Potassium Carbonate → HCID 44177596, compound

HRID 1673039Notes

Reaction equation

[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1[N:10]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([S:27]([CH3:30])(=[O:29])=[O:28])[CH:22]=3)=[CH:17][CH:16]=2)[CH:11]=[C:12](I)[N:13]=1.[S:31]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32]1.C(=O)([O-])[O-].[K+].[K+].[O-]S([O-])(=O)=O.[Na+].[Na+]>COCCOC.CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9]1[N:10]([C:15]2[CH:20]=[CH:19][C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([S:27]([CH3:30])(=[O:29])=[O:28])[CH:22]=3)=[CH:17][CH:16]=2)[CH:11]=[C:12]([C:33]2[CH:34]=[CH:35][S:31][CH:32]=2)[N:13]=1

Participants

Conditions

Temperature: 120 °C

Procedure

Into a 5 mL microwave vial was weighed 220 mg (0.39 mmol) of 2-(2,3-di-chlorophenyl)-4-iodo-1-(3′-(methylsulfonyl)biphenyl-4-yl)-1H-imidazole, 108 mg (0.84 mmol) of thiophen-3-ylboronic acid 25 mg (31 μmol) of PdCl2(dppf)-CH2Cl2. The mixture was taken up in 1,2-dimethoxyethane (2 mL), and treated with 400 μL (0.1.4 mmol) of 3.5M aqueous potassium carbonate. The mixture was heated in the Biotage Initiator microwave reactor for 30 minutes at 120° C. LC/MS at this time showed a large peak for the product and some smaller impurity peaks. The reaction mixture was diluted with EtOAc, treated with some decolorizing carbon and Na2SO4. The mixture was filtered through a pad of Celite and the pad was washed with EtOAc. The filtrate was concentrated in vacuo to afford a dark brown oil. The crude product was adsorbed onto silica, loaded onto the top of a 12 g silica column and eluted with a gradient from 0% to 100% EtOAc in hexane. The main product peak was collected and concentrated in vacuo to afford a brown powder that was impure. This impure product was further purified by reverse phase prep HPLC (3 injections). (Phenomenex Axia Gemini C18 30×100 mm 5 μm, A=H2O with 0.1% trifluoroacetic acid, B=acetonitrile with 0.1% trifluoroacetic acid, 17 minute gradient from 30% B to 100% B at 35 mL/minute). Product fractions were combined, made basic by the addition of sat. NaHCO3, and concentrated in vacuo to remove the acetonitrile. The resulting basic aqueous was extracted with CH2Cl2 (3×), and the organics were dried over Na2SO4, filtered and concentrated in vacuo. The resulting 2-(2,3-dichlorophenyl)-1-(3′-(methylsulfonyl)biphenyl-4-yl)-4-(thiophen-3-yl)-1H-imidazole was isolated as a white powder, yield: 89.8 mg (44%) 1H NMR (400 MHz, CDCl3): δ 8.14-8.12 (m, 1H), 7.96-7.92 (m, 1H), 7.87-7.83 (m, 1H) 7.73-7.70 (m, 1H), 7.66 (t, J=7.8 Hz, 1H), 7.61-7.57 (m, 2H), 7.55-7.50 (m, 2H), 7.49-7.46 (m, 2H), 7.40-7.37 (m, 1H), 7.32-7.25 (m, 4H); 3.10 (s, 3H), MS (ES): 525.2 [M+H]+.

Workup

filtrationThe mixture was filtered through a pad of Celite
washthe pad was washed with EtOAc
concentrationThe filtrate was concentrated in vacuo
customto afford a dark brown oil
washeluted with a gradient from 0% to 100% EtOAc in hexane
customThe main product peak was collected
concentrationconcentrated in vacuo
customto afford a brown powder that
customThis impure product was further purified by reverse phase prep HPLC (3 injections)
customwith 0.1% trifluoroacetic acid, 17 minute gradient
additionmade basic by the addition of sat. NaHCO3
concentrationconcentrated in vacuo
customto remove the acetonitrile
extractionThe resulting basic aqueous was extracted with CH2Cl2 (3×)
dry with materialthe organics were dried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-f421f4a4be4342d4a37c114eb7c6c942
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07998995B2

Reaction notes

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