Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[C:7]2[CH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.C(N(CC)CC)C.Br[CH2:25][CH2:26][C:27]([O:29]C(C)(C)C)=[O:28]>C(#N)C>[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[NH:9][CH:8]=[C:7]2[CH:11]1[CH2:16][CH2:15][N:14]([CH2:25][CH2:26][C:27]([OH:29])=[O:28])[CH2:13][CH2:12]1
Reactant: CC(C)(C)OC(=O)CCBr
Reactant: Clc1cccc2c(C3CCNCC3)c[nH]c12
Solvent: CC#N
Solvent: CCN(CC)CC
Product: O=C(O)CCN1CCC(c2c[nH]c3c(Cl)cccc23)CC1
Temperature: 80 °C
Reaction time: 3 h

Procedure:
A 25 mL round bottom flask was charged with polymer bound 7-chloro-3-(piperidin-4-yl)-1H-indole (1.0 g, 0.98 mmol), triethylamine (80.2 mL), tert-butyl 3-bromopropionate and dry acetonitrile (5 mL). The mixture was stirred at 80° C. for 3 h. After cooling to room temperature, the resin was filtered off and washed with dry acetonitrile (3×10 mL) and dry dichloromethane (3×10 mL). The resin was treated for 20 minutes with 8 mL of a 1:1 mixture of dichloromethane and trifluoroacetic acid containing anisole (2%, w/w) and methionine (0.2%, w/w) (Caution: Generation of carbon dioxide). The resin was filtered off and washed with dry dichloromethane (10 mL), a 1:1 mixture of dichloromethane:triethylamine (3×10 mL) and dry dichloromethane (3×10 mL). The resin was dried in vacuo (20° C., 20 h) to yield the title resin (1.0 g).
Reaction SMILES: [C:1]([OH:14])(=O)/[CH:2]=[CH:3]/[C:4]1[CH:12]=[CH:11][C:9]([OH:10])=[C:6]([O:7][CH3:8])[CH:5]=1.C(N(CC)CC)C.[OH:22][C:23]1[CH:24]=[C:25]([CH:29]=[CH:30][C:31]=1[OH:32])[CH2:26][CH2:27][NH2:28]>CN(C=O)C.ClCCl>[CH3:8][O:7][C:6]1[CH:5]=[C:4](/[CH:3]=[CH:2]/[C:1]([NH:28][CH2:27][CH2:26][C:25]2[CH:29]=[CH:30][C:31]([OH:32])=[C:23]([OH:22])[CH:24]=2)=[O:14])[CH:12]=[CH:11][C:9]=1[OH:10]
Reactant: NCCc1ccc(O)c(O)c1
Reactant: COc1cc(/C=C/C(=O)O)ccc1O
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: COc1cc(/C=C/C(=O)NCCc2ccc(O)c(O)c2)ccc1O
Temperature: 0 °C
Reaction time: 20 h

Procedure:
A solution of ferulic acid (300 mg; 1.54 mmol) and of triethylamine (1.5 eq; 2.31 mmol) in DMF (3.5 mL) is cooled to 3 or 4° C. using an ice bath. An amine, 3-hydroxytyramine (dopamine) (1 eq; 1.54 mmol) is added to the medium, followed by addition of a solution of BOP (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; (1 eq; 1.54 mmol) in dichloromethane (3.5 mL); the mixture is stirred for about thirty minutes in the ice bath and then for 20 hours at room temperature. Stirring is then stopped and the dichloromethane is evaporated off under vacuum. 30 mL of water are added to the remaining solution and the mixture obtained is extracted with ethyl acetate (3×75 mL). The organic phase is successively washed with 100 mL of 1N HCl solution, 100 mL of water and 100 mL of 1M sodium bicarbonate (NaHCO3) solution. It is then dried over sodium sulfate and evaporated to dryness. The product obtained is in the form of a white precipitate after chromatography on a column of silica gel.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([O:21][CH3:22])[CH:5]=[C:6]2[C:11]=1[O:10][CH:9]([C:12]([F:15])([F:14])[F:13])[C:8]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:7]2.[Cl:23]Cl>C(O)(=O)C>[Cl:23][C:5]1[C:4]([O:21][CH3:22])=[CH:3][C:2]([Cl:1])=[C:11]2[C:6]=1[CH:7]=[C:8]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:9]([C:12]([F:15])([F:14])[F:13])[O:10]2
Reactant: CCOC(=O)C1=Cc2cc(OC)cc(Cl)c2OC1C(F)(F)F
Reactant: ClCl
Solvent: CC(=O)O
Product: CCOC(=O)C1=Cc2c(Cl)c(OC)cc(Cl)c2OC1C(F)(F)F
Reaction time: 0.33 h
Yield: 7.4 %

Procedure:
To a solution of ethyl 8-chloro-6-methoxy-2-(trifluoromethyl)-2H-chromene-3-carboxylate prepared as in U.S. Pat. No. 6,271,253 B1 Example 40 (2.32 g, 6.89 mmole) in glacial acetic acid (100 mL) was added Cl2 gas for 0.5 minutes. After standing for 20 min, the solvent was removed in vacuo and the remaining acetic acid was azeotroped with hexanes to give a crystalline solid containing a mixture of regioisomers. The crude product was purified by recrystallization from ethyl acetate-hexanes to give 189 mg (7.4% yield) of the product as colorless needles: EIHRMS m/z 369.9986 (M+, C14H11C2lF3O4, Calc'd 369.9986).
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][C:6]([OH:12])=[CH:7][CH:8]=2)[N:3]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[CH3:32][O:33][C@@H:34]([CH3:37])[CH2:35]O.N(C(OC(C)C)=O)=NC(OC(C)C)=O.Cl>C1COCC1.CCOC(C)=O.O>[CH3:32][O:33][C@@H:34]([CH3:37])[CH2:35][O:12][C:6]1[CH:5]=[C:4]2[C:9]([CH:10]=[CH:11][C:2]([CH3:1])=[N:3]2)=[CH:8][CH:7]=1
Reactant: Cc1ccc2ccc(O)cc2n1
Reactant: CO[C@@H](C)CO
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CO[C@@H](C)COc1ccc2ccc(C)nc2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 50.8 %

Procedure:
To a stirred solution of 2-methylquinolin-7-ol (1.00 g, 6.28 mmol), PPh3 (4.12 g, 15.7 mmol) and (S)-2-methoxypropan-1-ol (0.679 g, 7.54 mmol) in THF (60 mL) was added dropwise diisopropyl azodicarboxylate (2.05 mL, 10.1 mmol) at 0° C. under nitrogen. The reaction mixture was stirred at ambient temperature overnight. The reaction was then heated at 50° C. for additional 2 hours. After cooling, to the reaction were added 4N HCl (3.1 mL), water (100 mL) and EtOAc (200 mL). The aqueous layer was separated and washed with EtOAc (100 mL). The aqueous was neutralized with ammonium hydroxide to about pH 9, extracted with EtOAc, washed with brine, dried and concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel (1:1 hexane/EtOAc) to give (S)-7-(2-methoxypropoxy)-2-methylquinoline (0.738 g, 51%).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:20])/[CH:5]=[C:6](/[C:13]1[CH:18]=[CH:17][C:16](Br)=[CH:15][CH:14]=1)\[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:2].[CH3:21][N:22]([CH3:26])[CH2:23][C:24]#[CH:25]>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I.ClCCl>[CH2:1]([O:3][C:4](=[O:20])/[CH:5]=[C:6](/[C:13]1[CH:18]=[CH:17][C:16]([C:25]#[C:24][CH2:23][N:22]([CH3:26])[CH3:21])=[CH:15][CH:14]=1)\[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH3:2]
Reactant: CCOC(=O)/C=C(\c1ccccc1)c1ccc(Br)cc1
Reactant: C#CCN(C)C
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: CCOC(=O)/C=C(\c1ccccc1)c1ccc(C#CCN(C)C)cc1

Procedure:
A solution of (E)-3-(4-bromo-phenyl)-3-phenyl-acrylic acid ethyl ester (0.728 g, 2.2 mmol), dimethyl-prop-2-ynyl-amine (0.56 ml, 6.58 mmol), bis(triphenylphosphine) palladium(II) chloride (0.061 g, 0.088 mmol), copper(I) iodide (1.25 mg, 0.0065 mmol) in dry triethyllamine (7 ml) were heated to 100° C. by microwave irradiation for 20 min. To the cooled reaction mixture was added dichloromethane (20 ml) and silica gel Fluka 60 (5 g) and the reaction mixture was evaporated in vacuo. The residue was purified by ISCO combiflash 16 (silica gel, hexane/ethyl acetate 85:15) giving (E)-3-[4-(3-dimethylamino-prop-1-ynyl)-phenyl]-3-phenyl-acrylic acid ethyl ester as an oil.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH3:12])[CH2:7]2.S(=O)(=O)(O)O.[N+:18]([O-])([OH:20])=[O:19].O.[Cl-].[Na+]>S(=O)(=O)(O)O>[OH:1][C:2]1[C:3]([N+:18]([O-:20])=[O:19])=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[N:8]([CH3:12])[CH2:7]2
Reactant: CN1Cc2cccc(O)c2C1=O
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Product: CN1Cc2ccc([N+](=O)[O-])c(O)c2C1=O
Temperature: -20 °C
Reaction time: 0.17 h
Yield: 11 %

Procedure:
2.49 g (91.5 mmol) of 7-hydroxy-2-methyl-2,3-dihydroisoindol-1-one were dissolved at 0° C. in 6 ml of concentrated sulfuric acid. The reaction medium was cooled to −20° C. and 1.8 ml of a 4/5 mixture of concentrated sulfuric acid/nitric acid at 70% were added. After 10 minutes, the reaction medium was hydrolyzed with water. Sodium chloride was added and the medium was extracted twice with ethyl acetate. The organic phases were combined, dried over anhydrous sodium sulfate and concentrated. The residue was chromatographed on a C18 column twice (40 g prepacked column, water/acetonitrile gradient). 350 mg of product were obtained in the form of a yellow solid. Yield=11%.
Reaction SMILES: [N:1]1([C:6]2[CH:7]=[CH:8][C:9]([CH3:41])=[C:10]([CH:40]=2)[C@@H:11]([C:28]2[C:37]([CH3:38])=[CH:36][C:31]([C:32]([O:34]C)=[O:33])=[CH:30][C:29]=2[CH3:39])[O:12]C(=O)[C@@H](NS(C2C=CC(C)=CC=2)(=O)=O)C)[CH:5]=[CH:4][N:3]=[CH:2]1>CN(C)C=O>[OH:12][C@H:11]([C:28]1[C:29]([CH3:39])=[CH:30][C:31]([C:32]([OH:34])=[O:33])=[CH:36][C:37]=1[CH3:38])[C:10]1[CH:40]=[C:6]([N:1]2[CH:5]=[CH:4][N:3]=[CH:2]2)[CH:7]=[CH:8][C:9]=1[CH3:41]
Reactant: COC(=O)c1cc(C)c([C@@H](OC(=O)[C@H](C)NS(=O)(=O)c2ccc(C)cc2)c2cc(-n3ccnc3)ccc2C)c(C)c1
Solvent: CN(C)C=O
Product: Cc1ccc(-n2ccnc2)cc1[C@H](O)c1c(C)cc(C(=O)O)cc1C

Procedure:
The compound obtained in Example 7 was treated in the same manner as in Example 2 to give 10.5 g of (S)-4-[α-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoic acid, melting point 286-288° C. (decomposition), optical rotation [α]D21 -261.50 (c=1.0, dimethylformamide).
Reaction SMILES: [CH2:1]([O:4][C:5]1([CH3:38])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[CH:17]=[C:18]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22](Br)[CH:21]=4)[N:19]=[C:15]3[CH:14]=[C:13]([CH3:27])[C:12]=2[C@H:28]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:29]([O:31][CH3:32])=[O:30])[CH2:7][CH2:6]1)[CH:2]=[CH2:3].[F:39][C:40]1[C:45]([F:46])=[CH:44][CH:43]=[C:42]([O:47][C@H:48]([CH2:50][CH:51]=[CH2:52])[CH3:49])[C:41]=1B1OC(=O)CN(C)CC(=O)O1.C(OC1(C)CCN(C2N3C=C(C4C=C(C5C=C(F)C(F)=CC=5O[C@H](CC=C)C)C=CC=4)N=C3C(C)=C(C)C=2[C@H](OC(C)(C)C)C(OC)=O)CC1)C=C>>[CH2:1]([O:4][C:5]1([CH3:38])[CH2:10][CH2:9][N:8]([C:11]2[N:16]3[CH:17]=[C:18]([C:20]4[CH:21]=[C:22]([C:41]5[C:42]([O:47][C@H:48]([CH2:50][CH:51]=[CH2:52])[CH3:49])=[CH:43][CH:44]=[C:45]([F:46])[C:40]=5[F:39])[CH:23]=[CH:24][CH:25]=4)[N:19]=[C:15]3[CH:14]=[C:13]([CH3:27])[C:12]=2[C@H:28]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:29]([O:31][CH3:32])=[O:30])[CH2:7][CH2:6]1)[CH:2]=[CH2:3]
Reactant: C=CCOC1(C)CCN(c2c([C@H](OC(C)(C)C)C(=O)OC)c(C)cc3nc(-c4cccc(Br)c4)cn23)CC1
Reactant: C=CC[C@H](C)Oc1ccc(F)c(F)c1B1OC(=O)CN(C)CC(=O)O1
Agent: C=CCOC1(C)CCN(c2c([C@H](OC(C)(C)C)C(=O)OC)c(C)c(C)c3nc(-c4cccc(-c5cc(F)c(F)cc5O[C@@H](C)CC=C)c4)cn23)CC1
Product: C=CCOC1(C)CCN(c2c([C@H](OC(C)(C)C)C(=O)OC)c(C)cc3nc(-c4cccc(-c5c(O[C@@H](C)CC=C)ccc(F)c5F)c4)cn23)CC1
Yield: 99 %

Procedure:
Prepared from (S)-methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(3-bromophenyl)-7-methylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate and (S)-2-(2,3-difluoro-6-(pent-4-en-2-yloxy)phenyl)-6-methyl-1,3,6,2-dioxazaborocane-4,8-dione in 99% yield following the same procedure as (S)-methyl 2-(5-(4-(allyloxy)-4-methylpiperidin-1-yl)-2-(4′,5′-difluoro-2′-((S)-pent-4-en-2-yloxy)-[1,1′-biphenyl]-3-yl)-7,8-dimethylimidazo[1,2-a]pyridin-6-yl)-2-(tert-butoxy)acetate. LCMS (ESI, M+1): 702.20.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][N:3]=[C:2]1[NH2:6].N1C=CN=C1.[S:12](Cl)(Cl)(=[O:14])=[O:13].Cl.[CH3:18][O:19][C:20]1[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[CH:22][C:21]=1[C:30]1[C:31]2[CH2:39][CH2:38][NH:37][CH2:36][C:32]=2[N:33]=[CH:34][N:35]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[CH3:18][O:19][C:20]1[CH:25]=[C:24]([C:26]([F:29])([F:27])[F:28])[CH:23]=[CH:22][C:21]=1[C:30]1[C:31]2[CH2:39][CH2:38][N:37]([S:12]([NH:6][C:2]3[S:1][CH:5]=[CH:4][N:3]=3)(=[O:14])=[O:13])[CH2:36][C:32]=2[N:33]=[CH:34][N:35]=1
Reactant: COc1cc(C(F)(F)F)ccc1-c1ncnc2c1CCNC2
Reactant: Nc1nccs1
Reactant: O=S(=O)(Cl)Cl
Agent: Cl
Agent: c1c[nH]cn1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc(C(F)(F)F)ccc1-c1ncnc2c1CCN(S(=O)(=O)Nc1nccs1)C2
Reaction time: 0.5 h
Yield: 60.4 %

Procedure:
A solution of thiazol-2-amine (0.097 g, 0.970 mmol) and imidazole (0.198 g, 2.91 mmol) in 4 mL of DCM was cooled to −78° C. Sulfuryl chloride (0.079 ml, 0.970 mmol) was added, the cooling bath was removed, and the reaction mixture was allowed to stir for an additional 30 minutes. 4-(2-methoxy-4-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine hydrochloride (0.150 g, 0.485 mmol) was added, followed by n,n-diisopropylethylamine (0.847 ml, 4.85 mmol), and the reaction mixture was heated to reflux for one hour, after which time the reaction was concentrated. Purification of the crude residue by reverse phase column chromatography [Puriflash C18, 30μ 55 g, 10-100% (0.1% NH4OH in MeOH)/(0.1% NH4OH in water)] gave 4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-5,6-dihydropyrido[3,4-d]pyrimidine-7(8H)-sulfonamide (0.138 g, 0.293 mmol, 60.4% yield). 1H NMR (MeCN-d3) δ: 8.96 (s, 1H), 7.33-7.42 (m, 3H), 6.93 (d, J=4.8 Hz, 1H), 6.55 (d, J=4.8 Hz, 1H), 4.35 (br. s., 2H), 3.79-3.87 (m, 3H), 3.08-3.53 (m, 2H), 2.39-2.89 (m, 1H); (M+H)+=472.0.
Reaction SMILES: [O:1]=[O+][O-].[CH:4]([C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:20])[C:8]=1[OH:21])=CC>C(OCC)(=O)C.C(O)(=O)C>[OH:21][C:8]1[C:9]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[CH3:20])=[CH:10][CH:11]=[CH:12][C:7]=1[CH:4]=[O:1]
Reactant: CC=Cc1cccc(Oc2ccccc2C)c1O
Reactant: O=[O+][O-]
Solvent: CC(=O)O
Solvent: CCOC(C)=O
Product: Cc1ccccc1Oc1cccc(C=O)c1O

Procedure:
Ozone gas was introduced into a solution of 2-(1-propenyl)-6-(o-tolyloxy)phenol (13.7 g) in a mixture of ethyl acetate (300 ml) and acetic acid (50 ml) at 0°-3° C. with stirring for an hour. The reaction mixture was washed with water, aqueous sodium bicarbonate and saline successively, dried over magnesium sulfate and when evaporated. The oily residue (12.9 g) was dissolved in diethyl ether, and the solution was washed with water, dried over magnesium sulfate and evaporated. The oily residue (11.7 g) was pulverized and recrystallized from methanol to give 2-hydroxy-3-(o-tolyloxy)benzaldehyde (4.8 g). mp 56°-58° C.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]2[S:21][CH:20]=[CH:19][N:5]2[C:6](=[O:18])[C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:16])[F:15])=[CH:10][CH:9]=1.[CH2:22]([O:27][C:28]1[C:35]([O:36][CH3:37])=[CH:34][CH:33]=[CH:32][C:29]=1[CH:30]=O)[CH2:23][CH:24]([CH3:26])[CH3:25].[O-]CC.[Na+]>C(O)C>[CH2:22]([O:27][C:28]1[C:35]([O:36][CH3:37])=[CH:34][CH:33]=[CH:32][C:29]=1/[CH:30]=[CH:1]/[C:2]1[N:3]=[C:4]2[S:21][CH:20]=[CH:19][N:5]2[C:6](=[O:18])[C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]([F:17])([F:15])[F:16])=[CH:10][CH:9]=1)[CH2:23][CH:24]([CH3:26])[CH3:25]
Reactant: COc1cccc(C=O)c1OCCC(C)C
Reactant: Cc1nc2sccn2c(=O)c1-c1ccc(C(F)(F)F)cc1
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: COc1cccc(/C=C/c2nc3sccn3c(=O)c2-c2ccc(C(F)(F)F)cc2)c1OCCC(C)C
Yield: 46.4 %

Procedure:
The title compound was synthesized by condensation of Intermediate 5 (400 mg, 1.289 mmol) with 2-isopentyloxy-3-methoxybenzaldehyde (400 mg, 1.812 mmol) in presence of sodium ethoxide (163 mg, 2.418 mmol) in ethanol (15 ml) according to the procedure described in Example 24 to give 308 mg of the desired product as an off-white solid; 1H NMR (300 MHz, DMSO-d6) δ 0.92 (d, J=6.3 Hz, 6H), 1.42 (q, J=6.3 Hz, 2H), 1.80-1.90 (m, 1H), 3.77 (s, 3H), 3.84 (t, J=6.3 Hz, 2H), 6.90-7.00 (m, 4H), 7.51 (d, J=4.8 Hz, 1H), 7.58 (d, J=7.8 Hz, 2H), 7.83 (d, J=7.8 Hz, 2H), 8.01 (d, J=4.8 Hz, 1H), 8.09 (d, J=15.6 Hz, 1H); ESI-MS (m/z) 515.52 (M+H)+.
Reaction SMILES: CC(C)=O.[Cl:5][C:6]1[CH:7]=[CH:8][C:9]2[S:13][C:12]([SH:14])=[N:11][C:10]=2[CH:15]=1.[Br:16][CH:17]([C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=1)[C:18](O)=O.C(OC(=O)C)(=O)C>C(O)(=O)C>[Br-:16].[Cl:5][C:6]1[CH:7]=[CH:8][C:9]2[S:13][C:12]3[S:14][C:17]([C:21]4[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=4)=[CH:18][N+:11]=3[C:10]=2[CH:15]=1
Reactant: O=C(O)C(Br)c1ccc(Cl)cc1
Reactant: Sc1nc2cc(Cl)ccc2s1
Solvent: CC(=O)OC(C)=O
Solvent: CC(C)=O
Solvent: CC(=O)O
Product: Clc1ccc(-c2c[n+]3c(s2)sc2ccc(Cl)cc23)cc1
Product: [Br-]
Yield: 70 %

Procedure:
An acetone solution of 10.0 g (0.05 moles) 5-chloro-2-mercaptobenzothiazole and 12.5 g. (0.01 moles) α-bromo-(p-chloro)phenylacetic acid containing 50 ml. glacial acetic acid and 20 ml. acetic anhydride is heated in an open flask. When the solution is concentrated to a small volume, the precipitated solid, weighing 15.1 g. (70% yield) is collected.
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1B(O)O.[Cl:14][C:15]1[C:20]([N+:21]([O-:23])=[O:22])=[C:19](Cl)[N:18]=[C:17]([CH3:25])[N:16]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC=CC=1>[Cl:14][C:15]1[C:20]([N+:21]([O-:23])=[O:22])=[C:19]([C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[C:2]([F:13])([F:12])[F:1])[N:18]=[C:17]([CH3:25])[N:16]=1
Reactant: OB(O)c1ccccc1C(F)(F)F
Reactant: Cc1nc(Cl)c([N+](=O)[O-])c(Cl)n1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: c1ccccc1
Product: Cc1nc(Cl)c([N+](=O)[O-])c(-c2ccccc2C(F)(F)F)n1
Yield: 38 %

Procedure:
Part A. A solution of 2-trifluoromethylphenylboronic acid (prepared according to the methods described in the review by N. Miyaura and A. Suzuki, Chem. Rev. 1995, 95, p. 2457) (1.00 g, 5.27 mmol), 4,6-dichloro-2-methyl-5-nitropyrimidine (0.91 g, 4.39 mmol) and tetrakis(triphenyl-phosphine)palladium (147 mg) in benzene (15 mL) was treated with aq. sodium carbonate solution (6 mL, 1 M). This mixture was heated to reflux for 6 h, then cooled and partitioned between water and ethyl acetate (60 mL each). The organic layer was washed with brine, and the aqueous layers were back-extracted in sequence with more ethyl acetate. The organic extracts were combined, dried over sodium sulfate, filtered and evaporated. The residue was separated by column chromatography (silica gel, 15:85 ethyl acetate-hexane) to afford 4-chloro-2-methyl-5-nitro-6-(2-trifluoromethylphenyl)pyrimidine (0.64 g, 2.01 mmol, 38%) as a waxy solid. Spectral data: RF 0.40 (20:80 ethyl acetate-hexane). 1H NMR (300 MHz, CDCl3) δ7.84-7.81 (1H, m), 7.69-7.63 (2H, m), 7.38-7.35 (1H, m), 2.84 (3H, s). MS (NH3-CI) m/e 320 (24), 319 (26), 318 (100).
Reaction SMILES: Br[C:2]1[C:15]2[C:16]3=[C:17]4[C:12](=[CH:13][CH:14]=2)[CH:11]=[C:10]([C:18]([CH3:21])([CH3:20])[CH3:19])[CH:9]=[C:8]4[CH:7]=[CH:6][C:5]3=[C:4](Br)[CH:3]=1.[Cl:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.C(=O)([O-])[O-].[Na+].[Na+].CO[CH2:41][CH2:42]OC>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[C:18]([C:10]1[CH:11]=[C:12]2[C:17]3=[C:16]4[C:15](=[C:2]([C:42]5[CH:41]=[CH:29][C:24]([Cl:23])=[CH:25][CH:26]=5)[CH:3]=[C:4]([C:27]5[CH:28]=[CH:29][C:24]([Cl:23])=[CH:25][CH:26]=5)[C:5]4=[CH:6][CH:7]=[C:8]3[CH:9]=1)[CH:14]=[CH:13]2)([CH3:19])([CH3:21])[CH3:20]
Reactant: OB(O)c1ccc(Cl)cc1
Reactant: COCCOC
Reactant: CC(C)(C)c1cc2ccc3c(Br)cc(Br)c4ccc(c1)c2c34
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Product: CC(C)(C)c1cc2ccc3c(-c4ccc(Cl)cc4)cc(-c4ccc(Cl)cc4)c4ccc(c1)c2c34
Temperature: 5 °C
Reaction time: 5 h

Procedure:
Then, a mixed solution of 20.0 g of 1,3-dibromo-7-t-butylpyrene, 16.52 g of 4-chlorophenylboronic acid, 0.034 g of bis(triphenylphosphine)dichloropalladium, 106 ml of an aqueous 2M sodium carbonate solution and 240 ml of 1,2-dimethoxyethane was heated and stirred for about 5 hours under a nitrogen stream and under refluxing, and this was cooled to 5° C. After 240 ml of water was added, and the precipitated solid was filtered, the solid was washed with 125 ml of water two times and 125 ml of methanol once. After the solid was vacuum dried, the gray solid was dissolved in 48 ml of toluene, 2 g of active carbon was added, this was stirred for about 15 minutes, and the active carbon was filtered. After the resulting filtrate was evaporated, 100 ml of hexane was added, and the mixture was stirred for about 1 hour, and filtered. After the resultant was vacuum dried, 7.7 g of 7-t-butyl-1,3-bis(4-chlorophenyl)pyrene was obtained.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[C:8]([Cl:10])[C:7](Cl)=[CH:6][C:5]=1C)(=[O:3])[CH3:2].[SH:13][CH2:14][C:15]([CH3:20])([CH3:19])[C:16]([OH:18])=[O:17].[CH3:21]N(C)C=O.C(=O)([O-])[O-].[K+].[K+]>O>[C:1]([C:4]1[CH:5]=[CH:6][C:7]([S:13][CH2:14][C:15]([CH3:20])([CH3:19])[C:16]([OH:18])=[O:17])=[C:8]([Cl:10])[C:9]=1[CH3:21])(=[O:3])[CH3:2]
Reactant: CC(C)(CS)C(=O)O
Reactant: CC(=O)c1cc(Cl)c(Cl)cc1C
Reactant: CN(C)C=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: CC(=O)c1ccc(SCC(C)(C)C(=O)O)c(Cl)c1C
Temperature: 25 °C
Yield: 78 %

Procedure:
A 100-ml three-necked round-bottomed flask was charged with 2.98 g (14.65 mmol) of 2-acetyl-4,5-dichlorotoluene, 1.72 g (12.84 mmol) of 3-mercaptopivalic acid and 15 ml of N,N-dimethylformamide under nitrogen atmosphere. Then, 3.04 g (22.00 mmol) of potassium carbonate was added. The reaction mixture was heated at 100~110° C. for 6 hours under nitrogen atmosphere. The reaction mixture was allowed to cool to room temperature, and about 150 ml of water was added. The mixture was washed with chloroform twice, and an aqueous layer was neutralized and acidified with a 5 wt % hydrochloric acid aqueous solution. A precipitated gummy substance was extracted with ethyl acetate, and an organic layer was washed with a 1 wt % hydrochloric acid aqueous solution, with water and with a saturated sodium chloride aqueous solution and dried over anhydrous sodium sulfate. Then, the solvent was distilled off under reduced pressure to give 3.02 g (yield 78%) of 3-(4-acetyl-2-chloro-methylphenylthio)pivalic acid.
Reaction SMILES: [N:1]12[CH2:7][C:4]([C:8]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=3)[OH:9])([CH2:5][CH2:6]1)[CH2:3][CH2:2]2.[C:22]1([O:28][CH2:29][CH2:30][CH2:31][CH2:32][Br:33])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>CC#N>[Br-:33].[OH:9][C:8]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:4]12[CH2:7][N+:1]([CH2:32][CH2:31][CH2:30][CH2:29][O:28][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)([CH2:6][CH2:5]1)[CH2:2][CH2:3]2
Reactant: BrCCCCOc1ccccc1
Reactant: OC(c1ccccc1)(c1ccccc1)C12CCN(CC1)C2
Solvent: CC#N
Product: OC(c1ccccc1)(c1ccccc1)C12CC[N+](CCCCOc3ccccc3)(CC1)C2
Product: [Br-]
Yield: 66.8 %

Procedure:
Following the general procedure outlined in Example 2, 1-azabicyclo[2.2.1]hept-4-yl(diphenyl)methanol (31.8 mg, 0.114 mmol) and 4-bromobutyl phenyl ether (44.3 mg, 0.193 mmol) in 2 CH3CN/3 CHCl3 (2.5 mL) were reacted to give the desired product (38.7 mg, 67%). EI-MS m/z 428 (M+) Rt (1.98 min).
Reaction SMILES: [CH:1]1([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:6]2[NH:7][C:8]3[C:13]([C:5]=2[CH2:4][CH2:3][NH:2]1)=[CH:12][CH:11]=[CH:10][CH:9]=3.[O-:19][C:20]#[N:21].[Na+]>O>[NH2:21][C:20]([N:2]1[CH2:3][CH2:4][C:5]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[NH:7][C:6]=2[CH:1]1[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[O:19]
Reactant: N#C[O-]
Reactant: CCOC(=O)C1NCCc2c1[nH]c1ccccc21
Agent: [Na+]
Solvent: O
Product: CCOC(=O)C1c2[nH]c3ccccc3c2CCN1C(N)=O
Temperature: 10 °C
Reaction time: 0.25 h

Procedure:
56.2 g (0.2 mol) of ethyl 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-1-carboxylate are heated to about 60° C. in 1,000 ml of water. A solution of 15.2 g (0.234 mol) of pulverulent sodium cyanate in 200 ml of water is added all at once. The mixture is stirred for 15 minutes and then cooled to about 10° C. The aqueous reaction phase is decanted and the compound is washed with water and recrystallised from ethanol.