Triethylamine → 3-[5-(3-Methyl-2-piperidinyl)-1,2,4-oxadiazol-3-yl]benzonitrile

HRID 1791375Notes

Reaction equation

C(OC([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([CH3:14])[CH:9]1[C:15]([OH:17])=O)=O)(C)(C)C.C([N:20]([CH2:23][CH3:24])CC)C.ClC(OCC(C)C)=O.Cl[C:34]1[CH:35]=[C:36]([CH:41]=C[CH:43]=1)[C:37]([NH:39]O)=[NH:38]>C1COCC1.CN(C=O)C>[CH3:14][CH:10]1[CH2:11][CH2:12][CH2:13][NH:8][CH:9]1[C:15]1[O:17][N:39]=[C:37]([C:36]2[CH:41]=[C:24]([CH:43]=[CH:34][CH:35]=2)[C:23]#[N:20])[N:38]=1

Participants

Conditions

Temperature: 135 °C

Procedure

2-[3-(3-cyano-phenyl)-[1,2,4]oxadiazol-5-yl]-3-methyl-piperidine-1-carboxylic acid tert-butyl ester (150 mg, 14.7%) was obtained as described in Example 25 from 3-methyl-piperidine-1,2-dicarboxylic acid 1-tert-butyl ester (672 mg, 2.765 mmol) with triethylamine (1.1 g, 11 mmol) in THF (8 mL) with isobutyl chloroformate (377.6 mg, 2.765 mmol). After 30 minutes, 3-chloro-N-hydroxy-benzamidine (445 mg, 2.765 mmol) in DMF (5 mL) was added and then the reaction mixture was heated to 135° C. for 3 h. The product was purified by column chromatography with 5% ethyl acetate in hexanes. 3-[5-(3-methyl-piperidin-2-yl)-[1,2,4]oxadiazol-3-yl]-benzonitrile (85 mg, 77.8%) was obtained as described in Example 25 from 2-[3-(3-Cyano-phenyl)-[1,2,4]oxadiazol-5-yl]-3-methyl-piperidine-1-carboxylic acid tert-butyl ester (150 mg, 0.407 mmol) with trifluoroacetic acid (0.5 mL) and dichloromethane (4 mL) at room temperature for 2 h.

Workup

customThe product was purified by column chromatography with 5% ethyl acetate in hexanes

Sources & evidence

ORD record: ord-372a76eb36294bcea2534834fde7aae0
Source dataset: uspto-grants-2006_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07074809B2

Reaction notes

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