Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([OH:22])=[C:6]([C:8]2[CH2:12][CH2:11][CH2:10][C:9]=2[C:13]2[CH:14]=[C:15]([CH:19]=[CH:20][CH:21]=2)[C:16]([OH:18])=[O:17])[CH:7]=1.[CH2:23](Br)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[OH-].[K+]>CS(C)=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([O:22][CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[C:6]([C:8]2[CH2:12][CH2:11][CH2:10][C:9]=2[C:13]2[CH:14]=[C:15]([CH:19]=[CH:20][CH:21]=2)[C:16]([OH:18])=[O:17])[CH:7]=1
Reactant: BrCc1ccccc1
Reactant: O=C(O)c1cccc(C2=C(c3cc(Br)ccc3O)CCC2)c1
Agent: [K+]
Agent: [OH-]
Solvent: CS(C)=O
Product: O=C(O)c1cccc(C2=C(c3cc(Br)ccc3OCc3ccccc3)CCC2)c1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
3-{2-[5-Bromo-2-(hydroxy)-phenyl]-cyclopent-1-enyl}-benzoic acid (0.04 g, 0.12 mmol), benzyl bromide (0.038 g, 0.22 moles), potassium hydroxide (˜0.15 g), in dimethyl sulphoxide (1.5 mL) were stirred at room temperature over 8 hrs under nitrogen. The reaction mixture was then quenched with ice/water (10/10 mL), stirred at room temperature for ˜1.5 hrs, acidified with 2N hydrochloric acid to pH˜3 and extracted with dichloromethane. The organic extract was then dried (magnesium sulphate) and concentrated down to an oil and was then chromatographed on Waters sep-pak cartridge (10 g) giving (0.028 g, 54%).
Reaction SMILES: [Br:1][C:2]1[N:6]2[CH2:7][CH2:8][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:10][C:5]2=[C:4]([C:18]([OH:20])=O)[N:3]=1.[CH3:21][NH:22][C:23](=[O:30])[C@H:24]([CH2:26][CH:27]([CH3:29])[CH3:28])[NH2:25].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[Br:1][C:2]1[N:6]2[CH2:7][CH2:8][N:9]([C:11]([O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:12])[CH2:10][C:5]2=[C:4]([C:18](=[O:20])[NH:25][C@@H:24]([CH2:26][CH:27]([CH3:29])[CH3:28])[C:23]([NH:22][CH3:21])=[O:30])[N:3]=1
Reactant: CNC(=O)[C@@H](N)CC(C)C
Reactant: CC(C)(C)OC(=O)N1CCn2c(Br)nc(C(=O)O)c2C1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CNC(=O)[C@H](CC(C)C)NC(=O)c1nc(Br)n2c1CN(C(=O)OC(C)(C)C)CC2
Reaction time: 2 h
Yield: 48 %

Procedure:
To a solution of 3-bromo-7-(tert-butoxycarbonyl)-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazine-1-carboxylic acid (11) (0.53 g, 1.53 mmol), L-leucine-N-methylamide (0.26 g, 1.80 mmol) and DIEA (0.5 mL, 2.9 mmol) in DMF (20 mL) was added TBTU (0.69 g, 2.15 mmol) in two batches over 10 minutes at 0° C. After stirring from 0° C. to room temperature for 2 hours, the reaction was quenched with water and evaporated under vacuum. The residue was extracted between saturated aqueous NaHCO3 and EtOAc. The organic layer was dried over anhydrous Na2SO4 and evaporated to dryness. The crude mixture was purified by column chromatography with 70% to 100% EtOAc/Hexanes to give the desired product 20C as an oil (48% yield). LCMS (+ESI) m/z 474.1, 475.1 [M+H]+.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]([Cl:20])[N:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][C:8]=12)(=[O:3])[NH2:2].C(OCC)(=O)C.[Br:27]N1C(=O)CCC1=O.O>ClCCl>[Br:27][C:5]1[C:4]([C:1](=[O:3])[NH2:2])=[C:8]2[CH2:9][N:10]([C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14])[CH2:11][CH2:12][N:7]2[C:6]=1[Cl:20]
Reactant: CC(C)(C)OC(=O)N1CCn2c(Cl)cc(C(N)=O)c2C1
Reactant: O=C1CCC(=O)N1Br
Solvent: O
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1CCn2c(Cl)c(Br)c(C(N)=O)c2C1
Temperature: 0 °C
Reaction time: 5 h
Yield: 37.6 %

Procedure:
To a solution of 10.5 g (35.1 mmol) of tert-butyl 8-carbamoyl-6-chloro-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate in 1 l of a mixture of 50% ethyl acetate in dichloromethane precooled to 0° C. is added slowly a solution of 6.90 g (38.6 mmol) of N-bromosuccinimide in 200 ml of dichloromethane. The reaction is stirred for 5 hours at 0° C. and then for 12 hours while allowing the temperature to return to room temperature. 300 ml of water are then added, the organic phase is separated out by settling and the aqueous phase is then washed with twice 200 ml of ethyl acetate. The organic phases are combined and partially concentrated under reduced pressure. The solution is taken up in 60 ml of water and the organic solvents are removed by evaporation under reduced pressure. The insoluble matter suspended in water is isolated by filtration, washed with water and then dried under reduced pressure in the presence of phosphorus pentoxide. The residue obtained is chromatographed on a column of silica gel, eluting with a mixture of 5 to 50% ethyl acetate in dichloromethane, to give 5.0 g of tert-butyl 7-bromo-8-carbamoyl-6-chloro-3,4-dihydropyrrolo[1,2-a]pyrazine-2(1H)-carboxylate in the form of a white solid after triturating in ethyl acetate and drying at 60° C. under reduced pressure.
Reaction SMILES: [CH3:1][N:2]1[C:6]([OH:7])=[C:5]([CH3:8])[C:4]([C:9]([F:12])([F:11])[F:10])=[N:3]1.C(=O)([O-])[O-].[K+].[K+].FC(F)(F)S(O[CH2:25][C:26]([F:29])([F:28])[F:27])(=O)=O.O>CN(C)C=O>[CH3:1][N:2]1[C:6]([O:7][CH2:25][C:26]([F:29])([F:28])[F:27])=[C:5]([CH3:8])[C:4]([C:9]([F:11])([F:10])[F:12])=[N:3]1
Reactant: Cc1c(C(F)(F)F)nn(C)c1O
Reactant: O=S(=O)(OCC(F)(F)F)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1c(C(F)(F)F)nn(C)c1OCC(F)(F)F
Temperature: 25 °C
Reaction time: 3 h
Yield: 95.3 %

Procedure:
To a solution of 4.4 g (24.4 mmol) of 1,4-dimethyl-5-hydroxy-3-trifluoromethyl-1H-pyrazole in 50 ml of N,N-dimethylformamide were added 5.1 g (36.6 mmol) of anhydrous potassium carbonate and 6.3 (26.8 mmol) of 2,2,2-trifluoroethyl trifluoromethanesulfonate, followed by 3 hours of stirring at room temperature. After the completion of the reaction was confirmed, the reaction solution was poured into water and extracted with ethyl acetate. The resulting organic layer was washed with water and saline, successively, and then dried over anhydrous magnesium sulfate. The solvent was removed by evaporation under reduced pressure to obtain 6.1 g (yield: 95.3%) of 1,4-dimethyl-5-(2,2,2-trifluoroethoxy)-3-trifluoromethyl-1H-pyrazole as a pale yellow liquid.
Reaction SMILES: N1C=CC=CC=1.[C:7](OC(=O)C)(=[O:9])[CH3:8].[NH2:14][C:15]1[C:19]2[CH:20]=[C:21]3[C:34](=[C:35]([F:36])[C:18]=2[O:17][N:16]=1)[N:33]1[CH2:37][C@@H:38]([CH3:42])[O:39][C@@H:40]([CH3:41])[C@@H:32]1[C:23]1([C:28](=[O:29])[NH:27][C:26](=[O:30])[NH:25][C:24]1=[O:31])[CH2:22]3>C(Cl)CCl>[F:36][C:35]1[C:18]2[O:17][N:16]=[C:15]([NH:14][C:7](=[O:9])[CH3:8])[C:19]=2[CH:20]=[C:21]2[C:34]=1[N:33]1[CH2:37][C@@H:38]([CH3:42])[O:39][C@@H:40]([CH3:41])[C@@H:32]1[C:23]1([C:28](=[O:29])[NH:27][C:26](=[O:30])[NH:25][C:24]1=[O:31])[CH2:22]2
Reactant: C[C@@H]1CN2c3c(cc4c(N)noc4c3F)CC3(C(=O)NC(=O)NC3=O)[C@H]2[C@H](C)O1
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Solvent: ClCCCl
Product: CC(=O)Nc1noc2c(F)c3c(cc12)CC1(C(=O)NC(=O)NC1=O)[C@H]1[C@H](C)O[C@H](C)CN31
Temperature: 130 °C
Reaction time: 12 h

Procedure:
Pyridine (0.01 mL, 0.2 mmol) and acetic anhydride (0.10 mL, 0.14 mmol) were added sequentially to a solution of (2R,4S,4aS)-rel-8-amino-11-fluoro-2,4-dimethyl-1,2,4,4a-tetrahydro-2′H,6H-spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5,5′-pyrimidine]-2′,4′,6′(1′H,3′H)-trione (Example 1, 54 mg, 0.13 mmol) in ethylene dichloride, and the mixture was stirred at 130° C. for 12 hours. After cooling to room temperature, solvent was removed, and the residue was purified over a silica gel flash column using a gradient of methanol in chloroform to give the title compound as a racemic mixture in the form of a yellow solid. Yield: 7.5 mg, (13%).
Reaction SMILES: C([Cl:4])(=O)C.C(OC(=O)[NH:11][C@H:12]1[C@H:18]([CH3:19])[N:17]([C:20](=[O:30])[C:21]2[CH:26]=[CH:25][C:24]([C:27](=[O:29])[CH3:28])=[CH:23][CH:22]=2)[C:16]2[CH:31]=[CH:32][CH:33]=[CH:34][C:15]=2[NH:14][C:13]1=[O:35])(C)(C)C>CO>[ClH:4].[C:27]([C:24]1[CH:25]=[CH:26][C:21]([C:20]([N:17]2[C@@H:18]([CH3:19])[C@H:12]([NH2:11])[C:13](=[O:35])[NH:14][C:15]3[CH:34]=[CH:33][CH:32]=[CH:31][C:16]2=3)=[O:30])=[CH:22][CH:23]=1)(=[O:29])[CH3:28]
Reactant: CC(=O)c1ccc(C(=O)N2c3ccccc3NC(=O)[C@@H](NC(=O)OC(C)(C)C)[C@@H]2C)cc1
Reactant: CC(=O)Cl
Solvent: CO
Product: CC(=O)c1ccc(C(=O)N2c3ccccc3NC(=O)[C@@H](N)[C@@H]2C)cc1
Product: Cl
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Acetyl chloride (1.0 ml, 14.1 mmol) was added dropwise to a solution of [(2S,3S)-1-(4-acetyl-benzoyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl]-carbamic acid tert-butyl ester (0.45 g, 1.03 mmol) in methanol at 0° C. and the reaction was allowed to warm to ambient temperature and stir for 2 h. The reaction was concentrated in vacuo to give (3S,4S)-5-(4-acetyl-benzoyl)-3-amino-4-methyl-1,3,4,5-tetrahydro-benzo[b][1,4]diazepin-2-one hydrochloride which was used in the subsequent step without further purification (0.36 g, 100%).
Reaction SMILES: [NH2:1][C:2]1[C:3](=[O:9])[NH:4][C:5](=[O:8])[NH:6][CH:7]=1.[CH:10](=O)/[CH:11]=[CH:12]/[CH3:13]>Cl>[O:8]=[C:5]1[NH:6][C:7]2[CH:10]=[CH:11][C:12]([CH3:13])=[N:1][C:2]=2[C:3](=[O:9])[NH:4]1
Reactant: C/C=C/C=O
Reactant: Nc1c[nH]c(=O)[nH]c1=O
Agent: Cl
Product: Cc1ccc2[nH]c(=O)[nH]c(=O)c2n1
Reaction time: 0.17 h

Procedure:
About 20 g of 5-aminouracil, 80 ml of 20% HCl and 4 ml of crotonaldehyde were heated together under reflux for 1 hour. The solution was evaporated to dryness under rotary evaporation. Water was added to the residue so as to make the mixture just stirrable and then it was triturated with ammonium hydroxide with strong stirring until the pH increased to 10-11. Stirring was continued for another 10 minutes. The precipitate was filtered and was washed with minimal methanol and then chloroform and dried to yield about 17.58 g of the compound of FIG. 17a.
Reaction SMILES: [C:1]([O:7][C:8]1[CH:9]=[C:10]([C:21](=[O:24])[CH2:22]C)[CH:11]=[CH:12][C:13]=1[O:14][C:15](=[O:20])[C:16]([CH3:19])([CH3:18])[CH3:17])(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].C(OC1C=C(C(=O)C)C=CC=1OC(=O)C(C)(C)C)(=O)C(C)(C)C.OC1C=C(C(=O)CC)C=CC=1O.C(Cl)(=O)C(C)(C)C.[Br:67]Br>C(N(CC)CC)C>[Br:67][CH2:22][C:21]([C:10]1[CH:11]=[CH:12][C:13]([O:14][C:15](=[O:20])[C:16]([CH3:19])([CH3:18])[CH3:17])=[C:8]([O:7][C:1](=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3])[CH:9]=1)=[O:24]
Reactant: BrBr
Reactant: CCC(=O)c1ccc(OC(=O)C(C)(C)C)c(OC(=O)C(C)(C)C)c1
Agent: CC(=O)c1ccc(OC(=O)C(C)(C)C)c(OC(=O)C(C)(C)C)c1
Agent: CC(C)(C)C(=O)Cl
Agent: CCC(=O)c1ccc(O)c(O)c1
Solvent: CCN(CC)CC
Product: CC(C)(C)C(=O)Oc1ccc(C(=O)CBr)cc1OC(=O)C(C)(C)C

Procedure:
3',4'-Bis(pivaloyloxy)propiophenone was first prepared as a mobile liquid (63.6 g.), in a similar manner to 3',4'-bis(pivaloyloxy)acetophenone in Example 1, starting from 3',4'-dihydroxypropiophenone (40 g.), pivaloylchloride (63.3 ml.) and triethylamine (73.2 ml.). This mobile liquid (40.1 g.) was then reacted with bromine (7.2 ml.) in a similar manner to that used in Example 1 to obtained 2-bromo-3',4'-bis(pivaloyloxy)acetophenone. The crude bromo compound thus obtained was purified by dry column chromatography on silica gel as described in Example 1 to give pure 2-bromo-3',4'-bis(pivaloyloxy)propiophenone as a solid (18.4 g.), m.p. 58°-60° C.
Reaction SMILES: [CH3:1][CH2:2][C:3]([C:5]1[CH:16]=[CH:15][C:8]([O:9][CH2:10][C:11]([O:13][CH3:14])=[O:12])=[CH:7][CH:6]=1)=[O:4].[N:17]1[CH:22]=[CH:21][C:20]([N:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)=[CH:19][CH:18]=1>C(#N)C>[N:17]1[CH:22]=[CH:21][C:20]([N:23]2[CH2:24][CH2:25][N:26]([CH:2]([CH3:1])[C:3]([C:5]3[CH:16]=[CH:15][C:8]([O:9][CH2:10][C:11]([O:13][CH3:14])=[O:12])=[CH:7][CH:6]=3)=[O:4])[CH2:27][CH2:28]2)=[CH:19][CH:18]=1
Reactant: CCC(=O)c1ccc(OCC(=O)OC)cc1
Reactant: c1cc(N2CCNCC2)ccn1
Solvent: CC#N
Product: COC(=O)COc1ccc(C(=O)C(C)N2CCN(c3ccncc3)CC2)cc1
Reaction time: 8 h

Procedure:
A solution of RS methyl 4-(2-methylacetyl)phenoxyacetate (1.2 g) in acetonitrile (10 ml) was added dropwise over 30 minutes to a stirred solution of 1-(4-pyridyl)piperazine (1.3 g) in acetonitrile (30 ml) and the mixture stirred overnight. The mixture was then filtered and the filtrate evaporated to give an oil. Purification by flash chromatography, eluting first with dichloromethane then successively 2.5%, 3%, 4%, 5% and 10% v/v methanol/dichloromethane gave the title compound, 220 mg as a solid: m.p. 81°-83° C.; NMR (d6DMSO) δ 8.13(2H,d), 8.06(2H,d), 7.02(2H,d), 6.77(2H,d), 4.92(2H,s), 4.33(1H,q), 3.72(3H,s), 3.26(4H,t), 2.63(4H,t), 1.16(3H,d); m/e 384(M+H)+ ; calculated for C21H25N3O4 : C, 65.8; H, 6.6; N, 11.0. found C, 65.7; H, 6.8; N, 10.9%.
Reaction SMILES: [CH2:1]([C:3]1[N:13]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][NH:22][C:23](=[O:31])OC3C=CC=CC=3)=[CH:16][CH:15]=2)[C:6]2=[N:7][C:8]([CH3:12])=[CH:9][C:10]([CH3:11])=[C:5]2[N:4]=1)[CH3:2].[S:32]1[CH:36]=[CH:35][CH:34]=[C:33]1[S:37]([NH2:40])(=[O:39])=[O:38]>>[CH2:1]([C:3]1[N:13]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][NH:22][C:23]([NH:40][S:37]([C:33]3[S:32][CH:36]=[CH:35][CH:34]=3)(=[O:39])=[O:38])=[O:31])=[CH:16][CH:15]=2)[C:6]2=[N:7][C:8]([CH3:12])=[CH:9][C:10]([CH3:11])=[C:5]2[N:4]=1)[CH3:2]
Reactant: CCc1nc2c(C)cc(C)nc2n1-c1ccc(CCNC(=O)Oc2ccccc2)cc1
Reactant: NS(=O)(=O)c1cccs1
Product: CCc1nc2c(C)cc(C)nc2n1-c1ccc(CCNC(=O)NS(=O)(=O)c2cccs2)cc1

Procedure:
The title compound was prepared according to the procedure described in step 2 of Example 18 from phenyl 2-[4-(2-ethyl-5,7-dimethyl-3H-imidazo[4,5-b]pyridin-3-yl)phenyl]ethylcarbamate (step 1 of Example 18) and 2-thiophenesulfonamide (Huang, H. C.; Reinhard, E. J.; Reitz, D. B. Tetrahedron Lett., 1994, 35, 7201; Graham, S. L.; Scholz, T. H. Synthesis, 1986, 1031).
Reaction SMILES: Br[C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][C:3]=1[CH3:9].C([Li])(C)(C)C.CCCCC.[B:20](OC)([O:23]C)[O:21]C>O1CCCC1>[CH3:9][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([CH3:8])[C:2]=1[B:20]([OH:23])[OH:21]
Reactant: Cc1cccc(C)c1Br
Reactant: COB(OC)OC
Agent: [Li]C(C)(C)C
Solvent: CCCCC
Solvent: C1CCOC1
Product: Cc1cccc(C)c1B(O)O

Procedure:
Following General Procedure A and using 1-bromo-2,6-dimethyl-benzene (Aldrich, 5 g, 27 mmol), 50 mL of anhydrous tetrahydrofuran, 1.7M solution of t-butyllithium in n-pentane (32 mL, 54 mmol) and trimethyl borate (6.05 mL, 54 mmol), the title compound was obtained after recrystallization from ethyl acetate-hexane mixture (0.7 g, 10%).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([OH:13])[CH2:10][CH:9]1[CH2:14][OH:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:23][S:24](Cl)(=[O:26])=[O:25]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([O:13][S:24]([CH3:23])(=[O:26])=[O:25])[CH2:10][CH:9]1[CH2:14][O:15][S:24]([CH3:23])(=[O:26])=[O:25])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)N1CC(O)CC1CO
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CC(OS(C)(=O)=O)CC1COS(C)(=O)=O
Temperature: 25 °C

Procedure:
To a stirred solution of the diol (344) (12.7 g, 58.5 mmol) and triethylamine (5 equiv., 41 mL) in CH2Cl2 (200 mL) at 0° C. was added methanesulfonyl chloride (NsCl) (2.4 equiv., 10.9 mL). The resulting suspension was removed from the ice bath and allowed to warm to room temperature with stirring at which point TLC analysis indicated complete consumption of the starting material and conversion to a single spot of higher Rf (5% MeOH/CHCl3, stained with K2MnO4). The reaction was quenched by the addition of water (20 mL) with vigorous stirring. NaHCO3 (sat., aqueous, 200 mL) was added and the organic layer was separated, washed with brine, dried (MgSO4) and purified by flash chromatography (1–10% MeOH/CHCl3) to yield the desired compound (345) as a colorless oil.
Reaction SMILES: I[C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH:5]=[O:6].[CH3:10][O:11][C:12]1[CH:13]=[C:14]([SH:18])[CH:15]=[CH:16][CH:17]=1.C([O-])([O-])=O.[K+].[K+].C(O)CO>[Cu]I.CC(O)C>[CH3:10][O:11][C:12]1[CH:13]=[C:14]([S:18][C:2]2[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=2)[CH:5]=[O:6])[CH:15]=[CH:16][CH:17]=1
Reactant: COc1cccc(S)c1
Reactant: O=Cc1cccc(I)c1
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: OCCO
Solvent: CC(C)O
Product: COc1cccc(Sc2cccc(C=O)c2)c1
Yield: 83.9 %

Procedure:
The general procedure in example 39 was followed. 3-Iodobenzaldehyde (232 mg, 1.0 mmol), 3-methoxythiophenol (124 μL, 1.0 mmol), CuI (10 mg, 0.05 mmol), K2CO3 (276 mg, 2.0 mmol), ethylene glycol (111 μL, 2.0 mmol) and 2-Propanol (1.0 mL) were used to obtain the 3-(3-methoxyphenyl)sulfanylbenzaldehyde (205 mg, 85% yield) as colorless liquid. Column chromatographic solvent (hexane/ethyl acetate=15/1). Rf=0.4 hexane/ethyl acetate=10/1). 1H NMR (CDCl3, 300 MHz) δ 9.91 (s, 1 H), 7.76-7.77 (m, 1 H), 7.71 (dt, 1 H, J=1.2 Hz, 7.2 Hz), 7.45-7.53 (m, 1 H), 7.42 (t, 1 H, J=7.5 Hz), 7.25 (t, 1 H, J=7.5 Hz), 6.91-6.98 (m, 2 H), 6.84 (ddd, 1 H, J=1.2 Hz, 2.4 Hz, 8.1 Hz), 3.77 (s, 3 H). 13C NMR (CDCl3, 75 MHz) δ 191.7, 160.3,138.4,137.3, 135.8,135.0,131.1, 130.5,129.9,127.9, 124.6,117.6,114.0,55.7. IR (neat, cm−1) 3060, 3006, 2960, 2937, 2834, 2726, 1698. MS (EI) m/z (relative intensity) 244 (100), 227 (30), 211 (40). Anal. Cald. for C14H12O2S, Cald. C: 68.83, H: 4.95; Found C: 69.04, H: 4.94.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1.[O:12]1[CH:16]=[CH:15][CH:14]=[C:13]1[CH:17]=O.CCN(CC)CC.CC(OC(C)=O)=O>Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5](/[C:8](=[CH:17]\[C:13]2[O:12][CH:16]=[CH:15][CH:14]=2)/[C:9]([OH:11])=[O:10])=[CH:6][CH:7]=1
Reactant: O=Cc1ccco1
Reactant: O=C(O)Cc1ccc(Br)cc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CC(=O)OC(C)=O
Product: O=C(O)/C(=C/c1ccco1)c1ccc(Br)cc1
Temperature: 140 °C

Procedure:
A mixture of 4-bromophenylacetic acid (12.90 g, 60.0 mmol), 2-furancarboxaldehyde (6.0 mL, 72.0 mmol), NEt3 (12.0 mL, 86.4 mmol), and Ac2O (12.0 mL, 127.2 mmol) were heated at 140° C. (bath) with stirring for 1¾ h. The reaction mixture was cooled in an ice bath, before being treated with 2M HCl (30 mL) to adjust the pH to 1. A solid precipitated out of solution. This solid was extracted into Et2O (500 mL). The Et2O layer was washed with H2O (100 mL), before being extracted with 5% w/v aqueous Na2CO3 solution (5×100 mL). The aqueous extracts were washed with Et2O (2×50 mL), before being carefully acidified with AcOH to pH 6. The cream solid generated was collected, washed with H2O, and recrystallised from MeOH—H2O to give the title compound: m/z (ES+)=604.0 [2M+NH4]+.
Reaction SMILES: Br[C:2]1[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][C:3]=1[CH2:4][N:5]1[CH2:9][CH2:8][O:7][C:6]1=[O:10].[CH3:19][O:20][C:21](=[O:40])[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[C:25](B2OC(C)(C)C(C)(C)O2)[CH:24]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.C(Cl)Cl.O.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>[CH3:19][O:20][C:21](=[O:40])[CH2:22][C:23]1[CH:24]=[C:25]([C:2]2[CH:14]=[CH:13][C:12]([C:15]([F:18])([F:17])[F:16])=[CH:11][C:3]=2[CH2:4][N:5]2[CH2:9][CH2:8][O:7][C:6]2=[O:10])[C:26]([O:29][CH3:30])=[CH:27][CH:28]=1
Reactant: O=C1OCCN1Cc1cc(C(F)(F)F)ccc1Br
Reactant: COC(=O)Cc1ccc(OC)c(B2OC(C)(C)C(C)(C)O2)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: O
Solvent: COCCOC
Product: COC(=O)Cc1ccc(OC)c(-c2ccc(C(F)(F)F)cc2CN2CCOC2=O)c1
Temperature: 90 °C
Reaction time: 4 h

Procedure:
3-(2-Bromo-5-trifluoromethyl-benzyl)-oxazolidin-2-one (0.234 g, 0.71 mmol), [4-methoxy-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-acetic acid methyl ester (0.181 g, 0.59 mmol), and potassium carbonate (0.209 g, 1.48 mmol) were combined in DME (2.5 mL) and H2O (1.2 mL) and purged with N2 for 30 minutes. Tetrakis(triphenylphosphine)palladium (0) (0.069 g, 0.06 mmol) was added, and the reaction was stirred at 90° C. for 4 hours. After cooling to room temperature, the mixture was diluted with CH2Cl2 and H2O. The aqueous layer was separated and extracted with CH2Cl2, and the combined organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified by silica gel chromatography (0-50% EtOAc in hexanes) to give the title compound.
Reaction SMILES: Br[C:2]1[N:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[C:8]1(B2OC(C)(C)C(C)(C)O2)[CH:13]=[CH:12][C:11]([B:14]2[O:18][C:17]([CH3:20])([CH3:19])[C:16]([CH3:22])([CH3:21])[O:15]2)=[CH:10][CH:9]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O>CN(C=O)C.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>[CH3:19][C:17]1([CH3:20])[C:16]([CH3:21])([CH3:22])[O:15][B:14]([C:11]2[CH:12]=[CH:13][C:8]([C:2]3[N:7]=[CH:6][CH:5]=[CH:4][N:3]=3)=[CH:9][CH:10]=2)[O:18]1
Reactant: CC1(C)OB(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)OC1(C)C
Reactant: Brc1ncccn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CC1(C)OB(c2ccc(-c3ncccn3)cc2)OC1(C)C
Reaction time: 16 h
Yield: 26.4 %

Procedure:
A degassed solution of 2-bromopyrimidine (1.5 g, 9.4 mmol), 2,2′-(1,4-phenylene)bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolane) (5.1 g, 16.0 mmol), 1.0 M aq K3PO4 (28.3 mL, 28.3 mmol), and Pd(PPh3)4 (330 mg, 0.31 mmol) in DMF (140 mL) was heated to 80° C. and stirred at this temperature for 16 h. Water (100 mL) was added to the reaction mixture and was extracted with EtOAc (3×200 mL). The combined organic phases were dried (Na2SO4), filtered, and concentrated under reduced pressure. The crude material was purified via flash chromatography using an eluent of 17% EtOAc in n-heptane to afford the title compound as a white solid (0.7 g, 28%). MS (LCMS) m/z 283.1 (M+1). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.36 (s, 12 H) 7.19 (t, J=4.68 Hz, 1 H) 7.93 (d, J=8.00 Hz, 2 H) 8.43 (d, J=7.81 Hz, 2 H) 8.81 (d, J=4.68 Hz, 2 H).
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[C:6]1([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][CH:14]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)[CH:15]([CH2:23][CH2:24][OH:25])[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:8][CH:7]=1.C(N(CC)CC)C>ClCCl>[C:6]1([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH:7]=[CH:8][C:9]([CH2:12][CH2:13][CH:14]([O:26][CH2:27][C:28]2[CH:29]=[CH:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=2)[CH:15]([CH2:23][CH2:24][O:25][S:2]([CH3:1])(=[O:4])=[O:3])[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:10][CH:11]=1
Reactant: CS(=O)(=O)Cl
Reactant: COc1ccc(COC(CCc2ccc(-c3ccccc3)cc2)C(CCO)C(=O)OC(C)(C)C)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccc(COC(CCc2ccc(-c3ccccc3)cc2)C(CCOS(C)(=O)=O)C(=O)OC(C)(C)C)cc1
Yield: 95.8 %

Procedure:
Methanesulfonyl chloride (64 μL, 0.83 mmol) was added in one portion to a stirred solution of 1,1-dimethylethyl 5-(4-biphenylyl)-2-(2-hydroxyethyl)-3-({[4-(methyloxy)phenyl]methyl}oxy)pentanoate (368 mg, 0.751 mmol) and triethylamine (15.4 mg, 209 μL, 1.52 mmol) in dichloromethane (2 mL) at room temperature under nitrogen. After stirring at room temperature for 1 h the crude mixture was partitioned between saturated aqueous citric acid solution (20 mL) and dichloromethane (20 mL). The phases were separated and the organic layer was evaporated to give the title compound (409 mg, 79%) as a yellow oil which was a mixture of diastereomers. LC/MS: 4.08 min; z/e 586, calcd (M+1) 586. 1H NMR (400 MHz: CDCl3): 7.50 (6H), 7.25 (4H), 7.15 (1H), 6.90 (2H), 4.50 (2H), 4.25 (2H), 3.80 (3H), 3.75 (1H), 2.95 (3H), 2.90-2.50 (3H), 2.05 (2H), 1.95-1.65 (2H), 1.55-1.35 (9H).