Acetic Acid → 2-cyclopropyl-7-[(1R*,3R*)-3-(dimethylamino)cyclopentyl]-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile

HRID 17592

Reaktionsgleichung

Reaktionsgleichung von HRID 17592
[CH:1]1([C:4]2[O:5][C:6]3[C:7](=[C:9]([C:26]#[N:27])[C:10]([CH3:25])=[C:11]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[C:12]=3[CH:13]3[CH2:17][CH2:16][C:15](=O)[CH2:14]3)[N:8]=2)[CH2:3][CH2:2]1.[CH3:28][NH:29][CH3:30].C(O)(=O)C.C([BH3-])#N.[Na+].C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.CO>[NH3:8].[CH3:4][OH:5].[CH:1]1([C:4]2[O:5][C:6]3[C:7](=[C:9]([C:26]#[N:27])[C:10]([CH3:25])=[C:11]([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)[C:12]=3[C@@H:13]3[CH2:17][CH2:16][C@@H:15]([N:29]([CH3:30])[CH3:28])[CH2:14]3)[N:8]=2)[CH2:3][CH2:2]1

Komponenten

9

Edukt 5

HCID 176Acetic AcidHCID 674DimethylamineHCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 685859442-Cyclopropyl-5-methyl-7-(3-oxocyclopentyl)-6-phenyl-1,3-benzoxazole-4-carbonitrile

Produkt 2

HCID 21705897Ammonia methanolHCID 685843542-cyclopropyl-7-[(1R*,3R*)-3-(dimethylamino)cyclopentyl]-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrileAusbeute 41,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6212ChloroformLösungsmittel2×

Versuchsvorschrift

2-Cyclopropyl-5-methyl-7-(3-oxocyclopentyl)-6-phenyl-1,3-benzoxazole-4-carbonitrile (I-303) (44 mg, 0.12 mmol) was dissolved in chloroform (1 ml) and methanol (1 ml), and at 0° C., dimethylamine (2 M tetrahydrofuran solution) (247 μl, 0.49 mmol), acetic acid (29 μl, 0.49 mmol) and sodium cyanoborohydride (33 mg, 0.49 mmol) were added. The solution was gradually warmed up to room temperature, then stirred for 21 hours, and fractionated with chloroform and an aqueous saturated sodium hydrogencarbonate solution. The aqueous layer was extracted twice with chloroform. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, the solvent was evaporated away and the resulting residue was purified by preparative TLC (eluent, chloroform:7 N ammonia/methanol solution=97:3, v/v) to obtain 2-cyclopropyl-7-[(1R*,3R*)-3-(dimethylamino)cyclopentyl]-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile (#141) (9.6 mg, 20%) as a white solid. Next, 2-cyclopropyl-7-[(1R*,3S*)-3-(dimethylamino)cyclopentyl]-5-methyl-6-phenyl-1,3-benzoxazole-4-carbonitrile (#142) (26 mg, 55%) was obtained as a white solid.

Aufarbeitung

  1. extractionThe aqueous layer was extracted twice with chloroform
  2. washwashed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe insoluble matter was separated by filtration
  5. customthe solvent was evaporated away
  6. customthe resulting residue was purified by preparative TLC (eluent, chloroform

Quellen und Nachweise

ORD-Eintrag
ord-c77bf07d1982405c9487cbd55e460a94
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07737166B2

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