Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:17][C:16]2[N:15]=[CH:14][CH:13]=[C:12]([CH3:18])[C:11]=2[C:10](=O)[CH2:9]1.[C:20]([NH:23][NH2:24])([NH2:22])=[NH:21].[ClH:25].Cl.O>C(O)C>[ClH:25].[Br:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:17][C:16]2[N:15]=[CH:14][CH:13]=[C:12]([CH3:18])[C:11]=2[C:10](=[N:24][NH:23][C:20]([NH2:22])=[NH:21])[CH2:9]1
Reactant: N=C(N)NN
Reactant: Cc1ccnc2c1C(=O)CC(c1ccccc1Br)C2
Agent: Cl
Solvent: O
Solvent: CCO
Product: Cc1ccnc2c1C(=NNC(=N)N)CC(c1ccccc1Br)C2
Yield: 74.2 %

Procedure:
A mixture of 7-(2-bromophenyl)-4-methyl-5,6,7,8-tetrahydroquinolin-5-one (0.49 g), aminoguanidine hydrochloride (0.19 g), concentrated hydrochloric acid (0.39 ml), water (0.39 ml) and ethanol (50 ml) was refluxed for 6.5 hours. Under reduced pressure, the solvent was evaporated, and the residue was dissolved in water. The solution was washed with ethyl acetate. Under reduced pressure, the solvent was evaporated, and the residue was recrystallized from ethanol-water to give 7-(2-bromophenyl)-5-guanidinoimino-4-methyl-5,6,7,8-tetrahydroquinoline hydrochloride (Compound 66) (0.47 g) as colorless crystals.
Reaction SMILES: C([O:3][C:4]([C:6]1[N:7]=[CH:8][C:9]2[NH:10][C:11]3[C:16]([C:17]=2[C:18]=1[CH2:19][O:20][CH3:21])=[C:15]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH:14]=[CH:13][CH:12]=3)=O)C.O.[NH2:31][NH2:32]>>[CH2:23]([O:22][C:15]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:16]=1[C:17]1[C:18]([CH2:19][O:20][CH3:21])=[C:6]([C:4]([NH:31][NH2:32])=[O:3])[N:7]=[CH:8][C:9]=1[NH:10]2)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: CCOC(=O)c1ncc2[nH]c3cccc(OCc4ccccc4)c3c2c1COC
Reactant: NN
Solvent: O
Product: COCc1c(C(=O)NN)ncc2[nH]c3cccc(OCc4ccccc4)c3c12

Procedure:
1.56 g of 5-benzyloxy-4-methoxymethyl-β-carboline-3-carboxylic acid-ethyl ester is refluxed in 20 ml of hydrazine hydrate (80%) for 4 hours. After cooling, the precipitated crystals are suctioned off and dried. 1.2 g of 5-benzyloxy-4-methoxymethyl-β-carboline-3-carboxylic acid-hydrazide of a melting point of 212°-213° C. is obtained.
Reaction SMILES: [BH4-].[Na+].C([O:6][C:7]1[CH:12]=[CH:11][C:10]([S:13][CH3:14])=[C:9]([O:15][CH3:16])[CH:8]=1)C=C.Cl.O>C1COCC1.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.CCOC(C)=O>[CH3:16][O:15][C:9]1[CH:8]=[C:7]([OH:6])[CH:12]=[CH:11][C:10]=1[S:13][CH3:14]
Reactant: C=CCOc1ccc(SC)c(OC)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: Cl
Agent: [BH4-]
Solvent: C1CCOC1
Solvent: O
Solvent: CCOC(C)=O
Product: COc1cc(O)ccc1SC
Temperature: 25 °C
Yield: 56.5 %

Procedure:
Sodium borohydride (18.92 g, 0.5 mol) was added portionwise to a solution of 4-(allyloxy)-2-methoxy-1-(methylsulfanyl)benzene (26.0 g, 0.124 mol), and tetrakis(triphenylphosphine)palladium (0) (7.14 g, 6.18 mol) in THF (600 ml) at 5° C. The resultant solution was allowed to warm to RT and then heated to 45° C. for 14 h whilst protected under an atmosphere of nitrogen. After cooling in an ice-bath, the reaction mixture was acidified to pH5 with HCl (2M, 200 ml). Water (200 ml) and EtOAc (300 ml) were added, and the aqueous phase separated and extracted with EtOAc (2×200 ml). The combined organics were dried over MgSO4 and concentrated to a black solid (40 g) which was purified by flash column chromatography on silica gel eluting with EtOAc:pentane (1:9 to 3:7) to afford the title compound as a white solid (11.85 g, 0.07 mol).
Reaction SMILES: [O:1]=[C:2]1[NH:6][CH:5]=[C:4]([C:7]([OH:9])=O)[O:3]1.[NH2:10][CH2:11][CH2:12][N:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][CH2:22][C:23]2[CH:28]=[C:27]([Cl:29])[CH:26]=[C:25]([Cl:30])[CH:24]=2)=[O:20])[CH2:15][CH2:14]1>>[O:1]=[C:2]1[NH:6][CH:5]=[C:4]([C:7]([NH:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][CH2:22][C:23]3[CH:28]=[C:27]([Cl:29])[CH:26]=[C:25]([Cl:30])[CH:24]=3)=[O:20])[CH2:15][CH2:14]2)=[O:9])[O:3]1
Reactant: O=C(O)c1c[nH]c(=O)o1
Reactant: NCCN1CCN(C(=O)OCc2cc(Cl)cc(Cl)c2)CC1
Product: O=C(NCCN1CCN(C(=O)OCc2cc(Cl)cc(Cl)c2)CC1)c1c[nH]c(=O)o1

Procedure:
The title compound was prepared from 2-oxo-2,3-dihydrooxazole-5-carboxylic acid (Example 21 step 1) and 3,5-dichlorobenzyl 4-(2-aminoethyl)piperazine-1-carboxylate (step 2) analogously to Example 15 step 3;
Reaction SMILES: O=C(CC)CC(OCC)=O.C(O)(=O)C(O)=O.C1(NN)CC1.[CH:22]1([C:25]2[N:29]([CH:30]([CH3:32])[CH3:31])[N:28]=[CH:27][C:26]=2[CH:33]=[O:34])[CH2:24]C1>>[CH:30]1([N:29]2[C:25]([CH2:22][CH3:24])=[C:26]([CH:33]=[O:34])[CH:27]=[N:28]2)[CH2:31][CH2:32]1
Reactant: CC(C)n1ncc(C=O)c1C1CC1
Agent: CCOC(=O)CC(=O)CC
Agent: NNC1CC1
Agent: O=C(O)C(=O)O
Product: CCc1c(C=O)cnn1C1CC1

Procedure:
1-Cyclopropyl-5-ethyl-1H-pyrazole-4-carbaldehyde was prepared with ethyl 3-oxopentanoate and cyclopropyl hydrazine oxalate (Gever, G. and Hayes, K. J. Org. Chem, 1949, 14, 813–818) in the same manner as 5-cyclopropyl-1-isopropyl-1H-pyrazole-4-carbaldehyde (Example 49).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[N:12]([S:13]([C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=3)(=[O:15])=[O:14])[CH:11]([CH2:23][OH:24])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.C(N(CC)CC)C>ClCCl.CS(C)=O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[N:12]([S:13]([C:16]3[CH:17]=[CH:18][C:19]([CH3:22])=[CH:20][CH:21]=3)(=[O:15])=[O:14])[CH:11]([CH:23]=[O:24])[CH2:10][CH2:9]2)=[CH:6][CH:7]=1
Reactant: Cc1ccc(S(=O)(=O)N2C(CO)CCC2c2ccc(F)cc2)cc1
Solvent: CS(C)=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1ccc(S(=O)(=O)N2C(C=O)CCC2c2ccc(F)cc2)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 99.3 %

Procedure:
To a stirred solution of (2RS,5SR)-[5-(4-fluoro-phenyl)-1-(toluene-4-sulfonyl)-pyrrolidin-2-yl]-methanol (8.12 g, 23.2 mmol) in dichloromethane (150 ml) was added triethylamine (16.2 ml, 116 mmol). To the cooled solution (0° C.) was added dropwise over a period of 15 min pyridine-SO3-complex (18.3 g, 116 mmol) dissolved in DMSO (75 ml) and the reaction mixture was stirred for 1 h at 0° C. Aqueous work-up yielded (2RS,5SR)-5-(4-fluoro-phenyl)-1-(toluene-4-sulfonyl)-pyrrolidine-2-carboxaldehyde (8.0 g, yield 99%) as a light brown oil.
Reaction SMILES: [Cl:1][C:2]1[CH:34]=[CH:33][C:5]([C:6]([O:8][C@H:9]2[C@H:16]([OH:17])[C@@H:15]([CH2:18][OH:19])[O:14][C@@H:11]([S:12][CH3:13])[C@@H:10]2[NH:20][C:21](=[C:23]2[C:28](=[O:29])[CH2:27][C:26]([CH3:31])([CH3:30])[CH2:25][C:24]2=[O:32])[CH3:22])=[O:7])=[CH:4][CH:3]=1.[Si:35](Cl)([C:48]([CH3:51])([CH3:50])[CH3:49])([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>CN(C)C1C=CN=CC=1.ClCCCl.C(Cl)(Cl)Cl>[Si:35]([O:19][CH2:18][C@H:15]1[O:14][C@@H:11]([S:12][CH3:13])[C@H:10]([NH:20][C:21](=[C:23]2[C:24](=[O:32])[CH2:25][C:26]([CH3:31])([CH3:30])[CH2:27][C:28]2=[O:29])[CH3:22])[C@@H:9]([O:8][C:6](=[O:7])[C:5]2[CH:33]=[CH:34][C:2]([Cl:1])=[CH:3][CH:4]=2)[C@@H:16]1[OH:17])([C:48]([CH3:51])([CH3:50])[CH3:49])([C:42]1[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1
Reactant: CS[C@@H]1O[C@H](CO)[C@@H](O)[C@H](OC(=O)c2ccc(Cl)cc2)[C@H]1NC(C)=C1C(=O)CC(C)(C)CC1=O
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: CN(C)c1ccncc1
Solvent: ClCCCl
Solvent: ClC(Cl)Cl
Product: CS[C@@H]1O[C@H](CO[Si](c2ccccc2)(c2ccccc2)C(C)(C)C)[C@@H](O)[C@H](OC(=O)c2ccc(Cl)cc2)[C@H]1NC(C)=C1C(=O)CC(C)(C)CC1=O
Temperature: 25 °C
Yield: 75.2 %

Procedure:
A mixture of methyl 3-O-(p-chlorobenzoyl)-2-deoxy-2-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-ethylamino]-1-thio-β-D-glucopyranoside (3) (1.00 g, 1.95 mmol), t-butyldiphenylsilylchloride (536 mg, 1.95) and 4-dimethylaminopyridine (238 mg, 1.95 mmol), in 1,2-dichloroethane (30 mL), was stirred under reflux for 6 hours. The reaction mixture was cooled to room temperature, diluted with chloroform (60 mL) and washed with diluted brine (3×50 mL, brine/water, 1:2), dried over MgSO4. The solvent was removed in vacuo and the residue was chromatographed using hexane—EtOAc 1:1 as the mobile phase to give a white solid, methyl 6-O(t-butyldiphenylsilyl)-3-O-(p-chlorobenzoyl)-2-deoxy-2-[1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)ethylamino]-1-thio-β-D-glucopyranoside (4) (1.1 g, 75%).
Reaction SMILES: [CH3:1][N:2]([N:9]=O)C(N[N+]([O-])=O)=N.[OH-].[K+].[N+:13](=[CH2:15])=[N-:14].[CH:16]1([C:22](Cl)=[O:23])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1>CCOCC>[N+:2](=[CH2:1])=[N-:9].[CH:16]1([C:22](=[O:23])[CH:15]=[N+:13]=[N-:14])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1
Reactant: O=C(Cl)C1CCCCC1
Reactant: CN(N=O)C(=N)N[N+](=O)[O-]
Agent: C=[N+]=[N-]
Agent: [K+]
Agent: [OH-]
Solvent: CCOCC
Product: [N-]=[N+]=CC(=O)C1CCCCC1
Reaction time: 1 h

Procedure:
A solution of diazomethane is prepared from N-methyl-N'-nitro-N-nitroso guanidine (12.5 g), potassium hydroxide (50%, 20 ml), and ether (300 ml). TEA (7.7 ml) is added to the diazomethane solution (65%) followed by cyclohexane carboxylic acid chloride (7.4 ml) slowly at 0° . The reaction is stirred at 0° for 1 hr then for 18 hrs at 22° . A porecipitate forms, it is filtered and washed with ether, and the filtrate concentrated. The resulting oil is cooled to -78° , triturated with ether, then warmed to 22° and concentrated with reduced pressure and heat to give the title compound as an oil, NMR (acetone-d6) 5.4 and 1.4-0.8 δ.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:19]=[CH:18][C:6]([CH:7]=[C:8]2[CH2:13][C:12]([CH3:15])([CH3:14])[NH:11][C:10]([CH3:17])([CH3:16])[CH2:9]2)=[C:5]([N+:20]([O-:22])=[O:21])[CH:4]=1.C=O.[C:25]([BH3-])#N.[Na+].C([O-])(O)=O.[Na+]>CO.CCOC(C)=O>[CH3:1][O:2][C:3]1[CH:19]=[CH:18][C:6]([CH:7]=[C:8]2[CH2:9][C:10]([CH3:17])([CH3:16])[N:11]([CH3:25])[C:12]([CH3:14])([CH3:15])[CH2:13]2)=[C:5]([N+:20]([O-:22])=[O:21])[CH:4]=1
Reactant: [BH3-]C#N
Reactant: COc1ccc(C=C2CC(C)(C)NC(C)(C)C2)c([N+](=O)[O-])c1
Agent: C=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CO
Product: COc1ccc(C=C2CC(C)(C)N(C)C(C)(C)C2)c([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 31.1 %

Procedure:
4-(4-methoxy-2-nitrobenzylidene)-2,2,6,6-tetramethylpiperidine (1.1 g; 3.23 mmol; 1 eq) is dissolved in MeOH (10 mL) then formaldehyde (0.19 g; 6.45 mmol; 2 eq) and sodium cyanoborohydride (0.41 g; 6.45 mmol; 2 eq) are added. The reaction mixture is stirred at room temperature overnight. The solvents are evaporated under reduced pressure and the residue obtained is taken up in EtOAc then a saturated aqueous solution of NaHCO3 is added. The organic phase is washed with brine, dried over MgSO4 and the solvent is evaporated under reduced pressure to afford 320 mg (31%) of the title compound as a yellow oil. 1H NMR (DMSO-d6) δ 7.53 (d, J=2.6 Hz, 1H), 7.20 (d, J=8.2 Hz, 1H), 7.10 (dd, J=8.6, 2.6 Hz, 1H), 6.49 (s, 1H), 3.87 (s, 3H), 2.22-2.15 (m, 6H), 1.20-1.10 (m, 6H), 1.00-0.90 (m, 6H). HPLC (max plot) 99.5%; Rt 2.84 min. LC/MS: (ES+): 319.1
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.C=O.[C:12]([BH3-])#N.[Na+].O>C1COCC1>[CH3:12][N:7]1[CH2:8][CH2:9][N:4]([CH2:3][CH2:2][OH:1])[CH2:5][CH2:6]1
Reactant: OCCN1CCNCC1
Reactant: [BH3-]C#N
Agent: C=O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CN1CCN(CCO)CC1
Temperature: 50 °C

Procedure:
In THF (30 ml) were added N-(2-hydroxyethyl)piperazine (500 mg, 3.84 mmol), a solution of formaldehyde (3117 mg, 38.41 mmol) and sodium cyanoborohydride (1207 mg, 19.20 mmol). The mixture was heated up to 50° C. overnight under stirring. After cooling some water was added and the mixture was extracted with DCM (3×). The organic layers were dried over MgSO4 and evaporated. The residue was purified over a silica plug with DCM/MeOH 9:1 as eluant to afford an oil (370 mg, Y=67%). 1H NMR (DMSO-d6) δ 4.45 (t, J=5.3 Hz, 1H), 3.51-3.45 (m, 2H), 3.02-2.84 (m, 4H), 2.71-2.64 (m, 2H), 2.61 (s, 3H), 2.58-2.53 (m, 2H), 2.47-2.43 (m, 2H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[NH:19][C:18]3[CH:20]=[CH:21][CH:22]=[CH:23][C:17]=3[N:16]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[CH2:27][CH2:28][CH2:29][C:30](=[O:32])[CH3:31].[Cl-].[NH4+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(=O)(O)[O-].[Na+].CO.ClCCl.CN(C)C=O.O1CCCC1>[C:1]([O:5][C:6]([N:8]1[CH2:14][CH2:13][CH2:12][N:11]([C:15]2[N:16]([CH2:27][CH2:28][CH2:29][C:30](=[O:32])[CH3:31])[C:17]3[CH:23]=[CH:22][CH:21]=[CH:20][C:18]=3[N:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(=O)CCCCl
Reactant: CC(C)(C)OC(=O)N1CCCN(c2nc3ccccc3[nH]2)CC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])O
Agent: [Br-]
Solvent: CO
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: CC(=O)CCCn1c(N2CCCN(C(=O)OC(C)(C)C)CC2)nc2ccccc21
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Combine 1-(t-butoxycarbonyl)-4-(1H-benzimidazol-2-yl)[1,4]diazepane (1.10 g, 3.5 mmol) and tetrahydrofuran (45 mL) and dimethylformamide (5 mL). Cool in an ice bath and add sodium hydride (0.21 g, 60% in oil, 5.22 mmol). After 1 hour, add 5-chloropentan-2-one, ethylene ketal (0.79 mL, 5.22 mmol) and tetra-n-butylammonium bromide (112 mg, 0.35 mmol) and warm to ambient temperature. Heat to reflux. After 18 hours, cool, add sodium hydride (0.1 g) and 5-chloropentan-2-one, ethylene ketal (0.50 mL) and again heat to reflux. After 24 hours, cool in a dry-ice/acetone bath and add a saturated aqueous solution of ammonium chloride. Warm to ambient temperature and dilute the reaction mixture with a saturated aqueous solution of sodium bicarbonate. Concentrate in vacuo to remove most to the tetrahydrofuran and extract three times with ethyl acetate. Extract the combined organic layers with water and then brine, dry, the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 5% methanol/dichloromethane/0.1% saturated aqueous ammonia solution to give 1-(t-butoxycarbonyl)-4-(1-(4-oxopentyl)-1H-benzimidazol-2-yl)[1,4]diazepane, ethylene ketal: Rf=0.47 (silica gel, 5% methanol/dichloromethane/0.1% saturated aqueous ammonia solution).
Reaction SMILES: Br[C:2]1[C:3]2[C:8]([C:9]([C:16]3[CH:21]=[C:20]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[CH:19]=[C:18]([C:28]4[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=4)[CH:17]=3)=[C:10]3[C:15]=1[CH:14]=[CH:13][CH:12]=[CH:11]3)=[CH:7][CH:6]=[CH:5][CH:4]=2.[C:34]1([C:40]([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)=[CH:41][C:42]2[CH:47]=[CH:46][C:45](OB(O)O)=[CH:44][CH:43]=2)[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.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>[C:34]1([C:40]([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)=[CH:41][C:42]2[CH:47]=[CH:46][C:45]([C:2]3[C:3]4[C:8]([C:9]([C:16]5[CH:21]=[C:20]([C:22]6[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=6)[CH:19]=[C:18]([C:28]6[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=6)[CH:17]=5)=[C:10]5[C:15]=3[CH:14]=[CH:13][CH:12]=[CH:11]5)=[CH:7][CH:6]=[CH:5][CH:4]=4)=[CH:44][CH:43]=2)[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1
Reactant: Brc1c2ccccc2c(-c2cc(-c3ccccc3)cc(-c3ccccc3)c2)c2ccccc12
Reactant: OB(O)Oc1ccc(C=C(c2ccccc2)c2ccccc2)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: C(=C(c1ccccc1)c1ccccc1)c1ccc(-c2c3ccccc3c(-c3cc(-c4ccccc4)cc(-c4ccccc4)c3)c3ccccc23)cc1
Yield: 81 %

Procedure:
Under an atmosphere of argon, 9-bromo-10-(3,5-diphenylphenyl)anthracene (3.9 g, 8.0 mmole), 4-(2,2-diphenylvinyl)phenylboric acid (2.7 g, 9.0 mmole, 1.1 eq) and tetrakis(triphenylphosphine)palladium(0) (0.18 g, 0.16 mmole, 2% Pd) were suspended in toluene (30 ml). To the obtained suspension, a 2M aqueous solution of sodium carbonate (2.9 g, 27 mmole, 3 eq/15 ml) was added, and the resultant mixture was refluxed for 10 hours. An organic layer was separated from the reaction mixture, washed with a saturated aqueous solution of sodium chloride (30 ml) and dried with magnesium sulfate. After the solvent was removed by distillation, a brown solid substance was obtained. The obtained solid substance was purified in accordance with the column chromatography (silica gel/hexane+10% dichloromethane, hexane+20% dichloromethane), and a white solid substance (4.3 g, the yield: 81%) was obtained. The result of examination of the obtained product in accordance with 1H-NMR was as follows:
Reaction SMILES: [CH2:1]1[O:9][C:8]2[CH:7]=[CH:6][C:5]([CH2:10][CH2:11][NH2:12])=[CH:4][C:3]=2[O:2]1.[C:13]([O:17][CH2:18][CH3:19])(=[O:16])[CH:14]=[CH2:15]>>[CH2:18]([O:17][C:13]([CH2:14][CH2:15][N:12]([CH2:11][CH2:10][C:5]1[CH:6]=[CH:7][C:8]2[O:9][CH2:1][O:2][C:3]=2[CH:4]=1)[CH2:15][CH2:14][C:13]([O:17][CH2:18][CH3:19])=[O:16])=[O:16])[CH3:19]
Reactant: C=CC(=O)OCC
Reactant: NCCc1ccc2c(c1)OCO2
Product: CCOC(=O)CCN(CCC(=O)OCC)CCc1ccc2c(c1)OCO2
Yield: 43.8 %

Procedure:
A mixture of 16.5 g of 3,4-methylenedioxyphenylethylamine and 40.5 g of ethyl acrylate is refluxed for 24 hours over an oil bath. After cooling, the mixture is concentrated under reduced pressure to distill away excess ethyl acrylate. 16 g of N,N-bis (β-ethoxycarbonylethyl)-3,4-methylenedioxyphenylethylamine is obtained as the residue.
Reaction SMILES: Cl.Cl.NCCSSCCN.[OH-].[Na+].N(C1C=CC(S(Cl)(=O)=O)=CC=1)=[N+]=[N-].[N:26]([C:29]1[CH:34]=[CH:33][C:32]([S:35]([NH:38][CH2:39][CH2:40][S:41][S:42][CH2:43][CH2:44][NH2:45])(=[O:37])=[O:36])=[CH:31][CH:30]=1)=[N+:27]=[N-:28].[C:46]1(=[O:52])[O:51][C:49](=[O:50])[CH2:48][CH2:47]1.Cl>O>[N:26]([C:29]1[CH:34]=[CH:33][C:32]([S:35]([NH:38][CH2:39][CH2:40][S:41][S:42][CH2:43][CH2:44][NH:45][C:46](=[O:52])[CH2:47][CH2:48][C:49]([OH:51])=[O:50])(=[O:37])=[O:36])=[CH:31][CH:30]=1)=[N+:27]=[N-:28]
Reactant: O=C1CCC(=O)O1
Reactant: [N-]=[N+]=Nc1ccc(S(=O)(=O)NCCSSCCN)cc1
Agent: Cl
Agent: NCCSSCCN
Agent: [N-]=[N+]=Nc1ccc(S(=O)(=O)Cl)cc1
Solvent: O
Product: [N-]=[N+]=Nc1ccc(S(=O)(=O)NCCSSCCNC(=O)CCC(=O)O)cc1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
2.2 g of cystamine dihydrochloride were dissolved in 20 ml of water and adjusted to pH 10 with NaOH. 2.1 g of p-azidobenzenesulfonyl chloride were suspended in this solution and the suspension was stirred at room temperature for 5 hours. The precipitated N-(p-azidobenzenesulfonyl)cystamine was reacted with 2 g of succinic anhydride and stirred overnight. The resulting solution was acidified with HCl, subsequently filtered and washed with water. The residue was dried at room temperature in a high vacuum and gave 1.53 g of N-(p-azidobenzenesulfonyl) N'-(3-carboxypropionyl) cystamine. The IR showed bands at 3283 (amide NH) 2134 (azide), 1714 (acid carbonyl), 1650 (amide), 1589+1547 (aromatic), 1284 (COOH), 1328+1180 (arylsulfonyl ), 839 (p-disubst.benzene). TLC (silica gel--NH3 conc./EtOH=1%) Rf=0.7. m.p.: dec. at 163°.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:6]([NH2:8])=[NH:7].[Cl:14][C:15]1[CH:26]=[C:25]([Cl:27])[CH:24]=[CH:23][C:16]=1[CH:17]=[C:18]([C:21]#[N:22])[C:19]#[N:20]>>[NH2:22][CH2:21][C:18]1[C:19]([NH2:20])=[N:7][C:6]([C:5]2[CH:9]=[CH:10][C:11]([O:12][CH3:13])=[C:3]([O:2][CH3:1])[CH:4]=2)=[N:8][C:17]=1[C:16]1[CH:23]=[CH:24][C:25]([Cl:27])=[CH:26][C:15]=1[Cl:14]
Reactant: COc1ccc(C(=N)N)cc1OC
Reactant: N#CC(C#N)=Cc1ccc(Cl)cc1Cl
Product: COc1ccc(-c2nc(N)c(CN)c(-c3ccc(Cl)cc3Cl)n2)cc1OC

Procedure:
The title compound, MS: m/e=405.3 (M+H+), was prepared from 3,4-dimethoxy-benzamidine and 2-(2,4-dichloro-benzylidene)-malononitrile in analogy to the process described in Example 11 as a solid.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[S:15][CH:16]=[C:17]([C:19]([OH:21])=O)[CH:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[NH:29]1[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH:12]=[C:11]([C:14]2[S:15][CH:16]=[C:17]([C:19]([N:29]3[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]3)=[O:21])[CH:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: C1CCCNCC1
Reactant: CC(C)(C)OC(=O)N1CC=C(c2cc(C(=O)O)cs2)CC1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CC=C(c2cc(C(=O)N3CCCCCC3)cs2)CC1
Reaction time: 2 h
Yield: 69.5 %

Procedure:
4-(4-Carboxy-thiophen-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (0.1 g, 0.35 mmol) was dissolved in DMF (2 mL) and triethylamine (1.0 mmol). Homopiperidine (1.4 mmol) was added with HATU (0.35 mmol) and the mixture stirred for 2 hours. The mixture was diluted with DCM (20 mL) and washed with water. The organic solution was separated, dried with anhydrous magnesium sulphate, filtered and evaporated. The residue was then purified by HPLC, eluting with 10%-98% acetonitrile in water (0.1% formic acid) over 30 minutes. The fractions containing the desired product were concentrated under vacuum to give the title compound (0.095 g). LCMS m/z 391.56 [M+H]+ RT=4.09min (Analytical Method 4).
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[C:5]([C:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:19][CH3:20])[C:14]=2Br)[CH:9]=1)(=[O:7])[CH3:6].BrC1C2C(=CC=CC=2)C=CC=1OC>CC1C=CC(C)=CC=1>[C:5]([C:8]1[CH:17]=[CH:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:19][CH3:20])[CH:14]=2)[CH:9]=1)(=[O:7])[CH3:6]
Reactant: COc1ccc2cc(C(C)=O)ccc2c1Br
Agent: COc1ccc2ccccc2c1Br
Agent: [Al+3]
Agent: [Cl-]
Solvent: Cc1ccc(C)cc1
Product: COc1ccc2cc(C(C)=O)ccc2c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
45.3 Ml of p-xylene and 8.2 g of anhydrous aluminum chloride are added to the solution of 2-acetyl-5-bromo-6-methoxynaphthalene obtained as in example 1a), while keeping the temperature at -10° C. The reaction mixture is kept for 16 hours under stirring at room temperature and then it is worked as in example 1 obtaining 42.8 g of product with a yield equal to 87.3% calculated on the basis of the starting material 1-bromo-2-methoxynaphthalene.
Reaction SMILES: [C:1]([O:5][C:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[CH:19]=[CH:18][C:17]([CH2:20][N:21]2[C:25]([C:26]#[N:27])=[C:24]([C:28](=[O:32])[CH2:29][CH2:30][CH3:31])[N:23]=[C:22]2[CH2:33][CH2:34][CH3:35])=[CH:16][CH:15]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>C(O)C>[C:1]([O:5][C:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]1[CH:19]=[CH:18][C:17]([CH2:20][N:21]2[C:25]([C:26]#[N:27])=[C:24]([CH:28]([OH:32])[CH2:29][CH2:30][CH3:31])[N:23]=[C:22]2[CH2:33][CH2:34][CH3:35])=[CH:16][CH:15]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CCCC(=O)c1nc(CCC)n(Cc2ccc(-c3ccccc3C(=O)OC(C)(C)C)cc2)c1C#N
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: CCCc1nc(C(O)CCC)c(C#N)n1Cc1ccc(-c2ccccc2C(=O)OC(C)(C)C)cc1
Yield: 94.3 %

Procedure:
Following a procedure similar to that described in Example 45(b), but using 1.13 g of 1-[(2'-t-butoxycarbonylbiphenyl-4-yl)methyl]-4-butyryl-2-propylimidazole-5-carbonitrile [prepared as described in step (a) above] and 0.091 g of sodium borohydride in 23 ml of ethanol, 1.07 g of the title compound were obtained as a viscous oil.
Reaction SMILES: Br[C:2]1[N:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[CH2:9]([O:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[CH:17][CH:18]=1)[CH2:10][CH3:11]>>[Br:8][C:5]1[CH:4]=[N:3][C:2]([C:17]2[CH:16]=[CH:15][CH:14]=[C:13]([O:12][CH2:9][CH2:10][CH3:11])[CH:18]=2)=[N:7][CH:6]=1
Reactant: Brc1cnc(Br)nc1
Reactant: CCCOc1cccc(B(O)O)c1
Product: CCCOc1cccc(-c2ncc(Br)cn2)c1

Procedure:
2,5-Dibromopyrimidine and 3-propoxybenzeneboronic acid are reacted analogously to Example 1 to give 5-bromo-2-(3-propoxyphenyl) pyrimidine. ##STR40##