Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Al].[CH2:2](Br)[C:3]#[CH:4].[Cl:6][C:7]1[CH:8]=[C:9]([C:16]([CH3:24])([CH3:23])[CH2:17][C:18](=[O:22])[CH:19]([F:21])[F:20])[C:10]2[O:14][CH2:13][CH2:12][C:11]=2[CH:15]=1>C1COCC1>[Cl:6][C:7]1[CH:8]=[C:9]([C:16]([CH3:24])([CH3:23])[CH2:17][C:18]([CH:19]([F:20])[F:21])([OH:22])[CH2:4][C:3]#[CH:2])[C:10]2[O:14][CH2:13][CH2:12][C:11]=2[CH:15]=1
Reactant: C#CCBr
Reactant: CC(C)(CC(=O)C(F)F)c1cc(Cl)cc2c1OCC2
Agent: [Al]
Solvent: C1CCOC1
Product: C#CCC(O)(CC(C)(C)c1cc(Cl)cc2c1OCC2)C(F)F
Temperature: 40 °C
Reaction time: 1 h
Yield: 96.8 %

Procedure:
Aluminum foil (108 mg, 4.00 mmol) and mercuric chloride (ca. 1 mg, 0.01 mmol) in 3.5 mL of anhydrous THF were vigorously stirred for 20 minutes. Propargyl bromide (80% in toluene, 0.45 mL, 4.00 mmol) was added slowly (the reaction mixture became warm) and the resulting mixture was stirred at 40° C. for 1 hour. The dark gray propargyl aluminum sesquibromide solution was added to a solution of 4-(5-chloro-2,3-dihydrobenzofuran-7-yl)-1,1-difluoro-4-methylpentan-2-one (380 mg, 1.32 mmol) in 10 mL of anhydrous THF at 0° C. and the reaction was allowed to slowly warmed to room temperature and stirred overnight. The mixture was concentrated in vacuo, quenched with ice and water, and the aqueous layer was extracted with ethyl acetate. The combined organic extracts were dried over magnesium sulfate and concentrated in vacuo to give 420 mg of the title product as an oil (97% yield), which was used without further purification.
Reaction SMILES: C([N:8]1[CH2:12][CH:11]2[C:13](=[O:17])[NH:14][C:15](=[O:16])[CH:10]2[CH2:9]1)C1C=CC=CC=1>C(O)C.[Pd]>[C:13]1(=[O:17])[CH:11]2[CH2:12][NH:8][CH2:9][CH:10]2[C:15](=[O:16])[NH:14]1
Reactant: O=C1NC(=O)C2CN(Cc3ccccc3)CC12
Agent: [Pd]
Solvent: CCO
Product: O=C1NC(=O)C2CNCC12
Reaction time: 16 h

Procedure:
A solution 5-benzyl-tetrahydropyrrolo[3,4-c]pyrrole-1,3-dione, (11.5 g; 49.9 mmol) in ethanol (200 ml) is placed in a ml autoclave and palladium-on-charcoal (5%; 2 g; 0.9 mmol) is then added. After having purged the reactor with nitrogen, the autoclave is placed under 58 bars of hydrogen at 70° C. for 16 hours. After returning to 20° C., filtration and washing of the catalyst, evaporation is carried out under reduced pressure and the solid obtained is then recrystallized from methanol (100 ml) and drying is carried out under reduced pressure at constant weight. Perhydropyrrolo[3,4-c]pyrrole-1,3-dione, (3.6 g) is isolated, the characteristics of which are as follows:
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]=[O:10])=[CH:4][CH:3]=1.[N-:11]=[N+:12]=[N-:13].[Na+].[Al+3].[Cl-].[Cl-].[Cl-]>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:9](=[O:10])[NH:13][N:12]=[N:11]2)=[CH:4][CH:3]=1
Reactant: O=C=Nc1ccc(Br)cc1
Reactant: [N-]=[N+]=[N-]
Agent: [Al+3]
Agent: [Cl-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=c1[nH]nnn1-c1ccc(Br)cc1

Procedure:
To a solution of 1-bromo-4-isocyanatobenzene (5.0 g, 25 mmol) and sodium azide (5.0 g, 77 mmol) in THF (30 mL) was added a solution of AlCl3 (4.0 g, 30 mmol) in THF (18 mL) dropwise. The reaction mixture was heated to reflux overnight. The organic solvent was removed under reduced pressure, then water (50 mL) was added. The solids formed were collected by filtration to obtain compound 53a as a white solid. Mass Spectrum (LCMS, ESI pos.): Calcd. for C7H5BrN4O: 241.0 (M+H). Found 241.1.
Reaction SMILES: [Br:1][C:2]1[C:3](Cl)=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[NH2:10][C:11]1([CH2:16][NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:15][CH2:14][CH2:13][CH2:12]1.BrC1C(NCCNC(=O)OC(C)(C)C)=NC(Cl)=NC=1>>[Br:1][C:2]1[C:3]([NH:10][C:11]2([CH2:16][NH:17][C:18](=[O:24])[O:19][C:20]([CH3:22])([CH3:21])[CH3:23])[CH2:12][CH2:13][CH2:14][CH2:15]2)=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1
Reactant: Clc1ncc(Br)c(Cl)n1
Reactant: CC(C)(C)OC(=O)NCC1(N)CCCC1
Agent: CC(C)(C)OC(=O)NCCNc1nc(Cl)ncc1Br
Product: CC(C)(C)OC(=O)NCC1(Nc2nc(Cl)ncc2Br)CCCC1

Procedure:
tert-butyl N-[[1-[(5-bromo-2-chloro-pyrimidin-4-yl)amino]cyclopentyl]methyl]carbamate is synthesized by treating 5-Bromo-2,4-dichloropyrimidine with tert-butyl N-[(1-aminocyclopentyl)methyl]carbamate using similar experimental conditions as described for the synthesis of tert-butyl N-[2-[(5-bromo-2-chloro-pyrimidin-4-yl)amino]ethyl]carbamate. LCMS (ESI) 405 (M+H)
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([CH2:7][CH2:8][NH:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[CH2:17][OH:18])[CH2:3][CH2:2]1>C1(C)C=CC=CC=1.O=[Mn]=O>[O:1]1[CH2:2][CH2:3][N:4]([CH2:7][CH2:8][NH:9][C:10]2[C:15]([F:16])=[CH:14][CH:13]=[CH:12][C:11]=2[CH:17]=[O:18])[CH2:5][CH2:6]1
Reactant: OCc1cccc(F)c1NCCN1CCOCC1
Agent: O=[Mn]=O
Solvent: Cc1ccccc1
Product: O=Cc1cccc(F)c1NCCN1CCOCC1
Yield: 71.8 %

Procedure:
(2-(2-Morpholinoethylamino)-3-fluorophenyl)methanol (695 mg, 2.733 mmol) was stirred with MnO2 (966 mg, 11.11 mmol) in toluene (12 mL) at 115° C. for 2 days. The reaction was filtered through a plug of Celite with CH2Cl2 and the crude product was purified by ISCO chromatography eluting with EtOAc/Hex (12 g redisep column, 5-40% gradient over 30 CV) to give 2-(2-morpholinoethylamino)-3-fluorobenzaldehyde (495 mg). FIA: 253.17 (M+1)
Reaction SMILES: C(N(CC)CC)C.[OH:8][CH2:9][CH2:10][C:11]1([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=2)[CH2:15][CH2:14][NH:13][CH2:12]1.[CH:24]([O:27][C:28]1[CH:29]=[C:30]([CH2:34][C:35](O)=[O:36])[CH:31]=[CH:32][CH:33]=1)([CH3:26])[CH3:25]>C(Cl)Cl>[OH:8][CH2:9][CH2:10][C:11]1([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=2)[CH2:15][CH2:14][N:13]([C:35](=[O:36])[CH2:34][C:30]2[CH:31]=[CH:32][CH:33]=[C:28]([O:27][CH:24]([CH3:25])[CH3:26])[CH:29]=2)[CH2:12]1
Reactant: CC(C)Oc1cccc(CC(=O)O)c1
Reactant: OCCC1(c2ccc(Cl)c(Cl)c2)CCNC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)Oc1cccc(CC(=O)N2CCC(CCO)(c3ccc(Cl)c(Cl)c3)C2)c1
Temperature: 0 °C

Procedure:
Triethylamine (22.5 ml) and 3-(2-hydroxyethyl)-3-(3,4-dichlorophenyl)pyrrolidine (22 grams) are added to a solution of 16 grams of 3-isopropoxyphenylacetic acid in 500 ml of methylene chloride. The mixture is cooled to 0° C. and 42.6 grams of benzotriazolyl-N-oxytrisdimethylaminophosphonium hexafluorophosphate are then added and the reaction mixture is allowed to warm up to room temperature. After thirty minutes, the mixture is concentrated under vacuum and the residue is taken up in diethyl ether and washed successively with water, a dilute sodium hydroxide solution, a saturated sodium chloride solution, a dilute hydrochloric acid solution, a saturated sodium chloride solution, and a solution of sodium bicarbonate. The organic fraction is dried over magnesium sulfate, filtered, and concentrated in vacuo to yield the title intermediate.
Reaction SMILES: [Si:1]([O:18][C@H:19]([CH3:40])[CH2:20][CH2:21][CH2:22][CH2:23][O:24][C:25]1([CH2:38]I)[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]1)([C:14]([CH3:17])([CH3:16])[CH3:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>CO.[Pd]>[Si:1]([O:18][C@H:19]([CH3:40])[CH2:20][CH2:21][CH2:22][CH2:23][O:24][C:25]1([CH3:38])[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH2:26]1)([C:14]([CH3:16])([CH3:17])[CH3:15])([C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: C[C@H](CCCCOC1(CI)CCN(C(=O)OC(C)(C)C)CC1)O[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Agent: [Pd]
Solvent: CO
Product: C[C@H](CCCCOC1(C)CCN(C(=O)OC(C)(C)C)CC1)O[Si](c1ccccc1)(c1ccccc1)C(C)(C)C
Reaction time: 16 h
Yield: 77.5 %

Procedure:
To a solution of (R)-tert-butyl 4-((5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-(iodomethyl)piperidine-1-carboxylate (13 g, 19.12 mmol) in MeOH (100 mL) was added TEA (5.33 mL, 38.2 mmol) followed by 10% Pd—C (1.018 g, 0.956 mmol) and the resulting mixture was subjected to hydrogenolysis under PAR at 50 PSI. After 16 h, mixture was filtered through a pad of celite and the filtrate was concentrated. The residue was then purified by Biotage (0-15% EtOAc/hexane) to afford (R)-tert-butyl 4-((5-((tert-butyldiphenylsilyl)oxy)hexyl)oxy)-4-methylpiperidine-1-carboxylate (8.2 g, 14.81 mmol, 77% yield) as light yellow oil. 1H NMR (500 MHz, CDCl3) δ 7.73-7.67 (m, 4H), 7.48-7.35 (m, 6H), 3.86 (sxt, J=5.8 Hz, 1H), 3.72 (br. s., 2H), 3.24 (t, J=6.3 Hz, 2H), 3.10 (br. s., 2H), 1.78-1.66 (m, 3H), 1.59-1.51 (m, 1H), 1.50-1.47 (m, 6H), 1.47 (s, 9H), 1.14 (s, 3H), 1.10-1.03 (m, 12H). LCMS (M+Na)=576.7.
Reaction SMILES: [C:1]([N:9]=[C:10]=[S:11])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:12]1([NH2:18])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1>ClCCl>[CH:12]1([NH:18][C:10]([NH:9][C:1](=[O:8])[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[S:11])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1
Reactant: O=C(N=C=S)c1ccccc1
Reactant: NC1CCCCC1
Solvent: ClCCl
Product: O=C(NC(=S)NC1CCCCC1)c1ccccc1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
Benzoyl isothiocyanate (19.4 g, 118.9 mmol) was dissolved in dichloromethane and cooled to 0° C. Cyclohexylamine (13 g, 131.1 mmol) was added dropwise. Then the reaction was stirred at room temperature for 2 h. The mixture was washed with water, dried over sodium sulfate. Concentration under vaccum gave the title compound as a pale white solid in quantitative yield.
Reaction SMILES: [N:1]([CH2:4][C@H:5]1[CH2:10][O:9][C@H:8]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[CH2:7][O:6]1)=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1COCC1.[NH4+]>O>[C:11]1([C@@H:8]2[CH2:7][O:6][C@@H:5]([CH2:4][NH2:1])[CH2:10][O:9]2)[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: [N-]=[N+]=NC[C@H]1CO[C@H](c2ccccc2)CO1
Agent: [NH4+]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: C1CCOC1
Product: NC[C@H]1CO[C@H](c2ccccc2)CO1
Temperature: 25 °C
Reaction time: 8 h
Yield: 99.2 %

Procedure:
Combine trans-2-azidomethyl-5-phenyl-1,4-dioxane (319 mg, 1.46 mmol), triphenylphosphine (765 mg, 2.92 mmol), and THF (20 mL) and H2O (5 mL). Stir the reaction mixture at room temperature overnight. Add Dowex AG 50W-X8 cation exchange resin (ammonium form, 200-400 mesh, 1 g) to the reaction and stir at ambient temperature for 20 minutes. Filter and sequentially wash the resin with THF (10 mL) then H2O (10 mL). Elute by rinsing the SCX resin with NH3 in MeOH (120 mL 7N) and concentrate the filtrate under reduced pressure to provide the title compound (280 mg, 99.6%) as a colorless oil. MS (m/z): 194 (M+1).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=1.[NH2:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]2[CH2:22][CH2:21][CH:20]([N:23]([CH3:25])[CH3:24])[CH2:19]2)=[CH:14][CH:13]=1>>[Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([N:18]3[CH2:22][CH2:21][CH:20]([N:23]([CH3:25])[CH3:24])[CH2:19]3)=[CH:14][CH:13]=2)=[O:8])=[CH:4][N:3]=1
Reactant: CN(C)C1CCN(c2ccc(N)cc2)C1
Reactant: O=C(O)c1ccc(Cl)nc1
Product: CN(C)C1CCN(c2ccc(NC(=O)c3ccc(Cl)nc3)cc2)C1

Procedure:
6-Chloronicotinic acid was reacted with [1-(4-amino-phenyl)pyrrolidin-3-yl]dimethylamine by method E-b. This resulted in the product with the molecular weight of 344.14 (C18H21CIN4O); MS (ESI): 345 (M+H+) as hydrotrifluoroacetate.
Reaction SMILES: ClC1N=CC(C[NH:9][CH2:10][CH2:11][N:12]2[CH2:16][CH2:15][NH:14][C:13]2=[CH:17][N+:18]([O-:20])=[O:19])=CC=1.[Cl:21][C:22]1[CH:29]=[CH:28][CH:27]=[CH:26][C:23]=1[CH:24]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].S([O-])([O-])(=O)=O.[Mg+2]>ClCCCl>[Cl:21][C:22]1[CH:29]=[CH:28][CH:27]=[CH:26][C:23]=1[CH2:24][NH:9][CH2:10][CH2:11][N:12]1[CH2:16][CH2:15][NH:14][C:13]1=[CH:17][N+:18]([O-:20])=[O:19]
Reactant: O=[N+]([O-])C=C1NCCN1CCNCc1ccc(Cl)nc1
Reactant: O=Cc1ccccc1Cl
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=S(=O)([O-])[O-]
Agent: [Mg+2]
Solvent: ClCCCl
Product: O=[N+]([O-])C=C1NCCN1CCNCc1ccccc1Cl
Temperature: 25 °C
Yield: 59 %

Procedure:
With stirring and cooling in an ice-water bath (0° C.) 0.12 grams (0.0004 mole) of [(6-chloro(3-pyridyl))methyl]{2-[2-(nitromethylene)imidazolidinyl]ethyl]amine, 0.06 gram (0.0004 mole) of 2-chlorobenzaldehyde, 0.13 gram (0.0006 mole) of sodium triacetoxyborohydride and 0.10 gram (0.0008 mole) of magnesium sulfate in about 20 mL of 1,2-dichloroethane were combined. Upon completion of addition, the cooling bath was removed and the reaction mixture was allowed to warm to ambient temperature as it stirred during an 18 hour period. After this time the reaction was quenched by the addition of five mL of water, then the reaction mixture was neutralized to pH of 8-9. The reaction mixture was then extracted with two 50 mL portions of methylene chloride. The combined extracts were dried with sodium sulfate, filtered and concentrated under reduced pressure, yielding 0.07 gram of Compound 501. The
Reaction SMILES: [NH2:1][C@H:2]1[CH2:9][CH2:8][CH2:7][NH:6][C:4](=[O:5])[CH2:3]1.C(N(CC)CC)C.[C:17]([S:20][CH2:21][CH:22]([CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:23](Cl)=[O:24])(=[O:19])[CH3:18].Cl>C(#N)C.O>[C:17]([S:20][CH2:21][CH:22]([CH2:26][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1)[C:23]([NH:1][C@H:2]1[CH2:9][CH2:8][CH2:7][NH:6][C:4](=[O:5])[CH2:3]1)=[O:24])(=[O:19])[CH3:18]
Reactant: N[C@H]1CCCNC(=O)C1
Reactant: CC(=O)SCC(Cc1ccccc1)C(=O)Cl
Agent: Cl
Solvent: CCN(CC)CC
Solvent: O
Solvent: CC#N
Product: CC(=O)SCC(Cc1ccccc1)C(=O)N[C@H]1CCCNC(=O)C1
Reaction time: 0.5 h

Procedure:
Combine 3(S)-amino-ε-caprolactam (1.00 g, 7.8 mmol) and triethylamine (0.87 g, 8.6 mmol) in acetonitrile (40ml) and H2O (20 ml). Add dropwise 2-acetylthiomethyl-3-phenylpropionyl chloride. After 30 min, add 1.0N HCl (13 ml), extract with ethyl acetate (EtOAc), dry and concentrate. Chromatograph on silica, eluting with 3%MeOH/CH2Cl2 to obtain the title compound as a foam. MS: M+1=349.
Reaction SMILES: [C:1]([C:5]1[N:10]=[CH:9][C:8]([C:11]2[N:12]([C:32](Cl)=[O:33])[C@@:13]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)([CH3:24])[C@@:14]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)([CH3:16])[N:15]=2)=[C:7]([O:35][CH2:36][CH3:37])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[C:38]([N:41]1[CH2:46][CH2:45][NH:44][CH2:43][CH2:42]1)(=[O:40])[CH3:39]>>[C:1]([C:5]1[N:10]=[CH:9][C:8]([C:11]2[N:12]([C:32]([N:44]3[CH2:45][CH2:46][N:41]([C:38](=[O:40])[CH3:39])[CH2:42][CH2:43]3)=[O:33])[C@@:13]([C:25]3[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=3)([CH3:24])[C@@:14]([C:17]3[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=3)([CH3:16])[N:15]=2)=[C:7]([O:35][CH2:36][CH3:37])[CH:6]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: CCOc1cc(C(C)(C)C)ncc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)Cl
Reactant: CC(=O)N1CCNCC1
Product: CCOc1cc(C(C)(C)C)ncc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)N1CCN(C(C)=O)CC1

Procedure:
In a manner analogous to the method described in examples 8, (4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl chloride (example 51) was coupled with 1-acetyl-piperazine (Aldrich) to give the title compound. HR-MS (ES, m/z) calculated for C35H42Cl2N5O3 [(M+H)+] 650.2659, observed 650.2662.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[S:11]([CH:14]1[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]1)(=[O:13])=[O:12].Cl[C:21]1[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][N:22]=1>>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[S:11]([CH:14]1[CH2:19][CH2:18][N:17]([C:21]2[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][N:22]=2)[CH2:16][CH2:15]1)(=[O:12])=[O:13]
Reactant: O=S(=O)(c1ccc2ccccc2c1)C1CCNCC1
Reactant: FC(F)(F)c1ccc(Cl)nc1
Product: O=S(=O)(c1ccc2ccccc2c1)C1CCN(c2ccc(C(F)(F)F)cn2)CC1
Yield: 83.9 %

Procedure:
Using the procedure from Example 7A, Step 7E, 4-(2-naphthylsulfonyl)piperidine (130 mg, 0.51 mmol) was reacted with 2-chloro-5-(trifluoromethyl)pyridine (181 mg, 1.0 mmol) to afford the title compound (180 mg), a white solid, in 84% yield.
Reaction SMILES: [N+:1]([C:4]1[CH:17]=[CH:16][CH:15]=[CH:14][C:5]=1[C:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:7])([O-])=O>C1COCC1.CO.O>[NH2:1][C:4]1[CH:17]=[CH:16][CH:15]=[CH:14][C:5]=1[C:6]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:7]
Reactant: O=C(c1ccccc1)c1ccccc1[N+](=O)[O-]
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: Nc1ccccc1C(=O)c1ccccc1
Temperature: 70 °C

Procedure:
A mixture of nitrobenzophenone resin, 3-Scheme 6, (950 mg), NaSH (1.0 g) in THF (10 mL), MeOH (5 mL), water (5 mL) was heated in an oil bath at 70° C. for 16 h. The mixture was cooled, filtered and washed with methanol, water, methylene chloride and finally with methanol. Drying at 60° (in vacuo gave a slight yellow resin. Recovered (900 mg). IR 1640 (broad).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][NH:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][S:19][CH2:20][CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[CH:13]=2)=[CH:4][CH:3]=1.[Cl:28][C:29]1[C:30]([OH:40])=[C:31]([S:36](Cl)(=[O:38])=[O:37])[CH:32]=[C:33]([Cl:35])[CH:34]=1.C(N(CC)C(C)C)(C)C>C1COCC1>[Cl:28][C:29]1[C:30]([OH:40])=[C:31]([S:36]([N:10]([CH2:9][CH2:8][C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][S:19][CH2:20][CH2:21][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[CH:13]=2)(=[O:38])=[O:37])[CH:32]=[C:33]([Cl:35])[CH:34]=1
Reactant: Fc1ccc(CCNCc2cccc(CSCCc3ccccc3)c2)cc1
Reactant: O=S(=O)(Cl)c1cc(Cl)cc(Cl)c1O
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: O=S(=O)(c1cc(Cl)cc(Cl)c1O)N(CCc1ccc(F)cc1)Cc1cccc(CSCCc2ccccc2)c1
Reaction time: 1.5 h
Yield: 44.9 %

Procedure:
To a solution of 2-(4-fluorophenyl)-N-(3-(phenethylthiomethyl)benzyl)ethanamine (70 mg, 0.184 mmol) in THF (3 mL) were added 3,5-dichloro-2-hydroxybenzenesulfonyl chloride (63 mg, 0.24 mmol) and N,N-diisopropylethylamine (0.1 mL, 0.55 mmol). The resulting reaction mixture was stirred at it for 1.5 h. The reaction mixture was concentrated and the residue was dissolved in MeOH. The mixture was purified by preparative HPLC. Fractions containing the desired product were combined, concentrated in vacuo and lyophilized to give the title compound (50 mg, 44%) as a white solid. 1H NMR (CDCl3) δ 9.15 (s, 1H), 7.55 (d, J=4.0 Hz, 1H), 7.45 (d, J=4.0 Hz, 1H), 7.34-7.15 (m, 9H), 6.98-6.89 (m, 4H), 4.40 (s, 2H), 3.70 (s, 2H), 3.35 (t, J=8.0 Hz, 2H), 2.86 (t, J=4.0 Hz, 2H), 2.69-2.63 (m, 4H). MS (ESI): 602.0 (M−H)−.
Reaction SMILES: [N+]([O-])(O)=O.[C:5]([NH:13][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][C:23]=1[N+:24]([O-])=O)[NH:20][C:19](=[O:27])[CH2:18][CH2:17]2)(=O)[C:6]1[CH:11]=[CH:10][N:9]=[CH:8][CH:7]=1>>[N:9]1[CH:10]=[CH:11][C:6]([C:5]2[NH:13][C:14]3=[CH:15][C:16]4[CH2:17][CH2:18][C:19](=[O:27])[NH:20][C:21]=4[CH:22]=[C:23]3[N:24]=2)=[CH:7][CH:8]=1
Reactant: O=C1CCc2cc(NC(=O)c3ccncc3)c([N+](=O)[O-])cc2N1
Solvent: O=[N+]([O-])O
Product: O=C1CCc2cc3[nH]c(-c4ccncc4)nc3cc2N1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
22.7 g. (85 mmole) of the above amide were slowly introduced at 5° C. into 120 ml. 65% nitric acid. The reaction mixture was further stirred at 25° C. for 1 hour, poured on to ice and filtered off with suction. The residue was purified over silica gel (elution agent: methylene chloride/methanol saturated with ammonia; 95:5 v/v) to give 2.4 g. (10% of theory) 6-isonicotinoylamino-7-nitro-1,2,3,4-tetrahydroquinolin-2-one; m.p. 285 -288° C.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:4][N:3]=1.C(N)[CH2:22][NH2:23]>CN(C)P(N(C)C)(N(C)C)=O>[C:22]([C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:4][N:3]=1)#[N:23]
Reactant: NCCN
Reactant: Clc1ccc(C(c2ccccc2)c2ccccc2)cn1
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: N#Cc1ccc(C(c2ccccc2)c2ccccc2)cn1

Procedure:
Heat a mixture of 16.5 g. (0.059 mole) of 2-chloro-5-(diphenylmethyl)-pyridine and 10.6 g. (0.059 mole) of cuprous cyanide in 120 ml. of hexamethylphosphoramide with stirring at 210°-220° C. for 7 hours. Pour the cooled reaction mixture into a solution of 200 ml. of ethylenediamine in 500 ml. of water, and extract with benzene. Wash the benzene extracts with 10% aqueous sodium cyanide, then with water, dry, treat with activated charcoal, filter, and concentrate to obtain 2-cyano-5-(diphenylmethyl)-pyridine. This compound is converted directly to the title compound by heating at reflux with 13 g. of potassium hydroxide pellets in 100 ml. water and 200 ml. ethylene glycol for 15 hours. Remove the ethylene glycol and water under reduced pressure, dissolve the residue in water, acidify with concentrated hydrochloric acid, and extract with chloroform. Dry the chloroform extracts. Concentrate the dried extracts to a residue and triturate the residue with isopropyl ether. Filter the solids, dry and recrystallize from ethanol to obtain 5-(diphenylmethyl)picolinic acid, m.p. 189°-191° C.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]=1[O:13][CH2:14][CH3:15])[C:7]([NH2:9])=[S:8])[CH3:2].[C:16]([CH:24]([CH2:30][C:31](=O)[CH2:32]Br)[C:25]([O:27][CH2:28][CH3:29])=[O:26])(=[O:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C(O)C>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([C:7]2[S:8][CH:32]=[C:31]([CH2:30][CH:24]([C:16](=[O:23])[C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:9]=2)[CH:10]=[CH:11][C:12]=1[O:13][CH2:14][CH3:15])[CH3:2]
Reactant: CCOc1ccc(C(N)=S)cc1OCC
Reactant: CCOC(=O)C(CC(=O)CBr)C(=O)c1ccccc1
Solvent: CCO
Product: CCOC(=O)C(Cc1csc(-c2ccc(OCC)c(OCC)c2)n1)C(=O)c1ccccc1
Temperature: 25 °C
Yield: 112.6 %

Procedure:
3,4-diethoxythiobenzamide (0.63 g, 2.8 mmol) was added to a solution (20 ml) of ethyl 2-benzoyl-5-bromo-4-oxopentanoate (0.90 g, 2.8 mmol) in ethanol, followed by heating under reflux for 1.5 hours. After cooling to room temperature, the solvent was distilled off under reduced pressure, and the residue was subjected to extraction with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogencarbonate solution and a saturated salt solution, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, to thereby obtain 1.43 g (yield: 65%) of ethyl 2-[2-(3,4-diethoxyphenyl)thiazole-4-ylmethyl]-3-oxo-3-phenylpropionate as a yellow oil.
Reaction SMILES: [CH3:1][C:2]1[CH:22]=[CH:21][CH:20]=[CH:19][C:3]=1[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]([C:16]#[C:17][CH3:18])[CH2:13][C:14]#[N:15])=[CH:8][CH:7]=1.[N-:23]=[N+:24]=[N-:25].[Na+].[Cl-].[NH4+].O>CN(C=O)C>[CH3:1][C:2]1[CH:22]=[CH:21][CH:20]=[CH:19][C:3]=1[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]([C:16]#[C:17][CH3:18])[CH2:13][C:14]2[NH:25][N:24]=[N:23][N:15]=2)=[CH:8][CH:7]=1
Reactant: [N-]=[N+]=[N-]
Reactant: CC#CC(CC#N)c1ccc(OCc2ccccc2C)cc1
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CC#CC(Cc1nnn[nH]1)c1ccc(OCc2ccccc2C)cc1
Temperature: 110 °C
Reaction time: 48 h
Yield: 2.9 %

Procedure:
To a solution of 23.3 (200 mg, 0.51 mmol) in DMF (5 mL) was added sodium azide (35 mg, 0.54 mmol) and ammonium chloride (29 mg, 0.54 mmol). The solution was stirred at 110° C. for 48 hours. The reaction mixture was poured into 50 mL of water and extracted with ethyl acetate (2×25 mL). The combined organic layers were concentrated under reduce pressure, and the resulting residue was purified via HPLC to yield 5 mg (3%) of 5-{2-[4-(2-Methyl-benzyloxy)-phenyl]-pent-3-ynyl}-1H-tetrazole (23) as a film. LC/MSD m/e: 333.1 (M+H). 1H NMR (400 MHz) (acetone-d6) δ 7.45 (1H, m), 7.34 (2H, m), 7.25 (3H, m), 7.00 (2H, m), 5.11 (2H, s), 4.17 (1H, m), 3.37 (2H, d, J=7 Hz), 2.39 (3H, s), 1.79 (3H, s).