Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][OH:5].N([O-])=O.[Na+].[N-:14]=[N+:15]=[N-].[Na+]>FC(F)(F)C(O)=O.O>[N:1]([C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH2:4][OH:5])=[N+:14]=[N-:15]
Reactant: [N-]=[N+]=[N-]
Reactant: Nc1ccccc1CO
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: [N-]=[N+]=Nc1ccccc1CO
Reaction time: 0.75 h
Yield: 72.3 %

Procedure:
To a solution of 2-aminobenzyl alcohol (12.0 g, 97.4 mmol) in 50 mL of trifluoroacetic acid at 0° C. was added sodium nitrite (7.39 g, 107.2 mmol). This solution was stirred for 45 min and then there was added sodium azide (6.33 g, 97.4 inmol) dropwise as a solution in water. The resulting mixture was stirred at 0° C. for 45 min and then was carefully quenched by slow addition of potassium carbonate. The reaction mixture was diluted with ethyl acetate, washed with brine, dried (MgSO4), filtered through a pad of silica gel and concentrated to afford 10.5 g (72%) of the title compound which was used without further purification. 1H NMR (CDCl3) δ7.33 (m, 2H), 7.14 (m, 2H), 4.59 (s, 2H), 2.69 (broad s, 1H).
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[CH:4][CH:3]=1.[C:10](Cl)(=[O:19])[C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=1>ClCCl>[NH2:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH:7][C:10](=[O:19])[C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)=[CH:4][CH:3]=1
Reactant: NCc1ccc(N)cc1
Reactant: COc1ccc(C(=O)Cl)cc1
Solvent: ClCCl
Product: COc1ccc(C(=O)NCc2ccc(N)cc2)cc1
Reaction time: 16 h
Yield: 100 %

Procedure:
To a solution of 4-aminobenzylamine (7.14 g, 58.4 mmol) in dichloromethane (120 mL) were added at 0° C. under N2 triethylamine (16.4 mL, 118 mmol) and a solution of p-anisoyl chloride (10 g, 58.4 mmol) in dichloromethane (20 mL). The mixture was allowed to reach 25° C., stirred 16 h, and poured onto water/ice (ca. 200 mL). The resulting suspension was stirred for 15 minutes and the white solid was filtered off and dried. Weight: 15 g (100% yield).
Reaction SMILES: [C:1]([Si:5]([CH3:20])([CH3:19])[O:6][CH2:7][CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][O:15][CH2:16][CH2:17]O)([CH3:4])([CH3:3])[CH3:2].C(Br)(Br)(Br)[Br:22].N1C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[Br:22][CH2:17][CH2:16][O:15][CH2:14][CH2:13][O:12][CH2:11][CH2:10][O:9][CH2:8][CH2:7][O:6][Si:5]([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:20])[CH3:19]
Reactant: CC(C)(C)[Si](C)(C)OCCOCCOCCOCCO
Reactant: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)OCCOCCOCCOCCBr
Temperature: 0 °C
Reaction time: 2 h
Yield: 83.2 %

Procedure:
Compound 5c (680 mg, 2.20 mmol) and carbon tetrabromide (947 mg, 2.86 mg) were dissolved in dichloromethane (20 ml). The solution was cooled down to 0° C. with an ice bath and pyridine (2.0 ml) was added followed by triphenylphosphine (749 mg, 0.286 mmol). The solution was stirred at 0° C. for half an hour and at room temperature for 2 hours. After standard workup with dichloromethane, the residue was purified by silica gel column chromatography (20% ethyl acetate in hexane) to afford compound 6c (680 mg, 79.6%): 1H NMR δ 3.79 (m, 4H), 3.66 (m, 8H), 3.56 (t, 2H), 3.47 (t, 2H), 0.89 (s, 9H), 0.07 (s, 6H).
Reaction SMILES: C([N-]C(C)C)(C)C.[Li+].[C:9]([O:12][C:13]([CH3:22])([CH2:15][CH2:16][CH2:17][CH:18]([CH3:21])[CH:19]=[CH2:20])[CH3:14])(=[O:11])[CH3:10].[CH:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][C:24]=1[C:33](Cl)=[O:34]>C1COCC1>[CH:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH:26]=[CH:25][C:24]=1[C:33](=[O:34])[CH2:10][C:9]([O:12][C:13]([CH3:22])([CH2:15][CH2:16][CH2:17][CH:18]([CH3:21])[CH:19]=[CH2:20])[CH3:14])=[O:11]
Reactant: O=C(Cl)c1ccc2ccccc2c1
Reactant: C=CC(C)CCCC(C)(C)OC(C)=O
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: C=CC(C)CCCC(C)(C)OC(=O)CC(=O)c1ccc2ccccc2c1
Temperature: -78 °C
Reaction time: 0.25 h

Procedure:
Lithium diisopropylamide in the amount of (100.0 mL of a 2.0 M solution, 0.201 mol) is placed into a 500 mL three-necked round-bottomed flask fitted with a magnetic stirrer, internal thermometer, argon inlet, and addition ftnnel. The flask is cooled to −78° C. 2,6-Dimethyl-7-octen-2-yl acetate in the amount of (18.75 g, 0.095 mol) is dissolved in THF (5 mL) and the resulting solution added to the flask over 45 min. Once addition is complete, the mixture is stirred for an additional 15 min before being treated with a solution of 2-naphthoyl chloride in the amount of (17.00 g, 0.089 mol) dissolved in THF (25 mL) over 30 min. The mixture is warmed to −20° C. and stirred at that temperature for 18 h. After warming to 0° C., the mixture is quenched with 20% HCl (55 mL). The mixture is poured into a separatory funnel containing ether (150 mL) and water (250 mL). The aqueous layer is extracted with ether (150 mL). The combined organic layers are washed with saturated NaHCO3 solution (2×100 mL), water (2×150 mL) and brine (150 mL), dried over MgSO4 and filtered. The solvent is removed by rotary evaporation to give an orange/red oil. The oil is purified by column chromatography (elution with 2% ethyl acetate dissolved in petrolewn ether) to give an oil. Purity of the product is determined by thin layer chromatography and the structure confirmed by 1H and 13C NMR.
Reaction SMILES: Cl.Cl[CH2:3][C:4]1[N:5]([CH:9]2[CH2:13][CH2:12][CH2:11][O:10]2)[CH:6]=[CH:7][N:8]=1.[CH3:14][O:15][C:16]1[CH:17]=[C:18]([OH:22])[CH:19]=[CH:20][CH:21]=1.CS(C)=O.C([O-])([O-])=O.[K+].[K+]>O>[CH3:14][O:15][C:16]1[CH:17]=[C:18]([CH:19]=[CH:20][CH:21]=1)[O:22][CH2:3][C:4]1[N:5]([CH:9]2[CH2:13][CH2:12][CH2:11][O:10]2)[CH:6]=[CH:7][N:8]=1
Reactant: ClCc1nccn1C1CCCO1
Reactant: COc1cccc(O)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: COc1cccc(OCc2nccn2C2CCCO2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 41.6 %

Procedure:
To a mixture of 2-chloromethyl-1-(tetrahydro-furan-2-yl)-1H-imidazole hydrochloride, (5.7 g, 30.6 mmol), 3-methoxyphenol (7.6 g, 61.2 mmol) and DMSO (30 mL) was added K2CO3 (12.7 g, 91.8 mmol). The mixture was stirred at ambient temperature under N2 overnight. Water (100 mL) was added and the mixture was extracted with CH2Cl2 (3×100 mL). The combined CH2Cl2 extracts were washed with 2N NaOH, dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography (silica gel, 1:2 hexane/EtOAc) to provide the desired 2-(3-methoxy-phenoxymethyl)-1-(tetrahydro-furan-2-yl)-1H-imidazole (3.49 g, 41%) as a colorless oil: ESI MS m/z 275 [C15H18N2O3+H]+.
Reaction SMILES: O=[C:2]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].C(C1C(=O)C(Cl)=C(Cl)C(=O)C=1C#N)#N.ClC1C=CC=CN=1.ClC1N=C(C2C=CC=CC=2)C(C(OCC)=O)=CC=1.N[C:55]1[N:60]=[C:59]([NH:61][CH2:62][CH2:63][NH:64][C:65]2[CH:70]=[CH:69]C(C3NC=CN=3)=C(C3C=CC(Cl)=CC=3Cl)[N:66]=2)[CH:58]=[CH:57][C:56]=1[N+:84]([O-:86])=[O:85]>CC#N.CCN(C(C)C)C(C)C>[N+:84]([C:56]1[CH:57]=[CH:58][C:59]([NH:61][CH2:62][CH2:63][NH:64][C:65]2[N:66]=[C:2]([C:9]3[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=3)[C:3]([C:4]([O:6][CH2:7][CH3:8])=[O:5])=[CH:69][CH:70]=2)=[N:60][CH:55]=1)([O-:86])=[O:85]
Reactant: CCOC(=O)CC(=O)c1ccccc1
Reactant: Nc1nc(NCCNc2ccc(-c3ncc[nH]3)c(-c3ccc(Cl)cc3Cl)n2)ccc1[N+](=O)[O-]
Agent: CCOC(=O)c1ccc(Cl)nc1-c1ccccc1
Agent: Clc1ccccn1
Agent: N#CC1=C(C#N)C(=O)C(Cl)=C(Cl)C1=O
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)c1ccc(NCCNc2ccc([N+](=O)[O-])cn2)nc1-c1ccccc1

Procedure:
ethyl 6-({2-[(5-nitro(2-pyridyl))amino]ethyl}amino)-2-phenylpyridine-3-carboxylate was prepared from ethyl 3-oxo-3-phenylpropanoate as the starting material and DDQ in the oxidation step. The final product is achieved directly from the chloropyridine by reacting ethyl 6-chloro-2-phenylpyridine-3-carboxylate with 2-(2-aminoethylamine)-5-nitropyridine in CH3CN and Hünig's base at 80° C. for 18 hours. The procedures are analogous to the general method for {2-[(6-amino-5-nitro(2-pyridyl))amino]ethyl}[6-(2,4-dichlorophenyl)-5-imidazolyl(2-pyridyl)]amine.
Reaction SMILES: [C:1]([C:5]1[N:10]=[C:9](O)[CH:8]=[C:7]([CH:12]2[CH2:14][CH2:13]2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].O=P(Cl)(Cl)[Cl:17]>C1(C)C=CC=CC=1.CN(C)C=O>[C:1]([C:5]1[N:10]=[C:9]([Cl:17])[CH:8]=[C:7]([CH:12]2[CH2:14][CH2:13]2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)c1nc(O)cc(C2CC2)n1
Reactant: O=P(Cl)(Cl)Cl
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: CC(C)(C)c1nc(Cl)cc(C2CC2)n1
Yield: 104.9 %

Procedure:
14.8 g 2-tert-butyl-4-hydroxy-6-cyclopropyl-pyrimidine (76.9 mmol) were dissolved in 100 ml of toluene and 3 ml of dimethylformamide. 23.6 ml of POCl3 (153.7 mmol) were added dropwise at 10° C. After stirring overnight at room temperature most of the toluene was evaporated. The mixture was cooled with ice and 20 ml of water were added cautiously. Subsequently, an additional 200 ml of water were added and the aqueous phase was extracted four times with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered, and then concentrated to dryness to yield 17 g of a yellowish oil (quant.).
Reaction SMILES: [C-:1]#[N:2].[Na+].Br[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>O.CCO>[CH:7]1[C:8]2[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:14]=[CH:15][C:6]=1[CH2:5][C:1]#[N:2]
Reactant: BrCc1ccc2ccccc2c1
Reactant: [C-]#N
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: N#CCc1ccc2ccccc2c1
Reaction time: 16 h
Yield: 81.9 %

Procedure:
To a stirred solution of sodium cyanide (10.5 g, 0.214 mol) in H2O (20 mL) was added a solution of 2-(bromomethyl)naphthalene (40.0 g, 0.181 mol) in EtOH (170 mL). The resulting mixture was heated at reflux for 3 h, then spin-evaporated in vacuo. The residue was partitioned between H2O (175 mL) and CH2Cl2 (200 mL). The aqueous layer was further extracted with CH2Cl2 (3×200 mL). The combined organic layers were dried over MgSO4 (5 g) and spin-evaporated in vacuo to a solid. The solid was dissolved in refluxing EtOH (100 mL). The clarified solution was stored at 3° C. for 16 h. Solids were collected by filtration and dried to constant weight in vacuo to give 24.8 g (81.9%) of product suitable for further transformation. A total of 257.2 g of material was prepared in this fashion.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([NH:8][CH2:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)=[N:6][CH:7]=1.C([Li])(C)(C)C.CN(C)[CH:27]=[O:28]>O1CCCC1>[F:17][C:16]([F:19])([F:18])[C:13]1[CH:14]=[CH:15][C:10]([CH2:9][NH:8][C:5]2[N:6]=[CH:7][C:2]([CH:27]=[O:28])=[CH:3][CH:4]=2)=[CH:11][CH:12]=1
Reactant: CN(C)C=O
Reactant: FC(F)(F)c1ccc(CNc2ccc(Br)cn2)cc1
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Product: O=Cc1ccc(NCc2ccc(C(F)(F)F)cc2)nc1
Temperature: -78 °C
Reaction time: 1.5 h
Yield: 56 %

Procedure:
To a solution of (5-bromo-pyridin-2-yl)-(4-trifluoromethyl-benzyl)-amine (17, 3.55 g, 0.0107 mol, commercially available, or prepared as described in Example 10) in tetrahydrofuran (150 mL) was added tert-butyllithium (13.2 mL, 1.70 M in pentane, 0.0224 mol) slowly under an atmosphere of nitrogen at −78° C. over 10 minutes. The reaction mixture was stirred at −78° C. for 90 minutes. N,N-Dimethylformamide (2.2 mL, 0.028 mol) was added slowly into the reaction mixture. The reaction mixture was stirred at −78° C. for 2 hours, then allowed to warm to room temperature. After stirring at room temperature for 2 hours, the reaction mixture was poured into ice water and extracted with ethyl acetate. The organic phase was washed with saturated sodium bicarbonate, brine, and dried over magnesium sulfate. After removal of solvent, the residue was purified by silica gel column chromatography eluting with ethyl acetate in hexane to provide the compound as a light yellow solid (18, 1.67 g, 56%).
Reaction SMILES: [CH3:1][C:2]([C@H:4]1[C@@H:8]2[C@@H:9]3[C@@:22]([CH3:25])([CH2:23][CH2:24][C@@:7]2([CH2:31][OH:32])[CH2:6][CH2:5]1)[C@@:21]1([CH3:26])[C@@H:12]([C@:13]2([CH3:30])[C@@H:18]([CH2:19][CH2:20]1)[C:17]([CH3:28])([CH3:27])[C@@H:16]([OH:29])[CH2:15][CH2:14]2)[CH2:11][CH2:10]3)=[CH2:3].CC(C)=O>O>[CH3:3][C:2]([C@H:4]1[C@@H:8]2[C@@H:9]3[C@@:22]([CH3:25])([CH2:23][CH2:24][C@@:7]2([CH:31]=[O:32])[CH2:6][CH2:5]1)[C@@:21]1([CH3:26])[C@@H:12]([C@:13]2([CH3:30])[C@@H:18]([CH2:19][CH2:20]1)[C:17]([CH3:28])([CH3:27])[C:16](=[O:29])[CH2:15][CH2:14]2)[CH2:11][CH2:10]3)=[CH2:1]
Reactant: C=C(C)[C@@H]1CC[C@]2(CO)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC[C@H](O)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Solvent: O
Solvent: CC(C)=O
Product: C=C(C)[C@@H]1CC[C@]2(C=O)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CCC(=O)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12

Procedure:
Betulinol was placed in a thermostated reactor, and acetone, in an amount of 100-110 ml per gram of betulinol, was added with stirring. An oxidizing mixture of CrO3/H2SO4 (molar ratio of 2:3, respectively) was then slowly poured into the reactor 20 with stirring. The reaction mixture was brought to reflux and maintained at reflux for 2.5-3 hrs. The reaction mixture was then cooled and water was added, resulting in the formation of a sediment. The sediment was filtered and recrystallized from ethanol. The resulting solid contained 93-95% of betulonic aldehyde and melted at a temperature from 154-156° C. The yield of purified betulonic aldehyde was 65%.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]=[CH:10][C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][C:12]=2[N+:18]([O-])=O)=[CH:5][CH:4]=1.[H][H]>[Pd].C(O)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][C:12]=2[NH2:18])=[CH:7][CH:8]=1
Reactant: COc1ccc(C=Cc2ccc(C)cc2[N+](=O)[O-])cc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: COc1ccc(CCc2ccc(C)cc2N)cc1
Yield: 96.7 %

Procedure:
To a solution of the product from Example 75A (164 mg, 0.6 mmol) and 10% palladium on charcoal (50 mg) in ethanol (20 ml) was hydrogenated with a hydrogen balloon for three days. The solvent was filtered through celite, washed with ethanol and evaporated under vacuum to provide the title compound (140 mg, 97%).
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[C:7]([NH:10][C:11]3[N:16]=[CH:15][C:14]([C:17]4[S:18][CH:19]=[C:20]([C:22]([O:24]CC)=O)[N:21]=4)=[C:13]([NH:27][CH:28]([CH3:30])[CH3:29])[CH:12]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1.[NH3:31]>CO>[S:1]1[C:5]2[CH:6]=[C:7]([NH:10][C:11]3[N:16]=[CH:15][C:14]([C:17]4[S:18][CH:19]=[C:20]([C:22]([NH2:31])=[O:24])[N:21]=4)=[C:13]([NH:27][CH:28]([CH3:29])[CH3:30])[CH:12]=3)[CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1
Reactant: N
Reactant: CCOC(=O)c1csc(-c2cnc(Nc3ccc4ncsc4c3)cc2NC(C)C)n1
Solvent: CO
Product: CC(C)Nc1cc(Nc2ccc3ncsc3c2)ncc1-c1nc(C(N)=O)cs1
Temperature: 80 °C

Procedure:
The ethyl 2-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)thiazole-4-carboxylate (Example 20) (200 mg, 0.455 mmol) was taken in a sealed tube, to it methanol (2 mL) was added, followed by addition of methanolic ammonia (10 mL). The reaction mixture was heated at 80° C. for 3 h. The reaction mixture was concentrated. The crude material was purified by column chromatography through silica gel and MeOH: CHCl3 as eluent. The material obtained was further purified on preparative TLC to obtain 2-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)thiazole-4-carboxamide. 1H NMR: 400 MHz, DMSO-d6: δ 1.33 (d, J=6.40 Hz, 6H), 3.64-3.72 (m, 1H), 6.15 (s, 1H), 7.58 (dd, J=2.00, 8.80 Hz, 1H), 7.63 (bs, 1H), 7.69 (bs, 1H), 7.95 (d, J=8.80 Hz, 1H), 8.14 (s, 1H), 8.32 (s, 1H), 8.35 (d, J=6.80 Hz, 1H), 8.49 (s, 1H), 8.72 (d, J=2.00 Hz, 1H), 9.15 (s, 1H), 9.35 (s, 1H). LC/MS: Ascentis Express C18, 5×2.1 mm-2.7 μm; Solvent A=2% ACN: 98% H2O: 10 mM NH4COOH; Solvent B=98% ACN: 2% H2O: 10 mM NH4COOH; gradient 0-100% B over 3 min; retention time: 1.933 min; LCMS (ES-API), m/z 411.0 (M+H). HPLC: Sunfire C18 (150×4.6 mm), 3.5 micron; Solvent A=5% ACN: 95% H2O: 0.05% TFA pH=2.5; Solvent B=95% ACN: 5% H2O: 0.05% TFA pH=2.5; gradient 0-100% B over 15 min (23 min run time); Flow rate: 1.0 μL/min; Retention time: 5.137 min; Purity: 99.8%.
Reaction SMILES: [Br:1][C:2]1[N:7]2[CH:8]=[C:9]([CH:11]=O)[N:10]=[C:6]2[C:5]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[N:4][CH:3]=1.[CH3:19][C:20]1[CH:29]=[CH:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[N:21]=1.Br[Si](C)(C)C>CN(C=O)C>[Br:1][C:2]1[N:7]2[CH:8]=[C:9](/[CH:11]=[CH:19]/[C:20]3[CH:29]=[CH:28][C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[N:21]=3)[N:10]=[C:6]2[C:5]([N:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[N:4][CH:3]=1
Reactant: O=Cc1cn2c(Br)cnc(N3CCOCC3)c2n1
Reactant: Cc1ccc2ccccc2n1
Agent: C[Si](C)(C)Br
Solvent: CN(C)C=O
Product: Brc1cnc(N2CCOCC2)c2nc(/C=C/c3ccc4ccccc4n3)cn12
Temperature: 25 °C
Yield: 93.3 %

Procedure:
To a solution of compound 2a (800 mg, 2.58 mmol) in DMF (10 mL) was added 2-methylquinoline (600 mg, 4.20 mmol) and bromotrimethylsilane (960 mg, 8.89 mmol). The reaction mixture was stirred in a 20 mL sealed tube at 90° C. for 4 h. After cooling to rt, the reaction was quenched with MeOH (20 mL). The solids were collected by filtration and washed with Et2O to obtain compound 2b as a red solid (1.05 g, 85% yield). Mass Spectrum (LCMS, ESI pos.): Calcd. for C21H18BrN5O: 436.1 (M+H). found: 436.1.
Reaction SMILES: [N:1]#[N:2].Cl.C[O:5][C:6](=[O:31])[C@H:7]([CH2:24][CH2:25][CH2:26][NH:27][C:28](=[NH:30])[NH2:29])[NH:8][S:9]([C:12]1[CH:21]=[CH:20][C:19]2[C:14](=[CH:15][CH:16]=[C:17]([O:22][CH3:23])[CH:18]=2)[CH:13]=1)(=[O:11])=[O:10].C(OCC)C.[CH2:37]([NH2:41])[CH2:38][CH2:39][CH3:40]>C(O)(=O)C>[N:1]#[N:2].[C:6]([OH:31])(=[O:5])[CH3:7].[CH3:23][O:22][C:17]1[CH:18]=[C:19]2[C:14](=[CH:15][CH:16]=1)[CH:13]=[C:12]([S:9]([NH:8][C@H:7]([C:6]([NH:41][CH2:37][CH2:38][CH2:39][CH3:40])=[O:5])[CH2:24][CH2:25][CH2:26][NH:27][C:28](=[NH:30])[NH2:29])(=[O:11])=[O:10])[CH:21]=[CH:20]2
Reactant: CCCCN
Reactant: COC(=O)[C@H](CCCNC(=N)N)NS(=O)(=O)c1ccc2cc(OC)ccc2c1
Agent: Cl
Agent: N#N
Solvent: CCOCC
Solvent: CC(=O)O
Product: CCCCNC(=O)[C@H](CCCNC(=N)N)NS(=O)(=O)c1ccc2cc(OC)ccc2c1
Reaction time: 48 h
Yield: 74 %

Procedure:
A 1.0 gram amount of N2 -(6-methoxy-2-naphthalene-sulfonyl)-L-arginine methyl ester hydrochloride was dissolved in 2 ml of butylamine with vigorous agitation. After the resulting solution was allowed to stand at room temperature for 2 days, the butylamine was removed in vacuo and the residual syrup was washed well with 5 ml of water to obtain a powdery product. And then this powder was dissolved in minimum volume of acetic acid. To this solution ethyl ether was added to precipitate the viscous oily product. Reprecipitation from ethanol-ethyl ether gave N2 -(6-methoxy-2-naphthalenesulfonyl)-N-butyl-L-argininamide acetate in a powder form in 74% yield.
Reaction SMILES: CCO.[CH3:4][O:5][C:6]([C:8]1[C:9]([OH:32])=[C:10]2[C:15](=[CH:16][N:17]=1)[N:14]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13](=[O:25])[C:12]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[CH:11]2)=[O:7]>C1COCC1.[Pd]>[CH3:4][O:5][C:6]([C:8]1[C:9]([OH:32])=[C:10]2[C:15](=[CH:16][N:17]=1)[N:14]([CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:13](=[O:25])[CH:12]([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH2:11]2)=[O:7]
Reactant: COC(=O)c1ncc2c(cc(-c3ccccc3)c(=O)n2Cc2ccccc2)c1O
Agent: [Pd]
Solvent: CCO
Solvent: C1CCOC1
Product: COC(=O)c1ncc2c(c1O)CC(c1ccccc1)C(=O)N2Cc1ccccc1
Reaction time: 120 h
Yield: 54.5 %

Procedure:
To a mixture of 10% Pd/C (50 mg) and EtOH (5 mL) was added a solution of 1-benzyl-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (40 mg, 0.104 mmol) in 5 mL of THF. The resulting mixture was placed under H2 (35 psi) for 5 days. The mixture was filtered through a pad of Celite and the filtrate was concentrated. The residue was purified by silica gel chromatography (0-50% EtOAc/hexanes+2% AcOH) to give 22 mg of the title compound as a white solid. MS: (+) m/z 389.34 (M+1).
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:17][CH2:16][C@H:15]([C:18]([O:20]CC)=[O:19])[CH2:14][C@H:13]1[NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[OH-].[Li+].Cl>O1CCCC1>[C:18]([C@H:15]1[CH2:16][CH2:17][C@H:12]([NH:11][C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])[C@H:13]([NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:14]1)([OH:20])=[O:19]
Reactant: CCOC(=O)[C@H]1CC[C@H](NC(=O)OCc2ccccc2)[C@H](NC(=O)OC(C)(C)C)C1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)N[C@@H]1C[C@@H](C(=O)O)CC[C@@H]1NC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 100.2 %

Procedure:
(1S,2R,4S)—N1-Benzyloxycarbonyl-N2-(tert-butoxy-carbonyl)-4-ethoxycarbonyl-1,2-cyclohexanediamine (620 mg) was dissolved in tetrahydrofuran (10 ml), and an aqueous solution (5.0 ml) of lithium hydroxide monohydrate (93 mg) was added to stir the mixture at room temperature for 16 hours. After lithium hydroxide monohydrate (221 mg) was additionally added to the reaction mixture, and the mixture was stirred at room temperature for 2 hours, the reaction mixture was neutralized with 1N hydrochloric acid and extracted with methylene chloride. An organic layer was washed with saturated saline and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain the title compound (580 mg) as a colorless foamy substance.
Reaction SMILES: [CH2:1]([C:4]1[CH:5]=[C:6]([OH:11])[C:7](=[CH:9][CH:10]=1)O)[CH2:2][CH3:3].[CH3:12][C:13]([CH3:15])=[O:14].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1C=CC=CC=1>[CH2:1]([C:4]1[C:5]2[O:14][C:13]([CH3:15])([CH3:12])[O:11][C:6]=2[CH:7]=[CH:9][CH:10]=1)[CH2:2][CH3:3]
Reactant: CCCc1ccc(O)c(O)c1
Reactant: CC(C)=O
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: c1ccccc1
Product: CCCc1cccc2c1OC(C)(C)O2

Procedure:
The same procedures as described in Example 10 were carried out by using a mixture of 7.61 g (50 mM) of 4-n-propylcatechol, 15 ml of acetone, 30 mg of p-toluenesulfonic acid monohydrate and 15 ml of benzene. 5 n-Propyl-2,2-dimethyl-1,3-benzodioxol was obtained in the yield of 9.13 g (47 mM) as colorless transparent liquid having a boiling point of 82°-87° C./3 mmHg.
Reaction SMILES: [CH:1]1([O:7][CH2:8][CH2:9][OH:10])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C:11]1([CH3:21])[CH:16]=[CH:15][C:14]([S:17](Cl)(=[O:19])=[O:18])=[CH:13][CH:12]=1>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[CH:1]1([O:7][CH2:8][CH2:9][O:10][S:17]([C:14]2[CH:15]=[CH:16][C:11]([CH3:21])=[CH:12][CH:13]=2)(=[O:19])=[O:18])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: OCCOC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OCCOC2CCCCC2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 54.5 %

Procedure:
To a solution of 2-(cyclohexyloxy)-1-ethanol (200 mg, 1.39 mmol) in pyridine (10 mL) at 0° C. was added p-toluenesulfonyl chloride (292 mg, 1.53 mmol) portionwise followed by 4-(dimethylamino)pyridine (a few crystals) and the mixture was stirred at room temperature for 16 hours. The solvent was removed in vacuo to give a crude residue that was partitioned between dichloromethane and 2N aqueous hydrochloric acid. The two layers were separated and the organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to give a yellow oil. This was purified by column chromatography on silica gel, eluting with dichloromethane, to give the title compound (226 mg, 54%) as a yellow oil.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7](Cl)=[O:8])([O-:3])=[O:2].[Cl:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[Cl-].[Al+3].[Cl-].[Cl-]>>[N+:1]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7]([C:17]1[CH:18]=[CH:19][C:14]([Cl:13])=[CH:15][CH:16]=1)=[O:8])([O-:3])=[O:2]
Reactant: O=C(Cl)c1cccc([N+](=O)[O-])c1
Reactant: Clc1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Product: O=C(c1ccc(Cl)cc1)c1cccc([N+](=O)[O-])c1
Temperature: 0 °C
Reaction time: 4 h
Yield: 76 %

Procedure:
A mixture of m-nitrobenzoyl chloride 23.25 g (0.12 mol), chlorobenzene 25 ml (0.25 mol) and anhydrous aluminum chloride 17.5 g (0.13 mol) was stirred at 80°-100° C. for 4 hrs. After cooling, the reaction mixture was poured into ice-water with rapid stirring. The white precipitate obtained was collected by filtration and washed with water and then hexane. The white solid was recrystallized from hexane/CH2Cl2 to provide a solid with a melting point of 95°-96° C.; yield 76%.