1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 1-((3-(4-Bromophenyl)-1,2,4-oxadiazol-5-yl)methyl)-3,3-bis(4-fluorophenyl)pyrrolidin-2-one

HRID 1667271Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:18]3[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=3)[CH2:12][CH2:11][N:10]([CH2:13][C:14](O)=[O:15])[C:9]2=[O:17])=[CH:4][CH:3]=1.[Br:25][C:26]1[CH:36]=[CH:35][C:29](/[C:30](=[N:33]/[H])/[NH:31]O)=[CH:28][CH:27]=1.C(N=C=NCCCN(C)C)C>ClC(Cl)C>[Br:25][C:26]1[CH:36]=[CH:35][C:29]([C:30]2[N:33]=[C:14]([CH2:13][N:10]3[CH2:11][CH2:12][C:8]([C:18]4[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=4)([C:5]4[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=4)[C:9]3=[O:17])[O:15][N:31]=2)=[CH:28][CH:27]=1

Participants

Conditions

Temperature: 85 °C

Procedure

2-(3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid (0.300 g, 0.905 mmol; Example 58D), (Z)-4-bromo-N-hydroxybenzimidamide (0.214 g, 0.996 mmol) and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine (0.211 g, 1.358 mmol) were stirred together in dichloroethane (5 mL) at room temperature for 3 hours. The reaction was then heated to 85° C. for 18 hours. The reaction was cooled, loaded onto a GraceResolv 80 g silica gel column (Grace Davison Discovery Sciences) and the product eluted with a gradient of 5% ethyl acetate/hexanes to 40% ethyl acetate/hexanes (Flow=40 mL/minute) over 40 minutes to give the title compound. 1H NMR (300 MHz, CDCl3) δ 7.85 (d, J=8.6, 2H), 7.62 (d, J=8.6, 2H), 7.38-7.30 (m, 4H), 7.07-6.97 (m, 4H), 4.87 (s, 2H), 3.56 (t, J=6.5, 2H), 2.83 (t, J=6.4, 2H); MS (ESI+) m/z 512.0 (M+H)+.

Workup

temperatureThe reaction was cooled
washthe product eluted with a gradient of 5% ethyl acetate/hexanes to 40% ethyl acetate/hexanes (Flow=40 mL/minute) over 40 minutes

Sources & evidence

ORD record: ord-2555fdb23aa9497e893da55479201142
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08044069B2

Reaction notes

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