Sodium Bicarbonate → 1-{[4-(3-Chloro-4-fluorophenyl)-5-(3-chlorophenyl)thiophen-2-yl]carbonyl}imidazolidin-4-one

HRID 1037002Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([C:14]([N:16]2[CH2:20][C:19](=[O:21])[NH:18][CH2:17]2)=[O:15])[S:5][C:6]=1[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([Cl:13])[CH:8]=1.[Cl:22][C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][C:28]=1[F:29].C(=O)(O)[O-].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:22][C:23]1[CH:24]=[C:25]([C:2]2[CH:3]=[C:4]([C:14]([N:16]3[CH2:20][C:19](=[O:21])[NH:18][CH2:17]3)=[O:15])[S:5][C:6]=2[C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([Cl:13])[CH:8]=2)[CH:26]=[CH:27][C:28]=1[F:29]

Participants

Conditions

Temperature: 150 °C

Procedure

Under argon, 70.0 mg of the compound from Example 24A having a purity of 76% (0.14 mmol) and 47.5 mg (0.27 mmol) of 3-chloro-4-fluorophenylboronic acid are provided in 2.6 ml of 1,2-dimethoxyethane, and 1.0 ml (0.91 mmol) of an aqueous sodium bicarbonate solution (10%) and 6.3 mg (0.005 mmol) of tetrakis(triphenylphosphine)palladium(0) are added. The mixture is heated in a closed glass vessel at 150° C. under microwave irradiation for 5 minutes. The reaction mixture is purified by preparative HPLC (RP18 column; eluent: acetonitrile/water gradient with addition of 0.1% formic acid) and additional preparative thin-layer chromatography (silica gel; mobile phase: ethyl acetate). 8.0 mg (13% of theory) of the title compound are obtained.

Workup

customThe reaction mixture is purified by preparative HPLC (RP18 column; eluent: acetonitrile/water gradient with addition of 0.1% formic acid) and additional preparative thin-layer chromatography (silica gel; mobile phase: ethyl acetate)

Sources & evidence

ORD record: ord-8f392b3526e74a18b0edff207864e479
Source dataset: uspto-grants-2013_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08546438B2

Reaction notes

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