Hydantoin → 4-(4,4-Dimethyl-2,5-dioxoimidazolidin-1-yl)-2-trifluoromethylbenzonitrile

HRID 2280970Notes

Reaction equation

CCCC(OC1C=CC(COCC#CC[N:19]2[C:25]([CH3:27])([CH3:26])[C:23](=[O:24])[N:22]([C:28]3[CH:33]=[CH:32][C:31]([C:34]#[N:35])=[C:30]([C:36]([F:39])([F:38])[F:37])[CH:29]=3)[C:20]2=[O:21])=CC=1C(NCN[C@@H]1[C@H](O)[C@H](C)OC(OC2C3C(=C(O)C4C(=O)C5C=CC=C(OC)C=5C(=O)C=4C=3O)C[C@@](O)(C(CO)=O)C2)C1)=O)=O.FC1C=CC(C#N)=C(C(F)(F)F)C=1.N1CC(=O)NC1=O.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(OCC)(=O)C>[CH3:26][C:25]1([CH3:27])[NH:19][C:20](=[O:21])[N:22]([C:28]2[CH:33]=[CH:32][C:31]([C:34]#[N:35])=[C:30]([C:36]([F:38])([F:37])[F:39])[CH:29]=2)[C:23]1=[O:24]

Participants

Conditions

Temperature: 45 °C

Procedure

(Cogan, P. S.; Koch, T. H. Rational Design and Synthesis of Androgen Receptor-Targeted Nonsteroidal Anti-Androgen Ligands for the Tumor-Specific Delivery of a Doxorubicin-Formaldehyde Conjugate. J. Med. Chem. 2003, 46, 5258-5270) 4-Fluoro-2-(trifluoromethyl)benzonitrile (4.02 g, 21.3 mmol) was added to Hydantoin (13.6 g, 106.3 mmol) and Potassium Carbonate (4.40 g, 31.9 mmol) in 60 mL DMF and stirred at 45° C. under argon for 48 hours. Reaction mixture was then diluted in ethyl acetate and washed three times with water. Organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. Column chromatography (eluent 30:1 DCM/Methanol) gave 1 as a white solid (4.62 g, 74%). 1H NMR (400 MHz, (CD3)2—CO) δ 1.54 (6H, s), 7.80 (1H, s), 8.13 (1H, dd, J=1.8 Hz, J=8.4 Hz), 8.20 (1H, d, J=8.4 Hz), 8.26 (1H, d, J=1.8 Hz)

Workup

customReaction mixture
washwashed three times with water
dry with materialOrganic layer was dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-5b33b03ddaae4a1c9a2f925d970b4434
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09139565B2

Reaction notes

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