Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:3]2[S:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Li]CCCC.[CH3:16][S:17]SC>C1COCC1>[Cl:1][C:2]1[C:3]2[S:10][C:9]([S:17][CH3:16])=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: Clc1ncnc2ccsc12
Reactant: CSSC
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CSc1cc2ncnc(Cl)c2s1
Reaction time: 0.25 h
Yield: 82 %

Procedure:
To a solution of 20 (shown in the scheme 4) (200 mg, 1.18 mmol) in THF (11 mL) was added n-BuLi (566 μL, 1.42 mmol, 2.5M in THF) very slowly at −78° C. and the mixture was stirred for 15 min at the same conditions. A solutions of dimethyl disulfide (160 uL, 1.77 mmol) and Mel (110 μL, 1.77 mmol) in THF (1 mL) was added drop wise. The reaction mixture was stirred for 2 h at −78° C., quenched with saturated aqueus NH4Cl solution, and extracted with DCM. The extract was dried over anhydrous Na2SO4 and concentrated to afford the title compound 280 (210 mg, 82% yield) as a yellowish solid. MS (m/z): 217.0(M+H) (found).
Reaction SMILES: [C:1]1([CH2:7][CH2:8][C:9]([OH:11])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.O1CCCC1.[N:29]1([CH2:34][CH2:35][CH2:36][NH2:37])[CH:33]=[CH:32][N:31]=[CH:30]1>O>[N:29]1([CH2:34][CH2:35][CH2:36][NH:37][C:9](=[O:11])[CH2:8][CH2:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:33]=[CH:32][N:31]=[CH:30]1
Reactant: O=C(O)CCc1ccccc1
Reactant: NCCCn1ccnc1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Solvent: O
Product: O=C(CCc1ccccc1)NCCCn1ccnc1
Reaction time: 18 h

Procedure:
A mixture of 1.50 g. of 3-phenylpropionic acid, 1.62 g. of 1,1'-carbonyldiimidazole, and 40 ml. of tetrahydrofuran was stirred for 3 hours and 2.0 g. of 1H-imidazole-1-propanamine was added. The mixture was stirred for 18 hours, 5 ml. of water was added, and the reaction mixture was heated at reflux temperature for 30 minutes. The mixture was concentrated and 10 ml. 1N sodium hydroxide and 100 ml. of methylene chloride were added. The layers were separated and the organic layer was washed with water, dried over magnesium sulfate, and concentrated. The desired product was obtained as an oil, which was converted to the fumarate salt, m.p. 90°-92° C.
Reaction SMILES: C[N:2](C)/[CH:3]=[CH:4]/[C:5]([C:7]1[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]2[CH:19]=[CH:18][C:17]([S:20]([C:23]([F:26])([F:25])[F:24])(=[O:22])=[O:21])=[CH:16][CH:15]=2)[N:8]=1)=O.[C:28]1([NH:34]N)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>>[C:28]1([N:34]2[C:5]([C:7]3[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]4[CH:19]=[CH:18][C:17]([S:20]([C:23]([F:25])([F:26])[F:24])(=[O:21])=[O:22])=[CH:16][CH:15]=4)[N:8]=3)=[CH:4][CH:3]=[N:2]2)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1
Reactant: CN(C)/C=C/C(=O)c1nn(-c2ccc(S(=O)(=O)C(F)(F)F)cc2)ccc1=O
Reactant: NNc1ccccc1
Product: O=c1ccn(-c2ccc(S(=O)(=O)C(F)(F)F)cc2)nc1-c1ccnn1-c1ccccc1

Procedure:
The product was obtained starting from 3-((E)-3-Dimethylamino-acryloyl)-1-(4-trifluoromethansulfonyl-phenyl)-1H-pyridazin-4-one (A-27) and phenylhydrazine according to the method described for example 1. MS: M=447.0 (M+H)+
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[C:12]([N:14]3[CH:19]([CH3:20])[CH2:18][O:17][CH2:16][CH:15]3[CH3:21])[N:11]=[C:10]([C:22]3[CH:27]=[CH:26][C:25]([NH:28][C:29]([NH:31][CH3:32])=[O:30])=[CH:24][CH:23]=3)[N:9]=2)=[CH:4][CH:3]=1.[C:33]([C:36]1[CH:37]=[C:38]([NH:42][C:43](=O)[O:44]C2C=CC=CC=2)[CH:39]=[CH:40][CH:41]=1)(=[O:35])[NH2:34]>>[CH3:21][CH:15]1[CH2:16][O:17][CH2:18][CH:19]([CH3:20])[N:14]1[C:12]1[N:11]=[C:10]([C:22]2[CH:27]=[CH:26][C:25]([NH:28][C:29](=[O:30])[NH:31][CH3:32])=[CH:24][CH:23]=2)[N:9]=[C:8]([C:5]2[CH:4]=[CH:3][C:2]([NH:1][C:43]([NH:42][C:38]3[CH:37]=[C:36]([CH:41]=[CH:40][CH:39]=3)[C:33]([NH2:34])=[O:35])=[O:44])=[CH:7][CH:6]=2)[N:13]=1
Reactant: NC(=O)c1cccc(NC(=O)Oc2ccccc2)c1
Reactant: CNC(=O)Nc1ccc(-c2nc(-c3ccc(N)cc3)nc(N3C(C)COCC3C)n2)cc1
Product: CNC(=O)Nc1ccc(-c2nc(-c3ccc(NC(=O)Nc4cccc(C(N)=O)c4)cc3)nc(N3C(C)COCC3C)n2)cc1
Yield: 4.1 %

Procedure:
The title compound was prepared by following the procedure of example 462 step 7 using 1-(4-(4-(4-aminophenyl)-6-(3,5-dimethylmorpholino)-1,3,5-triazin-2-yl)phenyl)-3-methylurea and phenyl 3-carbamoylphenylcarbamate. Yield 56 mg, 4.1% yield.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]1([C@@H:12](O)[CH3:13])[CH2:11][O:10]1.[N:15]1[CH:20]=[CH:19][C:18]([N:21]2[CH:25]=[N:24][NH:23][C:22]2=[O:26])=[N:17][CH:16]=1>>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]1([O:10][CH2:11]1)[C@H:12]([N:23]1[C:22](=[O:26])[N:21]([C:18]2[CH:19]=[CH:20][N:15]=[CH:16][N:17]=2)[CH:25]=[N:24]1)[CH3:13]
Reactant: O=c1[nH]ncn1-c1ccncn1
Reactant: C[C@H](O)[C@@]1(c2ccc(F)cc2F)CO1
Product: C[C@@H](n1ncn(-c2ccncn2)c1=O)[C@@]1(c2ccc(F)cc2F)CO1
Yield: 30.8 %

Procedure:
In the same manner as in Reference Example 5, starting from 536 mg of (1S)-1-[(2R)-2-(2,4-difluorophenyl)-2-oxiranyl]ethanol and 305 mg of 4-(4-pyrimidinyl)-3(2H,4H)-1,2,4-triazolone, 2-[(1R,2S)-2-(2,4-difluorophenyl)-2,3-epoxy-1methylpropyl]-4-(4-pyrimidinyl)-3(2H,4H)-1,2,4-triazolone (199 mg) was obtained as a colorless oil.
Reaction SMILES: [CH2:1]([NH:4][N:5]1[CH2:9][CH2:8][CH2:7][C:6]1=[O:10])[CH2:2][CH3:3].Cl.Cl[C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1.C1(O)C=CC=CC=1>ClCCl>[CH2:1]([N:4]([C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1)[N:5]1[CH2:9][CH2:8][CH2:7][C:6]1=[O:10])[CH2:2][CH3:3]
Reactant: Clc1ccncc1
Reactant: CCCNN1CCCC1=O
Agent: Cl
Solvent: ClCCl
Solvent: Oc1ccccc1
Product: CCCN(c1ccncc1)N1CCCC1=O
Temperature: 143 °C
Reaction time: 0.5 h
Yield: 39.6 %

Procedure:
A slurry consisting of 1-(propylamino)-2-pyrrolidinone (7.96 g), 4-chloropyridine hydrochloride (6.31 g) and phenol (20.9 g) was heated in a 143° C. oil bath under nitrogen. After 30 min., the resulting solution was treated with additional 4-chloropyridine hydrochloride (6.30 g) and heated for an additional 30 minutes. The mixture was cooled to room temperature and diluted with dichloromethane. The organic layer was washed with dilute aqueous sodium bicarbonate and the combined aqueous layers back-extracted with dichloromethane and ether. The combined organic layers were washed with brine and dried (K2CO3). Filtration, concentration, and purification via flash column chromatography (silica gel, 10% MeOH/DCM) and preparative HPLC afforded 3.65 g (30%) of 1-(propyl-4-pyridinylamino)-2-pyrrolidinone as an oil. The oxalate was prepared with 1.0 eq. oxalic acid in absolute ethanol, m.p. 194°-195.5° C.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[N:6]([CH2:12][C:13]([OH:16])([CH3:15])[CH3:14])[CH2:5]2.[H-].[Na+].[CH3:19]I.O>O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=[O:11])[N:6]([CH2:12][C:13]([OH:16])([CH3:14])[CH3:15])[CH:5]2[CH3:19]
Reactant: CI
Reactant: CC(C)(O)CN1Cc2cc(Br)ccc2C1=O
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CC1c2cc(Br)ccc2C(=O)N1CC(C)(C)O
Temperature: 25 °C

Procedure:
Under nitrogen atmosphere, 100 mg of 5-bromo-2-(2-hydroxy-2-methyl-propyl)-1-oxo-isoindoline obtained in Example 177-1) was dissolved in tetrahydrofuran, 40 mg of sodium hydride, 0.4 ml of methyl iodide were added and the mixture was heated under reflux for 2 hours. The reaction solution was cooled down to room temperature, water was added, and the products were extracted with ethyl acetate. Ethyl acetate layer was washed with saturated saline solution and dried with anhydrous sodium sulfate. The solvents were distilled outunder reduced pressure, and the residues were separated and purified by thin-layer silicagel column chromatography (ethyl acetate) to obtain 7 mg of the above compound as a white solid.
Reaction SMILES: [CH3:1][C:2]1([OH:8])[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.Br[CH2:10][CH2:11][CH2:12][Cl:13]>>[Cl:13][CH2:12][CH2:11][CH2:10][N:5]1[CH2:6][CH2:7][C:2]([CH3:1])([OH:8])[CH2:3][CH2:4]1
Reactant: ClCCCBr
Reactant: CC1(O)CCNCC1
Product: CC1(O)CCN(CCCCl)CC1

Procedure:
4-methylpiperidin-4-ol (made via literature methods) and 1-bromo-3-chloropropane are reacted using the procedure for Example OO to afford 1-(3-chloropropyl)-4-methylpiperidin-4-ol.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][O:14][C:15](=[O:25])[NH:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=1[F:24].Cl.[O:27]1CCC[CH2:28]1>O>[CH3:13][O:14][C:15](=[O:25])[NH:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[C:19]([CH:28]=[O:27])[C:18]=1[F:24]
Reactant: COC(=O)Nc1ccc(F)cc1F
Reactant: C1CCOC1
Agent: Cl
Agent: [Li]CCCC
Solvent: O
Solvent: CC(C)NC(C)C
Product: COC(=O)Nc1ccc(F)c(C=O)c1F
Temperature: -78 °C
Reaction time: 1 h
Yield: 84 %

Procedure:
Into a reaction flask under nitrogen, diisopropylamine (24.87 g, 250 mmol) is combined with 160 mL of anhydrous tetrahydrofuran and the solution is cooled to −78° C. n-Butyllithium (154 mL, 1.6 M in hexanes, 250 mmol) is added dropwise, maintaining the temperature below −70° C. After stirring at −78° C. for 1 hour, (2,4-difluoro-phenyl)-carbamic acid methyl ester (2, 20.00 g, 110 mmol) in 40 mL of tetrahydrofuran is added dropwise, maintaining the temperature below −70° C. The reaction is stirred at −78° C. for 1 hour, then warmed to room temperature and stirred for 1 minute. The reaction is poured into 250 mL of water, the pH is adjusted to 1 with addition of 2M hydrochloric acid, and the mixture is extracted with 3×250 mL of ethyl acetate. The organic layers are combined, dried over magnesium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material is slurried in hexane and the resulting solid is collected by filtration and dried to provide the desired compound (3, 19.38 g, 84%).
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[C:8]([O:14][CH3:15])[C:3]=1[C:4](OC)=[O:5].C(O)(=O)C.[CH:20](N)=[NH:21]>COCCO>[CH3:15][O:14][C:8]1[CH:9]=[C:10]([O:12][CH3:13])[CH:11]=[C:2]2[C:3]=1[C:4](=[O:5])[NH:21][CH:20]=[N:1]2
Reactant: N=CN
Reactant: COC(=O)c1c(N)cc(OC)cc1OC
Solvent: CC(=O)O
Solvent: COCCO
Product: COc1cc(OC)c2c(=O)[nH]cnc2c1
Yield: 92.8 %

Procedure:
A mixture of methyl 2-amino-4,6-dimethoxybenzoate (16 g), formamidine acetate (24 g) and 2-methoxyethanol (330 ml) was stirred and heated to reflux until all of the starting material had reacted. The mixture was evaporated and the residue was triturated under water (100 ml). The resultant solid was isolated, washed with water and dried under vacuum to give 5,7-dimethoxy-3,4-dihydroquinazolin-4-one (14.5 g); NMR Spectrum: (DMSOd6) 3.82 (s, 3H), 3.86 (s, 3H), 6.5 (s, 1H), 6.7 (s, 1H), 7.9 (s, 1H), 11.7 (br s, 1).
Reaction SMILES: [O:1]([C:8]1[CH:9]=[C:10]([CH2:14][CH:15]=[CH:16][C:17]([C:20]2[CH:25]=[CH:24][C:23]([CH3:26])=[CH:22][CH:21]=2)([CH3:19])[CH3:18])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O(C1C=C(C=CCC(C2C=CC(C)=CC=2)(C)C)C=CC=1)C1C=CC=CC=1.[H][H]>C([O-])(=O)C>[O:1]([C:8]1[CH:9]=[C:10]([CH2:14][CH2:15][CH2:16][C:17]([C:20]2[CH:21]=[CH:22][C:23]([CH3:26])=[CH:24][CH:25]=2)([CH3:18])[CH3:19])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: [H][H]
Reactant: Cc1ccc(C(C)(C)C=CCc2cccc(Oc3ccccc3)c2)cc1
Agent: CC(=O)[O-]
Agent: Cc1ccc(C(C)(C)CC=Cc2cccc(Oc3ccccc3)c2)cc1
Product: Cc1ccc(C(C)(C)CCCc2cccc(Oc3ccccc3)c2)cc1
Reaction time: 3 h

Procedure:
To 30 ml of ethyle acetate, 1.9 g of a mixture of 50% 1-(3-phenoxyphenyl)-4-(4-methylphenyl)-4-methyl-2-pentene and 50% 1-(3-phenoxyphenyl)-4-(4-methylphenyl)-4-methyl-1-pentene was added and dissolved, and thereto 0.4 g of 5% pd-C was added, and the mixture was stirred under a pressure of 20 kg/cm2G with hydrogen gas at room temperature. After three hours, pd-C was removed by filtration, and ethyl acetate was evaporated under reduced pressure.
Reaction SMILES: Cl[C:2]1[C:3]([F:12])=[N:4][CH:5]=[C:6](Cl)[C:7]=1[O:8][CH2:9][CH3:10].C([O-])(=O)C.[Na+].[H][H]>C(O)C.[Pd]>[CH2:9]([O:8][C:7]1[CH:6]=[CH:5][N:4]=[C:3]([F:12])[CH:2]=1)[CH3:10]
Reactant: CCOc1c(Cl)cnc(F)c1Cl
Reactant: [H][H]
Agent: [Pd]
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CCO
Product: CCOc1ccnc(F)c1
Temperature: 100 °C
Reaction time: 4 h

Procedure:
To a solution of 60.5 g (0.31 mol) of 3,5-dichloro-4-ethoxy-2-fluoropyridine and 32.2 g (0.32 mol) of sodium acetate in 400 mL of ethanol in a L stirred steel Parr bomb was added 3 g of 5 percent palladium on carbon catalyst. The reactor was charged with 500 pounds per square inch gauge (3550 kiloPascals) of hydrogen and heated with stirring to 100° C. for 4 hr. The mixture was cooled, filtered, and concentrated by evaporation. The residue was dissolved in ether and the resulting solution was dried over magnesium sulfate, filtered, and concentrated by evaporation. The residue was purified by bulb to bulb distillation (60°-80° C. at 0.5 mm Hg (67 Pascals ) to obtain 18.5 g (42 percent of theory ) of the title compound as a colorless oil which solidified upon standing and melted at 35 °-36° C.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][CH2:10][NH:11][C:12]1[C:13]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[N:14][C:15]2[C:20]([N:21]=1)=[CH:19][C:18]([C:22]([O:24][CH3:25])=[O:23])=[CH:17][CH:16]=2.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:11]1([C:12]2[C:13]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)=[N:14][C:15]3[C:20]([N:21]=2)=[CH:19][C:18]([C:22]([O:24][CH3:25])=[O:23])=[CH:17][CH:16]=3)[C:4]2[C:3](=[CH:2][CH:7]=[CH:6][CH:5]=2)[CH2:8][CH2:9][CH2:10]1
Reactant: COC(=O)c1ccc2nc(-c3ccccc3)c(NCCCc3ccccc3Br)nc2c1
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1
Solvent: C1COCCO1
Product: COC(=O)c1ccc2nc(-c3ccccc3)c(N3CCCc4ccccc43)nc2c1
Temperature: 100 °C
Reaction time: 8 h

Procedure:
Into a 20-mL sealed tube, was placed a solution of methyl 3-(3-(2-bromophenyl)propylamino)-2-phenylquinoxaline-6-carboxylate (240 mg, 0.50 mmol, 1.00 equiv) in dioxane (10 mL), CsCO3 (490 mg, 1.50 mmol, 3.00 equiv), Pd2(dba)3 (46 mg, 0.05 mmol, 0.10 equiv) and BINAP (125 mg, 0.20 mmol, 0.40 equiv) were added. The resulting solution was stirred overnight at 100° C. The mixture was concentrated under vacuum and purified by flash column chromatography with ethyl acetate/petroleum ether (1:50). This resulted in 180 mg (86%) of methyl 3-(3,4-dihydroquinolin-1(2H)-yl)-2-phenylquinoxaline-6-carboxylate as a yellow solid.
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([CH2:7][NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[N+:15]([O-])=O)=[CH:4][CH:3]=1.S1C=CC=C1.N.[H][H]>[Pd].CO>[CH3:1][C:2]1[O:6][C:5]([CH2:7][NH:8][C:9]2[C:10]([NH2:15])=[CH:11][CH:12]=[CH:13][CH:14]=2)=[CH:4][CH:3]=1
Reactant: Cc1ccc(CNc2ccccc2[N+](=O)[O-])o1
Reactant: [H][H]
Agent: [Pd]
Agent: N
Solvent: c1ccsc1
Solvent: CO
Product: Cc1ccc(CNc2ccccc2N)o1
Yield: 95 %

Procedure:
A mixture of 62 parts of 5-methyl-N-(2-nitrophenyl)-2-furanmethanamine, 2 parts of a solution of thiophene in metbanol 4% and 400 parts of methanol, saturated with ammonia, was hydrogenated at normal pressure and at room temperature with 4 parts of palladium-on-charcoal catalyst 10%. After the calculated amount of hydrogen was taken up, the catalyst was filtered off and the filtrate was evaporated, yielding 50.5 parts (95%) of N1 -[(5-methyl-2-furanyl)methyl]-1,2-benzenediamine as a residue (intermediate 8).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([S:14](Cl)(=[O:16])=[O:15])[CH:11]=[CH:12][CH:13]=2)=[CH:4][CH:3]=1.[NH2:18][C:19]1[CH:20]=[C:21]([C:25]2[NH:29][N:28]=[N:27][N:26]=2)[CH:22]=[CH:23][CH:24]=1>>[C:2]1([CH3:1])[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([S:14]([NH:18][C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]4[NH:29][N:28]=[N:27][N:26]=4)[CH:20]=3)(=[O:16])=[O:15])[CH:11]=[CH:12][CH:13]=2)=[CH:4][CH:3]=1
Reactant: Cc1ccc(-c2cccc(S(=O)(=O)Cl)c2)cc1
Reactant: Nc1cccc(-c2nnn[nH]2)c1
Product: Cc1ccc(-c2cccc(S(=O)(=O)Nc3cccc(-c4nnn[nH]4)c3)c2)cc1
Yield: 93.5 %

Procedure:
The product was prepared according to General Procedure 1, described in Example 1, starting from [3-(4-methylphenyl)phenyl sulfonyl chloride (14.7 mg, 0.055 mmol) and 5-(3-aminophenyl)tetrazole (8.0 mg, 0.05 mmol) yielding 18.3 mg (19%) of the title compound. MS (ESI+) calcd for C20H17N5O2S 391.110296, found 391.110156.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5](/[C:8](/[C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=2)=[CH:9]/[CH2:10][OH:11])=[CH:4][CH:3]=1.O[C:23]1[CH:34]=[CH:33][C:26]([O:27][CH2:28][C:29]([O:31][CH3:32])=[O:30])=[C:25]([CH3:35])[CH:24]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1(C)C=CC=CC=1.O1CCCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5](/[C:8](/[C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:19])([F:20])[F:21])=[CH:14][CH:13]=2)=[CH:9]/[CH2:10][O:11][C:23]2[CH:34]=[CH:33][C:26]([O:27][CH2:28][C:29]([O:31][CH3:32])=[O:30])=[C:25]([CH3:35])[CH:24]=2)=[CH:4][CH:3]=1
Reactant: OC/C=C(/c1ccc(Br)cc1)c1ccc(C(F)(F)F)cc1
Reactant: COC(=O)COc1ccc(O)cc1C
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: COC(=O)COc1ccc(OC/C=C(/c2ccc(Br)cc2)c2ccc(C(F)(F)F)cc2)cc1C
Temperature: 0 °C

Procedure:
The above allyl alcohol (0.77 g, 2.16 mmol), methyl (4-hydroxy-2-methylphenoxy)acetate (0.47 g, 2.37 mmol) and triphenylphosphine (0.68 g, 2.59 mmol) were dissolved in a mixture of anhydrous toluene (10 mL) and tetrahydrofuran (3 mL). The mixture was degassed, cooled to 0° C. and a degassed solution of diisopropyl azodicarboxylate (0.525 g, 2.60 mmol) in anhydrous tetrahydrofuran (3 mL) was added dropwise under nitrogen. The reaction mixture was stirred at ambient temperature over night. The solvents were evaporated in vacuo and the residue was submitted to column chromatography (silica gel Fluka 60, hexanes/ethyl acetate 95: 5-90:10) affording methyl (E)-[4-[3-(4-bromophenyl)-3-[4-trifluoromethyl phenyl]allyloxy]-2-methylphenoxy]acetate.
Reaction SMILES: [CH:1]1([N:7]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[C:8]([NH:10][C:11]2[S:12][CH:13]=[C:14]([CH2:16]Br)[N:15]=2)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:24]([O:26][C:27]([C:29]1[N:30]=[C:31]([SH:34])[NH:32][CH:33]=1)=[O:28])[CH3:25]>>[CH2:24]([O:26][C:27]([C:29]1[N:30]=[C:31]([S:34][CH2:16][C:14]2[N:15]=[C:11]([NH:10][C:8]([N:7]([CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)[CH:1]3[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)=[O:9])[S:12][CH:13]=2)[NH:32][CH:33]=1)=[O:28])[CH3:25]
Reactant: CCOC(=O)c1c[nH]c(S)n1
Reactant: O=C(Nc1nc(CBr)cs1)N(C1CCCCC1)C1CCCCC1
Product: CCOC(=O)c1c[nH]c(SCc2csc(NC(=O)N(C3CCCCC3)C3CCCCC3)n2)n1
Yield: 20 %

Procedure:
Prepared in 20% yield as described in general procedure (L) from 1,1-dicyclohexyl-3-(4-bromomethyl-thiazol-2-yl) urea and 2-mercapto-1H-imidazole-4-carboxylic acid ethyl ester.
Reaction SMILES: [Na+].[Br:2][CH2:3][CH2:4][CH2:5][CH2:6][S:7]([O-:10])(=O)=[O:8].S(Cl)([Cl:13])=O>>[Br:2][CH2:3][CH2:4][CH2:5][CH2:6][S:7]([Cl:13])(=[O:10])=[O:8]
Reactant: O=S(=O)([O-])CCCCBr
Reactant: O=S(Cl)Cl
Agent: [Na+]
Product: O=S(=O)(Cl)CCCCBr

Procedure:
4-Bromo-1-butane sulfonic acid sodium salt (1.25 g) was added to thionyl chloride (12.5 mL) with stirring under nitrogen. The reaction was heated under reflux for 3 h, cooled, and concentrated under reduced pressure. The residue was then diluted with diethyl ether, washed with water, dried, filtered and concentrated under reduced pressure to afford 760 mg of a 7:3 mixture of desired product and the 4-chloro analog (instead of the 4-bromo). 1H NMR (300 MHz, CDCl3) δ3.70 (t, 2H), 3.46 (t, 2H), 2.25 (m, 2H), 2.09 (m, 2H).
Reaction SMILES: N[C:2]1[C:10]([I:11])=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[I:12].N(OC(C)(C)C)=O.C(O)(=O)C1C=CC=CC=1.Cl>CN(C=O)C.C(OCC)C>[I:11][C:10]1[CH:9]=[C:5]([CH:4]=[C:3]([I:12])[CH:2]=1)[C:6]([OH:8])=[O:7]
Reactant: Nc1c(I)cc(C(=O)O)cc1I
Agent: CC(C)(C)ON=O
Agent: Cl
Agent: O=C(O)c1ccccc1
Solvent: CN(C)C=O
Solvent: CCOCC
Product: O=C(O)c1cc(I)cc(I)c1
Temperature: 50 °C

Procedure:
The titled compound was prepared according to previously reported synthetic procedures under modified conditions (see e.g., Mak et al., J. Org. Chem. 2001, 66, 4476-4486). 4-amino-3,5-diiodobenzoic acid (2.0 g, 5.4 mmol) was added portion-wise to a stirred solution of t-butyl nitrite (1.07 g, 10.4 mmol) in DMF (10 mL) heated at 50° C. in a 3-neck round bottom flask equipped with a reflux condenser. Additional DMF (10 mL) was added halfway through the addition. Gas evolution was observed after each addition of the benzoic acid. Upon completion of the addition the reaction mixture was heated at 60° C. for 30 minutes and then allowed to cool to room temperature. The brown solution was diluted with diethyl ether (60 mL) and poured over dilute HCl (100 mL, 3N). The ethereal layer was removed and washed with 3N HCl (2×20 mL), water (3×20 mL) and brine (1×20 mL) then dried over anhydrous MgSO4. Removal of diethyl ether in vacuo and subsequent recrystallization in methanol afforded the desired compound in 77% yield (1.5 g, 4.0 mmol); mp 234-236° C. 1H-NMR (300 MHz, DMSO-d6) δ (ppm): 13.49 (s, 1H), 8.31 (s, 1H), 8.17 (s, 2H)13C-NMR (75 MHz, DMSO-d6) δ (ppm): 165.1, 148.6, 137.5, 134.7, 96.6 HRMS (m/z): [M−H]− calc. for C7H3I2O2, 372.8222. found 372.8231.
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:13])=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[NH:9][CH2:8][CH2:7]2.I[C:15]1[CH:16]=[N:17][CH:18]=[CH:19][C:20]=1[CH3:21].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Cu](I)I.O1CCOCC1>[Cl:1][C:2]1[C:3]([F:13])=[CH:4][CH:5]=[C:6]2[C:11]=1[C:10](=[O:12])[N:9]([C:15]1[CH:16]=[N:17][CH:18]=[CH:19][C:20]=1[CH3:21])[CH2:8][CH2:7]2
Reactant: Cc1ccncc1I
Reactant: O=C1NCCc2ccc(F)c(Cl)c21
Agent: I[Cu]I
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Product: Cc1ccncc1N1CCc2ccc(F)c(Cl)c2C1=O
Yield: 27.4 %

Procedure:
Using analogous reaction conditions as described in Example 1, 8-chloro-7-fluoro-3,4-dihydro-2H-isoquinolin-1-one (250 mg, 1.2562 mmol) was reacted with 3-iodo-4-methyl-pyridine (275.12 mg, 1.2562 mmol), 1,4-dioxane (10 mL), copper iodide (23.9 mg, 0.12562 mmol), trans-N,N′-dimethyl-cyclohexyl-1,2-diamine (60 mL, 0.3768 mmol) and potassium phosphate (665.7 mg, 3.1405 mmol) to afford the crude product. Purification by column chromatography on silica gel (40% ethylacetate in hexane) afforded 100 mg of the product (27.44% yield).
Reaction SMILES: [CH2:1]([C:6]1[CH:11]=[CH:10][C:9](I)=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH2:4][CH3:5].C[Si]([C:17]#[CH:18])(C)C>C(NCC)C.[Cu]I>[CH2:1]([C:6]1[CH:11]=[CH:10][C:9]([C:17]#[CH:18])=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: C#C[Si](C)(C)C
Reactant: CCCCCc1ccc(I)cc1
Agent: [Cu]I
Solvent: CCNCC
Product: C#Cc1ccc(CCCCC)cc1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
A mixture of 0.1 mol of 4-pentyliodobenzene, 0.12 mol of trimetylsilylacetylene, 0.0014 mol of bis(triphenylphosphine)-palladium(II) Chloride Pd(PPh3)2Cl2 and 0.7 mmol of copper (I) iodide in 250 ml diethylamine is stirred at room temperature for 20 hours. After evaporation of the solvent the crude product is purified by chromatography on alumina (4:1 petrol/dichloromethane) to give 2-(4-pentylphenyl)-1-trimethylsilyacetylene. Removal of the trimethylsilylgroup is accomplished by treatment this acetylene is methanol with 1 M KOH for 1 hour at room temperature. Evaporation of the methanol and either extraction yields 4-pentylphenylacetylene.