Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13]O)[CH2:11][O:10][C:9]1([CH3:16])[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2].[SH:17][C:18]1[S:19][C:20]2[CH:26]=[CH:25][CH:24]=[CH:23][C:21]=2[N:22]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][S:17][C:18]2[S:19][C:20]3[CH:26]=[CH:25][CH:24]=[CH:23][C:21]=3[N:22]=2)[CH2:11][O:10][C:9]1([CH3:16])[CH3:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: Sc1nc2ccccc2s1
Reactant: CC(C)(C)OC(=O)N1[C@H](CO)COC1(C)C
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N1[C@H](CSc2nc3ccccc3s2)COC1(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 89.4 %

Procedure:
To a stirred, cooled (0° C.) solution of (R)-4-hydroxymethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (1.36 g; CAS 108149-65-1), 2-mercaptobenzothiazole (1.48 g) and triphenylphosphine (2.32 g) in THF (80 ml) under an argon atmosphere was added diethyl azodicarboxylate (4.1 ml; 40% solution in toluene). The mixture (soon turning to a yellow suspension, slowly warming up to r.t.) was stirred for 18 h overnight, then diluted with EtOAc and washed with sat. aq. Na2CO3. The aqueous phase was back extracted with EtOAc. The combined organics were washed with brine, dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography (SiO2; gradient: cyclohexane ->cyclohexane/EtOAc 85:15) to give (S)-4-(benzothiazol-2-ylsulfanyl-methyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (2.0 g) as light yellow viscous oil.
Reaction SMILES: I[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]3[N:15]=[C:14]([NH:16][CH:17]([CH3:19])[CH3:18])[O:13][N:12]=3)[CH:9]=2)[N:4]([S:20]([C:23]2[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=2)(=[O:22])=[O:21])[CH:3]=1.[CH:30]([O:33][C:34]1[CH:39]=[N:38][CH:37]=[C:36]([Sn](C)(C)C)[N:35]=1)([CH3:32])[CH3:31]>CN(C=O)C.[Cu]I.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:30]([O:33][C:34]1[N:35]=[C:36]([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:11]4[N:15]=[C:14]([NH:16][CH:17]([CH3:18])[CH3:19])[O:13][N:12]=4)[CH:9]=3)[N:4]([S:20]([C:23]3[CH:29]=[CH:28][C:26]([CH3:27])=[CH:25][CH:24]=3)(=[O:21])=[O:22])[CH:3]=2)[CH:37]=[N:38][CH:39]=1)([CH3:32])[CH3:31]
Reactant: Cc1ccc(S(=O)(=O)n2cc(I)c3cc(-c4noc(NC(C)C)n4)ccc32)cc1
Reactant: CC(C)Oc1cncc([Sn](C)(C)C)n1
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Product: Cc1ccc(S(=O)(=O)n2cc(-c3cncc(OC(C)C)n3)c3cc(-c4noc(NC(C)C)n4)ccc32)cc1
Temperature: 90 °C
Yield: 43.7 %

Procedure:
Argon gas was bubbled through a solution of 3-(3-iodo-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,2,4-oxadiazol-5-amine (450 mg, 0.86 mmol) and 2-isopropoxy-6-(trimethylstannyl)pyrazine (311 mg, 1.03 mmol) in dry DMF (4.5 ml) for 15 min. To the mixture was added CuI (163 mg, 0.86 mmol) and Pd(PPh3)4 (99 mg, 0.086 mmol) and argon gas was further bubbled for additional 15 min. The reaction was heated at 90° C. for 1 h then cooled to RT. The reaction was quenched with ice cold water. The resulting suspension was filtered and washed with water. The solid was purified with basic alumina column chromatography (eluent: 20% EtOAc in petroleum ether) to give 3-(3-(6-isopropoxypyrazin-2-yl)-1-tosyl-1H-indol-5-yl)-N-isopropyl-1,2,4-oxadiazol-5-amine (200 mg, 43.5%). MS (ESI, pos. ion) m/z: 533.3 (M+1).
Reaction SMILES: B(Br)(Br)Br.C[O:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]#[C:14][C:15]2[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=2)=[CH:9][CH:8]=1.[OH-].[Na+].Cl>ClCCl>[N:18]1[CH:19]=[CH:20][C:15]([C:14]#[C:13][C:10]2[CH:9]=[CH:8][C:7]([OH:6])=[CH:12][CH:11]=2)=[CH:16][CH:17]=1
Reactant: COc1ccc(C#Cc2ccncc2)cc1
Agent: BrB(Br)Br
Agent: Cl
Agent: [Na+]
Solvent: ClCCl
Product: Oc1ccc(C#Cc2ccncc2)cc1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
Boron tribromide (1M in dichloromethane, 9.7 mL, 9.7 mmol) was added at 0° C. to a solution of 4-(2-(4-methoxyphenyl)ethynyl)pyridine (810 mg, 3.88 mmol) in dichloromethane (10 mL) and the mixture was stirred at RT for 5 h. Aqueous 1N sodium hydroxide (20 mL) was added and after 40 min the pH was brought between 7 and 8 by addition of 1N HCl. The resulting mixture was extracted with 4:1 dichloromethane:2-propanol (3×30 mL). The organic layers were dried, concentrated and evaporated and the residue chromatographed on silica in a gradient from 25% to 80% ethyl acetate-hexanes giving a brown solid. Yield 450 mg, 60%. 1H NMR (CDCl3 containing CD3OD, 400 mHz) δ 8.50 (br, 2H), 7.38 (br, 2H), 7.37 (d, 2H, J=8.7 Hz), 6.77 (d, 2H, J=8.7 Hz), 3.11 (br, 2H, OH+H2O). MS (AP+) m/e 196 (MH+).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[CH2:8]([N:12]1[N:16]=[C:15]2[CH:17]=[CH:18][C:19]([CH3:21])=[CH:20][C:14]2=[N:13]1)[CH2:9][C:10]#[CH:11]>>[CH3:21][C:19]1[CH:18]=[CH:17][C:15]2=[N:16][N:12]([CH2:8][CH2:9][C:10]#[C:11][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=3)[N:13]=[C:14]2[CH:20]=1
Reactant: C#CCCn1nc2ccc(C)cc2n1
Reactant: Brc1ccccn1
Product: Cc1ccc2nn(CCC#Cc3ccccn3)nc2c1
Yield: 36.8 %

Procedure:
The title compound was prepared in accordance with the general method of Example 1, from 2-bromo-pyridine (66 mg, 0.42 mmol) and 2-but-3-ynyl-5-methyl-2H-benzo[d][1,2,3]triazole (70 mg, 0.38 mmol, Example 165(B)). Reaction time: 3 hours. The crude residue was purified by flash chromatography (DCM/MeOH 99:1) to yield 36 mg (0.14 mmol, 37%) of 5-methyl-2-(4-(pyridin-2-yl)but-3-ynyl)-2H-benzo[d][1,2,3]triazole as an orange solid.
Reaction SMILES: [CH:1]1([NH:4][C:5]([C:7]2[NH:11][N:10]=[C:9]([N+:12]([O-])=O)[CH:8]=2)=[O:6])[CH2:3][CH2:2]1>C(O)C.[Pt](=O)=O>[NH2:12][C:9]1[CH:8]=[C:7]([C:5]([NH:4][CH:1]2[CH2:2][CH2:3]2)=[O:6])[NH:11][N:10]=1
Reactant: O=C(NC1CC1)c1cc([N+](=O)[O-])n[nH]1
Agent: O=[Pt]=O
Solvent: CCO
Product: Nc1cc(C(=O)NC2CC2)[nH]n1
Yield: 108.1 %

Procedure:
N-cyclopropyl-3-nitro-1H-pyrazole-5-carboxamide (1.0 g, 5.10 mmol) and platinum (iv) oxide (0.116 g, 0.510 mmol) in ethanol were hydrogenated at 50 psi for 2 hours. The reaction mixture was filtrated through Celite and the filtrate was concentrated to give 0.916 g of 3-amino-N-cyclopropyl-1H-pyrazole-5-carboxamide as a solid. The crude was used without purification. MS (ESI) m/z 167.1 (M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])/[C:12](=[CH:15]\[C:16]3[CH:23]=[CH:22][C:19]([C:20]#[N:21])=[CH:18][CH:17]=3)/[N:11]([CH3:24])[C:10]2=[O:25])[CH:5]=[C:6]([Cl:8])[CH:7]=1.NCC(O)=O.[CH2:31]1N2CN3CN(C2)[CH2:33][N:32]1C3.C(N)CN.C1(C)C=CC(C([C@](C(O)=O)(O)[C@](C(C2C=CC(C)=CC=2)=O)(O)C(O)=O)=O)=CC=1>CN1CCCC1=O.C1(C)C=CC=CC=1.[Cl-].[Na+].O.C(Cl)Cl.CC(OC)(C)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]2[C:13](=[O:14])[C@@:12]3([C@H:15]([C:16]4[CH:17]=[CH:18][C:19]([C:20]#[N:21])=[CH:22][CH:23]=4)[CH2:33][NH:32][CH2:31]3)[N:11]([CH3:24])[C:10]2=[O:25])[CH:5]=[C:6]([Cl:8])[CH:7]=1
Reactant: CN1C(=O)N(c2cc(Cl)cc(Cl)c2)C(=O)/C1=C\c1ccc(C#N)cc1
Reactant: C1N2CN3CN1CN(C2)C3
Agent: Cc1ccc(C(=O)[C@@](O)(C(=O)O)[C@](O)(C(=O)O)C(=O)c2ccc(C)cc2)cc1
Agent: NCC(=O)O
Agent: [Cl-]
Solvent: CN1CCCC1=O
Solvent: NCCN
Solvent: O
Product: CN1C(=O)N(c2cc(Cl)cc(Cl)c2)C(=O)[C@]12CNC[C@H]2c1ccc(C#N)cc1
Temperature: 138 °C
Reaction time: 3 h
Yield: 47.9 %

Procedure:
A mixture of (E)-4-((1-(3,5-dichlorophenyl)-3-methyl-2,5-dioxoimidazolidin-4-ylidene)methyl)benzonitrile (10.0 g, 26.9 mmol), glycine (5.06 g, 67.4 mmol), hexamethylenetetramine (2.82 g, 20.1 mmol) in 50 mL N-methylpyrrolidinone and 25 mL of toluene under nitrogen was heated to 138° C. for approximately 12 h. Next, 25 mL toluene and 25 mL H2O were added. The aqueous and nonaqueous layers were split, and the aqueous layer was washed with 25 mL of toluene, and the nonaqueous layers were combined to form a nonaqueous mixture. The nonaqueous mixture was heated to 45-50° C. and ethylene diamine (7.0 mL) was added. The nonaqueous mixture was stirred for 3 hours and then cooled to room temperature. Next, 50 mL H2O was added, followed by the addition of 10 mL brine. The next addition was 25 mL toluene, which was followed by the addition of 125 mL CH2Cl2. The bottom layer of the mixture was removed through a filter. Next, (+)-Di-p-toluoyl-D-tartaric acid (2.59 g, 6.7 mmol) was added and the mixture was stirred for 18 h to form a slurry. Slowly 40 mL of MTBE was added to the slurry. A wash solution containing 7 mL of MTBE and 11 mL of CH2Cl2 was prepared. Filter paper was wetted with 1 mL of the wash solution. The slurry was filtered and then the filtered to form a cake. The filter, the wash reaction flask, and the cake were washed with the remaining 16 mL of the wash solution. Next, the cake was washed with 10 mL MTBE. 4-[(5S, 9R)-3-(3,5-Dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-9-yl]-benzonitrile semi (+)-DTTA salt (4.0 g, 20% yield) was obtained as a white solid (98.7% HPLC AP and 98.3% ee).
Reaction SMILES: F[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[C:4]([F:11])[C:3]=1[CH2:12][C:13]#[N:14].[NH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>CS(C)=O.O>[F:11][C:4]1[C:3]([CH2:12][C:13]#[N:14])=[C:2]([NH:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=1
Reactant: N#CCc1c(F)ccc([N+](=O)[O-])c1F
Reactant: Nc1ccccc1
Solvent: O
Solvent: CS(C)=O
Product: N#CCc1c(F)ccc([N+](=O)[O-])c1Nc1ccccc1
Yield: 17.6 %

Procedure:
A solution of (2,6-difluoro-3-nitrophenyl)acetonitrile (4 g, 20.1 mmol) and aniline (1.83 mL, 20.1 mmol) in DMSO (20 mL) was heated at 100° C. for 16 h. The reaction mixture was diluted with water (100 mL) and extracted with EtOAc (3×20 mL). The combined organic extracts were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, eluting with 0-100% EtOAc in cyclohexane) to yield the title compound as brown oil (959 mg, 18%). 1H NMR 400 MHz 6 (CDCl3): 8.27 (1H, dd, J=9.4, 5.9 Hz), 7.38-7.32 (2H, m), 7.17-7.12 (1H, m), 6.98-6.90 (3H, m), 3.44 (2H, d, J=1.7 Hz).
Reaction SMILES: C1CCCC([O:7][C:8]2[CH:17]=[C:16]([NH:18][C:19](=[O:21])[CH3:20])[C:15]([Cl:22])=[CH:14][C:9]=2[C:10]([O:12][CH3:13])=[O:11])C=1>C(OCC)(=O)C.CCCCCC>[CH:16]1([C:17]2[C:16]([NH:18][C:19](=[O:21])[CH3:20])=[C:15]([Cl:22])[CH:14]=[C:9]([C:10]([O:12][CH3:13])=[O:11])[C:8]=2[OH:7])[CH2:15][CH2:14][CH:9]=[CH:8][CH2:17]1
Reactant: COC(=O)c1cc(Cl)c(NC(C)=O)cc1OC1C=CCCC1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: COC(=O)c1cc(Cl)c(NC(C)=O)c(C2CC=CCC2)c1O
Temperature: 220 °C

Procedure:
A mixture of 0.6 g of methyl 2-(cyclohexen-3-yloxy)-4-acetylamino-5-chlorobenzoate and 0.5 ml diethylamiline is placed under house vacuum and heated to 220° C. for 2 hours. This reaction mixture is then diluted with 40% ethyl acetate/hexane and purified by dry column chromatography using the same solvent system as eluent. Three fractions are separated: 1. diethylaniline; 2. starting benzoate compound; and 3. methyl 3-(3-cyclohexenyl)-4-acetylamino-5-chlorosalicylate. The latter is used directly in the next step.
Reaction SMILES: [BH4-].[Na+].[C:3]([O:7][C@@H:8]([C@H:10]1[CH2:14][O:13][C:12](=[O:15])[N:11]1[C:16]1[N:21]=[C:20]([Cl:22])[N:19]=[C:18]([C:23](OC)=[O:24])[CH:17]=1)[CH3:9])([CH3:6])([CH3:5])[CH3:4]>CO>[C:3]([O:7][C@@H:8]([C@H:10]1[CH2:14][O:13][C:12](=[O:15])[N:11]1[C:16]1[CH:17]=[C:18]([CH2:23][OH:24])[N:19]=[C:20]([Cl:22])[N:21]=1)[CH3:9])([CH3:4])([CH3:5])[CH3:6]
Reactant: COC(=O)c1cc(N2C(=O)OC[C@@H]2[C@@H](C)OC(C)(C)C)nc(Cl)n1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: C[C@@H](OC(C)(C)C)[C@H]1COC(=O)N1c1cc(CO)nc(Cl)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 59.6 %

Procedure:
Sodium borohydride (60 mg, 1.59 mmol, 1.4 equiv) was added to a suspension of methyl 6-((R)-4-((R)-1-(tert-butoxy)ethyl)-2-oxooxazolidin-3-yl)-2-chloropyrimidine-4-carboxylate (400 mg, 1.12 mmol) in methanol (11.2 mL) at 0° C. The ice bath was removed and the reaction was stirred at room temperature for 1 hour. The reaction was quenched with saturated aqueous ammonium chloride (100 mL) and extracted with ethyl acetate (3×50 mL). The combined extracts were washed with saturated aqueous sodium chloride (30 mL), dried over Na2SO4, filtered and concentrated. Silica gel column chromatography (EtOAc/Heptane) provided (R)-4-((R)-1-(tert-butoxy)ethyl)-3-(2-chloro-6-(hydroxymethyl)pyrimidin-4-yl)oxazolidin-2-one (0.220 g, white solid) in 60% yield. 1H NMR (400 MHz, CDCl3) δ 8.18 (s, 1H), 4.77-4.72 (m, 3H), 4.66 (dd, J=9.4, 2.9 Hz, 1H), 4.48 (m, 1H), 4.41 (m, 1H), 2.83 (m, 1H), 1.26 (s, 9H), 1.03 (d, J=6.6 Hz, 3H). MS m/z 330.1 (M+H)+; Rt-0.86 min.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH:12]=[C:11]([C:13](OC)=[O:14])[C:10]([CH3:17])=[N:9]1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1.C1(C)C=CC=CC=1.[O-2].[O-2].[Mn+4]>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[CH:12]=[C:11]([CH:13]=[O:14])[C:10]([CH3:17])=[N:9]1
Reactant: COC(=O)c1cn(-c2ccccc2Cl)nc1C
Agent: [Mn+4]
Agent: [Al+3]
Agent: [H-]
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: Cc1nn(-c2ccccc2Cl)cc1C=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 15.3 %

Procedure:
A solution (20 mL) of methyl 1-(2-chlorophenyl)-3-methyl-1H-pyrazole-4-carboxylate (2.0 g) synthesized in the above-mentioned (1) in tetrahydrofuran was added to an ice-cooled solution (20 mL) of lithium aluminum hydride (0.30 g) in tetrahydrofuran. The ice bath was removed, and the reaction mixture was stirred at room temperature for 1 hr. The mixture was ice-cooled again, and water (0.80 mL), 1N aqueous sodium hydroxide solution (4.0 mL) and water (0.80 mL) were successively added dropwise to quench the reaction. The residue was filtered through celite, and the filtrate was concentrated under reduced pressure to give a crude product (0.36 g) of 1-(2-chlorophenyl)-3-methyl-1H-pyrazole-4-methanol as a pale-yellow oil. This was dissolved in toluene (10 mL), manganese dioxide (2.0 g) was added, and the mixture was heated under reflux with a Dean-Stark trap for 1 hr. The reaction mixture was allowed to cool to room temperature, and manganese dioxide was collected by filtration. The solvent was evaporated under reduced pressure to give the title object compound (0.27 g, 15%) as a colorless solid.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]([NH:14][C:15](=[O:28])[CH2:16][CH2:17][CH2:18][C:19]2[CH:24]=[CH:23][C:22]([B:25]([OH:27])[OH:26])=[CH:21][CH:20]=2)[CH:6]=[CH:7][C:8]=1S(CC)(=O)=O)#[N:2].Br[C:30]1C=CC(CCCC(NC2C=CC=C(C#N)C=2)=O)=C(C)C=1>>[C:1]([C:3]1[CH:4]=[C:5]([NH:14][C:15](=[O:28])[CH2:16][CH2:17][CH2:18][C:19]2[CH:20]=[CH:21][C:22]([B:25]([OH:26])[OH:27])=[CH:23][C:24]=2[CH3:30])[CH:6]=[CH:7][CH:8]=1)#[N:2]
Reactant: Cc1cc(Br)ccc1CCCC(=O)Nc1cccc(C#N)c1
Reactant: CCS(=O)(=O)c1ccc(NC(=O)CCCc2ccc(B(O)O)cc2)cc1C#N
Product: Cc1cc(B(O)O)ccc1CCCC(=O)Nc1cccc(C#N)c1
Yield: 56 %

Procedure:
Using a procedure analogous to that used to prepare 6D, 55C (200 mg, 0.56 mmol) was reacted with 5,5′,5′-tetramethyl-[2,2′]bi[[1,3,2]dioxaborinanyl] to give 55D (200 mg, 56%) as a solid. MS (ESI) m/z 323.2 (M+H)+.
Reaction SMILES: [C:1]([N:5]([CH3:15])[C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][CH:7]=1)(=[O:4])[CH:2]=[CH2:3].[CH2:16]([NH:23][CH3:24])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[CH2:16]([N:23]([CH2:3][CH2:2][C:1]([N:5]([CH3:15])[C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][CH:7]=1)=[O:4])[CH3:24])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: C=CC(=O)N(C)c1ccc([N+](=O)[O-])cc1
Reactant: CNCc1ccccc1
Product: CN(CCC(=O)N(C)c1ccc([N+](=O)[O-])cc1)Cc1ccccc1

Procedure:
Prepared from N-acryloyl-N-methyl-4-nitro-aniline and N-benzyl-N-methyl-amine
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:20])=[C:6]([CH2:8][C:9]2[N:14]=[C:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:12]=[CH:11][CH:10]=2)[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[Cl:27][C:28]1[CH:35]=[CH:34][CH:33]=[CH:32][C:29]=1[CH2:30]Br>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:20][CH2:30][C:29]2[CH:32]=[CH:33][CH:34]=[CH:35][C:28]=2[Cl:27])=[C:6]([CH2:8][C:9]2[N:14]=[C:13]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:12]=[CH:11][CH:10]=2)[CH:7]=1
Reactant: Clc1ccccc1CBr
Reactant: CCOC(=O)c1cccc(Cc2cc(Cl)ccc2O)n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1cccc(Cc2cc(Cl)ccc2OCc2ccccc2Cl)n1
Temperature: 80 °C

Procedure:
A solution of ethyl 6-[(5-chloro-2-hydroxyphenyl)methyl]-2-pyridinecarboxylate (60 mg, 0.21 mmol) in dry dimethylformamide (2.1 ml) was stirred at room temperature under an atmosphere of argon. Potassium carbonate (44 mg, 0.32 mmol) was added to the stirred solution. 2-Chlorobenzyl bromide (51 mg, 0.25 mmol) was added to the stirred solution. The solution was heated to 80° C. for ˜17 hours (overnight). The reaction was worked up to yield the title compound.
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[O:3][C:4]1[CH:9]=[CH:8][C:7](Br)=[CH:6][CH:5]=1.[CH2:13]1[O:15][CH2:14]1.Cl>CCOCC>[F:1][C:2]([F:12])([F:11])[O:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:13][CH2:14][OH:15])=[CH:6][CH:5]=1
Reactant: C1CO1
Reactant: FC(F)(F)Oc1ccc(Br)cc1
Agent: Cl
Solvent: CCOCC
Product: OCCc1ccc(OC(F)(F)F)cc1
Temperature: -50 °C
Reaction time: 1 h
Yield: 32 %

Procedure:
A Grignard reagent prepared from 4-trifluoromethoxybromobenzene (54 g, 220 mmol) and dried Mg (5.4 g, 220 mmol) in 250 ml ether solvent was cooled down to -50° C., followed by gradually dropwise adding thereto ethylene oxide (29.3 g, 670 mmol), gradually heating the resulting reaction mixture up to room temperature, further stirring it for one hour at room temperature, adding the reaction solution to 6N HCl (300 ml), extracting the resulting product with ethyl acetate, washing the extraction solution successively with a saturated aqueous solution of sodium bicarbonate and water, drying over magnesium sulfate, distilling off the solvent, distilling the residue under reduced pressure by means of a Vigoureaux tube, to isolate a colorless liquid, 2-(4-trifluoromethoxyphenyl)ethanol (14.5 g, 70.3 mmol) having a b.p. of 82° to 84° C. under 3.5 Torr, adding to this liquid, xylene (60 ml) and HBr aqueous solution (47%) (60 ml), refluxing the mixture for 9 hours, adding water to the reaction mixture, extracting the resulting product with toluene, washing the reaction solution successively with a saturated aqueous solution of sodium bicarbonate and water, drying the resulting organic layer over magnesium sulfate, distilling off the solvent, distilling the residue under reduced pressure using Vigoureux tube, to isolate a colorless liquid, 2-(4-trifluoromethoxyphenyl)bromoethane (12.0 g, 51.9 mmol) having a b.p. of 75° C. under 4 Torr. The yield of this product from 4-trifluoromethoxybromobenzene was 23.6%.
Reaction SMILES: [Mg].[C:2]1([CH2:8][CH2:9][CH2:10][CH2:11]Br)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:13]([N:20]1[C:24]([CH:25]=[O:26])=[CH:23][N:22]=[CH:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.O>O1CCCC1>[CH2:13]([N:20]1[C:24]([CH:25]([OH:26])[CH2:11][CH2:10][CH2:9][CH2:8][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:23][N:22]=[CH:21]1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: BrCCCCc1ccccc1
Reactant: O=Cc1cncn1Cc1ccccc1
Agent: [Mg]
Solvent: O
Solvent: C1CCOC1
Product: OC(CCCCc1ccccc1)c1cncn1Cc1ccccc1
Temperature: 25 °C

Procedure:
2,1 g of magnesium turnings are covered with 60 ml of dry tetrahydrofuran. A solution of 4-phenylbutylbromide (18,8 g) in 20 ml of dry tetrahydrofuran is then added dropwise to the mixture at such a rate that a smooth reaction is maintained. After the addition is complete, the reaction mixture is refluxed for one additional hour and cooled to room temperature. The reaction mixture is then added dropwise to a solution of 1-benzyl-5-imidazolecarbaldehyde (6,5 g) in 80 ml of tetrahydrofuran at 60° C. After the addition is complete, the reaction mixture is refluxed for 2 hours, cooled and poured into cold water. Tetrahydrofuran is evaporated and conc. hydrochloric acid is added to the solution. The product which is separated as an oil, is extracted with methylene chloride and evaporated to dryness.
Reaction SMILES: [C:1](Cl)(=[O:4])[CH2:2][CH3:3].[O:6]=[C:7]1[N:11]([CH:12]2[CH2:17][CH2:16][N:15]([C@H:18]3[CH2:23][CH2:22][N:21]([C:24](=[O:33])[C:25]4[CH:30]=[C:29]([CH3:31])[CH:28]=[C:27]([CH3:32])[CH:26]=4)[C@@H:20]([CH2:34][C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[CH2:19]3)[CH2:14][CH2:13]2)[C:10]2[CH:41]=[CH:42][CH:43]=[CH:44][C:9]=2[NH:8]1>>[CH3:31][C:29]1[CH:30]=[C:25]([CH:26]=[C:27]([CH3:32])[CH:28]=1)[C:24]([N:21]1[CH2:22][CH2:23][C@H:18]([N:15]2[CH2:14][CH2:13][CH:12]([N:11]3[C:10]4[CH:41]=[CH:42][CH:43]=[CH:44][C:9]=4[N:8]([C:1](=[O:4])[CH2:2][CH3:3])[C:7]3=[O:6])[CH2:17][CH2:16]2)[CH2:19][C@@H:20]1[CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:33]
Reactant: Cc1cc(C)cc(C(=O)N2CC[C@H](N3CCC(n4c(=O)[nH]c5ccccc54)CC3)C[C@@H]2Cc2ccccc2)c1
Reactant: CCC(=O)Cl
Product: CCC(=O)n1c(=O)n(C2CCN([C@H]3CCN(C(=O)c4cc(C)cc(C)c4)[C@@H](Cc4ccccc4)C3)CC2)c2ccccc21

Procedure:
Using the same reaction procedure as described in example B6, propionyl chloride was reacted with (±)-cis-4-[4-(2,3-dihydro-2-oxo-1H-benzimidazol-1-yl)-1-piperidinyl]-1-(3,5-dimethylbenzoyl)-2-(phenylmethyl)piperidine to form (±)-cis-1[1-[1-(3,5-dimethylbenzoyl)-2-(phenyl-methyl)-4-piperidinyl]-4-piperidinyl]-1,3-dihydro-3-(1-oxopropyl)-2H-benzimidazol-2-one (compound 34).
Reaction SMILES: Cl[O-:2].[Na+].[Cl+].Cl[O-].[O:7]=[CH:8][C@@H:9]([C@H:11]([C@@H:13]([C@@H:15]([CH2:17][OH:18])[OH:16])[OH:14])[OH:12])[OH:10]>>[O:7]=[CH:8][C@@H:9]([C@H:11]([C@@H:13]([C@@H:15]([CH2:17][OH:18])[OH:16])[OH:14])[OH:12])[OH:10].[O:7]=[C:8]([OH:2])[C@@H:9]([C@H:11]([C@@H:13]([C@@H:15]([CH2:17][OH:18])[OH:16])[OH:14])[OH:12])[OH:10]
Reactant: [O-]Cl
Agent: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: [Cl+]
Agent: [Na+]
Product: O=C(O)[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Reaction time: 2 h

Procedure:
Over two hours, 164 g. of 12% active chlorine sodium hypochlorite solution are added, a quantity corresponding with a molar weight 1:1 with respect to the glucose, by maintaining the pH value between 7.0 and 9.0 and, at the end of the addition, the stirring is continued for other 30 minutes. The control of the accomplished execution is carried out through HPLC or through polarimetric readings. The oxidation of glucose to gluconic acid is obtained, as it can be verified by the 13C NMR spectrum depicted in FIG. 1.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][S:9]([CH3:12])(=[O:11])=[O:10])[N:3]=1.Br[CH2:14][CH2:15]Br>>[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]2([S:9]([CH3:12])(=[O:11])=[O:10])[CH2:15][CH2:14]2)[N:3]=1
Reactant: CS(=O)(=O)Cc1cccc(Br)n1
Reactant: BrCCBr
Product: CS(=O)(=O)C1(c2cccc(Br)n2)CC1
Yield: 53 %

Procedure:
The title compound was prepared from 2-bromo-6-methanesulfonylmethyl-pyridine and 1,2-dibromoethane following a procedure analogous to that described in Step 3 for Intermediate 4. Yield: 53% of theory; LC (method 3): tR=2.56 min; Mass spectrum (ESI+): m/z=276/278 (Br) [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[C:9]2[N:13]([CH3:14])[CH:12]=[N:11][CH:10]=2)=[CH:4][C:3]=1[CH:22]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[CH:25]=1)O.[SH:31][CH2:32][C:33]([OH:35])=[O:34]>Cl>[ClH:21].[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[C:9]2[N:13]([CH3:14])[CH:12]=[N:11][CH:10]=2)=[CH:4][C:3]=1[CH:22]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[CH:25]=1)[S:31][CH2:32][C:33]([OH:35])=[O:34]
Reactant: Cn1cncc1C(c1ccc(Cl)cc1)c1ccc(N)c(C(O)c2cccc(Cl)c2)c1
Reactant: O=C(O)CS
Agent: Cl
Product: Cn1cncc1C(c1ccc(Cl)cc1)c1ccc(N)c(C(SCC(=O)O)c2cccc(Cl)c2)c1
Yield: 203.2 %

Procedure:
A mixture of intermediate (17) (0.0269 mol) and mercapto-acetic acid (0.0269 mol) in HCl 6N (150 ml) was stirred and refluxed for 2 hours and brought to room temperature. The solvent was evaporated till dryness, yielding 15 g (96%) of [[[2-amino-5-[(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]phenyl](3-chlorophenyl)methyl]thio]-acetic acid hydrochloride salt (intermediate 18).