Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[C:5]2([CH2:10][CH2:9][CH:8]([OH:11])[CH2:7][CH2:6]2)[O:4][CH2:3][CH2:2]1.[CH3:12][S:13](Cl)(=[O:15])=[O:14]>C(Cl)Cl>[CH3:12][S:13]([O:11][CH:8]1[CH2:9][CH2:10][C:5]2([O:4][CH2:3][CH2:2][O:1]2)[CH2:6][CH2:7]1)(=[O:15])=[O:14]
Reactant: CS(=O)(=O)Cl
Reactant: OC1CCC2(CC1)OCCO2
Solvent: ClCCl
Product: CS(=O)(=O)OC1CCC2(CC1)OCCO2

Procedure:
When n is the bridging group --C(Cl)=CH--, 1,4-cyclohexanedione mono-ethylene ketal is reduced with sodium borohydride in ethanol, yielding the corresponding 1,4-dioxaspiro[4.5]decan-8-ol. The so-prepared alcohol is then treated with methanesulfonyl chloride under basic conditions in methylene chloride, affording 8-methylsulfonyloxy-1,4-dioxaspiro[4.5]decane, which is in turn treated with sodium hydride in tetrahydrofuran, and then is reacted with trimethylsilylacetylene, yielding 8-(trimethylsilylethynyl)-1,4-dioxaspiro[4.5]decane. This compound is then treated with sodium carbonate in methanol to unprotect the ethynyl moiety, affording 8-ethynyl-1,4-dioxaspiro[4.5]decane. The so-prepared ethynyl compound is reacted with an appropriately substituted or unsubstituted phenyl iodide, for example, 3,5-di(trifluoromethyl)phenyl iodide, under basic conditions in the presence of bis(triphenylphosphine)palladium(II) chloride and copper(I) iodide in acetonitrile, and then is treated with 1N hydrochloric acid, yielding the corresponding 4-(phenylethynyl)cyclohexanone. The cyclohexanone is then reacted with cyanoguanidine, as previously described, affording the 2,4-diamino-6-phenylethynyl-5,6,7,8-tetrahydroquinazoline. Chlorination of the 6-phenylethynyl-5,6,7,8-tetrahydroquinazoline, using the methods of J. Cousseau (JCS Faraday II, 1973, 1821, and JCS Perkin I, 1977, 1797), affords the targeted 2,4-diamino-6-[1-chloro-2-phenylethenyl]-5,6,7,8-tetrahydroquinazoline. Example 8 provides a detailed description of how this reaction is conducted.
Reaction SMILES: [OH:1][C@H:2]([CH3:11])[CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7].N1C=CN=C1.[C:17]([Si:21](Cl)([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)([CH3:20])([CH3:19])[CH3:18].O>CN(C=O)C>[Si:21]([O:1][C@H:2]([CH3:11])[CH2:3][CH2:4][CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])([C:17]([CH3:20])([CH3:19])[CH3:18])([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: CCOC(=O)CCC[C@@H](C)O
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)CCC[C@@H](C)O[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Temperature: 25 °C
Reaction time: 16 h
Yield: 80.4 %

Procedure:
To a solution of (R)-ethyl 5-hydroxyhexanoate (5 g, 31.2 mmol) in DMF (100 mL) at 0° C. was added imidazole (3.19 g, 46.8 mmol) followed by tert-butylchlorodiphenylsilane (12.00 mL, 46.8 mmol) and the resulting mixture was stirred at room temp for 16 h. Water (30 mL) was then added and the mixture was extracted with ether (2×100 mL). Ether layer was then washed with brine (50 mL), dried (Na2SO4), filtered and concentrated. The residue was purified via Biotage (0-10% EtOAc/hexane) to afford (R)-ethyl 5-((tert-butyldiphenylsilyl)oxy)hexanoate (10 g, 25.09 mmol, 80% yield) as clear viscous liquid. 1H NMR (500 MHz, CDCl3) δ 7.73-7.68 (m, 4H), 7.48-7.36 (m, 6H), 4.13 (q, J=7.2 Hz, 2H), 3.96-3.76 (m, 1H), 2.31-2.16 (m, 2H), 1.72-1.62 (m, 2H), 1.58-1.40 (m, 2H), 1.27 (t, J=7.1 Hz, 3H), 1.12-1.05 (m, 12H).
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:15])[C:11]([F:14])([F:13])[F:12])=[C:5]([CH3:16])[CH:4]=1)#[N:2].S(Cl)([Cl:20])(=O)=O.Cl>C(Cl)(Cl)(Cl)Cl>[Cl:20][CH2:16][C:5]1[CH:4]=[C:3]([C:1]#[N:2])[CH:8]=[CH:7][C:6]=1[NH:9][C:10](=[O:15])[C:11]([F:13])([F:12])[F:14]
Reactant: O=S(=O)(Cl)Cl
Reactant: Cc1cc(C#N)ccc1NC(=O)C(F)(F)F
Agent: Cl
Solvent: ClC(Cl)(Cl)Cl
Product: N#Cc1ccc(NC(=O)C(F)(F)F)c(CCl)c1
Temperature: 25 °C

Procedure:
In a round-bottomed flask N-(4-cyano-2-methylphenyl)-2,2,2-trifluoroacetamide (Intermediate 1, 19.37 g, 85 mmol), sulfuryl dichloride (27.6 ml, 340 mmol) and diphenylperoxyanhydride (1.028 g, 4.24 mmol) were heated in carbon tetrachloride (210 ml) at 100° C. for 3 h. The mixture was cooled to room temperature and then the reaction mixture was poured into 2M HCl (350 mL). The organic layer was then collected and the solvent was removed to give N-[2-(chloromethyl)-4-cyanophenyl]-2,2,2-trifluoroacetamide as an orange oil, (25.54 g) which was used in the next step without further purification. This oil was added to triphenylphosphine (26.2 g, 100 mmol) and the mixture was heated in toluene (300 ml) at 110° C. for 3 h. The mixture was cooled to room temperature overnight and the precipitate was filtered and washed with small amounts of toluene and diethyl ether to give the title compound as an off-white solid (29.91 g);
Reaction SMILES: [OH-].[K+].[N+:3]([C:6]1[CH:14]=[C:13]2[C:9]([CH:10]=[CH:11][NH:12]2)=[CH:8][CH:7]=1)([O-:5])=[O:4].[CH3:15][N:16]1[CH2:21][CH2:20][C:19](=O)[CH2:18][CH2:17]1>CO>[CH3:15][N:16]1[CH2:21][CH2:20][CH:19]([C:10]2[C:9]3[C:13](=[CH:14][C:6]([N+:3]([O-:5])=[O:4])=[CH:7][CH:8]=3)[NH:12][CH:11]=2)[CH2:18][CH2:17]1
Reactant: CN1CCC(=O)CC1
Reactant: O=[N+]([O-])c1ccc2cc[nH]c2c1
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: CN1CCC(c2c[nH]c3cc([N+](=O)[O-])ccc23)CC1
Temperature: 90 °C
Reaction time: 6 h
Yield: 37.5 %

Procedure:
KOH (3.96 g, 70.71 mmol) was added to a solution of 6-nitro-1H-indole (5 g, 30.86 mmol) in methanol (50 mL). 1-methylpiperidin-4-one (4.53 g, 40.09 mmol) was then added, and the resulting solution was stirred for 6 hours at 90° C. After cooling, the mixture was concentrated and the residue was recrystallized from ethanol (20 mL) to afford 3.0 g (36%) of 3-(1-methylpiperidin-4-yl)-6-nitro-1H-indole as a yellow powder.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]3[C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=4[NH:14][C:13]4[N:21]=[CH:22][CH:23]=[CH:24][C:12]=4[N:11]3[C:25]=2[C:26]2[CH:31]=[CH:30][C:29]([C:32]3([NH:36]C(=O)OC(C)(C)C)[CH2:35][CH2:34][CH2:33]3)=[CH:28][CH:27]=2)[CH:5]=[CH:6][CH:7]=1.[ClH:44].O1CCOCC1>C(Cl)Cl>[ClH:44].[ClH:44].[ClH:44].[ClH:44].[NH2:36][C:32]1([C:29]2[CH:28]=[CH:27][C:26]([C:25]3[N:11]4[C:12]5[CH:24]=[CH:23][CH:22]=[N:21][C:13]=5[NH:14][C:15]5[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=5[C:10]4=[N:9][C:8]=3[C:4]3[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=3)[NH2:1])=[CH:31][CH:30]=2)[CH2:33][CH2:34][CH2:35]1
Reactant: CC(C)(C)OC(=O)NC1(c2ccc(-c3c(-c4cccc(N)c4)nc4n3-c3cccnc3Nc3ccccc3-4)cc2)CCC1
Agent: Cl
Solvent: C1COCCO1
Solvent: ClCCl
Product: Nc1cccc(-c2nc3n(c2-c2ccc(C4(N)CCC4)cc2)-c2cccnc2Nc2ccccc2-3)c1
Temperature: 25 °C
Reaction time: 15.5 h
Yield: 83.8 %

Procedure:
tert-Butyl (1-{4-[2-(3-aminophenyl)-9H-imidazo[1,2-d]pyrido[2,3-b][1,4]benzodiazepin-3-yl]phenyl}cyclobutyl)carbamate (40.0 mg, 0.0701 mmol) was dissolved in DCM (1 mL). 4M HCl/dioxane (1 mL) was added to the mixture and stirred at room temperature for 15.5 hours. The mixture was concentrated and solidified with ether. The precipitated solids were collected by filtration and washed with ether to afford desired product (36.2 mg, 83.8%) as pale red solid. 1H-NMR (DMSO-d6) 400 MHz δ: 8.78 (br s, 2H), 8.63 (s, 1H), 8.11 (dd, J=4.8, 1.6 Hz, 1H), 7.96-7.92 (m, 1H), 7.60-7.48 (m, 3H), 7.42-7.09 (m, 8H), 6.93 (dd, J=8.2, 1.4 Hz, 1H), 6.75 (dd, J=7.8, 4.6 Hz, 1H), 2.65-2.48 (m, 4H), 2.27-2.13 (m, 1H), 1.90-1.76 (m, 1H); LCMS: 471 [M+H].
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:3]=1[CH:4]=O.[CH:11]1([NH2:14])[CH2:13][CH2:12]1>>[Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:3]=1[CH2:4][NH:14][CH:11]1[CH2:13][CH2:12]1
Reactant: O=Cc1c(F)cccc1Cl
Reactant: NC1CC1
Product: Fc1cccc(Cl)c1CNC1CC1

Procedure:
Synthesized according to typical procedure J from 2-chloro-6-fluorobenzaldehyde and cyclopropylamine.
Reaction SMILES: [OH-].[Na+].[Br:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]([C:15]2[C:35]([CH:36]3[CH2:38][CH2:37]3)=[CH:34][C:18]3[C:19]([C:29]([O:31]CC)=[O:30])=[C:20]([C:22]4[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=4)[O:21][C:17]=3[CH:16]=2)[S:11]([CH3:14])(=[O:13])=[O:12])=[CH:6][C:5]=1[Cl:39].CCOC(C)=O.Cl>C1COCC1.CO>[Br:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]([C:15]2[C:35]([CH:36]3[CH2:37][CH2:38]3)=[CH:34][C:18]3[C:19]([C:29]([OH:31])=[O:30])=[C:20]([C:22]4[CH:23]=[CH:24][C:25]([Cl:28])=[CH:26][CH:27]=4)[O:21][C:17]=3[CH:16]=2)[S:11]([CH3:14])(=[O:12])=[O:13])=[CH:6][C:5]=1[Cl:39]
Reactant: CCOC(=O)c1c(-c2ccc(Cl)cc2)oc2cc(N(c3ccc(Br)c(Cl)c3)S(C)(=O)=O)c(C3CC3)cc12
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: CO
Product: CS(=O)(=O)N(c1ccc(Br)c(Cl)c1)c1cc2oc(-c3ccc(Cl)cc3)c(C(=O)O)c2cc1C1CC1
Temperature: 60 °C
Yield: 93.6 %

Procedure:
A 1M solution of NaOH (1.877 mL, 1.877 mmol) was added to a solution of ethyl 6-(N-(4-bromo-3-chlorophenyl)methylsulfonamido)-2-(4-chlorophenyl)-5-cyclopropylbenzofuran-3-carboxylate (234 mg, 0.375 mmol) in THF (2 mL) and MeOH (1 mL) at RT. After 1 h a white precipitate formed but starting material is still evident by LCMS. THF (3 mL) and a 4N solution of NaOH (1 mL) were added and the mixture was heated to 60° C. for 4 h. EtOAc was added and the aqueous layer was made acidic with the addition of 1N HCl. The organic layer was separated, washed with water, brine, dried over Na2SO4, filtered and concentrated to give 6-(N-(4-bromo-3-chlorophenyl)methylsulfonamido)-2-(4-chlorophenyl)-5-cyclopropylbenzofuran-3-carboxylic acid (220 mg, 0.351 mmol, 94% yield) as a white solid. LCMS (m/z, ES+)=594.0 (M−H).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:11][CH2:10][CH2:9]2)=[CH:4][C:3]=1[O:17][CH2:18][C:19]([F:22])([F:21])[F:20].C1C(=O)N([Cl:30])C(=O)C1>C(Cl)(Cl)Cl.O>[NH2:1][C:2]1[C:3]([O:17][CH2:18][C:19]([F:20])([F:21])[F:22])=[CH:4][C:5]([C:8]2([C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH2:11][CH2:10][CH2:9]2)=[CH:6][C:7]=1[Cl:30]
Reactant: O=C1CCC(=O)N1Cl
Reactant: CCOC(=O)C1(c2ccc(N)c(OCC(F)(F)F)c2)CCC1
Solvent: O
Solvent: ClC(Cl)Cl
Product: CCOC(=O)C1(c2cc(Cl)c(N)c(OCC(F)(F)F)c2)CCC1
Temperature: 25 °C
Yield: 18.1 %

Procedure:
To a stirred solution of ethyl 1-(4-amino-3-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate (2.0 g, 6.3 mmol) in dry CHCl3 (30 mL), NCS (0.842 g, 6.3 mmol) was added at 0° C. The reaction mixture was allowed to stir for 3 at room temperature to complete the reaction. The reaction mixture was diluted with water, extracted with DCM (2×100 mL), the combined organic solvents was dried over Na2SO4, filtered and concentrated in vacuo. The crude reaction mixture was purified by Flash column chromatography to yield ethyl 1-(4-amino-3-chloro-5-(2,2,2-trifluoroethoxy)phenyl)cyclobutanecarboxylate (0.4 g) as thick syrup.
Reaction SMILES: F[C:2]([F:20])(F)[C:3](=[N:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=1)[C:4]#[C:5][C:6]([O:8][CH3:9])=[O:7].[Cl:21][C:22]1[CH:29]=[CH:28][C:25]([CH2:26][NH2:27])=[CH:24][CH:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCCC1>[CH3:18][O:17][C:14]1[CH:13]=[CH:12][C:11]([NH:10][C:3]2[C:2]([F:20])=[C:26]([C:25]3[CH:28]=[CH:29][C:22]([Cl:21])=[CH:23][CH:24]=3)[N:27]=[C:5]([C:6]([O:8][CH3:9])=[O:7])[CH:4]=2)=[CH:16][CH:15]=1
Reactant: COC(=O)C#CC(=Nc1ccc(OC)cc1)C(F)(F)F
Reactant: NCc1ccc(Cl)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1CCOC1
Solvent: O
Product: COC(=O)c1cc(Nc2ccc(OC)cc2)c(F)c(-c2ccc(Cl)cc2)n1
Temperature: 80 °C

Procedure:
In a typical reaction, methyl 5,5,5-trifluoro-4-((4-methoxyphenyl)imino)pent-2-ynoate is mixed with about a 2.5 to 3 fold excess of 4-chlorobenzyl amine and about a 2.5 to 3 fold excess of cesium carbonate in anhydrous terahydrofuran. The mixture is heated at about 80° C. until the reaction is complete. After cooling, an extraction solvent like a halogenated hydrocarbon is added to the mixture along with water. The organic layer is recovered, washed with brine and dried. The solvent is evaporated to provide crude methyl 4-(4-methoxyphenylamino)-5-fluoro-6-(4-chlorophenyl)picolinate.
Reaction SMILES: O1CCCCC1[N:7]1[CH:15]=[C:14]2[C:9]([CH:10]=[C:11]([C:17]3[CH:22]=[CH:21][C:20]([O:23]C4CCCCO4)=[CH:19][CH:18]=3)[CH:12]=[C:13]2[NH2:16])=[N:8]1.[Br:30][C:31]1[N:36]=[C:35]([C:37](O)=[O:38])[CH:34]=[CH:33][CH:32]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[Br:30][C:31]1[N:36]=[C:35]([C:37]([NH:16][C:13]2[CH:12]=[C:11]([C:17]3[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=3)[CH:10]=[C:9]3[C:14]=2[CH:15]=[N:7][NH:8]3)=[O:38])[CH:34]=[CH:33][CH:32]=1
Reactant: Nc1cc(-c2ccc(OC3CCCCO3)cc2)cc2nn(C3CCCCO3)cc12
Reactant: O=C(O)c1cccc(Br)n1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(Nc1cc(-c2ccc(O)cc2)cc2[nH]ncc12)c1cccc(Br)n1
Temperature: 70 °C
Reaction time: 120 h

Procedure:
2-(Tetrahydro-2H-pyran-2-yl)-6-[4-(tetrahydro-2H-pyran-2-yloxy)phenyl]-2H-indazol-4-amine (500 mg, 1.27 mmol), 6-bromo-2-pyridinecarboxylic acid (272 mg, 1.35 mmol), HATU (531 mg, 1.35 mmol) and DIPEA (0.442 ml, 2.54 mmol) were combined in DMF (10 ml) and heated at 70° C. overnight. The solvent was removed in vacuo and the residue was purified by silica gel chromatography, eluting with DCM:MeOH:ammonia. Appropriate fractions were combined and the solvent was removed in vacuo. The residue was dissolved in Methanol (20 ml) and 4 M HCl in dioxane (2 ml) and stirred at RT for 5 days. A small amount of the reaction mixture was removed (2 ml), the solvent was removed in vacuo and the residue purified by MDAP (Method B) to give the title compound.
Reaction SMILES: Cl.Cl.[F:3][C:4]([F:20])([F:19])[C:5]1[N:9]2[CH2:10][CH2:11][NH:12][C:13]3([CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)[C:8]2=[CH:7][CH:6]=1.[CH:21]([O:24][C:25]1[CH:33]=[CH:32][C:28]([C:29](O)=[O:30])=[CH:27][C:26]=1[O:34][CH3:35])([CH3:23])[CH3:22].ON1C2C=CC=CC=2N=N1.C(N=C=NCCCN(C)C)C.CN1CCOCC1>C(Cl)Cl.O>[CH:21]([O:24][C:25]1[CH:33]=[CH:32][C:28]([C:29]([N:16]2[CH2:15][CH2:14][C:13]3([NH:12][CH2:11][CH2:10][N:9]4[C:5]([C:4]([F:3])([F:19])[F:20])=[CH:6][CH:7]=[C:8]34)[CH2:18][CH2:17]2)=[O:30])=[CH:27][C:26]=1[O:34][CH3:35])([CH3:23])[CH3:22]
Reactant: COc1cc(C(=O)O)ccc1OC(C)C
Reactant: FC(F)(F)c1ccc2n1CCNC21CCNCC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: ClCCl
Solvent: CN1CCOCC1
Product: COc1cc(C(=O)N2CCC3(CC2)NCCn2c(C(F)(F)F)ccc23)ccc1OC(C)C
Temperature: 25 °C
Reaction time: 16 h
Yield: 96.5 %

Procedure:
To a stirred solution of 6-(trifluoromethyl)spiro[3,4-dihydro-2H-pyrrolo[1,2-a]pyrazine-1,4′-piperidine]dihydrochloride (475 mg, 1.43 mmol), 4-isopropoxy-3-methoxy-benzoic acid (361 mg, 1.72 mmol) and 1-hydroxybenzotriazole (232 mg, 1.72 mmol) in CH2Cl2 (5.5 mL) at ambient temperature was added 3-(ethyliminomethyleneamino)-N,N-dimethyl-propan-1-amine (266 mg, 1.72 mmol) followed by 4-methylmorpholine (786 μL, 7.15 mmol). The mixture was stirred for 16 h at room temperature. The mixture was poured into water and was extracted with EtOAc (3×). The organics were combined, washed with 0.1 N HCl, 1N NaOH, water, brine, dried (Na2SO4) and evaporated to dryness. The residue was purified by column chromatography (0-100% ethyl acetate/hexanes) to give (4-isopropoxy-3-methoxy-phenyl)-[6-(trifluoromethyl)spiro[3,4-dihydro-2H-pyrrolo[1,2-a]pyrazine-1,4′-piperidine]-1′-yl]methanone (623 mg, 96%). ESI-MS m/z calc. 451.2, found 452.3 (M+1)+; Retention time: 1.30 minutes (3 min run). 1H NMR (400 MHz, CDCl3) δ 7.03 (d, J=1.9 Hz, 1H), 6.98 (dd, J=8.2, 1.9 Hz, 1H), 6.88 (d, J=8.3 Hz, 1H), 6.54 (d, J=3.7 Hz, 1H), 5.93 (d, J=3.8 Hz, 1H), 4.56 (dd, J=12.2, 6.1 Hz, 1H), 4.52 (s, 1H), 3.94 (s, 2H), 3.88 (s, 3H), 3.69 (s, 1H), 3.47 (s, 2H), 3.27 (s, 2H), 1.87 (s, 4H), 1.38 (d, J=6.1 Hz, 6H).
Reaction SMILES: [Mg].[Cl:2][C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[Cl:11])[CH2:6]Cl.[Si:12]([O:19][CH:20]([CH3:23])[CH:21]=[O:22])([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13].[Cl-].[NH4+]>BrCCBr.C(OCC)C>[Si:12]([O:19][CH:20]([CH3:23])[CH:21]([OH:22])[CH2:6][C:5]1[CH:8]=[CH:9][C:10]([Cl:11])=[C:3]([Cl:2])[CH:4]=1)([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]
Reactant: CC(C=O)O[Si](C)(C)C(C)(C)C
Reactant: ClCc1ccc(Cl)c(Cl)c1
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: CCOCC
Solvent: BrCCBr
Product: CC(O[Si](C)(C)C(C)(C)C)C(O)Cc1ccc(Cl)c(Cl)c1
Reaction time: 3 h
Yield: 33.7 %

Procedure:
2.45 g of magnesium (turnings) was added to 100 ml of ethyl ether, and a few drops of 1,2-dibromoethane were added thereto to activate magnesium. Then, 100 ml of an ethyl ether solution of 19.2 g of 3,4-dichlorobenzyl chloride was dropwise added thereto over a period of 3 hours with stirring under cooling with ice. Then, 50 ml of an ethyl ether solution of 6.11 g of 2-(tert-butyldimethylsilyloxy)propionaldehyde (which was produced by silylating ethyl 2-hydroxypropionate with tert-butyldimethylchlorosilane, followed by reducing with diisobutylaluminum hydride) was dropwise added to this solution over a period of 30 minutes with stirring under cooling with ice, and the mixture was stirred at the same temperature for 1 hour. Then, a saturated ammonium chloride aqueous solution was added thereto, and the mixture was further stirred at room temperature for 10 minutes. The organic layer was collected by separation, washed with a saturated sodium chloride aqueous solution and then dried over anhydrous magnesium sulfate. The drying agent was separated by filtration, and then the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 3.82 g (yield: 33%) of 3-(tert-butyldimethylsilyloxy)-1-(3,4-dichlorophenyl)-2-butanol.
Reaction SMILES: O.[C:2]([NH:12][NH2:13])(=[O:11])[CH2:3][CH2:4][CH2:5][CH2:6][C:7]([NH:9][NH2:10])=[O:8]>CC(=O)C>[CH:2](=[N:10][NH:9][C:7](=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][C:2]([NH:12][N:13]=[CH:5][CH2:6][CH3:7])=[O:11])[CH2:3][CH3:4]
Reactant: NNC(=O)CCCCC(=O)NN
Solvent: CC(C)=O
Solvent: O
Product: CCC=NNC(=O)CCCCC(=O)NN=CCC

Procedure:
In a stainless steel flask equipped with an agitator, 58.6 grams of water were added, the agitator was turned on, then 25 grams of adipic acid dihydrazide were added. The mixture was agitated for at least 10 minutes until a stable dispersion was formed. 16.4 grams of 2-propanone were then added under mixing. A clear solution formed after a few minutes. Mixing was continued for at least another hour until reaction product precipitated and formed a stable dispersion.
Reaction SMILES: [SH:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6]([OH:8])=[O:7].C1CCN2C(=NCCC2)CC1.[C:23]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])(=[O:26])[CH:24]=[CH2:25]>C(#N)C>[C:28]([O:27][C:23](=[O:26])[CH2:24][CH2:25][S:1][CH2:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6]([OH:8])=[O:7])([CH3:31])([CH3:30])[CH3:29]
Reactant: C=CC(=O)OC(C)(C)C
Reactant: O=C(O)c1cccc(CS)c1
Solvent: CC#N
Solvent: C1CCC2=NCCCN2CC1
Product: CC(C)(C)OC(=O)CCSCc1cccc(C(=O)O)c1
Temperature: 80 °C
Reaction time: 8 h
Yield: 47 %

Procedure:
Into a 500-mL round bottom flask, was placed a solution of 3-(mercaptomethyl)benzoic acid (12 g, 71.43 mmol, 1.00 equiv) in acetonitrile (200 mL), tert-butyl acrylate (60 mL), and DBU (21.7 g, 142.76 mmol, 2.00 equiv). The resulting solution was stirred overnight at 80° C. in an oil bath. The resulting mixture was concentrated under vacuum. The resulting solution was diluted with 200 mL of water and adjusted to pH 2-3 with 10% hydrochloric acid. The resulting solution was extracted with 3×200 mL of ethyl acetate and the organic layers combined. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with petroleum ether/ethyl acetate (50:1) to give 10.5 g (47%) of 3-((3-tert-butoxy-3-oxopropylthio)methyl)benzoic acid as red oil. 1H-NMR (300 MHz, CDCl3, ppm): δ 8.08 (s, 1H), 8.04 (d, J=7.8 Hz, 1H), 7.62 (d, J=7.8 Hz, 1H), 7.46 (t, 1H), 3.81 (s, 2H), 2.68 (t, 2H), 2.50 (t, 2H), 1.48 (s, 9H). MS (ES, m/z): 295 [M−H]−.
Reaction SMILES: [CH:1]1[C:18]2=[C:19]3[C:8]([C:9]4[C:20]5[C:13](=[CH:14][CH:15]=[CH:16][C:17]2=5)[CH:12]=[CH:11][CH:10]=4)=[CH:7][CH:6]=[C:5]2[C:21](=[O:25])[NH:22][C:23](=[O:24])[C:3](=[C:4]23)[CH:2]=1.[OH-].[K+].Br[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42]>CS(C)=O>[CH2:42]([N:22]1[C:21](=[O:25])[C:5]2[C:4]3[C:19]4[C:8](=[CH:7][CH:6]=2)[C:9]2[C:20]5[C:13]([CH:12]=[CH:11][CH:10]=2)=[CH:14][CH:15]=[CH:16][C:17]=5[C:18]=4[CH:1]=[CH:2][C:3]=3[C:23]1=[O:24])[CH2:41][CH2:40][CH2:39][CH2:38][CH2:37][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH3:29]
Reactant: CCCCCCCCCCCCCCBr
Reactant: O=C1NC(=O)c2ccc3c4cccc5cccc(c6ccc1c2c63)c54
Agent: [K+]
Agent: [OH-]
Solvent: CS(C)=O
Product: CCCCCCCCCCCCCCN1C(=O)c2ccc3c4cccc5cccc(c6ccc(c2c36)C1=O)c54
Temperature: 25 °C
Reaction time: 90 h

Procedure:
0.40 g (1.25 mmol) of perylene-3,4-dicarboximide and 0.45 g (8 mmol) of KOH powder are suspended in 30 ml of DMSO, 1.38 g of 1-bromotetradecane are added, and the mixture is stirred at room temperature for 90 h. For precipitation, 300 ml of dist. water are added, the precipitated product is filtered off with suction and washed with dist. water and dilute sodium chloride solution. Chromatographic filtration, followed by column chromatography, in each case on silica gel using chloroform, gives a yellow and a red fraction. According to thin-layer chromatography on silica gel using 3:2 xylene/petroleum ether, the yellow fraction contains 3 products having such similar Rf values that no further purification is undertaken. Yield 30 mg. A colour comparison shows that the red fraction is N-(1-tetradecyl)perylene-3,4-dicarboximide. Yield 30 mg (5%) of a red powder showing a strong solid fluorescence. Rf (CHCl3 /silica gel)=0.81.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]([N:13]3[CH2:17][CH2:16][CH2:15][C@H:14]3[CH2:18][O:19][CH3:20])=[O:12])[S:10][C:3]=12.[CH2:21]([NH:25][C:26]([C:28]1[C:32]2[CH:33]=[CH:34][C:35]([OH:37])=[CH:36][C:31]=2[O:30][C:29]=1[CH3:38])=[O:27])[CH:22]([CH3:24])[CH3:23].C([O-])([O-])=O.[Cs+].[Cs+]>>[CH2:21]([NH:25][C:26]([C:28]1[C:32]2[CH:33]=[CH:34][C:35]([O:37][C:2]3[CH:7]=[CH:6][N:5]=[C:4]4[CH:8]=[C:9]([C:11]([N:13]5[CH2:17][CH2:16][CH2:15][CH:14]5[CH2:18][O:19][CH3:20])=[O:12])[S:10][C:3]=34)=[CH:36][C:31]=2[O:30][C:29]=1[CH3:38])=[O:27])[CH:22]([CH3:24])[CH3:23]
Reactant: COC[C@@H]1CCCN1C(=O)c1cc2nccc(Cl)c2s1
Reactant: Cc1oc2cc(O)ccc2c1C(=O)NCC(C)C
Agent: O=C([O-])[O-]
Agent: [Cs+]
Product: COCC1CCCN1C(=O)c1cc2nccc(Oc3ccc4c(C(=O)NCC(C)C)c(C)oc4c3)c2s1

Procedure:
This material was prepared by the reaction of 7-chloro-2-[(R)-2-methoxymethylpyrrolidine-1-carbonyl]thieno[3,2-b]pyridine 2a with 6-hydroxy-2-methyl-benzofuran-3-carboxylic acid isobutyl amide 84b and Cs2CO3 in a manner as previously described for example 1. 1H NMR (CD3CN) δ 8.53 (1H,d, J=5.3 Hz), 7.87 (1H, s), 7.82 (1H, d, J=8.5 Hz), 7.41 (1H, d, J=1.9 Hz), 7.20 (1H, dd, J=8.5, 1.9 Hz), 6.70 (1H, d, J=5.5 Hz), 4.38 (1H, m), 3.85 (2H, m), 3.65–3.41 (2H, m), 3.32 (3H, s), 3.23 (2H, t, J=6.4 Hz), 2.65 (3H, s), 2.15–1.94 (4H,m, partially obscured by CD3CN), 1.73 (1H, m),
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[CH:5]=[C:4]([Br:12])[CH:3]=1.[CH2:13]=[C:14](B(O)O)[CH3:15].C([O-])([O-])=O.[K+].[K+].O>O1CCOCC1.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>[Br:12][C:4]1[CH:3]=[C:2]([C:14]([CH3:15])=[CH2:13])[CH:7]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[CH:5]=1
Reactant: CC(C)(C)c1cc(Br)cc(Br)c1
Reactant: C=C(C)B(O)O
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: O
Solvent: C1COCCO1
Product: C=C(C)c1cc(Br)cc(C(C)(C)C)c1
Temperature: 90 °C
Reaction time: 8 h

Procedure:
To a solution of 1,3-dibromo-5-(tert-butyl)benzene (2.92 g, 10 mmol) in dioxane (20 mL) was added Pd(PPh3)4 (3.0 g, 2.6 mmol), prop-1-en-2-ylboronic acid (1.0 g, 12 mmol), K2CO3 (2.8 g, 20 mmol) and H2O (1 mL) under N2. The resulting mixture was stirred at 90° C. overnight, concentrated and purified by CC (hexane) to give compound P24a (2.5 g, 100%; 80% by GC/MS) as a liquid.