Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:7]=[CH:8][CH:9]=1)([O-])=O>[Pd].CO>[NH2:1][C:4]1[CH:5]=[C:6]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:7]=[CH:8][CH:9]=1
Reactant: O=[N+]([O-])c1cccc(-c2ccccc2)c1
Agent: [Pd]
Solvent: CO
Product: Nc1cccc(-c2ccccc2)c1
Reaction time: 8 h
Yield: 77.1 %

Procedure:
3-nitrobiphenyl (500 mg, 2.5 mmol) and 10% palladium on carbon (267 mg, 2.5 mmol) were dissolved in methanol (1 mL) and purged with nitrogen and placed under an atmosphere of hydrogen overnight. The reaction mixture was filtered and evaporated to yield 326 mg of the desired amine, which was used directly in Example 12.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][C:10]=2[F:16])[CH:5]=[CH:4][N:3]=1.[F:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][C:25]([N:27]=[C:28]=[S:29])=[O:26])=[CH:20][CH:19]=1>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:28]([NH:27][C:25](=[O:26])[CH2:24][C:21]3[CH:22]=[CH:23][C:18]([F:17])=[CH:19][CH:20]=3)=[S:29])=[CH:11][C:10]=2[F:16])[CH:5]=[CH:4][N:3]=1
Reactant: Nc1ccc(Oc2ccnc(Cl)c2)c(F)c1
Reactant: O=C(Cc1ccc(F)cc1)N=C=S
Solvent: ClCCl
Product: O=C(Cc1ccc(F)cc1)NC(=S)Nc1ccc(Oc2ccnc(Cl)c2)c(F)c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 64 %

Procedure:
4-Fluorophenylacetylchloride (Aldrich, 0.072 mL, 0.525 mmol, 2.5 eq) was added to a solution of sodium thiocyanate (0.056 g, 0.695 mmol, 3.3 eq) in ethyl acetate (2.0 mL) at room temperature and the reaction mixture was stirred for 1.5 h to afford a solution of 2-(4-fluorophenyl)ethanoyl isothiocyanate (0.263 M). A solution of 4-(2-chloropyridin-4-yloxy)-3-fluorobenzenamine (0.050 g, 0.21 mmol, 1.0 eq) in CH2Cl2 (1.0 mL) was added dropwise to the 2-(4-fluorophenyl)ethanoyl isothiocyanate solution and the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo and the resulting residue was purified by silica gel flash chromatography (Merck, 40-63 μM, 230-240 mesh, eluting 3/1 hexane/ethyl acetate) to afford the title compound (0.058 g, 64%) as a solid. 1H NMR (DMSO-d6) δ 12.46 (s, 1H), 11.84 (s, 1H), 8.35-8.33 (m, 1H), 8.02-8.33 (m, 1H), 6.99-7.52 (m, 8H), 3.84 (s, 2H); MS(ESI+) m/z 434 (M+H)+; HRMS(ESI+) calcd.: 434.0542, found: 434.0547.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:13])[CH3:12])=[C:6]([CH3:14])[CH:5]=1.I[CH3:16]>>[Cl:1][CH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]([CH3:16])[C:11](=[O:13])[CH3:12])=[C:6]([CH3:14])[CH:5]=1
Reactant: CC(=O)Nc1ccc(CCCl)cc1C
Reactant: CI
Product: CC(=O)N(C)c1ccc(CCCl)cc1C
Yield: 100 %

Procedure:
N-[4-(2-Chloro-ethyl)-2-methyl-phenyl]-N-methyl-acetamide was prepared according to the general method as outlined in Preparation 43 starting from N-[4-(2-chloro-ethyl)-2-methyl-phenyl]-acetamide (0.450 g, 2.126 mmol) and iodomethane (0.176 ml, 2.834 mmol). After chromatographic purification, the product was isolated as a viscous oil (0.480 g, 2.125 mmol). Yield=100%. MS (APCI): 226 [M+H]+; 1H NMR (400 MHz, CDCl3) δ 7.13(bs, 1H), 7.08 (bd, J=7.57 Hz, 1H), 7.05 (d, J=7.57 Hz, 1H), 3.71 (t, J=7.06 Hz, 1H), 3.15 (s, 3H), 3.04 (t, J=7.06 Hz, 2H), 2.20 (s, 3H), 1.75 (s, 3H).
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[N-]=C=O.[CH2:22]([O:29][C:30]1[CH:35]=[C:34]([I:36])[CH:33]=[CH:32][C:31]=1[N:37]1[S:41](=[O:43])(=[O:42])[N:40](CC[Si](C)(C)C)[C:39](=[O:50])[CH2:38]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C1COCC1>[CH2:22]([O:29][C:30]1[CH:35]=[C:34]([I:36])[CH:33]=[CH:32][C:31]=1[N:37]1[S:41](=[O:43])(=[O:42])[NH:40][C:39](=[O:50])[CH2:38]1)[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1
Reactant: C[Si](C)(C)CCN1C(=O)CN(c2ccc(I)cc2OCc2ccccc2)S1(=O)=O
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Agent: [N-]=C=O
Solvent: C1CCOC1
Product: O=C1CN(c2ccc(I)cc2OCc2ccccc2)S(=O)(=O)N1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Tetrabutylammonium fluoride (1.0M in THF, 15 mL) is added to a solution of PS-isocyanate resin (3.5 g) in THF. The mixture is stirred at RT for 2 h. The resin is filtered off and the filtrate is added to a solution of 5-(2-benzyloxy-4-iodophenyl)-1,1-dioxo-2-(2-trimethylsilanylethyl)-1,2,5-thiadiazolidin-3-one (5.0 g, 9.18 mmol) in THF. The reaction is stirred at 50° C. for 18 h. The mixture is cooled and concentrated. The residue is partitioned between EtOAc and water and the organic layer is washed with 1N HCl (5×50 mL) and brine. The organic layer is dried over Na2SO4 and concentrated. The residue is purified by reverse phase chromatography using a 10-60% gradient of EtOH/water as eluent to afford the title compound as a light yellow solid: (M−1)−=442.
Reaction SMILES: [C:1]([O:5][OH:6])([CH3:4])([CH3:3])[CH3:2].[OH-].[K+].[C:9](Cl)(=[O:13])[CH:10]([CH3:12])[CH3:11].Cl.CCCCCCCCCC(C)C>O>[C:9]([O:6][O:5][C:1]([CH3:4])([CH3:3])[CH3:2])(=[O:13])[CH:10]([CH3:12])[CH3:11]
Reactant: CC(C)(C)OO
Reactant: CC(C)C(=O)Cl
Agent: CCCCCCCCCC(C)C
Agent: Cl
Agent: [K+]
Solvent: O
Product: CC(C)C(=O)OOC(C)(C)C
Yield: 92.8 %

Procedure:
Before the start of the reaction, the loop reactor is filled with a solution of 24.4% by weight of tert-butyl hydroperoxide and 12.7% by weight of potassium hydroxide in water. Initially 33.6 kg/h of a solution of 70% by weight of tert-butyl hydroperoxide in water, 27.0 kg/h of a solution of 45% by weight of potassium hydroxide in water, 35.0 kg/h of water and 18.4 kg/h of isobutyroyl chloride are then fed to the loop reactor. Cooling with cooling water keeps the internal temperature at 11° C. in the loop reactor and at 12° C. in the stirred cell reactor. The partial neutralization is effected with 3.6 kg/h of 31% by weight hydrochloric acid with addition of 8.0 kg/h of isododecane at a temperature of 8° C. The organic phase is extracted with 33.0 kg/h of a 15% by weight aqueous solution of potassium hydroxide. This affords 39.8 kg/h of aqueous extract comprising 17.1% by weight of tert-butyl hydroperoxide and 12.2% by weight of potassium hydroxide, which are feeded into the loop reactor. From the time at which aqueous extract is recycled into the loop reactor, the metered addition of the feedstocks is changed to 23.8 kg/h of a solution of 70% by weight of tert-butyl hydroperoxide in water, 16.0 kg/h of a solution of 45% by weight of potassium hydroxide in water and 15.8 kg/h of water. After the extraction, the organic phase is washed with 36 kg/h of a solution of 3% by weight of sodium sulphite and 1% by weight of sulphuric acid, and dried by stripping at 18° C. and 58 mbar. 33.4 kg/h of a 76.5% by weight solution of tert-butyl peroxyisobutyrate in isododecane are obtained (92.8% yield based on isobutyroyl chloride).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]([N+:15]([O-])=O)=[C:12]([CH:14]=2)[NH2:13])=[CH:4][CH:3]=1.Cl.C(=O)(O)[O-].[Na+]>C(O)C.O.[Zn]>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:14]=[C:12]([NH2:13])[C:11]([NH2:15])=[CH:10][CH:9]=2)=[CH:6][CH:7]=1
Reactant: Nc1cc(-c2ccc(Cl)cc2)ccc1[N+](=O)[O-]
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: Nc1ccc(-c2ccc(Cl)cc2)cc1N
Temperature: 85 °C
Reaction time: 2 h
Yield: 75.6 %

Procedure:
To a solution of 5-chloro-2-nitroaniline (2 g, 11.59 mmol) in dioxane (100 ml) and water (10 ml) was added (4-chlorophenyl)boronic acid (3.6 g, 23.02 mmol), K3PO4 (5.01 g, 23.18 mmol) and Pd(PPh3)4 (0.7 g, 0.58 mmol) with stirring for 4 h at 95° C. maintained with an inert atmosphere of nitrogen. Then the resulting mixture was concentrated under vacuum to give a residue, which was purified by a silica gel column with 2% to 5% ethyl acetate in petroleum ether to afford 4-(4-chlorophenyl)-2-nitroaniline as a yellow solid (2.0 g, 69%). Next, to a solution of 5-(4-chlorophenyl)-2-nitroaniline (300 mg, 1.21 mmol) in ethanol (10 ml) was added hydrogen chloride (0.5 ml, 3.63 mmol) and Zn powder (800 mg, 12.3 mmol) in portions at room temperature and stirred for 2 h at 85° C. The resulting mixture was concentrated under vacuum to give a residue and dissolved in water (100 ml), adjusted to pH 8 with aqueous sodium bicarbonate. The mixture was extracted with ethyl acetate (3×100 ml) and dried and concentrated under vacuum to give a residue, which was purified by a silica gel column with 10% to 20% ethyl acetate in petroleum ether to produce 4-(4-chlorophenyl)benzene-1,2-diamine as an off-white solid (200 mg, 76%). Finally, a solution of 4-(4-chlorophenyl)benzene-1,2-diamine (150 mg, 0.69 mmol) in heptafluorobutanoic acid (2 ml) was stirred for 8 h at 120° C. Then the reaction was quenched with water (50 ml), adjusted to pH 7 with sodium bicarbonate and extracted with ethyl acetate(3×100 ml). The combined organic layers were dried over anhydrous magnesium sulfate and concentrated under vacuum to give a residue, which was purified by a silica gel column with 5% to 10% ethyl acetate in petroleum ether to produce 6-(4-chlorophenyl)-2-(heptafluoropropyl)-1H-1,3-benzodiazole as a white solid (49.5 mg, 18%).
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[C:5](Cl)(=[O:7])[CH3:6].[CH2:9]([C:12]1[NH:13][C:14]2[C:19]([CH:20]=1)=[CH:18][CH:17]=[C:16]([C:21]([O:23][CH3:24])=[O:22])[CH:15]=2)[CH2:10][CH3:11]>ClCCl>[C:5]([C:20]1[C:19]2[C:14](=[CH:15][C:16]([C:21]([O:23][CH3:24])=[O:22])=[CH:17][CH:18]=2)[NH:13][C:12]=1[CH2:9][CH2:10][CH3:11])(=[O:7])[CH3:6]
Reactant: CCCc1cc2ccc(C(=O)OC)cc2[nH]1
Reactant: CC(=O)Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CCCc1[nH]c2cc(C(=O)OC)ccc2c1C(C)=O
Temperature: 20 °C
Reaction time: 1 h

Procedure:
To a stirring suspension of aluminum chloride (294 mg) and acetyl chloride (0.08 ml) in dichloromethane (10 ml) was added methyl 2-propylindole-6-carboxylate (200 mg), and the mixture was stirred at 20° C. for 1 hour. The resulting mixture was poured onto ice and extracted with ethyl acetate. The combined organic phase was washed with aqueous sodium bicarbonate and brine, then dried over sodium sulfate and evaporated in vacuo. The residue was triturated with isopropyl ether to give methyl 3-acetyl-2-propylindole-6-carboxylate (78 mg) as colorless crystals.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:30])[C@@H:12]([NH:22]C(OC(C)(C)C)=O)[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20]#[N:21])[S:8][CH:9]=1)=[O:4].FC(F)(F)C(O)=O>ClCCl>[CH3:1][O:2][C:3]([C:5]1[N:6]=[C:7]([NH:10][C:11](=[O:30])[C@@H:12]([NH2:22])[CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:20]#[N:21])[S:8][CH:9]=1)=[O:4]
Reactant: COC(=O)c1csc(NC(=O)[C@H](Cc2ccccc2C#N)NC(=O)OC(C)(C)C)n1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)c1csc(NC(=O)[C@@H](N)Cc2ccccc2C#N)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 85.9 %

Procedure:
2-[(S)-2-tert-Butoxycarbonylamino-3-(2-cyano-phenyl)-propionylamino]-thiazole-4-carboxylic acid methyl ester (3.2 g, 7.4 mmol) was dissolved into dry dichloromethane (20 mL) and trifluoroacetic acid (25 mL, 325 mmol) was added. The reaction mixture was stirred at room temperature for 1 hour. The mixture was concentrated to dryness. The residue was cooled in an ice bath, then neutralized with saturated aqueous sodium bicarbonate solution. The mixture was extracted with ethyl acetate. The organic layer was separated, dried over sodium sulfate and concentrated to give crude 2-[(S)-2-amino-3-(2-cyano-phenyl)-propionylamino]-thiazole-4-carboxylic acid methyl ester as a pale yellow solid (2.1 g, 86%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([S:9]([N:12]([CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[NH:18][CH2:17][CH2:16]3)(=[O:11])=[O:10])[CH:5]=[C:6]([Cl:8])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[C:36](Cl)(=[O:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1.O>ClCCl>[C:36]([N:18]1[C:19]2[C:15](=[CH:14][C:13]([N:12]([CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[S:9]([C:4]3[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[CH:3]=3)(=[O:11])=[O:10])=[CH:21][CH:20]=2)[CH2:16][CH2:17]1)(=[O:43])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: CC(C)(C)OC(=O)CN(c1ccc2c(c1)CCN2)S(=O)(=O)c1cc(Cl)cc(Cl)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)CN(c1ccc2c(c1)CCN2C(=O)c1ccccc1)S(=O)(=O)c1cc(Cl)cc(Cl)c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
150 mg tert.butyl [(3,5-dichloro-phenylsulphonyl)-(2,3-dihydro-1H-indol-5-yl)-amino]-acetate are dissolved in 5 ml dichloromethane. 110 mg potassium carbonate and 45 μl benzoyl chloride are added, the mixture is stirred for 3 hours at ambient temperature and then divided between dichloromethane and water. The organic phase is washed with water and then dried on magnesium sulphate. The solvents are eliminated in vacuo.
Reaction SMILES: C(OC([NH:8][CH2:9][CH2:10][CH2:11][NH:12][C:13]([CH2:15][O:16][C:17]1[CH:18]=[C:19]([CH:40]=[CH:41][CH:42]=1)[CH2:20][NH:21][C:22]1[N:26]([C@@H:27]2[O:33][C@H:32]([CH2:34][OH:35])[C@@H:30]([OH:31])[C@H:28]2[OH:29])[C:25]2[CH:36]=[CH:37][CH:38]=[CH:39][C:24]=2[N:23]=1)=[O:14])=O)(C)(C)C>Cl.C(O)C>[NH2:8][CH2:9][CH2:10][CH2:11][NH:12][C:13]([CH2:15][O:16][C:17]1[CH:18]=[C:19]([CH:40]=[CH:41][CH:42]=1)[CH2:20][NH:21][C:22]1[N:26]([C@@H:27]2[O:33][C@H:32]([CH2:34][OH:35])[C@@H:30]([OH:31])[C@H:28]2[OH:29])[C:25]2[CH:36]=[CH:37][CH:38]=[CH:39][C:24]=2[N:23]=1)=[O:14]
Reactant: CC(C)(C)OC(=O)NCCCNC(=O)COc1cccc(CNc2nc3ccccc3n2[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c1
Agent: Cl
Solvent: CCO
Product: NCCCNC(=O)COc1cccc(CNc2nc3ccccc3n2[C@@H]2O[C@H](CO)[C@@H](O)[C@H]2O)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 72.4 %

Procedure:
2-{3-[(3-t-Butoxycarbonylaminopropylcarbamoyl)methoxy]benzylamino}-1-(β-D-ribofuranosyl)-1H-benzimidazole (15 mg) was dissolved in 22% hydrochloride-ethanol solution, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, and the obtained residue was purified by preparative reverse phase column chromatography (Shiseido CAPSELL PAC C18UG80, 5 μm, 20×50 mm, flow rate 30 mL/minutes linear gradient, water/methanol=90/10-10/90) to give the title compound (9 mg).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][CH:28]=1)[C:5]([NH:7][C:8]1[CH:13]=[C:12]([S:14][C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=2)[C:11]([N+:22]([O-])=O)=[CH:10][C:9]=1[CH3:25])=[O:6].OC1C=CC(SC2C([N+]([O-])=O)=CC(C)=C(NC(=O)CC3C=CC=CC=3)C=2)=CC=1>>[NH2:22][C:11]1[C:12]([S:14][C:15]2[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=2)=[CH:13][C:8]([NH:7][C:5](=[O:6])[C:4]2[CH:26]=[CH:27][CH:28]=[C:2]([Br:1])[CH:3]=2)=[C:9]([CH3:25])[CH:10]=1
Reactant: Cc1cc([N+](=O)[O-])c(Sc2ccc(O)cc2)cc1NC(=O)c1cccc(Br)c1
Agent: Cc1cc([N+](=O)[O-])c(Sc2ccc(O)cc2)cc1NC(=O)Cc1ccccc1
Product: Cc1cc(N)c(Sc2ccc(O)cc2)cc1NC(=O)c1cccc(Br)c1
Yield: 86 %

Procedure:
The product from Example 266B was reacted according to the procedure from Example 265C substituting the product from Example 266B for the product from Example 265B to provide the title compound as a brown solid (0.164 g, 86%). This material was utilized without purification by silica gel chromatography.
Reaction SMILES: [CH2:1]([NH2:4])[CH:2]=[CH2:3].C1C2NC3C(=CC=CC=3)C=2C=CC=1.[CH3:18][SiH:19]([O:22][CH3:23])[O:20][CH3:21]>C(O)C>[NH2:4][CH2:1][CH2:2][CH2:3][Si:19]([CH3:18])([O:22][CH3:23])[O:20][CH3:21]
Reactant: CO[SiH](C)OC
Reactant: C=CCN
Agent: c1ccc2c(c1)[nH]c1ccccc12
Solvent: CCO
Product: CO[Si](C)(CCCN)OC
Temperature: 60 °C
Reaction time: 4 h
Yield: 74 %

Procedure:
Into the same reactor as used in Example 1, 17.1 parts of allylamine, 0.3 part of carbazole, 0.00005 part as platinum atom of the same platinum complex as in Example 1 were charged, 31.8 parts of methyldimethoxysilane were added dropwise at 40° C. over 5 minutes, followed further by continuing stirring for 4 hours while maintaining the liquid temperature at 60° C. After cooling, 1.7 parts of ethanol were added and distillation was carried out to give 36.2 parts of γ-aminopropylmethyldimethoxysilane boiling at 105° to 109° C./50 Torr. This corresponded to 74% yield based on the theoretical amount.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[C:16]([CH3:18])[C:15]([O:19][CH2:20][CH2:21][OH:22])=[C:14]([CH3:23])[CH:13]=1)[NH:6][C:5]2=[O:24].[C:25](OC(=O)C)(=[O:27])[CH3:26].C([O-])([O-])=O.[K+].[K+]>N1C=CC=CC=1>[OH:22][CH2:21][CH2:20][O:19][C:15]1[C:16]([CH3:18])=[CH:17][C:12]([C:7]2[NH:6][C:5](=[O:24])[C:4]3[C:9](=[CH:10][CH:11]=[C:2]([NH:1][C:25](=[O:27])[CH3:26])[CH:3]=3)[N:8]=2)=[CH:13][C:14]=1[CH3:23]
Reactant: CC(=O)OC(C)=O
Reactant: Cc1cc(-c2nc3ccc(N)cc3c(=O)[nH]2)cc(C)c1OCCO
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: c1ccncc1
Product: CC(=O)Nc1ccc2nc(-c3cc(C)c(OCCO)c(C)c3)[nH]c(=O)c2c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 61 %

Procedure:
To a solution of 2-amino-5-nitro-benzamide (680 mg, 3.75 mmol) and 4-[2-(tert-butyldimethylsilanoxy)ethoxy]-3,5-dimethylbenzaldehyde (1.16 g, 3.75 mmol) in N,N-dimethyl acetamide (35 mL), NaHSO3 (736 mg, 4.14 mmol) and p-TSA (71 mg, 0.375 mmol) were added and the reaction mixture was heated at 150° C. for 5 h. The solvent was evaporated under reduced pressure. The residue was diluted with water and the solids were filtered off to give crude product (590 mg, 44%). To a solution of above crude product (490 mg. 1.38 mmol) in DMF (20 mL) and MeOH (20 mL), Pd—C (100 mg, 10%) was added and the reaction mixture was hydrogenated for 4 h at room temperature at 30 psi H2. The reaction mixture was filtered and the solvent was evaporated to give crude product. The crude was purified by column chromatography (silica gel 230-400 mesh; 4% methanol in CH2Cl2 as eluent) to give 6-amino-2-(4-(2-hydroxy ethoxy)-3,5-dimethyl phenyl)-3H-quinazolin-4-one (190 mg, 42% yield). To a solution of 6-amino-2-(4-(2-hydroxy ethoxy)-3,5-dimethyl phenyl)-3H-quinazolin-4-one (95 mg, 0.29 mmol) in pyridine (5 mL), acetic anhydride (108 mg, 0.73 mmol) was added and the mixture was stirred for 16 h at room temperature. The solvent was removed and the solids were dissolved in a mixture of MeOH (10 mL) and THF (10 mL) (compound was partially soluble). Then K2CO3 (100 mg, 0.73 mmol) was added and the reaction mixture was stirred for 3 h at room temperature. The solvent was removed and the crude was purified by column chromatography (silica gel 230-400 mesh; 5% methanol in CH2Cl2 as eluent) to give N-(2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-4-oxo-3,4-dihydroquinazolin-6-yl)acetamide (65 mg, 60%). Selected data: MS (ES) m/z: 368.09; MP>300° C.
Reaction SMILES: [C:1]1([C:7]2[N:8]=[C:9]([C:12]([NH2:14])=O)[NH:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.P(Cl)(Cl)(Cl)=O.O.C(=O)([O-])[O-].[K+].[K+]>N1C=CC=CC=1>[C:1]1([C:7]2[N:8]=[C:9]([C:12]#[N:14])[NH:10][CH:11]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: NC(=O)c1nc(-c2ccccc2)c[nH]1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: c1ccncc1
Solvent: O=P(Cl)(Cl)Cl
Product: N#Cc1nc(-c2ccccc2)c[nH]1
Temperature: -20 °C
Yield: 49.1 %

Procedure:
A suspension of 4.55 g of 4-phenyl-1H-imidazole-2-carboxamide in pyridine (30 ml) was stirred and cooled to -20° C. and treated dropwise with phosphorous oxychloride (2.3 ml) keeping the internal temperature below 0° C. After 40 min the reaction mixture was cooled to -25° C. and water (5 ml) was slowly added. The resultant suspension was poured into stirred water, carefully basified with potassium carbonate, and then filtered. The filtered solid was dissolved in dichloromethane and passed through a short column of fine silica. The column was eluted with dichloromethaneethyl acetate (9:1), the appropriate fractions were collected and evaporated to give 4-phenyl-1H-imidazole-2-carbonitrile (2.02 g), which was treated in the manner as described in Example 3b and converted with methanesulphone acid into N-hydroxy-4-phenyl-1H-imidazole-2-carboximidamide methanesulphonate (1:2), m.p. 151°-153° C.
Reaction SMILES: O[CH2:2][C:3]1[C:12]([CH3:13])=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=1.P(Br)(Br)[Br:15]>CCOCC>[Br:15][CH2:2][C:3]1[C:12]([CH3:13])=[CH:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=1
Reactant: BrP(Br)Br
Reactant: Cc1cc2ccccc2cc1CO
Solvent: CCOCC
Product: Cc1cc2ccccc2cc1CBr
Temperature: 0 °C
Reaction time: 1.25 h
Yield: 86.8 %

Procedure:
To a stirred solution of 2-hydroxymethyl-3-methylnaphthalene (2.47 g, 14.4 mmol) in dry Et2O (50 mL) cooled to 0° C. was added phosphorus tribromide (4.88 g, 18 mmol) dropwise over 20 minutes. The resulting heterogeneous mixture was stirred at 0° C. for 1.25 hours and then quenched with H2O (50 mL). The reaction mixture was diluted further with H2O (50 mL) and extracted with Et1O (2×150 mL). The combined organic layers were washed with H2O (1×100 mL), dried (MgSO4) and concentrated in vacuo. The residue was purified by filtration through silica gel using CH2Cl2 as eluent to give the product as an off-white solid (2.94 g, 87%).
Reaction SMILES: Br[CH:2]([CH3:11])[C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:4].[CH3:12][O:13][CH2:14][CH2:15][NH2:16].[ClH:17]>CCOCC>[ClH:17].[CH3:12][O:13][CH2:14][CH2:15][NH:16][CH:2]([CH3:11])[C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:4]
Reactant: COCCN
Reactant: CC(Br)C(=O)c1ccccc1
Agent: Cl
Solvent: CCOCC
Product: COCCNC(C)C(=O)c1ccccc1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A solution of α-bromopropiophenone (2.13 g, 0.010 mole) in ether (10 ml) was added dropwise to a stirred solution of 2-methoxyethylamine (1.50 g, 0.020 mole) in ether (20 ml). The mixture was then stirred at ambient temperature for 18 hr. The ether layer was decanted from an insoluble oil, washed with water (20 ml), and then extracted with 2N hydrochloric acid solution (20 ml). The acid extract was basified to pH 10 with 6N sodium hydroxide solution, and this solution extracted with ether (50 ml). The extract was dried over magnesium sulfate and concentrated to give a clear yellow oil. The oil was dissolved in ether and treated with excess ethereal hydrogen chloride. The product separated from solution as an oil, but solidified upon trituration. The yield was 0.85 g (35%), m.p. 133°-134° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:37])[CH:4]([N:16]1[CH2:21][CH2:20][N:19](S(C2C=CC=CC=2[N+]([O-])=O)(=O)=O)[CH:18]([CH2:34][O:35][CH3:36])[CH2:17]1)[CH2:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].SC1C=CC(O)=CC=1.Cl>CN(C=O)C>[CH3:1][O:2][C:3](=[O:37])[CH:4]([N:16]1[CH2:21][CH2:20][NH:19][CH:18]([CH2:34][O:35][CH3:36])[CH2:17]1)[CH2:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH:7]=1
Reactant: COCC1CN(C(Cc2ccc3ccccc3c2)C(=O)OC)CCN1S(=O)(=O)c1ccccc1[N+](=O)[O-]
Agent: Cl
Agent: O=C([O-])[O-]
Agent: Oc1ccc(S)cc1
Solvent: CN(C)C=O
Product: COCC1CN(C(Cc2ccc3ccccc3c2)C(=O)OC)CCN1
Temperature: 25 °C
Reaction time: 6 h
Yield: 97 %

Procedure:
To a solution of 2-[3-methoxymethyl-4-(2-nitro-benzenesulfonyl)-piperazine-1-yl]-3-naphthalen-2-yl-propionic acid methyl ester, 61, (3.5 g, 6.67 mmol) in anhydrous DMF (40 mL) is added potassium carbonate (5.5 g, 40.0 mmol) and 4-mercaptophenol (2.5 g, 20.0 mmol). The reaction mixture is stirred for six hours at room temperature, then cooled in a ice bath and pH is adjusted to 3 with 1M HCl. The reaction mixture is extracted with Et2O (4×100 mL). All organic layers are combined and extracted with 1M HCl (100 mL). All aqueous layers are combined and cooled in a ice bath and the pH is adjusted to 10 with K2CO3. The aqueous layer is extracted with EtOAc (4×125 mL) and dried over Na2SO4. The solvent is removed in vacuo to afford 2.2 g (97% yield) of the desired product. 1H NMR (CDCl3, δ): 7.85–7.78 (m, 3H), 7.65 (s, 1H), 7.54–7.40 (m, 2H), 7.35 (dd, J=7.2, 2.4Hz, 1H), 3.59 (s, 3H), 3.56 (dd, J=6.0, 2.5 Hz, 1H), 3.40–3.10 (m, 5H), 3.38 (s, 3H), 3.05–2.78 (m, 5H), 2.59 (dt, J=7.2, 2.5 Hz, 1H), 2.20 (t, J=10.8 Hz, 1H); 13C NMR, δ 171.8, 135.9, 133.7, 132.5, 128.2, 127.9, 127.8, 126.2, 125.7, 74.8, 69.9, 59.4, 55.2, 52.3, 51.4, 50.8, 45.6, 35.8.