1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 1-{[3-(4-Fluorophenyl)-1,2,4-oxadiazol-5-yl]methyl}-3,3-diphenylpiperidin-2-one

HRID 1667186Notes

Reaction equation

[F:1][C:2]1[CH:12]=[CH:11][C:5](/[C:6](=[N:9]/[H])/[NH:7][OH:8])=[CH:4][CH:3]=1.[O:13]=[C:14]1[C:19]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:18][CH2:17][CH2:16][N:15]1[CH2:32][C:33](O)=O.Cl.C(N=C=NCCCN(C)C)C>ClCCCl>[F:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]2[N:9]=[C:33]([CH2:32][N:15]3[CH2:16][CH2:17][CH2:18][C:19]([C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:14]3=[O:13])[O:8][N:7]=2)=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 85 °C

Procedure

A solution of (Z)-4-fluoro-N-hydroxybenzimidamide (0.025 g, 0.162 mmol), 2-(2-oxo-3,3-diphenylpiperidin-1-yl)acetic acid (Example 68E, 0.050 g, 0.162 mmol) and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.046 g, 0.242 mmol) was stirred in 1,2-dichloroethane (0.5 mL) at room temperature. After stirring for 1 hour, the reaction was heated to 85° C. and stirred overnight. The reaction was cooled, loaded directly onto a SF15-12 silica gel column (Analogix®, Burlington, Wis.), and the title compound was eluted using a gradient of 5% to 100% ethyl acetate/hexanes over 20 minutes (flow=30 mL/minute). 1H NMR (300 MHz, CDCl3) δ ppm 8.09-8.15 (m, 2H), 7.24-7.34 (m, 10H), 7.16-7.24 (m, 2H), 4.91 (s, 2H), 3.62 (t, J=6.4 Hz, 2H), 2.68-2.73 (m, 2H), 1.87-1.96 (m, 2H); MS (ESI+) m/z 428 (M+H)+.

Workup

stirringstirred overnight
temperatureThe reaction was cooled
washthe title compound was eluted
customover 20 minutes

Sources & evidence

ORD record: ord-3ded16500c494df4b87b6f657a0dfe38
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08044069B2

Reaction notes

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