Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:17]=[CH:16][CH:15]=[CH:14][C:3]=1[O:4][C:5]1[N:10]=[CH:9][C:8]([N+:11]([O-])=O)=[CH:7][N:6]=1.CN(C=O)C.[Sn](Cl)Cl.O.[OH-].[Na+]>CCOC(C)=O>[Br:1][C:2]1[CH:17]=[CH:16][CH:15]=[CH:14][C:3]=1[O:4][C:5]1[N:6]=[CH:7][C:8]([NH2:11])=[CH:9][N:10]=1
Reactant: O=[N+]([O-])c1cnc(Oc2ccccc2Br)nc1
Agent: Cl[Sn]Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: Nc1cnc(Oc2ccccc2Br)nc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of 2-(2-bromophenoxy)-5-nitropyrimidine (5.30 g, 17.9 mmol) in DMF (35.8 ml, 17.9 mmol) was added tin (II) chloride (17.0 g, 89.5 mmol) and water (4.48 ml, 17.9 mmol). The reaction was sonicated for 15 min and became deep red and exothermic in nature. The reaction was stirred at RT. After 4 h, the reaction was diluted with EtOAc, cooled to 0° C. and neutralized with 10% NaOH. Tin residue precipitated out of the solution. The reaction was diluted with EtOAc. The suspension was allowed to settle. The organic layer was decanted and passed through a fritted funnel. This procedure was repeated two more times to extract product into the organic layer. The organic layer, containing the product, was washed with brine, dried over MgSO4, filtered, and concentrated. The product was purified by column chromatography on silica gel using 90:10 DCM:(90:10:1 DCM:MeOH:NH4OH). Upon concentration of the product fractions, the resulting brown solid was dissolved/suspended in DCM, washed with water to remove the DMF, washed with brine, dried over MgSO4, filtered, and concentrated. Yellow solid, 2-(2-bromophenoxy)pyrimidin-5-amine was obtained. MS Calc'd for C10H8BrN3O: [M]+=265. Found: [M+H]+=266, [M+2H]+=267.
Reaction SMILES: [OH:1][CH:2]([CH:6]([NH:14][C:15](=[O:33])[C:16]1[CH:21]=[CH:20][CH:19]=[N:18][C:17]=1[N:22]1[CH:26]=[CH:25][C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)=[N:23]1)[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:3]([OH:5])=O.Cl.[CH2:35]([O:38][NH2:39])[CH:36]=[CH2:37]>>[CH2:35]([O:38][NH:39][C:3](=[O:5])[CH:2]([OH:1])[CH:6]([NH:14][C:15](=[O:33])[C:16]1[CH:21]=[CH:20][CH:19]=[N:18][C:17]=1[N:22]1[CH:26]=[CH:25][C:24]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)=[N:23]1)[CH2:7][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[CH:36]=[CH2:37]
Reactant: O=C(NC(Cc1ccccc1)C(O)C(=O)O)c1cccnc1-n1ccc(-c2ccccc2)n1
Reactant: C=CCON
Agent: Cl
Product: C=CCONC(=O)C(O)C(Cc1ccccc1)NC(=O)c1cccnc1-n1ccc(-c2ccccc2)n1

Procedure:
The reaction was carried out in analogy to reaction step 1.3 by reacting 2-hydroxy-4-phenyl-3-(2-(3-phenyl-1H-pyrazol-1-yl)nicotinamido)butanoic acid with O-allylhydroxylamine hydrochloride. ESI-MS [M+H]+: 498.2
Reaction SMILES: [CH3:1][N:2]([CH3:21])[C:3]1([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:8][CH2:7][C:6](=[O:9])[CH:5](C2SC=CC=2)[CH2:4]1.[CH:22]1[CH:23]=[CH:24][C:25]2[NH:30][CH:29]=[C:28]([CH2:31][CH2:32]O)[C:26]=2[CH:27]=1.C[Si](O[S:39]([C:42](F)(F)F)(=O)=O)(C)C.[OH-].[Na+]>ClCCl>[CH3:1][N:2]([CH3:21])[C:3]1([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:8][CH2:7][C:6]2([C:29]3[NH:30][C:25]4[C:26]([C:28]=3[CH2:31][CH2:32][O:9]2)=[CH:27][CH:22]=[CH:23][CH:24]=4)[CH:5]([S:39][C:42]2[CH:7]=[CH:8][CH:3]=[CH:4][CH:5]=2)[CH2:4]1
Reactant: OCCc1c[nH]c2ccccc12
Reactant: CN(C)C1(c2ccccc2)CCC(=O)C(c2cccs2)C1
Reactant: C[Si](C)(C)OS(=O)(=O)C(F)(F)F
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: CN(C)C1(c2ccccc2)CCC2(OCCc3c2[nH]c2ccccc32)C(Sc2ccccc2)C1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
A mixture of (±)-4-dimethylamino-4-phenyl-2-thiophenylcyclohexanone (300 mg, 0.92 mmol) together with tryptophol (148 mg, 0.92 mmol) was dissolved in dichloromethane (50 ml) and mixed with trifluoromethane sulphonic acid trimethylsilyl ester (0.2 ml, 1.1 mmol). The batch was stirred for 20 h at RT. For work up the reaction mixture was mixed with 2N NaOH (10 ml) and stirred for 2 h. The organic phase was separated and the aqueous phase extracted with dichloromethane (4×20 ml). The combined organic phases were dried with MgSO4. The solvent was then removed in a vacuum. One of the four possible diastereoisomers was isolated from the residue obtained (420 mg) as vitreous solid, which solidified after rubbing with ethanol (2 ml), by means of chromatographic purification [silica gel 60 G (10 g); cyclohexane/ethyl acetate 4:1 (150 ml)]. The product could thus be obtained with a yield of 79 mg (18%) with a melting point of 228-233° C. (from 120° C. upon crystal transformation).
Reaction SMILES: O.[C@@H:2]1([N:11]2[C:20]3[C:14](=[C:15]([N+:17]([O-])=[CH:18][N:19]=3)[NH2:16])[N:13]=[CH:12]2)[O:10][C@H:7]([CH2:8][OH:9])[C@@H:5]([OH:6])[C@H:3]1[OH:4].[OH-].[Na+].[NH4+].N1C=CC=CC=1.C(=S)=[S:32]>>[CH:12]1[N:11]([C@@H:2]2[O:10][C@H:7]([CH2:8][OH:9])[C@@H:5]([OH:6])[C@H:3]2[OH:4])[C:20]2[C:14](=[C:15]([NH2:16])[NH:17][C:18]([N:19]=2)=[S:32])[N:13]=1
Reactant: S=C=S
Reactant: Nc1c2ncn([C@@H]3O[C@H](CO)[C@@H](O)[C@H]3O)c2nc[n+]1[O-]
Agent: [NH4+]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: c1ccncc1
Product: Nc1[nH]c(=S)nc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Yield: 98 %

Procedure:
In the same manner as described in Example 11, 9.6 g of adenosine 1-oxide monohydrate was treated with a 5N sodium hydroxide aqueous solution and Diaion SK-1B (ammonium-type) to obtain a residue. 200 ml of pyridine and then 60 ml of carbon disulfide were added to the above residue, and the resulting mixture was allowed to react in an autoclave at 120° C for 5 hours under autogenous pressure (about 10 Kg/cm2). The reaction mixture was concentrated to dryness, and the residue was worked up in the same manner as described in Example 11 to obtain 9.35 g of 2-thioadenosine as crystals having a melting point of 197° C (with decomposition) in a 98% yield.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[C:4]([F:15])[CH:3]=1.[CH2:16]([O:18][CH2:19][CH2:20][O:21][C:22]1[CH:27]=[C:26]([CH3:28])[C:25]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([CH:35]=O)[CH:30]=2)=[C:24]([CH3:37])[CH:23]=1)[CH3:17]>C1(C)C=CC=CC=1>[CH2:16]([O:18][CH2:19][CH2:20][O:21][C:22]1[CH:27]=[C:26]([CH3:28])[C:25]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([CH2:35][NH:1][C:2]3[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[C:4]([F:15])[CH:3]=3)[CH:30]=2)=[C:24]([CH3:37])[CH:23]=1)[CH3:17]
Reactant: CCOC(=O)CCc1ccc(N)cc1F
Reactant: CCOCCOc1cc(C)c(-c2cccc(C=O)c2)c(C)c1
Solvent: Cc1ccccc1
Product: CCOCCOc1cc(C)c(-c2cccc(CNc3ccc(CCC(=O)OCC)c(F)c3)c2)c(C)c1
Temperature: 25 °C
Reaction time: 30 h
Yield: 83.4 %

Procedure:
To a solution of ethyl 3-(4-amino-2-fluorophenyl)propanoate (1.48 g, 7.00 mmol) and 4′-(2-ethoxyethoxy)-2′,6′-dimethylbiphenyl-3-carbaldehyde (2.09 g, 7.00 mmol) in toluene (15 mL) were added molecular sieves (0.4 nm, beads, 3.5 g), and the mixture was stirred at room temperature for 30 hr. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The obtained residue was dissolved in ethanol (20 mL), 10% palladium-carbon (50% water-containing product, 0.5 g) was added, and the mixture was stirred under a hydrogen atmosphere (balloon pressure) at room temperature for 12 hr. The catalyst was filtered off, and the obtained filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (5%-30% ethyl acetate/hexane) to give the title compound (2.88 g, yield 83%) as a colorless oil.
Reaction SMILES: C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.[CH2:13]1[O:23][C:16]2([CH2:21][CH2:20][CH2:19][CH2:18][C:17]2=O)[O:15][CH2:14]1.CC[O:26]CC>O1CCCC1>[N:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[C:19]1([OH:26])[CH2:20][CH2:21][C:16]2([O:23][CH2:13][CH2:14][O:15]2)[CH2:17][CH2:18]1
Reactant: Brc1ccccn1
Reactant: O=C1CCCCC12OCCO2
Reactant: CCOCC
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: OC1(c2ccccn2)CCC2(CC1)OCCO2
Temperature: -78 °C
Yield: 48 %

Procedure:
A mixture of n-butyllithium (1.6 M in hexanes, 8.8 ml) and anhydrous ether (20 ml) was stirred at −78° C. under argon and a solution of 2-bromopyridine (1.22 ml) in anhydrous ether (20 ml) added dropwise over 10 minutes. The resulting deep red solution was stirred for 10 minutes and a solution of cyclohexanedione monoethylene ketal (2 g) in tetrahydrofuran (20 ml) then introduced dropwise over 10 minutes. The resulting green suspension was maintained at −78° C. for one hour then warmed to −20° C. and stirred for a further hour, after which a yellow solution had formed. The reaction was quenched with saturated aqueous ammonium chloride (60 ml) and the layers separated. The aqueous was partitioned with dichloromethane (2×80 ml) and combined organics were dried (sodium sulphate) and concentrated in vacuo to give a yellow oil. This was adsorbed onto silica for purification by chromatography eluting with 0-100% ethyl acetate/isohexane to give 8-pyridin-2-yl-1,4-dioxaspiro[4.5]decan-8-ol as a pale yellow solid (1.45 g, 48%).
Reaction SMILES: [CH2:1]1[C:13]2[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5]=2[CH2:4][CH2:3][CH2:2]1.C1COCC1.C([Li:23])CCC>CCCCCC>[CH:10]1([Li:23])[C:11]2[CH2:12][C:13]3[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=3)[C:6]=2[CH2:7][CH2:8][CH2:9]1
Reactant: c1ccc2c(c1)CC1=C2CCCC1
Reactant: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: [Li]C1CCCC2=C1Cc1ccccc12
Temperature: -78 °C

Procedure:
5.3 g (31.1 mmol) of the 1,2,3,4-tetrahydrofluorene (4HFluH) obtained in the item (C) of Example 1 was placed in a 500 mL four-neck flask, to which 100 mL of THF was added under a nitrogen atmosphere. 13 mL (2.6 mol/L) of a hexane solution of n-butyllithium was slowly added dropwise to the solution under stirring at −78° C., followed by stirring at room temperature for 2 hours. Thereafter, a precipitate was collected by filtering, and the solid matter was rinsed with hexane and dried to provide 4.4 g of 1,2,3,4-tetrahydrofluorenyllithium (4HFluHLi).
Reaction SMILES: [CH3:1][C:2]1[N:3]=[N:4][N:5]([CH2:7][C@@H:8]2[C@H:11]([NH:12]C(=O)OCC3C=CC=CC=3)[C:10](=[O:23])[NH:9]2)[N:6]=1>CCOC(C)=O.CO.[Pd]>[NH2:12][C@H:11]1[C@@H:8]([CH2:7][N:5]2[N:4]=[N:3][C:2]([CH3:1])=[N:6]2)[NH:9][C:10]1=[O:23]
Reactant: Cc1nnn(C[C@H]2NC(=O)[C@H]2NC(=O)OCc2ccccc2)n1
Agent: [Pd]
Solvent: CO
Solvent: CCOC(C)=O
Product: Cc1nnn(C[C@H]2NC(=O)[C@H]2N)n1

Procedure:
Prepared in an analogous manner to example 4, step 3 using benzyl ((2R,3S)-2-((5-methyl-2H-tetrazol-2-yl)methyl)-4-oxoazetidin-3-yl)carbamate (111 mg, 0.351 mmol) and Pd on C (10%, 50 mg) in EtOAc:MeOH (5:1, 7.0 mL) for 3 h. The crude residue was used as such in following step. LCMS: Rt=0.14 min, m/z=183.2 (M+1) Method 2m_acidic.
Reaction SMILES: [C:1]([CH:9]([N:11]1[CH2:16][CH2:15][C:14]([N:20]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:21](=[O:24])[CH2:22][CH3:23])([CH2:17][O:18][CH3:19])[CH2:13][CH2:12]1)[CH3:10])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+]>CO>[OH:8][CH:1]([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[CH:9]([N:11]1[CH2:16][CH2:15][C:14]([N:20]([C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:21](=[O:24])[CH2:22][CH3:23])([CH2:17][O:18][CH3:19])[CH2:13][CH2:12]1)[CH3:10]
Reactant: CCC(=O)N(c1ccccc1)C1(COC)CCN(C(C)C(=O)c2ccccc2)CC1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CCC(=O)N(c1ccccc1)C1(COC)CCN(C(C)C(O)c2ccccc2)CC1
Reaction time: 8 h

Procedure:
To a stirred solution of 13.2 parts of N-[1-(1-benzoylethyl)-4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide in 164 parts of methanol are added portionwise 1.34 parts of sodium borohydride (slightly exothermic reaction). Upon completion, stirring is continued first for 2 hours at 35° C. and further overnight at room temperature. The reaction mixture is evaporated. The residue is taken up in 50 parts of water and the whole is warmed for a while. After cooling, the product is extracted three times with 75 parts of trichloromethane. The combined extracts are washed with water, dried, filtered and evaporated. The oily residue is purified twice by column-chromatography over silicagel using a mixture of trichloromethane and 3% of methanol as eluent. The pure fractions are collected and the eluent is evaporated. The oily residue is triturated in petroleumether. The product is filtered off, crystallized from 2,2'-oxybispropane and a drop of 4-methyl-2-pentanone, filtered off again and dried at 110° C., yielding N-[1-(2-hydroxy-1-methyl-2-phenylethyl)-4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide; mp. 154.2° C.
Reaction SMILES: [NH2:1][CH:2]([P:7]([OH:10])(=[O:9])[OH:8])[P:3]([OH:6])(=[O:5])[OH:4].[P:11]([OH:14])([OH:13])[OH:12].[CH2:15]=O>>[P:11]([CH:15]=[N:1][CH:2]([P:7]([OH:10])(=[O:8])[OH:9])[P:3]([OH:6])(=[O:4])[OH:5])([OH:14])([OH:13])=[O:12]
Reactant: C=O
Reactant: NC(P(=O)(O)O)P(=O)(O)O
Reactant: OP(O)O
Product: O=P(O)(O)C=NC(P(=O)(O)O)P(=O)(O)O

Procedure:
Reaction of amino methane diphosphonic acid with slightly more than one mole of phosphorous acid and formaldehyde yields mainly N-phosphono methylene amino methane diphosphonic acid. The reaction proceeds in a similar manner with other 1-amino alkane-1,1-diphosphonic acids such as, for instance, with 1-amino ethane-1,1-diphosphonic acid or with 1-amino propane-1,1-diphosphonic acid.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([B:8]([OH:10])[OH:9])[CH:5]=[CH:6][CH:7]=1.COC(N1[C:19](=[O:20])[CH:18]=[CH:17][C:16]1=[O:21])=O.OS(O)(=O)=O>C([O-])(O)=O.[Na+].O>[C:16]1(=[O:21])[N:1]([C:2]2[CH:3]=[C:4]([B:8]([OH:10])[OH:9])[CH:5]=[CH:6][CH:7]=2)[C:19](=[O:20])[CH:18]=[CH:17]1
Reactant: COC(=O)N1C(=O)C=CC1=O
Reactant: Nc1cccc(B(O)O)c1
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Product: O=C1C=CC(=O)N1c1cccc(B(O)O)c1
Temperature: 0 °C
Reaction time: 0.58 h
Yield: 64.1 %

Procedure:
(3-Aminophenyl)boronic acid (1.26 grams, 0.01 mole) is dissolved in saturated NaHCO3 (50 ml) by briefly heating the mixture on a hot plate. The solution is cooled in an ice bath to approximately 0° C., and N-methoxycarbonylmaleimide (1.55 grams, 0.01 mole) added with vigorous stirring. After 10 min. the solution is diluted with water (200 ml) and then stirred at room temperature for 30 to 40 min. The pH is adjusted to approximately 5.5 by addition of 1M H2SO4, and the precipitate collected by filtration. The precipitate is washed with 1M H2SO4 (2×50 ml), and then dried overnight in vacuo over NaOH pellets to afford 1.39 grams (64% yield) of (3-maleimidophenyl)boronic acid. The structure was confirmed by 300 MHz, 1H NMR spectrometry in d6 -DMSO.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([S:6][S:7][C:8]2[CH:12]=[CH:11][S:10][C:9]=2[C:13]([O-:15])=[O:14])=[C:2]1[C:16]([O:18]C)=[O:17].Cl>[OH-].[Na+].C(O)C>[S:1]1[CH:5]=[CH:4][C:3]([S:6][S:7][C:8]2[CH:12]=[CH:11][S:10][C:9]=2[C:13]([OH:15])=[O:14])=[C:2]1[C:16]([OH:18])=[O:17]
Reactant: COC(=O)c1sccc1SSc1ccsc1C(=O)[O-]
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)c1sccc1SSc1ccsc1C(=O)O

Procedure:
(aaa) 38.9 g of methyl 3,3'-dithiobis-thiophene-2-carboxylate was suspended in 1500 ml of 1N sodium hydroxide solution and 700 ml of ethanol, whereupon the suspension was heated under reflux until the reaction finished. After cooling, in an ice-bath and mixture was acidified with 25 percent hydrochloric acid, whereby the product crystallized out. By recrystallization from water, there was obtained 3,3'-dithio-bis-thiophene-2-carboxylic acid as colorless crystals of m.p. 256°-257°.
Reaction SMILES: [CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.[NH2:52][C:53]1[N:54]=[N:55][CH:56]=[CH:57][CH:58]=1>CN(C)C=O>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[C:8]([NH:52][C:53]2[N:54]=[N:55][CH:56]=[CH:57][CH:58]=2)=[O:10])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: Nc1cccnn1
Reactant: O=C(O)C(CC1CCCC1)c1ccc(Cl)c(Cl)c1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(Nc1cccnn1)C(CC1CCCC1)c1ccc(Cl)c(Cl)c1
Yield: 62.2 %

Procedure:
A solution of 3-cyclopentyl-2-(3,4-dichlorophenyl)-propionic acid (prepared as in Example 38A, 625.2 mg, 2.18 mmol), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (908.3 mg, 2.39 mmol), N,N-diisopropylethylamine (1.1 mL, 6.53 mmol), and 3-aminopyridazine (310.6 mg, 3.27 mmol) in dry N,N-dimethylformamide (11 mL) was stirred at 25° C. under nitrogen for 72 h. The reaction mixture was concentrated in vacuo to remove N,N-dimethylformamide. The resulting residue was diluted with ethyl acetate (200 mL). The organic layer was washed with a 10% aqueous hydrochloric acid solution and a saturated aqueous sodium chloride solution. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 1/1 hexanes/ethyl acetate) afforded 3-cyclopentyl-2-(3,4-dichlorophenyl)-N-pyridazin-3-yl-propionamide (493.8 mg, 62%) as a white foam: mp 70-71° C.; EI-HRMS m/e calcd for C18H19Cl2N3O (M+) 363.0905, found 363.0908.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].Br[C:8]1[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]([Cl:18])[CH:9]=1.CC1(C)C(C)(C)OB([C:27]2[CH:28]=[N:29][C:30]([NH2:33])=[N:31][CH:32]=2)O1>O.C1(C)C=CC=CC=1.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>[NH2:33][C:30]1[N:31]=[CH:32][C:27]([C:8]2[CH:17]=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10]([Cl:18])[CH:9]=2)=[CH:28][N:29]=1
Reactant: COC(=O)c1ccc(Br)cc1Cl
Reactant: CC1(C)OB(c2cnc(N)nc2)OC1(C)C
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: CCO
Solvent: O
Solvent: Cc1ccccc1
Product: COC(=O)c1ccc(-c2cnc(N)nc2)cc1Cl
Temperature: 120 °C
Yield: 59.6 %

Procedure:
A solution of potassium carbonate (0.39 g, 2.8 mmol) in water (3 mL) was added to a mixture of methyl 4-bromo-2-chlorobenzoate (0.49 g, 2.0 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-amine (0.31 g, 1.4 mmol), and tetrakis(triphenylphosphine)palladium (0.08 g, 0.07 mmol) in toluene (5.3 mL) and ethanol (3 mL). The resulting mixture was heated at 120° C. for 15 min. The reaction mixture was extracted with EtOAc (3×20 mL). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated. The residue was recrystallized from methanol and ether. The precipitate was collected by filtration, and washed with ether to afford the desired product (0.22 g, 59%). LCMS: (M+H)=264.0/266.0.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([CH:22]=O)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH:24]1[CH2:29][CH2:28][CH:27]([CH2:30][OH:31])[CH2:26][CH2:25]1>CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C(O)C>[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:11]=[CH:12][C:13]([C:16]3([CH2:22][N:24]4[CH2:29][CH2:28][CH:27]([CH2:30][OH:31])[CH2:26][CH2:25]4)[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:14][CH:15]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: O=CC1(c2ccc(OCCCN3CCCC3)cc2)CCOCC1
Reactant: OCC1CCNCC1
Agent: [Ti+4]
Agent: CC(C)[O-]
Solvent: CCO
Product: OCC1CCN(CC2(c3ccc(OCCCN4CCCC4)cc3)CCOCC2)CC1
Yield: 89.3 %

Procedure:
4-[4-(3-Pyrrolidin-1-ylpropoxy)phenyl]tetrahydro-2H-pyran-4-carbaldehyde (700 mg, 2.205 mmol, 1 wt), 4-piperidinemethanol (485 mg, 4.21 mmol), absolute ethanol (28 ml, 40 vol), activated 3 Å molecular sieves (700 mg), titanium (IV) isopropoxide (3.25 ml, 11.03 mmol) and STAB (3.97 g, 18.7 mmol) was reacted in accordance with the general procedure D. The isolated waxy solid was purified by column chromatography on silica eluting with DCM:MeOH:NH3 95:4:1 to give the title compound as a colorless oil (820 mg, 72%). 1H NMR (400 MHz, CDCl3) δ7.20 (d, 2H), 6.85 (d, 2H), 4.02 (t, 2H), 3.75 (dt, 2H), 3.59-3.46 (m, 2H), 3.42 (d, 2H), 2.63 (t, 2H), 2.53 (br s, 4H), 2.39-2.26 (m, 4H), 2.15-1.03 (m, 18H).
Reaction SMILES: [C:1]1([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2C(=O)[C:9]([C:26]3[CH:27]=[C:28]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[CH:29]=[CH:30][CH:31]=3)=[C:10]([C:19]3[CH:24]=[CH:23][C:22](Br)=[CH:21][CH:20]=3)[C:11]=2[C:12]2[CH:17]=[CH:16][C:15](Br)=[CH:14][CH:13]=2)[CH:2]=1.[Br:45][C:46]1[CH:51]=[CH:50][C:49]([C:52]#[C:53][C:54]2[CH:59]=[CH:58][C:57]([Br:60])=[CH:56][CH:55]=2)=[CH:48][CH:47]=1>C1(OC2C=CC=CC=2)C=CC=CC=1.CCCCCC>[Br:45][C:46]1[CH:47]=[CH:48][C:49]([C:52]2[C:7]([C:3]3[CH:2]=[C:1]([C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=4)[CH:6]=[CH:5][CH:4]=3)=[C:11]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:10]([C:19]3[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=3)=[C:9]([C:26]3[CH:27]=[C:28]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[CH:29]=[CH:30][CH:31]=3)[C:53]=2[C:54]2[CH:55]=[CH:56][C:57]([Br:60])=[CH:58][CH:59]=2)=[CH:50][CH:51]=1
Reactant: O=C1C(c2cccc(-c3ccccc3)c2)=C(c2ccc(Br)cc2)C(c2ccc(Br)cc2)=C1c1cccc(-c2ccccc2)c1
Reactant: Brc1ccc(C#Cc2ccc(Br)cc2)cc1
Solvent: CCCCCC
Solvent: c1ccc(Oc2ccccc2)cc1
Product: Brc1ccc(-c2c(-c3ccc(Br)cc3)c(-c3cccc(-c4ccccc4)c3)c(-c3ccccc3)c(-c3ccccc3)c2-c2cccc(-c3ccccc3)c2)cc1
Temperature: 25 °C

Procedure:
A degassed solution of 300 mg of 2,5-di([1,1′-biphenyl]-3-yl)-3,4-bis(4-bromophenyl)cyclopenta-2,4-dienone (8a, 0.432 mmol) and 77.0 mg of 4,4′-dibromotolane (0.432 mmol) in 3 ml of diphenyl ether was heated to 230° C. in a microwave reactor at power 300 watts and a maximum pressure of 7 bar for 3×12 h. After cooling to room temperature, the reaction solution was diluted with hexane and purified by column chromatography (silica, hexane with 6% ethyl acetate). After purification by means of recycling GPC and drying under high vacuum, 145 mg of monomer 6a were obtained in the form of colorless crystals (40%, 0.172 mmol). Elemental analysis measured: C 76.7; H 3.1% (calculated for C54H36Br2: C, 76.8; H, 4.3%); 1H NMR (700 MHz, d8-THF) δ=7.30-7.25 (m, 4H, CH), 7.23-7.17 (m, 6H, CH), 7.13 (d, J=1.5 Hz, 1H, CH), 7.12-7.11 (m, 1H, CH), 7.11-7.09 (m, 4H, CH), 7.09-7.06 (m, 2H, CH), 6.95 (s, 1H, CH), 6.94 (br s, 2H, CH), 6.93 (s, 1H, CH), 6.91 (t, J=4.1 Hz, 2H, CH), 6.89 (d, J=8.0 Hz, 2H, CH), 6.85 (d, J=7.0 Hz, 4H, CH), 6.83 (d, J=2.0 Hz, 2H, CH), 6.81 (d, J=1.4 Hz, 1H, CH), 6.79 (d, J=8.3 Hz, 2H, CH), 6.78 (s, 1H, CH); 13C NMR (125 MHz, d2-TCE) δ=141.05, 140.74, 140.20, 140.00, 139.44, 139.03, 138.52, 133.03, 132.92, 131.30, 131.15, 130.26, 129.92, 129.85, 128.42, 127.17, 126.87, 126.62, 126.52, 125.20, 124.15, 120.18, 119.51; MS (MALDI-TOF): m/z (%): 845.1 (100) [M+] (calculated for C54H36Br2: 844.1); Rf (hexane with 6% ethyl acetate)=0.40; m.p. (° C.): decomposition at >400° C.
Reaction SMILES: [CH2:1]([N:3]([CH2:15][CH3:16])[CH2:4][CH2:5][C:6]([C:8]1[CH:13]=[CH:12][C:11](F)=[CH:10][CH:9]=1)=[O:7])[CH3:2].[CH2:17]([NH2:20])[C:18]#[CH:19].C(=O)([O-])[O-].[K+].[K+].[F-].[K+]>CS(C)=O.O>[CH2:1]([N:3]([CH2:15][CH3:16])[CH2:4][CH2:5][C:6]([C:8]1[CH:13]=[CH:12][C:11]([NH:20][CH2:17][C:18]#[CH:19])=[CH:10][CH:9]=1)=[O:7])[CH3:2]
Reactant: C#CCN
Reactant: CCN(CC)CCC(=O)c1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [F-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: C#CCNc1ccc(C(=O)CCN(CC)CC)cc1

Procedure:
3-(Diethylamino)-1-[4-fluorophenyl]-1-propanone (Pharmazie, 35, H.7 (1980)), 5 g (0.022 mol), is treated with a mixture of propargylamine, 2.47 g (0.045 mol), potassium carbonate, 3.09 g, and potassium fluoride, 1.3 g (0.022 mol), in dimethylsulfoxide between 50° and 100° C. until TLC shows formation of the aminated product is complete. The reaction is poured into water and the solid is collected. Chromatography of the crude material over silica gel affords the desired product.