Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6](=[O:14])[C:7]([CH2:12]O)([CH2:10]O)[CH2:8]O)([CH3:4])([CH3:3])[CH3:2].[C:15]1([CH3:25])[CH:20]=[CH:19][C:18]([S:21](Cl)(=[O:23])=[O:22])=[CH:17][CH:16]=1.ClCCl>N1C=CC=CC=1>[C:1]([O:5][C:6](=[O:14])[C:7]([CH2:12][S:21]([C:18]1[CH:19]=[CH:20][C:15]([CH3:25])=[CH:16][CH:17]=1)(=[O:23])=[O:22])([CH2:10][S:21]([C:18]1[CH:19]=[CH:20][C:15]([CH3:25])=[CH:16][CH:17]=1)(=[O:23])=[O:22])[CH2:8][S:21]([C:18]1[CH:19]=[CH:20][C:15]([CH3:25])=[CH:16][CH:17]=1)(=[O:23])=[O:22])([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: CC(C)(C)OC(=O)C(CO)(CO)CO
Solvent: c1ccncc1
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)CC(CS(=O)(=O)c2ccc(C)cc2)(CS(=O)(=O)c2ccc(C)cc2)C(=O)OC(C)(C)C)cc1
Reaction time: 15 h

Procedure:
A solution of t-butyl-tris(hydroxymethyl)acetate (9.9 g, 0.048 mol) in 50 mL of pyridine is cooled to 0° C. and then portions of p-toluenesulfonyl chloride (30.1 g, 0.158 mol) are added over 1 hr. The mixture is kept at 0° C. for 15 hrs. Then dichloromethane (200 mL) is added and the solution is washed four times with 100 mL of 10% hydrochloric acid, once with 100 mL of saturated sodium bicarbonate and once with 100 mL of saturated sodium chloride. The organic layer is dried over anhydrous sodium sulfate and evaporated under reduced pressure to give t-butyl-tris(tosylmethyl)acetate.
Reaction SMILES: [H-].[Na+].[CH:3]1([S:6]([NH2:9])(=[O:8])=[O:7])[CH2:5][CH2:4]1.[CH3:10][C:11]1([CH3:39])[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:21](O)=[O:22])[CH:19]=2)[NH:14][CH:13]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30](=[O:38])[NH:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH:25]=2)[CH2:12]1.C(N1C=CN=C1)(N1C=CN=C1)=O>CN(C)C=O.O>[CH:3]1([S:6]([NH:9][C:21]([C:18]2[CH:19]=[C:20]3[C:15](=[CH:16][CH:17]=2)[NH:14][CH:13]([C:24]2[CH:25]=[C:26]([CH:27]=[CH:28][CH:29]=2)[C:30]([NH:31][C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)=[O:38])[CH2:12][C:11]3([CH3:39])[CH3:10])=[O:22])(=[O:8])=[O:7])[CH2:5][CH2:4]1
Reactant: CC1(C)CC(c2cccc(C(=O)Nc3ccccc3)c2)Nc2ccc(C(=O)O)cc21
Reactant: NS(=O)(=O)C1CC1
Agent: O=C(n1ccnc1)n1ccnc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CC1(C)CC(c2cccc(C(=O)Nc3ccccc3)c2)Nc2ccc(C(=O)NS(=O)(=O)C3CC3)cc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 6 %

Procedure:
To a suspension of 60% sodium hydride (198 mg, 4.95 mmol) in N,N-dimethylformamide (2 mL) was added cyclopropanesulfonic acid amide (605 mg, 5 mmol) at room temperature. The resulting mixture was stirred at 25° C. for 1 h to afford Solution A21. A solution of 4,4-dimethyl-2-(3-phenylcarbamoyl-phenyl)-1,2,3,4-tetrahydro-quinoline-6-carboxylic acid (400 mg, 1 mmol) and 1,1′-carbonyldiimidazole (324 mg, 2 mmol) in N,N-dimethylformamide (2 mL) was stirred at 70° C. for 1 h and cooled to room temperature to afford Solution B21. Solution B21 was added to Solution A21 and the resulting mixture was stirred at 25° C. for 1 h. To the reaction mixture was added water (0.5 mL). The mixture was filtered to remove the insoluble solid, and the filtrate was purified by Waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% ammonium hydroxide in water) afforded 3-(6-cyclopropanesulfonylaminocarbonyl-4,4-dimethyl-1,2,3,4-tetrahydro-quinolin-2-yl)-N-phenyl-benzamide (30 mg, 6%) as a white solid: MS (ESI) M+1=504.2.
Reaction SMILES: [CH2:1]([P:20](=[O:37])([O:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])[O:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[P:2](=[O:19])([O:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[O:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].C=O.[CH2:40](NCC)C>CO>[C:1]([P:2](=[O:19])([O:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[O:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])([P:20](=[O:37])([O:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[O:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])=[CH2:40]
Reactant: CCCCCCCOP(=O)(CP(=O)(OCCCCCCC)OCCCCCCC)OCCCCCCC
Reactant: CCNCC
Agent: C=O
Solvent: CO
Product: C=C(P(=O)(OCCCCCCC)OCCCCCCC)P(=O)(OCCCCCCC)OCCCCCCC
Yield: 74.4 %

Procedure:
56.81 g (44.0 mmol) of tetra-n-heptyl methylenebisphosphonate, 6.61 g (220.0 mmol) of paraformaldehyde and 3.22 g (64.0 mmol) of diethylamine are combined with the same reactants and the same conditions as described above in Example I. This mixture is then refluxed for 48 hours. After the methanol is eliminated as described above in Example I, about 19 g of tetra-n-heptyl ethenylidenebisphosphonate is produced as a clear liquid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:5]=[C:6]([Cl:9])[C:7]=1[OH:8].C(=O)([O-])[O-].[K+].[K+].[F:22][C:23]([F:27])([F:26])[CH2:24]I>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH:5]=[C:6]([Cl:9])[C:7]=1[O:8][CH2:24][C:23]([F:27])([F:26])[F:22]
Reactant: CCOC(=O)Cc1cc(Cl)c(O)c(Br)c1
Reactant: FC(F)(F)CI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)Cc1cc(Cl)c(OCC(F)(F)F)c(Br)c1
Temperature: 100 °C
Reaction time: 4 h
Yield: 29.4 %

Procedure:
To a stirred solution of ethyl 2-(3-bromo-5-chloro-4-hydroxyphenyl)acetate (2 g, 6.8 mmol), potassium carbonate (2.35 g, 17.0 mmol) in dry DMF (20 mL), was slowly added trifluoro ethyl iodide (8.58 g, 4.0 mL, 40.8 mmol) at room temperature, the reaction mixture was slowly heated to 100° C. and heating was continued for 4 h. Upon which the reaction mixture was poured onto water and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with water, dried over Na2SO4 and evaporated under reduced pressure. Purification by column chromatography over silica gel (hexane/EtOAc) to gave compound ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-acetate (0.750 g, 30% yield). 1H NMR (CDCl3, 400 MHz): 7.43 (s, 1H); 7.34 (s, 1H); 4.4 (q, 2H), 4.13 (q, 2H); 3.55 (t, 1H); 1.93 (m, 1H), 1.58 (m, 1H); 1.45 (m, 1H); 1.24 (t, 3H), 0.92 (d, 6H);
Reaction SMILES: C[CH:2]([CH2:4][CH2:5][CH2:6][C@H:7]([CH2:9][CH2:10][CH2:11][C@H:12]([CH2:14][CH2:15][CH2:16]/[C:17](=[CH:19]/[CH2:20][OH:21])/C)C)C)[CH3:3].CC([CH2:25][CH2:26][CH2:27][C@H:28]([C@@H:30]1[C@:48]2(C)[C@H:33]([C@H:34]3[C@H:45]([CH2:46][CH2:47]2)[C@]2(C)[C:37]([CH2:38][C@H:39](CC2)[OH:40])=[CH:36][CH2:35]3)[CH2:32][CH2:31]1)C)C>O>[C:39]([O:21][CH2:20][CH2:19][CH2:17][CH2:16][CH2:15][CH2:14][CH2:12][CH2:11][CH2:10][CH2:9][CH2:7][CH2:6][CH2:5][CH2:4][CH2:2][CH3:3])(=[O:40])[CH2:38][CH2:37][CH2:36][CH2:35][CH2:34][CH2:45][CH2:46][CH2:47][CH2:48][CH2:33][CH2:32][CH2:31][CH2:30][CH2:28][CH2:27][CH2:26][CH3:25]
Reactant: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
Reactant: C/C(=C\CO)CCC[C@H](C)CCC[C@H](C)CCCC(C)C
Solvent: O
Product: CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC

Procedure:
The encapsulant is soluble in the polymerizer, and solid at room temperature. Examples of encapsulants are polymers and waxes. Waxes include waxy polymers. Waxes are water insoluble, organic materials that are solid or semi-solid at room temperature and usually of lower density than water, and typically can be melted above room temperature to form a liquid. Preferred waxes include any naturally occurring and synthetic waxes, wax esters, and greases that generally have a melting temperature of 30° C. or more with a melting range of less than 10° C. and are usually non-reactive with the reagents or solvents to which they are exposed. Examples of waxes are esters of various long-chain (fatty) alcohols and long-chain acids, preferably where at least one member of the ester has 10 or more carbon atoms, including various unsaturated and branched chain types and also those esters of glycerols and sterols. Also, certain free alcohols or acids have wax-like properties of melting temperature and inertness. Examples of saturated fatty acids that can be used are capric, lauric, myristic, palmitic, margaric, stearic, arachidic, behenic, tetracosanic, lignoceric, cerotic, and melissic. Some examples of unsaturated fatty acids that can be used are tiglic, hypogaeic, gaidic, physetoleic, elaidic, oleic, isooleic, erudic, brassidic, and isoerudic. Some examples of fatty alcohols that can be used are octadecyl, carnaubyl, ceryl, melissyl, and phytol. Also included are various esters of these and other fatty acids with any suitable fatty alcohols, or sterols such as cholesterol, or glycerols. Other examples are natural or suitably modified or derivatized waxes such as various plant derived waxes, greases and oils including carnauba wax, cranberry wax, ouricuri wax, candelilla wax, raphia wax, apple, cotton and cactus waxes; waxes (including greases) produced by bacteria (e.g. cetyl stearate); fungi, protozoa and algae; various invertebrate waxes and greases including insect waxes such as beeswaxes (e.g. triacontyl palmitate, palmatyl palmitate), and Coccus sp. derived waxes (e.g. lac, cochineal and Chinese insect); other animal fats (e.g. triglycerides) and waxes including spermaceti (e.g. cetyl palmitate), lanolin and wool grease.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[CH:9][C:10]2[CH:15]=[CH:14][C:13]([Br:16])=[CH:12][CH:11]=2)=[CH:4][CH:3]=1.[C:17](#[N:20])[CH:18]=[CH2:19].C(N(CCCC)CCCC)CCC.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[Br:16][C:13]1[CH:14]=[CH:15][C:10]([CH:9]=[CH:8][C:5]2[CH:6]=[CH:7][C:2]([CH:19]=[CH:18][C:17]#[N:20])=[CH:3][CH:4]=2)=[CH:11][CH:12]=1
Reactant: C=CC#N
Reactant: Brc1ccc(C=Cc2ccc(Br)cc2)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: CCCCN(CCCC)CCCC
Product: N#CC=Cc1ccc(C=Cc2ccc(Br)cc2)cc1
Reaction time: 7 h
Yield: 16.1 %

Procedure:
6.76 g (0.02 mol) of 4,4'-dibromostilbene, 1.06 g (0.02 mol) of acrylonitrile, 4.08 g (0.022 mol) of tri-n-butylamine, 0.0898 g (0.4 mmol) of palladium acetate and 0.2098 g (0.8 mmol) of triphenylphosphine are added under argon to 10 ml of toluene. The reaction mixture is stirred at 100°-115° C. for 7 hours. Working up gives 1 g (16% of theory) of 4-bromostilbene-4'-acrylonitrile in the form of a pale yellow powder. Melting point 258° C.
Reaction SMILES: [NH:1]([C:10]([CH3:12])=[O:11])[CH2:2][C:3]([NH:5][CH2:6][C:7](O)=[O:8])=[O:4].C1CCC(N=C=NC2CCCCC2)CC1.[NH2:28][C@H:29]([C:33]([NH2:35])=[O:34])[CH:30]([CH3:32])[CH3:31]>C(#N)C.O>[NH:1]([C:10]([CH3:12])=[O:11])[CH2:2][C:3]([NH:5][CH2:6][C:7]([NH:28][C@H:29]([C:33]([NH2:35])=[O:34])[CH:30]([CH3:32])[CH3:31])=[O:8])=[O:4]
Reactant: CC(C)[C@H](N)C(N)=O
Reactant: CC(=O)NCC(=O)NCC(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CC#N
Solvent: O
Product: CC(=O)NCC(=O)NCC(=O)N[C@H](C(N)=O)C(C)C
Temperature: 0 °C

Procedure:
1.75 g (10 mmoles) Ac-Gly-Gly-OH and 1.73 g (15 mmoles) HONSu were dissolved in 25 ml acetonitrile and cooled to 0° C. 2.46 g DCC (12 mmoles) were then added, the mixture allowed to warm to room temperature and stirred for 2 hours until complete formation of the active ester. After filtering off the DCU, 1.16 g of Val-NH2 free base (10 mmoles) in 25 ml H2O at pH 8 were added slowly and pH maintained above 7. At completion of the reaction the acetonitrile was removed under vacuum and a small residue filtered off from the aqueous phase. The product was then purified by reverse phase HPLC using water/ethanol/acetic acid buffers.
Reaction SMILES: Cl.Cl.[NH2:3][CH2:4][CH2:5][CH2:6][S:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1.C(N(CC)CC)C.[O:21]1[CH:25]=[CH:24][CH:23]=[C:22]1[C:26](Cl)=[O:27]>C(Cl)Cl>[O:21]1[CH:25]=[CH:24][CH:23]=[C:22]1[C:26]([NH:3][CH2:4][CH2:5][CH2:6][S:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1)=[O:27]
Reactant: O=C(Cl)c1ccco1
Reactant: NCCCSc1ccncc1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(NCCCSc1ccncc1)c1ccco1
Yield: 88.2 %

Procedure:
To a solution of 1.00 g (4.15 mmol) of 4-(3-aminopropylthio)pyridine dihydrochloride and 2.78 ml (19.9 mmol) of triethylamine in 40 ml of methylene chloride, 0.49 ml (4.98 mmol) of 2-furoyl chloride was added under ice-cooling with stirring. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was washed with a saturated aqueous solution of sodium bicarbonate and water and dried, and then the solvent was distilled off. The residue was purified by column chromatography (eluent: ethyl acetate) to obtain powder. The powder was washed with ether and dried to obtain 960 mg of the desired compound (yield: 87.3% colorless powder)
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:9]2[O:10][C:11]([CH:14]3[CH2:16][CH2:15]3)=[N:12][N:13]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.C([O-])([O-])=O.[K+].[K+].[CH3:23][N:24]1[C:32]2[C:27](=[CH:28][C:29](B(O)O)=[CH:30][CH:31]=2)[CH:26]=[CH:25]1>O1CCOCC1.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>[CH:14]1([C:11]2[O:10][C:9]([C:4]3[C:5]([NH2:8])=[N:6][CH:7]=[C:2]([C:29]4[CH:28]=[C:27]5[C:32](=[CH:31][CH:30]=4)[N:24]([CH3:23])[CH:25]=[CH:26]5)[CH:3]=3)=[N:13][N:12]=2)[CH2:16][CH2:15]1
Reactant: Cn1ccc2cc(B(O)O)ccc21
Reactant: Nc1ncc(Br)cc1-c1nnc(C2CC2)o1
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: C1COCCO1
Solvent: O
Product: Cn1ccc2cc(-c3cnc(N)c(-c4nnc(C5CC5)o4)c3)ccc21
Temperature: 100 °C
Reaction time: 18 h

Procedure:
To a solution of 5-bromo-3-(5-cyclopropyl-[1,3,4]oxadiazol-2-yl)-pyridin-2-ylamine (500 mg, 1.77 mmol) in dioxane (15.0 mL) and water (5.0 mL) were added K2CO3 (730 mg, 5.31 mmol) and N-methylindole-5-boronic acid (140 mg, 1.95 mmol) in a sealed tube. The reaction mixture was degassed with argon for 20 min, then Pd(PPh3)4 (100 mg, 0.088 mmol) was added and stirred for 18 h at 100° C. The reaction mixture was diluted with water (20 mL) and extracted with ethyl acetate (3×20 mL). The organic layer was washed with brine, dried over anhydrous sodium sulphate and concentrated under reduced pressure to get crude title compound. Crude product was purified by column chromatography using 100-200 mesh silica gel and compound was eluted with 40% ethyl acetate in petroleum ether to afford the title compound.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:20])[CH2:4][NH:5][CH2:6][C@@H:7]([NH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@@H:8]([CH3:11])[CH2:9][CH3:10].[C:21]1([CH:31]=O)[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=[CH:23][CH:22]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:1][O:2][C:3](=[O:20])[CH2:4][N:5]([CH2:6][C@@H:7]([NH:12][C:13]([O:15][C:16]([CH3:18])([CH3:17])[CH3:19])=[O:14])[C@@H:8]([CH3:11])[CH2:9][CH3:10])[CH2:31][C:21]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=[CH:23][CH:22]=1
Reactant: O=Cc1cccc2ccccc12
Reactant: CC[C@H](C)[C@@H](CNCC(=O)OC)NC(=O)OC(C)(C)C
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Product: CC[C@H](C)[C@@H](CN(CC(=O)OC)Cc1cccc2ccccc12)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 16 h

Procedure:
N-[2 (S)-(t-Butoxycarbonylamino)-3 (S)-methylpentyl] glycine methyl ester (2.00 g, 6.97 mmol) was dissolved in 1,2dichloroethane (56 ml) and 3A molecular sieves were added followed by 1-naphthaldehyde (1.89 ml, 13.9 mmol) and sodium triacetoxyborohydride (6.65 g, 31.4 mmol). The mixture was stirred at ambient temperature for 16 h, filtered and evaporated in vacuo. The residue was partitioned between EtOAc (100 ml) and sat. aq. NaHCO3 (25 ml). The aqueous layer was extracted with EtOAc (3×50 ml). The organic extracts were combined, dried (Na2 SO4), filtered, and evaporated in vacuo to afford a residue which was purified by chromatography (SiO2, 15-33% ethyl acetate in hexanes) to afford the title compound as an oil.
Reaction SMILES: [C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17](OS(C(F)(F)F)(=O)=O)[CH:18]=2)[C:13]=1[C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].[N:38]1[CH:43]=[CH:42][C:41](B(O)O)=[CH:40][CH:39]=1.C([O-])([O-])=O.[K+].[K+]>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>[C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:41]3[CH:42]=[CH:43][N:38]=[CH:39][CH:40]=3)[CH:18]=2)[C:13]=1[C:31]1[CH:36]=[CH:35][C:34]([Cl:37])=[CH:33][CH:32]=1)[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:2])([CH3:3])[CH3:4]
Reactant: CCOC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2cc(OS(=O)(=O)C(F)(F)F)ccc2c1-c1ccc(Cl)cc1
Reactant: OB(O)c1ccncc1
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: COCCOC
Product: CCOC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2cc(-c3ccncc3)ccc2c1-c1ccc(Cl)cc1
Temperature: 110 °C

Procedure:
A solution of (S)-ethyl 2-tert-butoxy-2-(1-(4-chlorophenyl)-3-methyl-6-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetate (0.060 g, 0.11 mmol), pyridin-4-ylboronic acid (0.020 g, 0.16 mmol), and Pd(PPh3)4 (0.012 g, 0.011 mmol) in DME (1 mL) was treated with 2 M K2CO3 (0.16 mL, 0.32 mmol) and sparged with Ar for 10 min. Following microwave heating at 110° C. for 20 min, the reaction mixture was absorbed onto silica gel in vacuo and purified by Yamazen column chromatography (15-100% EtOAc/Hex) to afford 0.043 g (82%) as a colorless glass. LCMS-ESI+ (m/z): [M+H]+ calcd for C30H31ClNO3: 488.20; found: 488.70.
Reaction SMILES: [C:1]([CH2:6][CH2:7][CH:8]1[C:13](=O)[CH2:12][CH2:11][CH2:10][C:9]1=[O:15])([O:3]CC)=O.[CH2:16]([NH2:18])[CH3:17]>>[CH2:16]([N:18]1[C:13]2[CH2:12][CH2:11][CH2:10][C:9](=[O:15])[C:8]=2[CH2:7][CH2:6][C:1]1=[O:3])[CH3:17]
Reactant: CCN
Reactant: CCOC(=O)CCC1C(=O)CCCC1=O
Product: CCN1C(=O)CCC2=C1CCCC2=O

Procedure:
21.2 g (0.1 mol) of 2-(2-carbethoxy-ethyl)-cyclohexan- 1,3-dione and 200 ml of 24% ethanolic ethylamine solution are heated to 180° C. in a stirred autoclave for 3 hours. The reaction solution is evaporated down using a rotary evaporator and the residue is chromatographed on a silica gel column with cyclohexane/ethyl acetate (1:1).
Reaction SMILES: [F:1][C:2]1[CH:22]=[CH:21][C:5]([O:6][C:7]2[CH:8]=[C:9]([C:17]([O:19]C)=[O:18])[CH:10]=[C:11]([CH:16]=2)[C:12]([O:14]C)=[O:13])=[CH:4][CH:3]=1.C(=O)(O)[O-].[Na+]>CO.O>[F:1][C:2]1[CH:22]=[CH:21][C:5]([O:6][C:7]2[CH:16]=[C:11]([C:12]([OH:14])=[O:13])[CH:10]=[C:9]([CH:8]=2)[C:17]([OH:19])=[O:18])=[CH:4][CH:3]=1
Reactant: COC(=O)c1cc(Oc2ccc(F)cc2)cc(C(=O)OC)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CO
Product: O=C(O)c1cc(Oc2ccc(F)cc2)cc(C(=O)O)c1
Temperature: 80 °C
Yield: 11.6 %

Procedure:
A mixture of dimethyl 5-(4-fluorophenoxy)isophthalate (3.8 g, 12.49 mmol) and sodium bicarbonate (1.2 g, 14.28 mmol) in MeOH (100 mL) and water (15 mL) was heated at 80° C. overnight. An additional 500 mg of sodium bicarbonate was added to the reaction mixture and continued to heat at 100° C. for 6 h. HPLC showed a mixture of monoacid (major), diacid (minor) and a small amount of starting material. Prep HPLC provided diacid, 5-(4-fluorophenoxy)isophthalic acid (0.4 g, 1.448 mmol, 11.60% yield) and monoacid, 3-(4-fluorophenoxy)-5-(methoxycarbonyl)benzoic acid (2.2 g, 7.58 mmol, 60.7% yield) as a white solid.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]#[N:10].[CH3:11][C:12]1([CH3:26])[C:17]2[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][C:16]=2[NH:15][C:14](=[O:25])[O:13]1>>[CH3:11][C:12]1([CH3:26])[O:13][C:14](=[O:25])[NH:15][C:16]2[CH:21]=[CH:20][C:19]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=3[CH2:8][C:9]#[N:10])=[CH:18][C:17]1=2
Reactant: CC1(C)OC(=O)Nc2ccc(B(O)O)cc21
Reactant: N#CCc1ccccc1Br
Product: CC1(C)OC(=O)Nc2ccc(-c3ccccc3CC#N)cc21

Procedure:
Prepared according to procedure B from 2-bromophenylacetonitrile and (1,4-dihydro-4,4-dimethyl-2-oxo-2H-3,1-benzoxazin-6-yl)boronic acid. White solid; mp 176-179° C.; 1H-NMR (DMSO-d6), δ10.31 (s, 1H), 7.53 (m, 1H), 7.48(m,2H), 7.22-7.32(m,3H), 6.98(d,1H; J=8.0 Hz), 3.90(s,2H), 1.64(s,6H). MS (+)APCI [M+H]+ m/z=293. Anal. Calc. For C18H16N2O2: C, 73.95, H, 5.52, N, 9.58. Found: C,73.51, H 5.70, N, 9.39.
Reaction SMILES: CS(O)(=O)=O.[Cl:6][C:7]1[CH:12]=[C:11]([Cl:13])[CH:10]=[CH:9][C:8]=1[C:14]1([CH2:17][N:18]2[CH:22]=[N:21][CH:20]=[N:19]2)[CH2:16][O:15]1.[Cl:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][SH:29])=[CH:26][CH:25]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[Cl:23][C:24]1[CH:31]=[CH:30][C:27]([CH2:28][S:29][CH2:16][C:14]([C:8]2[CH:9]=[CH:10][C:11]([Cl:13])=[CH:12][C:7]=2[Cl:6])([OH:15])[CH2:17][N:18]2[CH:22]=[N:21][CH:20]=[N:19]2)=[CH:26][CH:25]=1
Reactant: Clc1ccc(C2(Cn3cncn3)CO2)c(Cl)c1
Reactant: SCc1ccc(Cl)cc1
Agent: CS(=O)(=O)O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: OC(CSCc1ccc(Cl)cc1)(Cn1cncn1)c1ccc(Cl)cc1Cl
Yield: 53.6 %

Procedure:
2-(2,4-Dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)oxirane methanesulphonate salt (0.336 g, 1 mmole), 4-chlorobenzyl mercaptan, (0.159 g, 1 mmole) and anhydrous potassium carbonate (0.414 g, 3 mmole) were stirred in dry N,N-dimethylformamide (15 ml) at 70° C. for 72 hours. The reaction mixture was diluted with water (70 ml) and extracted with ethyl acetate (2×70 ml). The extracts were combined and evaporated to give an oil which crystallized on standing. Recrystallization from a mixture of ethyl acetate and n-hexane gave the title compound (0.23 g, 53%) m.p. 106°-107° C.
Reaction SMILES: [C:1]1([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:2]([NH2:7])=[CH:3][CH:4]=[CH:5][CH:6]=1.Br[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=1[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C(O[Na])(C)(C)C>C1(C)C=CC=CC=1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[C:1]1([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:26]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:16]1[CH:15]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: Nc1ccccc1-c1ccccc1
Reactant: Brc1ccccc1-c1ccccc1
Agent: CC(C)(C)O[Na]
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Solvent: Cc1ccccc1
Product: c1ccc(-c2ccccc2Nc2ccccc2-c2ccccc2)cc1
Temperature: 110 °C
Yield: 70.9 %

Procedure:
Trisdibenzylideneacetonedipalladium (0.276 g, 0.3 mmol) and tri-tert-butylphosphine (0.121 g, 0.6 mmol) were put into a flask, and then dissolved in 40 mL of toluene. Subsequently, 2-biphenylamine (2.53 g, 15 mmol), 2-bromobiphenyl (3.50 g, 15 mmol) and tert-butoxy sodium (2.16 g, 22.5 mmol) were added into the flask, and then refluxed at a temperature of 110° C. for 12 hours. After the flask including the reactant mixture was cooled to room temperature, the reactant mixture was washed using an ammonium chloride aqueous solution (150 mL) to separate an organic layer. The separated organic layer was washed with distilled water three times, and was then dried with magnesium sulfate. Thereafter, residues from which volatile components were removed at reduced pressure were purified using a silica gel chromatography tube in a mixed solvent of hexane and ethylacetate (1:10), and were then recrystallized in normal hexane to produce 3.42 g of dibiphenyl-2-yl amine.
Reaction SMILES: [C:1]1([CH:7]2[C:12](=[O:13])[NH:11][CH2:10][CH2:9][NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Cl:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=1[Cl:23])[CH2:18]Cl.CC(C)=O>C(N(CC)CC)C>[Cl:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=1[Cl:23])[CH2:18][N:8]1[CH2:9][CH2:10][NH:11][C:12](=[O:13])[CH:7]1[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: ClCc1ccc(Cl)c(Cl)c1
Reactant: O=C1NCCNC1c1ccccc1
Solvent: CCN(CC)CC
Solvent: CC(C)=O
Product: O=C1NCCN(Cc2ccc(Cl)c(Cl)c2)C1c1ccccc1

Procedure:
140 g. of 2-phenyl-3-keto piperazine are boiled under reflux with 163 g. of 3,4-dichloro benzylchloride in 1,600 cc. of acetone for 6 hours while 330 cc. of triethylamine are added. The hot reaction mixture is filtered to remove precipitated triethyl ammonium chloride and is concentrated by fractional distillation. The resulting crystal fractions are twice recrystallized from 4 l. of 96% ethanol.