Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3](=[O:24])[CH2:4][C:5]1[CH:14]=[C:13]([O:15]CC2C=CC=CC=2)[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:23])[CH:11]=2)[CH:6]=1.[H][H].C(OCC)(=O)C.CCCCCC>CO.[Pd]>[CH3:1][O:2][C:3](=[O:24])[CH2:4][C:5]1[CH:14]=[C:13]([OH:15])[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([F:23])[CH:11]=2)[CH:6]=1
Reactant: [H][H]
Reactant: COC(=O)Cc1cc(OCc2ccccc2)c2cc(F)ccc2c1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: CO
Product: COC(=O)Cc1cc(O)c2cc(F)ccc2c1
Yield: 76.7 %

Procedure:
To a stirred solution of (4-benzyloxy-6-fluoro-naphthalen-2-yl)-acetic acid methyl ester (18.5 g, 57.0 mmol) in methanol (200 mL) was added 10% palladium on carbon (2.78 g). The resulting mixture was vigorously stirred under a balloon of hydrogen overnight. The reaction mixture was filtered through celite. The filtrate was concentrated in vacuo to obtain a crude product. Silica gel chromatography (10% ethyl acetate-hexane) afforded (6-fluoro-4-hydroxy-naphthalen-2-yl)-acetic acid methyl ester (10.24 g, 76%) as a white solid. MS cald. for C13H12FO3 [(M+H)+]: 235, obsd. 235.2.
Reaction SMILES: CO[C:3](=[O:28])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[C:13]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)=[N:14][O:15][C:16]=2[C:17]([F:20])([F:19])[F:18])=[N:6][CH:5]=1.COC(=O)C1C=CC(OCC2C(C3C=CC=C(F)C=3)=NOC=2C)=NC=1.[CH:54]1([NH2:57])[CH2:56][CH2:55]1>>[CH:54]1([NH:57][C:3](=[O:28])[C:4]2[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]3[C:13]([C:21]4[CH:22]=[CH:23][C:24]([F:27])=[CH:25][CH:26]=4)=[N:14][O:15][C:16]=3[C:17]([F:20])([F:18])[F:19])=[N:6][CH:5]=2)[CH2:56][CH2:55]1
Reactant: NC1CC1
Reactant: COC(=O)c1ccc(OCc2c(-c3ccc(F)cc3)noc2C(F)(F)F)nc1
Agent: COC(=O)c1ccc(OCc2c(-c3cccc(F)c3)noc2C)nc1
Product: O=C(NC1CC1)c1ccc(OCc2c(-c3ccc(F)cc3)noc2C(F)(F)F)nc1
Yield: 54 %

Procedure:
As described for example 89, 6-[3-(4-fluoro-phenyl)-5-trifluoromethyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester (100 mg, 0.25 mmol), instead of 6-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-ylmethoxy]-nicotinic acid methyl ester, was converted, using cylopropylamine instead of 2,2,2-trifluoroethylamine, to the title compound (90 mg, 54%) which was obtained as a white solid. MS: m/e=422.1 [M+H]+.
Reaction SMILES: [C:1]([C:5]1[NH:9][C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[C:7]([C:16]2[CH:21]=[CH:20][NH:19][C:18](=[O:22])[CH:17]=2)[CH:6]=1)([CH3:4])([CH3:3])[CH3:2]>C1COCC1>[C:1]([C:5]1[NH:9][C:8]2[C:7](=[C:16]3[C:17](=[C:11]4[CH:12]=[CH:13][CH:14]=[CH:15][C:10]4=2)[C:18](=[O:22])[NH:19][CH:20]=[CH:21]3)[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)c1cc(-c2cc[nH]c(=O)c2)c(-c2ccccc2)[nH]1
Solvent: C1CCOC1
Product: CC(C)(C)c1cc2c3cc[nH]c(=O)c3c3ccccc3c2[nH]1

Procedure:
A solution of 4-(5-tert-Butyl-2-phenyl-1H-pyrrol-3-yl)pyridin-2(1H)-one (144 mg, 0.5 mmol) in THF (145 mL) was irradiated with a sun lamp for 5 h. The solution was then concentrated in vacuo and the product purified by flash chromatography using EtOAc-Pet. spirit (80:20) as eluant, to separate the pure product as a cream solid (113 mg, 80%).
Reaction SMILES: [C:1]([OH:6])(=[O:5])[CH2:2][CH2:3][CH3:4].[CH3:7][S:8][CH2:9]Cl.C(N(CC)CC)C>>[C:1]([O:6][CH2:7][S:8][CH3:9])(=[O:5])[CH2:2][CH2:3][CH3:4]
Reactant: CSCCl
Reactant: CCCC(=O)O
Solvent: CCN(CC)CC
Product: CCCC(=O)OCSC

Procedure:
This product was prepared according to the procedure described in Example 1, by reacting butyric acid with chloromethyl methyl sulfide in the presence of one equivalent of triethylamine; b.p. 71°-73° C./12 mm Hg, nD20 1.4521.
Reaction SMILES: [CH3:1][C:2](=[CH2:4])[CH3:3].[CH3:5][C:6]1[CH:19]=[CH:18][C:9]([CH2:10][S:11][CH2:12][C@@H:13]([C:15]([OH:17])=[O:16])[NH2:14])=[CH:8][CH:7]=1.OS(O)(=O)=O.[OH-].[Na+].Cl>O1CCOCC1.CCOCC>[C:2]([O:17][C:15](=[O:16])[C@H:13]([CH2:12][S:11][CH2:10][C:9]1[CH:8]=[CH:7][C:6]([CH3:5])=[CH:19][CH:18]=1)[NH2:14])([CH3:3])([CH3:1])[CH3:4]
Reactant: C=C(C)C
Reactant: Cc1ccc(CSC[C@H](N)C(=O)O)cc1
Agent: Cl
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CCOCC
Solvent: C1COCCO1
Product: Cc1ccc(CSC[C@H](N)C(=O)OC(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a cold solution of isobutylene (50 ml) in dioxane (80 ml), add S-(4-methylbenzyl)-L-cysteine (5.0 g) and concentrated H2SO4 (10 ml). Seal the vessel, allow to warm to room temperature, and stir for 18 hr. Pour into 5% NaOH (500 ml), extract with Et2O (3×400 ml), dry (MgSO4) and concentrate the Et2O in vacuo to give an oil. Treat the oil with HCl in Et2O to give the title compound, white needles (2.76 g) m.p. 218° (dec).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[CH:9][C:4]=1[CH2:5][N:6]=[C:7]=[O:8].[N+:13](=[C:15]1[N:19]=[CH:18][N:17]=[C:16]1[C:20]([NH2:22])=[O:21])=[N-:14]>CS(C)=O>[CH3:1][O:2][C:3]1[CH:12]=[CH:11][CH:10]=[CH:9][C:4]=1[CH2:5][N:6]1[C:7](=[O:8])[N:19]2[CH:18]=[N:17][C:16]([C:20]([NH2:22])=[O:21])=[C:15]2[N:13]=[N:14]1
Reactant: COc1ccccc1CN=C=O
Reactant: [N-]=[N+]=C1N=CN=C1C(N)=O
Solvent: CS(C)=O
Product: COc1ccccc1Cn1nnc2c(C(N)=O)ncn2c1=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Ortho-methoxybenzyl isocyanate (Sigma Aldrich) (0.390 g, 2.4 mmol) was added drop wise to a suspension of 5-diazoimidazole-4-carboxamide (0.274 g, 2 mmol) in dry DMSO (2.5 mL) at room temperature under nitrogen. The resulting mixture was stirred at room temperature overnight. The reaction was quenched by the addition of ice and the solid product (off-white) removed by filtration, washed with water and ethyl acetate then recrystallised from chloroform/hexane. Yield: 0.343 g, 57%. IR vmax/cm−1 3460, 3094, 1728, 1683, 1589, 1454. 1H NMR δH (DMSO-d6) 5.45 (2H, s, CH2Ar), 6.91 (1H, td, J 7.5, 0.8, ArH), 7.06 (1H, d, J 7.8, ArH), 7.27 (1H, d, J 7.5, 1.4, ArH), 7.30-7.33 (1H, m, ArH), 7.69 (1H, br s, NH), 7.81 (1H, br s, NH), 8.84 (1H, s, 6-H). δC 47.9, 56.0, 111.3, 120.7, 123.7, 129.1, 129.4, 129.7, 131.4, 134.9, 139.6, 157.1, 162.0. MS Found 301.1100. Calc for (M+H): 301.1049. Found C, 51.6; H, 3.9; N, 28.0. Calc. for C13H12N6O3C, 52.0; H, 4.0; N, 28.0%.
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1)=[CH2:2]>C1(C)C=CC(S(O)(=O)=O)=CC=1.C(#N)C>[CH:2]#[C:1][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][CH:4]=1
Reactant: C=Cc1ccc(O)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CC#N
Product: C#Cc1ccc(O)cc1
Reaction time: 1 h
Yield: 17.1 %

Procedure:
50.5 g of the same p-vinylphenol fraction as used in Example 1, obtained by vacuum flash distillation was placed in a 300-ml flask together with 50.5 g of acetonitrile. To the resulting mixture being stirred was dropwise added 0.3 ml of an acetonitrile solution containing 0.03 g of p-toluenesulfonic acid. A polymerization reaction was conducted for 1 hour in the same manner as in Example 1 to obtain 8.5 g of a poly(p-vinylphenol). The polymer had a Mw of 15,000, a Mn of 11,500, a light transmittance at 248 nm, of 75.5% and a light transmittance at 450 nm, of 95.4%.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:28])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([NH:10][C:11](=[O:27])[CH2:12][C:13](=[O:26])[CH2:14][O:15][C:16]23[CH2:25][CH:20]4[CH2:21][CH:22]([CH2:24][CH:18]([CH2:19]4)[CH2:17]2)[CH2:23]3)[CH:5]=1.O.[N:30]([O-])=[O:31].[Na+]>C(O)(=O)C.C1COCC1>[CH3:1][O:2][C:3](=[O:28])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([NH:10][C:11](=[O:27])[C:12](=[N:30][OH:31])[C:13](=[O:26])[CH2:14][O:15][C:16]23[CH2:25][CH:20]4[CH2:21][CH:22]([CH2:24][CH:18]([CH2:19]4)[CH2:17]2)[CH2:23]3)[CH:5]=1
Reactant: O=N[O-]
Reactant: COC(=O)c1cccc(NC(=O)CC(=O)COC23CC4CC(CC(C4)C2)C3)c1
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: O
Product: COC(=O)c1cccc(NC(=O)C(=NO)C(=O)COC23CC4CC(CC(C4)C2)C3)c1
Temperature: 5 °C
Reaction time: 1 h
Yield: 94.9 %

Procedure:
To a solution of 3-[4-(adamantan-1-yloxy)-3-oxo-butyrylamino]-benzoic acid methyl ester (9.95 g, 25.8 mmol) in acetic acid (100 mL) and THF (90 mL) was added water (12 mL). The mixture was cooled to 5° C. and an aqueous solution (16 mL) of sodium nitrite (2.31 g, 35.0 mmol) was added dropwise while maintaining the temperature below 10° C. Upon completion of the addition, the reaction mixture was allowed to warm to room temperature and stirred for 1 h. The solvent was removed under reduced pressure and the residue was partitioned between saturated aqueous NaHCO3 and ethyl acetate. The aqueous phase was discarded and the organic phase was washed with further saturated aqueous NaHCO3 and brine. The organic phase was dried (MgSO4) and the solvent was evaporated at reduced pressure to afford the title product as a yellow foam (10.15 g, 95%). 1H NMR (CDCl3) 11.06 (1H, br s), 8.25 (1H, s), 7.93-7.90 (1H, m), 7.84-7.81 (1H, m), 7.51-7.41 (1H, m), 4.83 (2H, s), 3.95 (3H, s), 2.20 (3H, s), 1.82-1.57 (12H, m).
Reaction SMILES: [NH2:1][C:2]1[CH:34]=[CH:33][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[N:13](CC4C=CC(OC)=CC=4)[N:14]=[C:15]([NH:16][CH:17]4[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]4)[C:8]=23)=[C:4]([F:35])[CH:3]=1.[F:36][C:37]1[CH:42]=[CH:41][C:40]([N:43]2[C:48](=[O:49])[C:47]([C:50](O)=[O:51])=[CH:46][CH:45]=[N:44]2)=[CH:39][CH:38]=1.C([O-])(O)=O.[Na+]>>[F:35][C:4]1[CH:3]=[C:2]([NH:1][C:50]([C:47]2[C:48](=[O:49])[N:43]([C:40]3[CH:41]=[CH:42][C:37]([F:36])=[CH:38][CH:39]=3)[N:44]=[CH:45][CH:46]=2)=[O:51])[CH:34]=[CH:33][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[NH:13][N:14]=[C:15]([NH:16][CH:17]3[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]3)[C:8]=12
Reactant: O=C(O)c1ccnn(-c2ccc(F)cc2)c1=O
Reactant: COc1ccc(Cn2nc(NC3CCN(C)CC3)c3c(Oc4ccc(N)cc4F)ccnc32)cc1
Agent: O=C([O-])O
Agent: [Na+]
Product: CN1CCC(Nc2n[nH]c3nccc(Oc4ccc(NC(=O)c5ccnn(-c6ccc(F)cc6)c5=O)cc4F)c23)CC1
Yield: 96 %

Procedure:
Prepared by a 2-step process from 4-(4-amino-2-fluorophenoxy)-1-(4-methoxybenzyl)-N-(1-methylpiperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine and 2-(4-fluorophenyl)-3-oxo-2,3-dihydropyridazine-4-carboxylic acid (prepared as in Example 19, Step C) according to the procedure described for Example 21, Steps A and B, except that the crude was treated with aqueous NaHCO3). The crude was rinsed with Et2O to afford 34 mg (96%) of the desired product. LRMS (ESI pos) m/e 573.0 (M+1). 1H-NMR (400 MHz, CDCl3/CD3OD) δ 8.39 (d, 1H), 8.32 (d, 1H), 8.14 (d, 1H), 8.03 (dd, 1H), 7.66 (m, 2H), 7.48 (m, 1H), 7.39 (t, 1H), 7.28 (t, 2H), 6.12 (d, 1H), 3.76 (m, 1H), 3.25 (m, 2H), 2.51 (m, 2H), 2.46 (s, 3H), 2.25 (m, 2H), 1.73 (m, 2H); 19F-NMR (376 MHz, CDCl3/CD3OD) δ −113.8, −128.4.
Reaction SMILES: [N:1]1([CH2:6][C:7]2[CH:15]=[C:14]3[C:10]([CH:11]=[C:12]([C:16]([OH:18])=O)[NH:13]3)=[CH:9][CH:8]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.N[CH2:20][C:21]([NH2:23])=[O:22]>>[C:5]([CH2:4][NH:23][C:21]([C@@H:20]1[CH2:8][CH2:9][CH2:10][CH2:11][C@@H:12]1[NH:13][C:16]([C:12]1[NH:13][C:14]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[C:7]([CH2:6][N:1]1[CH:5]=[CH:4][N:3]=[CH:2]1)[CH:15]=2)=[O:18])=[O:22])#[N:1]
Reactant: O=C(O)c1cc2ccc(Cn3ccnc3)cc2[nH]1
Reactant: NCC(N)=O
Product: N#CCNC(=O)[C@@H]1CCCC[C@@H]1NC(=O)c1cc2ccc(Cn3ccnc3)cc2[nH]1

Procedure:
6-Imidazol-1-ylmethyl-1H-indole-2-carboxylic acid [(1S,2R)-2-(cyanomethyl-carbamoyl)-cyclohexyl]-amide was prepared from 6-imidazol-1-ylmethyl-1H-indole-2-carboxylic acid using the coupling procedure of Example 10 and replacing leucinamide with 2-aminoacetamide.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[CH:4][C:5]2[NH:11][C:10](=[O:12])[CH2:9][CH2:8][N:7]([CH:13]3[CH2:17][CH2:16][CH2:15][C:14]3([CH3:19])[CH3:18])[C:6]=2[N:20]=1.IC.[CH3:23]N(C)C(=O)C.[H-].[Na+]>O>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[N:11]([CH3:23])[C:10](=[O:12])[CH2:9][CH2:8][N:7]([CH:13]3[CH2:17][CH2:16][CH2:15][C:14]3([CH3:18])[CH3:19])[C:6]=2[N:20]=1
Reactant: CC(=O)N(C)C
Reactant: CC1(C)CCCC1N1CCC(=O)Nc2cnc(Cl)nc21
Agent: [H-]
Agent: [Na+]
Solvent: CI
Solvent: O
Product: CN1C(=O)CCN(C2CCCC2(C)C)c2nc(Cl)ncc21
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a mixture of 0.14 g (0.0005 mole) of (rac)-2-chloro-9-(2,2-dimethyl-cyclopentyl)-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VI-59), 0.047 mL (0.00075 mole) of iodomethane and 1 mL of N,N-dimethylacetamide at 0 degrees, was added 0.03 g (0.00075 mole) of 60% sodium hydride in oil. The mixture was stirred at ambient temperature for 1 hour, then 20 mL of water was added. The precipitate was collected by filtration to give 0.130 g of (rac)-2-chloro-5-methyl-9-(2,2-dimethyl-cyclopentyl)-5,7,8,9-tetrahydro-pyrimido[4,5-b][1,4]diazepin-6-one (VII-59) as a yellow solid.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[O:12][C:11]([C:13]2[CH:23]=[CH:22][C:16]([C:17]([O:19]CC)=[O:18])=[CH:15][CH:14]=2)=[N:10][N:9]=1.[OH-].[Na+].Cl>O1CCCC1>[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[O:12][C:11]([C:13]2[CH:23]=[CH:22][C:16]([C:17]([OH:19])=[O:18])=[CH:15][CH:14]=2)=[N:10][N:9]=1
Reactant: CCOC(=O)c1ccc(-c2nnc(-c3ccccc3N)o2)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: Nc1ccccc1-c1nnc(-c2ccc(C(=O)O)cc2)o1
Yield: 84.1 %

Procedure:
A mixture of ethyl 4-[5-(2-aminophenyl)-1,3,4-oxadiazol-2-yl]benzoate (0.17 g),. 1 M aqueous sodium hydroxide solution (1.1 ml) and tetrahydrofuran (2 ml) was heated under reflux for 30 min. After cooling, 1 M hydrochloric acid was added to acidify the mixture. The crystals were collected by filtration to give 4-[5-(2-aminophenyl)-1,3,4-oxadiazol-2-yl]benzoic acid (0.13 g, yield 87%). Recrystallization from hexane-tetrahydrofuran gave colorless prism crystals. melting point: >300° C.
Reaction SMILES: [CH:1]([C:4]1[CH:5]=[CH:6][C:7]([N:10]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][C:29]([F:32])([F:31])[F:30])=[CH:24][CH:23]=2)[CH2:11][CH2:12][CH2:13][C:14]2[CH:15]=[C:16]([OH:20])[CH:17]=[CH:18][CH:19]=2)=[N:8][CH:9]=1)([CH3:3])[CH3:2].C([O:35][C:36](=[O:41])[C:37](Br)([CH3:39])[CH3:38])C>>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([N:10]([CH2:21][C:22]2[CH:23]=[CH:24][C:25]([O:28][C:29]([F:32])([F:30])[F:31])=[CH:26][CH:27]=2)[CH2:11][CH2:12][CH2:13][C:14]2[CH:15]=[C:16]([CH:17]=[CH:18][CH:19]=2)[O:20][C:37]([CH3:39])([CH3:38])[C:36]([OH:41])=[O:35])=[N:8][CH:9]=1)([CH3:3])[CH3:2]
Reactant: CCOC(=O)C(C)(C)Br
Reactant: CC(C)c1ccc(N(CCCc2cccc(O)c2)Cc2ccc(OC(F)(F)F)cc2)nc1
Product: CC(C)c1ccc(N(CCCc2cccc(OC(C)(C)C(=O)O)c2)Cc2ccc(OC(F)(F)F)cc2)nc1

Procedure:
Similarly prepared by alkylation of 3-(3-{(5-isopropylpyridin-2-yl)[4-(trifluoromethoxy)benzyl]amino}propyl)phenol with ethyl-2-bromo-isobutyrate followed by standard base-mediated hydrolysis.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[CH3:10]O>>[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH3:10])([CH3:3])[CH3:2]
Reactant: CO
Reactant: CC(C)c1ccccc1
Product: Cc1ccccc1C(C)C

Procedure:
Isopropylbenzene could not be selectively alkylated with methanol to form isopropyltoluene. At 200° C. disproportionation of the isopropylbenzene was the predominate reaction. The product was 41% diisopropylbenzene, 24% benzene and 20% isopropyltoluene. Part of the benzene was alkylated as shown by the presence of 6% toluene.
Reaction SMILES: [N+:1]([C:4]1[C:17]2[C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:19])[C:8]=2[CH:7]=[CH:6][CH:5]=1)([O-])=O.[CH:20](N)([CH3:22])[CH3:21]>>[CH:20]([NH:1][C:4]1[C:17]2[C:16](=[O:18])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9](=[O:19])[C:8]=2[CH:7]=[CH:6][CH:5]=1)([CH3:22])[CH3:21]
Reactant: O=C1c2ccccc2C(=O)c2c1cccc2[N+](=O)[O-]
Reactant: CC(C)N
Product: CC(C)Nc1cccc2c1C(=O)c1ccccc1C2=O
Yield: 70 %

Procedure:
The use of polar solvents as reaction media results in only very poor yields and lengthy reaction times are required. For example, the reaction of 1-nitroanthraquinone with a 300% excess of isopropylamine at 75° C after 100 hours gives a yield of only 70% of 1-isopropylaminoanthraquinone.
Reaction SMILES: O.[CH3:2][C:3]1[CH:4]=[CH:5][C:6]([CH3:9])=[CH:7][CH:8]=1.[C:10]1(C)C=CC=CC=1>>[CH2:2]([C:3]1[CH:8]=[CH:7][C:6]([CH3:9])=[CH:5][CH:4]=1)[CH3:10]
Reactant: Cc1ccccc1
Reactant: Cc1ccc(C)cc1
Solvent: O
Product: CCc1ccc(C)cc1
Temperature: 90 °C
Reaction time: 14 h
Yield: 88.7 %

Procedure:
The same Ca-P-ZSM-5 catalyst is then treated with a stream of air which is first moistened with water at ambient temperature and is then passed for 14 hours at the rate of 300 cc/minute into the catalyst bed maintained at 90° C. After calcination at 500° C. for 1 hour, disproportionation and ethylation of toluene are again carried out under the same conditions used with the untreated catalyst. Toluene disproportionation gives 12.6% toluene conversion with a para-selectivity of 66.3% p-xylene in xylenes. Toluene ethylation gives 19.1% conversion of toluene with a para-selectivity of 88.7% p-ethyltoluene in ethyltoluenes.
Reaction SMILES: Br[C:2]1[C:3]([O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]([C:17]3[NH:18][C:19]4[C:20]([N:25]=3)=[N:21][CH:22]=[CH:23][CH:24]=4)=[O:16])=[CH:11][CH:10]=2)=[N:4][CH:5]=[CH:6][CH:7]=1.[O:26]1[CH2:31][CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH2:28][CH2:27]1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.O>[O:26]1[CH2:27][CH:28]=[C:29]([C:2]2[C:3]([O:8][C:9]3[CH:14]=[CH:13][C:12]([C:15]([C:17]4[NH:18][C:19]5[C:20]([N:25]=4)=[N:21][CH:22]=[CH:23][CH:24]=5)=[O:16])=[CH:11][CH:10]=3)=[N:4][CH:5]=[CH:6][CH:7]=2)[CH2:30][CH2:31]1
Reactant: O=C(c1ccc(Oc2ncccc2Br)cc1)c1nc2ncccc2[nH]1
Reactant: CC1(C)OB(C2=CCOCC2)OC1(C)C
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: O=C(c1ccc(Oc2ncccc2C2=CCOCC2)cc1)c1nc2ncccc2[nH]1
Temperature: 120 °C

Procedure:
To a glass microwave vial was added (4-(3-bromopyridin-2-yloxy)phenyl)(1H-imidazo[4,5-b]pyridin-2-yl)methanone (1.1099 g, 2.81 mmol), 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.180 g, 5.62 mmol), trans-dichlorobis(triphenylphosphine) palladium (II) (0.158 g, 0.225 mmol), and sodium carbonate (0.893 g, 8.43 mmol) in DMF (7.02 mL) and water (2.340 mL). The reaction mixture was stirred and heated in a Biotage Initiator microwave reactor at 120° C. for 20 min. The reaction mixture was diluted with water and extracted with DCM. The organic extract was washed with water, brine, dried with magnesium sulfate, filtered, and concentrated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage pre-packed silica gel column (40M), eluting with a gradient of 1% to 5% MeOH in DCM, to provide (4-(3-(3,6-dihydro-2H-pyran-4-yl)pyridin-2-yloxy)phenyl)(1H-imidazo[4,5-b]pyridin-2-yl)methanone. MS (ESI, pos. ion) m/z: 398.9 (M+1).
Reaction SMILES: C([NH:8][C:9]1[CH:10]=[C:11]([CH:16]([O:27][CH3:28])[C:17]2([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:19][CH2:18]2)[CH:12]=[CH:13][C:14]=1[Cl:15])C1C=CC=CC=1>C(OCC)(=O)C.[Pd]>[NH2:8][C:9]1[CH:10]=[C:11]([CH:16]([O:27][CH3:28])[C:17]2([C:20]([O:22][C:23]([CH3:24])([CH3:25])[CH3:26])=[O:21])[CH2:18][CH2:19]2)[CH:12]=[CH:13][C:14]=1[Cl:15]
Reactant: COC(c1ccc(Cl)c(NCc2ccccc2)c1)C1(C(=O)OC(C)(C)C)CC1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: COC(c1ccc(Cl)c(N)c1)C1(C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
6.20 g (15.4 mmol) of (+/−)-tert-butyl 1-{[3-(benzylamino)-4-chlorophenyl](methoxy)methyl}-cyclopropanecarboxylate were dissolved in 300 ml of ethyl acetate and inertized with argon, and 350 mg of palladium (10% on carbon) were added. At RT, the reaction mixture was stirred for a total of 24 h under an atmosphere of hydrogen at atmospheric pressure. The reaction mixture was then filtered through Celite, the residue was washed thoroughly with ethyl acetate and the combined filtrate was concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 30:1→10:1). This gave 3.36 g of the target compound (69.9% of theory).
Reaction SMILES: [F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:5]=[C:6]([C:10](=O)[CH3:11])[CH:7]=[CH:8][CH:9]=1.[CH3:15][C:16]([S@:19]([NH2:21])=[O:20])([CH3:18])[CH3:17]>>[CH3:15][C:16]([S@:19]([NH:21][CH:10]([C:6]1[CH:7]=[CH:8][CH:9]=[C:4]([O:3][C:2]([F:14])([F:13])[F:1])[CH:5]=1)[CH3:11])=[O:20])([CH3:18])[CH3:17]
Reactant: CC(=O)c1cccc(OC(F)(F)F)c1
Reactant: CC(C)(C)[S@](N)=O
Product: CC(N[S@](=O)C(C)(C)C)c1cccc(OC(F)(F)F)c1
Yield: 83 %

Procedure:
The title compound is prepared in 83% yield (0.38 g, a white solid) from 1-(3-(trifluoromethoxy)phenyl)ethanone (0.30 g, 1.47 mmol) and (R)-2-methylpropane-2-sulfinamide by the similar manner in Step-4 of Amine-1.
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].OS(O)(=O)=O.O=S(=O)=O.[N+]([O:17][C:18]1[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=1)([O-])=O>>[N+:1]([C:19]1[CH:20]=[N:21][CH:22]=[CH:23][C:18]=1[OH:17])([O-:4])=[O:2]
Reactant: O=[N+]([O-])O
Reactant: O=[N+]([O-])Oc1ccncc1
Agent: O=S(=O)(O)O
Agent: O=S(=O)=O
Product: O=[N+]([O-])c1cnccc1O
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
A nitric acid solution (HNO3>90%, 13.3 ml) is added slowly to a solution of oleum (H2SO4 containing 20% SO3, d=1.9, 10.5 ml) cooled to 0° C. 4-Pyridol nitrate (10 g, 63 mmol) is added, at 0° C., to the mixture, which is then heated at 90° C. for 1 h 30 min. The reaction mixture is poured over 50 g of ice. The suspension is stirred for 30 min at 0° C. and is then filtered. The solid is washed with a few ml of water and then air-dried. 6.59 g of product are obtained in the form of a white powder.
Reaction SMILES: FC(F)(F)C(O)=O.[N+:8]([C:11]1[CH:28]=[CH:27][C:14]([CH2:15][NH:16][C:17]([N:19]([CH:21]2[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]2)[CH3:20])=[O:18])=[CH:13][CH:12]=1)([O-:10])=[O:9].[CH:29]([C@@H:31]1[C@@H:35]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH2:34][N:33]([C@H:42]([CH:55]2[CH2:60][CH2:59][CH2:58][CH2:57][CH2:56]2)[C:43]([O:45]CC2C=CC(OC)=CC=2)=[O:44])[CH2:32]1)=O>>[N+:8]([C:11]1[CH:12]=[CH:13][C:14]([CH2:15][NH:16][C:17]([N:19]([CH:21]2[CH2:22][CH2:23][N:24]([CH2:29][C@@H:31]3[C@@H:35]([C:36]4[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=4)[CH2:34][N:33]([C@H:42]([CH:55]4[CH2:60][CH2:59][CH2:58][CH2:57][CH2:56]4)[C:43]([OH:45])=[O:44])[CH2:32]3)[CH2:25][CH2:26]2)[CH3:20])=[O:18])=[CH:27][CH:28]=1)([O-:10])=[O:9]
Reactant: COc1ccc(COC(=O)[C@@H](C2CCCCC2)N2C[C@H](c3ccccc3)[C@@H](C=O)C2)cc1
Reactant: CN(C(=O)NCc1ccc([N+](=O)[O-])cc1)C1CCNCC1
Solvent: O=C(O)C(F)(F)F
Product: CN(C(=O)NCc1ccc([N+](=O)[O-])cc1)C1CCN(C[C@H]2CN([C@@H](C(=O)O)C3CCCCC3)C[C@@H]2c2ccccc2)CC1
Yield: 60.8 %

Procedure:
The title compound was prepared from 4-(N-(N-(4-nitrobenzyl)carbamoyl)-N-methylamino)-piperidine trifluoroacetate (41 mg, 0.1 mmol, from Step A) and 2-(R)-(3-(R)-formyl-4-(S)-phenyl-pyrrolidin-1-yl)-2(cyclohexyl)acetic acid, 4-(methoxy)benzyl ester (26 mg, 0.05 mmol, Aldehyde 5) according to the method described in Example 1, Step C to give 18 mg (61%) of the title compound. ESI-MS: 592.4 (M+H); BPLC A: 2.12 min.
Reaction SMILES: [NH2:1][C:2]1[C:3]2[C:8]([N:9]=[C:10]3[C:15]=1[C:14](=[O:16])[CH:13]([CH2:17][CH2:18][CH:19]1[CH2:24][CH2:23][N:22]([CH2:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)[CH2:21][CH2:20]1)[CH2:12][CH2:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.CO.[BH4-].[Na+]>O>[NH2:1][C:2]1[C:3]2[C:8]([N:9]=[C:10]3[C:15]=1[CH:14]([OH:16])[CH:13]([CH2:17][CH2:18][CH:19]1[CH2:24][CH2:23][N:22]([CH2:25][C:26]4[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=4)[CH2:21][CH2:20]1)[CH2:12][CH2:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2
Reactant: Nc1c2c(nc3ccccc13)CCC(CCC1CCN(Cc3ccccc3)CC1)C2=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: Nc1c2c(nc3ccccc13)CCC(CCC1CCN(Cc3ccccc3)CC1)C2O
Temperature: 25 °C
Reaction time: 2 h
Yield: 68 %

Procedure:
0.41 gm of 9-amino-2-(2-(1-benzylpiperidin-4-yl)ethyl)-1,2,3,4-tetrahydroacridin-1-one was dissolved into 10 ml of methanol. To the solution was added 0.15 gm of sodium borohydride, and the mixture was stirred for 2 hours at room temperature. After the addition of 30 ml of water, the reaction mixture was extracted with chloroform. The extract was washed with saturated brine, dried, and evaporated under reduced pressure. 0.28 gm of 9-amino-2-(2-(1-benzylpiperidin-4-yl)ethyl]-1,2,3,4-tetrahydroacridin-1-ol (Compound (I) with R1 =R3 =H, R2 =--NH2, A=>CH(CH2)n --, Y=>CHOH, m=2, and n=2) was obtained by recrystallizing the residue from ethyl acetate.