Phosphorus oxychloride → 6-Chloro-8-[5-(3-cyclobutyl-3-aza bicyclo[3.1.0]hex-6-yl)-[1,3,4]oxadiazol-2-yl]chroman-5-ylamine

HRID 1523735Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1523735
[CH:1]1([N:5]2[CH2:10][CH:9]3[CH:7]([CH:8]3[C:11]([OH:13])=O)[CH2:6]2)[CH2:4][CH2:3][CH2:2]1.P(Cl)(Cl)(Cl)=O.[NH2:19][C:20]1[C:29]([Cl:30])=[CH:28][C:27]([C:31]([NH:33][NH2:34])=O)=[C:26]2[C:21]=1[CH2:22][CH2:23][CH2:24][O:25]2>>[Cl:30][C:29]1[C:20]([NH2:19])=[C:21]2[C:26](=[C:27]([C:31]3[O:13][C:11]([CH:8]4[CH:7]5[CH:9]4[CH2:10][N:5]([CH:1]4[CH2:2][CH2:3][CH2:4]4)[CH2:6]5)=[N:34][N:33]=3)[CH:28]=1)[O:25][CH2:24][CH2:23][CH2:22]2

Komponenten

4

Edukt 3

HCID 24813Phosphorus oxychlorideHCID 867249123-Cyclobutyl-3-aza bicyclo[3.1.0]hexane-6-carboxylic acidHCID 867249165-Amino-6-chloro-chroman-8-carboxylic acid hydrazide

Produkt 1

HCID 715347776-Chloro-8-[5-(3-cyclobutyl-3-aza bicyclo[3.1.0]hex-6-yl)-[1,3,4]oxadiazol-2-yl]chroman-5-ylamineAusbeute 14,1 %

Versuchsvorschrift

To 3-cyclobutyl-3-aza bicyclo[3.1.0]hexane-6-carboxylic acid (74 mg, 0.40 mmol, obtained in preparation 8) was added phosphoryl chloride (1 mL). The mixture was stirred for 15 minutes and 5-amino-6-chloro chroman-8-carboxylic acid hydrazide (80 mg, 0.33 mmol) was added. The reaction mixture was gradually heated to reflux for 1 hour. The reaction mixture was cooled to room temperature, triturated with hexanes (2×20 mL) and the crude mass was basified with aqueous sodium bicarbonate solution. The basified mixture was extracted with 10% methanol in dichloromethane The organic layer was dried over anhydrous sodium sulphate and the solvent was removed under reduced pressure and was purified by silica gel column to obtain 6-chloro-8-[5-(3-cyclobutyl-3-aza bicyclo[3.1.0]hex-6-yl)-[1,3,4]oxadiazol-2-yl]chroman-5-yl amine (18 mg).

Aufarbeitung

  1. temperatureThe reaction mixture was gradually heated
  2. temperatureto reflux for 1 hour
  3. customtriturated with hexanes (2×20 mL)
  4. extractionThe basified mixture was extracted with 10% methanol in dichloromethane The organic layer
  5. dry with materialwas dried over anhydrous sodium sulphate
  6. customthe solvent was removed under reduced pressure
  7. customwas purified by silica gel column

Quellen und Nachweise

ORD-Eintrag
ord-1aed4c554da44c39906336c9b94dc936
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09079894B2

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