C@H:13]2[CH2:12][NH:11][CH2:10]3)=[CH:5][CH:4]=1.[Cl:17][CH:18]([CH3:31])[CH2:19][CH2:20][CH2:21][N:22]1[CH:27]=[C:26]([CH3:28])[C:25](=[O:29])[NH:24][C:23]1=[O:30].[Cl-].[NH4+]>CN(C=O)C>[ClH:17].[CH3:28][C:26]1[C:25](=[O:29])[NH:24][C:23](=[O:30])[N:22]([CH2:21][CH2:20][CH2:19][CH2:18][CH2:31][N:11]2[CH2:12][C@H:13]3[C@:9]([C:6]4[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:15])[F:16])=[CH:8][CH:7]=4)([CH2:14]3)[CH2:10]2)[CH:27]=1

Komponenten

5

Edukt 3

HCID 25517Ammonium ChlorideHCID 59337591(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexaneHCID 686935801-(4-chloropentyl)-5-methyl-2,4(1H,3H)-pyrimidinedione

Produkt 1

HCID 686879535-methyl-1-(5-{(1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo-[3.1.0]hex-3-yl}pentyl)-2,4(1H,3H)-pyrimidinedione hydrochlorideAusbeute 35,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of (1S,5R)-1-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane (41 mg), 1-(4-chloropentyl)-5-methyl-2,4(1H,3H)-pyrimidinedione (Prep11, 50 mg) and TEA (50 μl) in DMF (0.5 mL) was heated at 100° C. overnight. Ammonium chloride was then added and the solution was extracted with dichloromethane. The organic phase was dried and concentrated in vacuo. The crude product was purified by a SCX cartridge followed by a preparative HPLC [column: ABZ plus 20×100 mm, 5 uM, mobile phase A: H2O+0.1% formic acid, mobile phase B: acetonitrile+0.1% formic acid, gradient: from 1 to 20% (B) in 10 min, flow rate: 20 mL/min, UV wavelength range: 210-350 nm, ionization: ES+, mass range: 100-900 amu (ES+)], to give 29 mg of the title compound which was further purified by flash chromatography eluting with DCM/MeOH/NH4OH from 99/1/0.1, to 98/2/0.1, to 97/3/0.1 to give the free base of the title compound (25 mg).

Aufarbeitung

  1. extractionthe solution was extracted with dichloromethane
  2. customThe organic phase was dried
  3. concentrationconcentrated in vacuo
  4. customThe crude product was purified by a SCX cartridge
  5. customfollowed by a preparative HPLC [column: ABZ plus 20×100 mm, 5 uM, mobile phase A: H2O+0.1% formic acid, mobile phase B: acetonitrile+0.1% formic acid, gradient: from 1 to 20% (B) in 10 min, flow rate: 20 mL/min, UV wavelength range: 210-350 nm, ionization: ES+, mass range: 100-900 amu (ES+)]

Quellen und Nachweise

ORD-Eintrag
ord-2c6f8300a25b4e1abc55717cd57e132b
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07727988B2

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