N'-Hydroxy-4-(trifluoromethyl)benzene-1-carboximidamide → 3,3-Bis(4-fluorophenyl)-1-({3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl}methyl)pyrrolidin-2-one

HRID 1667230Notes

Reaction equation

[OH:1][NH:2]/[C:3](=[N:14]\[H])/[C:4]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][CH:5]=1.[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2([C:33]3[CH:38]=[CH:37][C:36]([F:39])=[CH:35][CH:34]=3)[CH2:27][CH2:26][N:25]([CH2:28][C:29](O)=O)[C:24]2=[O:32])=[CH:19][CH:18]=1.Cl.C(N=C=NCCCN(C)C)C>ClC(Cl)C>[F:39][C:36]1[CH:35]=[CH:34][C:33]([C:23]2([C:20]3[CH:19]=[CH:18][C:17]([F:16])=[CH:22][CH:21]=3)[CH2:27][CH2:26][N:25]([CH2:28][C:29]3[O:1][N:2]=[C:3]([C:4]4[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][CH:5]=4)[N:14]=3)[C:24]2=[O:32])=[CH:38][CH:37]=1

Participants

Conditions

Temperature: 85 °C

Procedure

A solution of (Z)—N-hydroxy-4-(trifluoromethyl)benzimidamide (0.204 g, 1.0 mmol), 2-(3,3-bis(4-fluorophenyl)-2-oxopyrrolidin-1-yl)acetic acid (Example 58D, 0.331 g, 1.0 mmol) and N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (0.383 g, 2.00 mmol) were stirred together in dichloroethane (5.0 mL) at room temperature for 2 hours under nitrogen. The reaction was then heated to 85° C. and stirred overnight. The reaction mixture was cooled, concentrated, loaded onto a SF25-40 column (Analogix®, Burlington, Wis.) and the product eluted using a gradient of 10% ethyl acetate/hexanes to 70% ethyl acetate over 30 minutes (Flow=30 mL/minute) to give the title compound. 1H NMR (300 MHz, CDCl3) δ ppm 8.10 (d, J=8.1, 2H), 7.75 (d, J=8.3, 2H), 7.44-7.31 (m, 4H), 7.08-6.94 (m, 4H), 4.90 (s, 2H), 3.57 (t, J=6.5, 2H), 2.84 (t, J=6.5, 2H); MS (DCI) m/z 500.1 (M+H)+.

Workup

temperatureThe reaction mixture was cooled
concentrationconcentrated
washthe product eluted
customover 30 minutes

Sources & evidence

ORD record: ord-86abcc6f62fa44b79ff907cddf202b45
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08044069B2

Reaction notes

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