Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH:6]=[C:7]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[NH:8]2)([O-:3])=[O:2].[H-].[Na+].CI.[C:22](=O)([O-])O.[Na+]>O1CCCC1>[CH3:22][N:8]1[C:9]2[C:5](=[C:4]([N+:1]([O-:3])=[O:2])[CH:12]=[CH:11][CH:10]=2)[CH:6]=[C:7]1[C:13]([O:15][CH2:16][CH3:17])=[O:14]
Reactant: O=C([O-])O
Reactant: CCOC(=O)c1cc2c([N+](=O)[O-])cccc2[nH]1
Agent: [H-]
Agent: [Na+]
Solvent: CI
Solvent: C1CCOC1
Product: CCOC(=O)c1cc2c([N+](=O)[O-])cccc2n1C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 21 %

Procedure:
To a stirred solution of ethyl 4-nitroindole-2-carboxylate (1.57 g, 6.70 mmol) in anhydrous tetrahydrofuran (20 mL) at 0° C. under nitrogen was added sodium hydride (60% in oil, 0.375 g, 9.4 mmol, 1.4 equivalents), and the resulting effervescing mixture was stirred at room temperature under nitrogen for 30 minutes. Then, methyl iodide (1.71 g, 12.0 mmol, 1.8 equivalents) was added dropwise, and the resulting reaction solution was stirred at room temperature under nitrogen for 48 hours. A saturated solution of sodium hydrogen carbonate was then added, and the resulting aqueous mixture was extracted with ethyl acetate (2×30 mL). The organic extracts were combined, dried (sodium sulfate), and evaporated under reduced pressure. The residue was chromatographed using silica gel (approximately 50 g) and elution with 20% ethyl acetate in hexanes to afford the title compound (0.35 g, 1.41 mmol, 21%) as a yellow solid: Rf=0.30 in 20% ethyl acetate in hexanes; 1H NMR (acetone-d6) δ8.18 (d, J=7.9 Hz, 1H), 8.08 (d, J=8.1 Hz, 1H), 7.78 (s, 1H), 7.57 (t, J=8.1 Hz, 1H), 4.43 (q, J=7.1 Hz, 2H), 4.21 (s, 3H), 1.42 (t, J=7.1 Hz, 3H).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([S:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:12]=2[F:18])[N:3]=1.[H-].[Na+].[CH3:21][CH:22]([OH:24])[CH3:23]>>[Cl:8][C:6]1[CH:7]=[C:2]([O:24][CH:22]([CH3:23])[CH3:21])[N:3]=[C:4]([S:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[C:12]=2[F:18])[N:5]=1
Reactant: CC(C)O
Reactant: Fc1cccc(CSc2nc(Cl)cc(Cl)n2)c1F
Agent: [H-]
Agent: [Na+]
Product: CC(C)Oc1cc(Cl)nc(SCc2cccc(F)c2F)n1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 4,6-dichloro-2-[(2,3-difluorobenzyl)thio]pyrimidine ((the product of example 1 step ii), 3 g) in propan-2-ol (20 ml) was added NaH (0.43 g) slowly and the reaction was then allowed to stir overnight at RT. The reaction mixture was then partitioned between DCM (100 ml) and H2O (100 ml). The organics were separated and the aqueous layer was re-extracted with DCM (2×100 ml). Organics were combined, dried (MgSO4) and reduced in vacuo to give the subtitle compound as a pale yellow solid. Yield: 1.8 g
Reaction SMILES: [CH2:1]([N:8]1[CH:12]=[C:11]([CH:13]([C:15]2[C:16]([CH3:27])=[N:17][O:18][C:19]=2[C:20]2[CH:25]=[CH:24][C:23](Br)=[CH:22][CH:21]=2)[OH:14])[N:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:28]([O:30][C:31]([CH2:33][CH2:34][C:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1)=[O:32])[CH3:29]>>[CH2:28]([O:30][C:31](=[O:32])[CH2:33][CH2:34][C:35]1[CH:40]=[CH:39][C:38]([C:23]2[CH:24]=[CH:25][C:20]([C:19]3[O:18][N:17]=[C:16]([CH3:27])[C:15]=3[CH:13]([C:11]3[N:10]=[N:9][N:8]([CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[CH:12]=3)[OH:14])=[CH:21][CH:22]=2)=[CH:37][CH:36]=1)[CH3:29]
Reactant: Cc1noc(-c2ccc(Br)cc2)c1C(O)c1cn(Cc2ccccc2)nn1
Reactant: CCOC(=O)CCc1ccc(B(O)O)cc1
Product: CCOC(=O)CCc1ccc(-c2ccc(-c3onc(C)c3C(O)c3cn(Cc4ccccc4)nn3)cc2)cc1

Procedure:
Prepared according to the procedure described in Example 1, Step 10, using (1-benzyl-1H-[1,2,3]triazol-4-yl)-[5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-methanol and [4-(2-ethoxycarbonylethyl)phenyl]boronic acid.
Reaction SMILES: [Li]CCCC.[Se:6]1[CH:10]=[CH:9][CH:8]=[C:7]1[C:11]1[Se:12][CH:13]=[CH:14][CH:15]=1.CN(CCN(C)C)C.[CH3:24][Sn:25](Cl)([CH3:27])[CH3:26]>C1COCC1.CC#N>[CH3:24][Sn:25]([CH3:27])([CH3:26])[C:10]1[Se:6][C:7]([C:11]2[Se:12][C:13]([Sn:25]([CH3:27])([CH3:26])[CH3:24])=[CH:14][CH:15]=2)=[CH:8][CH:9]=1
Reactant: c1c[se]c(-c2ccc[se]2)c1
Reactant: C[Sn](C)(C)Cl
Agent: CN(C)CCN(C)C
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC#N
Product: C[Sn](C)(C)c1ccc(-c2ccc([Sn](C)(C)C)[se]2)[se]1
Temperature: 17 °C
Reaction time: 0.33 h

Procedure:
A solution of BuLi in hexanes (10.6 ml of a 1.6 M solution, 17 mmol) is added dropwise to a cooled (−78° C.) solution of 2,2′-biselenophene (2.00 g, 7.7 mmol) in THF (50 ml) and TMEDA (1.98 g, 17 mmol). On addition of the BuLi an immediate colour change is observed (dark red). After stirring for 20 min, the reaction mixture appeared dark yellow. The mixture is stirred for 6 h allowing to warm to 16-18° C. While warming the reaction mixture changed appearance to a green suspension. The reaction mixture is then cooled to −70° C. Trimethylstannyl chloride (3.38 g, 17 mmol) is added as a solid to the reaction mixture. After 10 min, the reaction mixture appeared brown. The reaction mixture is allowed to warm to room temperature overnight. The reaction is quenched with water (100 mL) and the mixture stirred for 1 h. Ethylacetate (100 mL) is added to the mixture. The layers are separated. The combined organic extracts are washed with water, brine and then dried (Na2SO4). After filtration the crude product is concentrated to yield a brown oil. MeCN is added and the mixture is stirred for 5 min. The mixture is recrystallized three times from acetonitrile. The material is used without further purification. MS (EI) 588 (M+).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([Cl:11])[C:3]=1[CH2:12][C:13]([NH:15][C:16]1[CH:21]=[CH:20][N:19]=[CH:18][C:17]=1[CH:22]=O)=[O:14].C([O-])([O-])=O.[Na+].[Na+].C(OCC)(=O)C>CO>[Cl:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[C:4]([Cl:11])[C:3]=1[C:12]1[C:13](=[O:14])[NH:15][C:16]2[C:17]([CH:22]=1)=[CH:18][N:19]=[CH:20][CH:21]=2
Reactant: O=Cc1cnccc1NC(=O)Cc1c(Cl)cc([N+](=O)[O-])cc1Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CO
Solvent: CCOC(C)=O
Product: O=c1[nH]c2ccncc2cc1-c1c(Cl)cc([N+](=O)[O-])cc1Cl

Procedure:
2-(2,6-Dichloro-4-nitro-phenyl)-N-(3-formyl-pyridin-4-yl)-acetamide (3.0 g, 8.47 mmol) is dissolved in dry methanol (240 mL). Na2CO3 (1.80 g, 16.94 mmol) is added. The reaction is refluxed for 30 minutes, diluted by ethyl acetate (210 mL) and filtered. The solvents are evaporated to give crude product, which is recrystallized by ethyl acetate/hexanes to give 3-(2,6-dichloro-4-nitro-phenyl)-1H-[1,6]-naphthyridin-2-one as a slightly yellow solid (3.07 g).
Reaction SMILES: N(=[C:3]1[C:7]2=[C:8]3[C:13](=[CH:14][CH:15]=[C:6]2[NH:5][C:4]1=[O:16])[N:12]=[CH:11][CH:10]=[CH:9]3)N.[O-]CC.[Na+].C(O)(=O)C>O>[CH2:3]1[C:7]2=[C:8]3[C:13](=[CH:14][CH:15]=[C:6]2[NH:5][C:4]1=[O:16])[N:12]=[CH:11][CH:10]=[CH:9]3
Reactant: NN=C1C(=O)Nc2ccc3ncccc3c21
Agent: CC[O-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: O=C1Cc2c(ccc3ncccc23)N1
Yield: 33.2 %

Procedure:
A solution of 2.3 g (12 mmol) of 3-H-pyrrolo[3,2-f]quinoline-1,2-dione and 2.0 ml (0.06 mol) of hydrazine in 50 ml of DMF and 50 ml of ethanol was stirred at reflux for 2 h. The resulting suspension was allowed to cool to ambient temperature and was then chilled in an ice bath and filtered. The solid was washed with a small volume of ethanol and allowed to air dry to give 1-hydrazono-1,3-dihydropyrrolo[3,2-f]quinolin-2-one as an orange solid (1.8 g, 73%): 1H NMR (DMSO-d6): δ7.37 (d, J=8.8 Hz, 1H), 7.47 (dd, J=8.4, 4.2 Hz, 1H), 7.81 (d, J=8.8 Hz, 1H), 8.71 (dd, J=4.2, 1.6 Hz, 1H), 8.80 (d, J=8.4 Hz, 1H), 9.90 (br d, J=14.7 Hz, 1H), 10.89 (br d, J=14.7 Hz, 1H), 10.95 (br s, 1H); ESI−MS m/z 213 (M+H)+. A solution 1.8 g (8.5 mmol) of 1-hydrazono-1,3-dihydropyrrolo[3,2-f]quinolin-2-one in 50 ml of freshly prepared 0.5 M sodium ethoxide solution was stirred at reflux for 3 h. The solution was diluted with 50 ml of water, neutralized with acetic acid, and concentrated on a rotary evaporator until cloudy. The solution was stored in a refrigerator overnight. The solid was filtered off, and the filtrate was extracted with three 80-ml portions of EtOAc. A solution of the solid in MeOH/EtOAc was combined with the extracts and passed through a short pad of silica gel, eluting with EtOAc. The solution was then concentrated to a small volume on a rotary evaporator, and the resulting suspension was diluted with an equal volume of ethanol, sonicated, and filtered to give 3-H-pyrrolo[3,2-f]quinoline-2-one as a light green solid (0.52 g, 33%); 1H NMR (DMSO-d6): δ3.80 (s, 2H), 7.35 (d, J=8.8 Hz, 1H), 7.44 (dd, J=8.4, 4.2 Hz, 1H), 7.88 (d, J=8.8 Hz, 1H), 8.08 (d, J=8.4 Hz, 1H), 8.70 (dd, J=4.2, 1.6 Hz, 1H), 10.57 (br s, 1H); APCI−MS m/z 183 (M−H)−.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:13]2[NH:12][C:11]([NH2:14])=[N:10][C:9]=2[CH:8]=[CH:7][CH:6]=1)=[O:4].[N+:15]([O-])([O-:17])=[O:16].[K+].N>OS(O)(=O)=O>[CH3:1][O:2][C:3]([C:5]1[C:13]2[N:12]=[C:11]([NH2:14])[NH:10][C:9]=2[CH:8]=[C:7]([N+:15]([O-:17])=[O:16])[CH:6]=1)=[O:4]
Reactant: COC(=O)c1cccc2nc(N)[nH]c12
Reactant: O=[N+]([O-])[O-]
Agent: N
Agent: O=S(=O)(O)O
Agent: [K+]
Product: COC(=O)c1cc([N+](=O)[O-])cc2[nH]c(N)nc12
Temperature: -30 °C
Reaction time: 0.25 h
Yield: 69.2 %

Procedure:
1.0 g (5.2 mmol) of 2-amino-3H-benzoimidazole-4-carboxylic acid methyl ester was suspended in 10 mL of conc. H2SO4 at −15° C. and cooled to −30° C. Potassium nitrate (0.58 g, 5.72 mmol) dissolved in 10 mL of sulfuric acid and cooled to 0° C. was then added dropwise to the reaction mixture. The reaction mixture was stirred −30° C. for 15 min then warmed to −10° C. over 30 min. Then the mixture was poured into a beaker containing ice and neutralized (˜pH=8) with concentrated aqueous ammonia solution. The resulting solid was filtered. The solid obtained was washed with cold water and ether, and dried under vacuum to provide 0.85 g (70%) 2-amino-6-nitro-1H-benzoimidazole-4-carboxylic acid methyl ester as a solid. LCMS: 239 (M+1)+.
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]#[N:9])=[CH:6][C:5]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)=[CH:4][C:3]=1[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1.Cl.N([O-])=O.[Na+].[N-:31]=[N+:32]=[N-].[Na+]>C(O)C>[N:1]([C:2]1[C:7]([C:8]#[N:9])=[CH:6][C:5]([C:10]2[CH:11]=[CH:12][C:13]([O:16][CH3:17])=[CH:14][CH:15]=2)=[CH:4][C:3]=1[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)=[N+:31]=[N-:32]
Reactant: [N-]=[N+]=[N-]
Reactant: COc1ccc(-c2cc(C#N)c(N)c(-c3ccc(OC)cc3)c2)cc1
Agent: Cl
Agent: O=N[O-]
Agent: [Na+]
Solvent: CCO
Product: COc1ccc(-c2cc(C#N)c(N=[N+]=[N-])c(-c3ccc(OC)cc3)c2)cc1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 44.6 %

Procedure:
4′-Amino-4,4″-dimethoxy-[1,1′:3′,1″-terphenyl]-5′-carbonitrile (226 mg, 0.68 mmol) was heated in ethanol (28 mL) to bring most of the material into solution. After cooling to room temperature, 17% aqueous HCl (4 mL) was added and the reaction was cooled in an ice bath. Sodium nitrite (76 mg, 1.09 mmol) was added and the orange-red solution was stirred for 15 min in the ice bath. Sodium azide (71 mg, 1.09 mmol) was then added. After 20 min, the reaction was partitioned between ethyl acetate and sufficient saturated aqueous sodium bicarbonate to neutralize the reaction. The organic phase was separated, washed with brine, and dried with sodium sulfate. Silica gel radial chromatograph using step gradient elution with hexane containing 5 to 20% ethyl acetate afforded 4′-azido-4,4″-dimethoxy-[1,1′:3′,1″-terphenyl]-5′-carbonitrile (108 mg, 44%) as a solid. 1H NMR (500, CDCl3) δ ppm 7.72 (1H, d, J=2.14 Hz), 7.62 (1H, d, J=2.14 Hz), 7.47 (2H, d, J=8.55 Hz), 7.39 (2H, d, J=8.55 Hz), 7.01 (2H, d, J=8.55 Hz), 6.97 (2H, d, J=8.85 Hz), 3.87 (3H, s), 3.84 (3H, s).
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][N:11]([CH2:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=O)=[CH:25][CH:24]=1)[CH:12]1[C:21]2[N:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH2:15][CH2:14][CH2:13]1.[NH:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1.C([BH3-])#N.[Na+]>CO>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][N:11]([CH2:22][C:23]1[CH:30]=[CH:29][C:26]([CH2:27][N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)=[CH:25][CH:24]=1)[CH:12]1[C:21]2[N:20]=[CH:19][CH:18]=[CH:17][C:16]=2[CH2:15][CH2:14][CH2:13]1
Reactant: O=Cc1ccc(CN(Cc2nc3ccccc3[nH]2)C2CCCc3cccnc32)cc1
Reactant: C1COCCN1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: c1cnc2c(c1)CCCC2N(Cc1ccc(CN2CCOCC2)cc1)Cc1nc2ccccc2[nH]1
Temperature: 25 °C
Reaction time: 24 h
Yield: 6.8 %

Procedure:
Using General Procedure A: To a stirred solution of 4-{[(1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzaldehyde (0.285 g, 0.72 mmol) in dry MeOH (5 mL) was added morpholine (0.068 mL, 0.78 mmol) and sodium cyanoborohydride (0.107 g, 1.7 mmol) and the mixture stirred at room temperature for 24 h. Purification of the crude product by radial chromatography on a 2 mm TLC grade silica gel plate (CH2Cl2/MeOH/NH4OH, 100:1:1) afforded the desired product (23 mg, 7%) as a colourless oil.
Reaction SMILES: [CH2:1]([S:8][C:9]1[N:20]=[C:12]2[N:13]=[C:14]([CH3:19])[C:15]([Cl:18])=[C:16](O)[N:11]2[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:23])=O>>[CH2:1]([S:8][C:9]1[N:20]=[C:12]2[N:13]=[C:14]([CH3:19])[C:15]([Cl:18])=[C:16]([Cl:23])[N:11]2[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: Cc1nc2nc(SCc3ccccc3)nn2c(O)c1Cl
Product: Cc1nc2nc(SCc3ccccc3)nn2c(Cl)c1Cl
Yield: 68 %

Procedure:
This material was prepared in 68% yield from 2-benzylthio-6-chloro-7-hydroxy-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine and phosphorus oxychloride following the general procedure described in Example 20. The desired product was isolated as a solid, m.p. 103°-105° C. IR and 1H NMR spectra were in agreement with the assigned structure.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][CH:3]=1.[C:9](OC(=O)C)(=[O:11])[CH3:10]>>[CH3:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:9](=[O:11])[CH3:10])=[CH:3][CH:4]=1
Reactant: CC(=O)OC(C)=O
Reactant: Cc1ccc(N)cc1
Product: CC(=O)Nc1ccc(C)cc1
Temperature: 25 °C
Yield: 96.8 %

Procedure:
Into three neck round bottom flask (5 L) equipped with a mechanical stirrer, a condenser, and an addition funnel, were added p-toluidine (995 grams, 9.3 mol) and hexanes (1.6 L). Acetic anhydride (960 mL, 10.2 mol) was added dropwise for 2 hour enough to reflux. Then it was refluxed for 1 hour and cooled to room temperature to give a brown solid. This was collected by suction filtration, transferred into a beaker, and washed with water (2 L) for 30 minutes. The filtration and washing procedures were repeated. The wet white crystals was air dried for 7 days to N-(4-Methylphenyl)acetamide (1,343 g, 97% yield). Melting point: 150-152° C. (Lit. 153° C., Merck Index 11, 67).
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[O:12][C:11]([CH3:17])([CH3:16])[CH2:10][C:9]2=O)[CH2:2][CH2:3][CH3:4].[Cl-].[OH:20][NH3+:21].C([O-])(=O)C.[Na+]>C(O)C.O>[CH2:1]([O:5][C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[O:12][C:11]([CH3:17])([CH3:16])[CH2:10][C:9]2=[N:21][OH:20])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOc1ccc2c(c1)C(=O)CC(C)(C)O2
Reactant: [NH3+]O
Agent: CC(=O)[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CCCCOc1ccc2c(c1)C(=NO)CC(C)(C)O2
Reaction time: 3 h
Yield: 100.4 %

Procedure:
A solution of 52.0 g (0.21 mol) of 6-butoxy-2,2-dimethylchroman-4-one in 420 ml of ethanol were added dropwise in 30 min to a solution of 43.7 g (0.628 mol) of hydroxylammonium chloride and 51.5 g (0.628 mol) of sodium acetate in 420 ml of water and the mixture was kept at 60° C. for 3 h. The oily product phase was separated off and the aqueous phase was extracted with methylene chloride. After drying the organic phases over magnesium sulfate and concentrating in vacuo, 55.5 g of 6-butoxy-2,2-dimethylchroman-4-one oxime were obtained, which it was possible to crystallize by stirring with PE.
Reaction SMILES: [CH3:1][N:2]1[C:6]([CH3:7])=[N:5][N:4]=[N:3]1.C([Li])CCC.[F:13][C:14]1[CH:29]=[CH:28][C:17]([C:18]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[CH3:27])=[O:19])=[C:16]([CH3:30])[CH:15]=1>O1CCCC1>[F:13][C:14]1[CH:29]=[CH:28][C:17]([C:18]([C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=2[CH3:27])([OH:19])[CH2:7][C:6]2[N:2]([CH3:1])[N:3]=[N:4][N:5]=2)=[C:16]([CH3:30])[CH:15]=1
Reactant: Cc1cc(F)ccc1C(=O)c1ccc(F)cc1C
Reactant: Cc1nnnn1C
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: Cc1cc(F)ccc1C(O)(Cc1nnnn1C)c1ccc(F)cc1C
Reaction time: 0.17 h
Yield: 67 %

Procedure:
To a suspension of 1,5-dimethyltetrazole (3.8 g, 39.0 mmoles) in tetrahydrofuran (40 mL) at -40° C. was added butyl lithium (17.7 mL of a 2.2M solution, 39.0 mmoles). Aftering stirring for 10 minutes, 4,4'-difluoro-2,2'-dimethylbenzophenone (8 g, 32.5 mmoles) was added and the solution stirred for 3 hours. The reaction was quenched with 1N hydrochloric acid. The aqueous layer was separated and extracted with ethyl acetate. The combined organic phases were dried (MgSO4) and concentrated in vacuo to give 7.5 g of the title compound; m.p.=186°-188° C.
Reaction SMILES: Cl[C:2]1[C:3]([C:9]([OH:11])=[O:10])=[N:4][C:5](Cl)=[CH:6][CH:7]=1.[CH:12]1([SH:18])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1>>[CH:12]1([S:18][C:2]2[C:3]([C:9]([OH:11])=[O:10])=[N:4][C:5]([S:18][CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]3)=[CH:6][CH:7]=2)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1
Reactant: O=C(O)c1nc(Cl)ccc1Cl
Reactant: SC1CCCCC1
Product: O=C(O)c1nc(SC2CCCCC2)ccc1SC1CCCCC1

Procedure:
The compound 3,6-bis(cyclohexylthio)-2-pyridinecarboxylic acid, m.p. 100°-101° C. was prepared by reacting 3,6-dichloro-2-pyridinecarboxylic acid and cyclohexyl mercaptan utilizing procedures substantially as described herein.
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[C@H:4](/[CH:5]=[C:6]2/[C:7](=[O:11])[O:8][CH2:9][CH2:10]/2)[C@H:3]1[C:12]([OH:14])=[O:13].[CH:16](NC(=NC(C)C)OCC)(C)[CH3:17]>C(O)C>[CH3:1][C:2]1([CH3:15])[C@H:4](/[CH:5]=[C:6]2/[C:7](=[O:11])[O:8][CH2:9][CH2:10]/2)[C@H:3]1[C:12]([O:14][CH2:16][CH3:17])=[O:13]
Reactant: CC1(C)[C@H](/C=C2\CCOC2=O)[C@H]1C(=O)O
Reactant: CCOC(=NC(C)C)NC(C)C
Solvent: CCO
Product: CCOC(=O)[C@@H]1[C@@H](/C=C2\CCOC2=O)C1(C)C
Yield: 56.6 %

Procedure:
Using the procedure of Example 17, 7.8 g of (1R,trans) 2,2-dimethyl-3-[(E) (dihydro-2-oxo-3(2H)-furanylidene)-methyl]-cyclopropane-1-carboxylic acid and 7 g of ethyl N,N'-diisopropylcarbamimidate were reacted to obtain 5 g of ethyl (1R,trans) 2,2-dimethyl-3-[(E) (dihydro-2-oxo-3-(2H)-furanylidene)-methyl]-cyclopropane-1-carboxylate with a specific rotation of [α]D20 =+50°±2° (c=0.5% in ethanol).
Reaction SMILES: [C:1]([CH:3]([CH3:21])[CH2:4][CH:5]1[CH2:10][CH:9]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=2)[CH2:8][CH2:7][C:6]1=O)#[N:2].Br.C(O)(=[O:25])C>>[CH3:19][O:18][C:15]1[CH:16]=[CH:17][C:12]([CH2:11][CH:9]2[CH2:8][CH2:7][C:6]3[NH:2][C:1](=[O:25])[CH:3]([CH3:21])[CH2:4][C:5]=3[CH2:10]2)=[CH:13][CH:14]=1
Reactant: CC(=O)O
Reactant: COc1ccc(CC2CCC(=O)C(CC(C)C#N)C2)cc1
Agent: Br
Product: COc1ccc(CC2CCC3=C(C2)CC(C)C(=O)N3)cc1
Reaction time: 2 h

Procedure:
2-(2-Cyanopropyl)-4-(4-methoxybenzyl)cyclohexanone (1.5 g) was added to glacial acetic acid (20 ml) containing 45% w/v hydrogen bromide in acetic acid (5 ml) and the mixture was left to stir for 21/2 hours. The solvent was removed under reduced pressure, the residue was suspended in water and filtered to give the title compound on recrystallisation (0.5 g) mp 182°-184° C.
Reaction SMILES: [CH3:1][C:2](=[CH2:10])[CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].[N+](=[CH2:13])=[N-]>CCOCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:10][C:2]1([CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH2:13][CH2:1]1
Reactant: C=C(C)CCC(=O)OCC
Reactant: C=[N+]=[N-]
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: CCOCC
Product: CCOC(=O)CCC1(C)CC1
Temperature: 0 °C

Procedure:
To an ice cold solution of ethyl 4-methyl-4-pentenoate (1.11 g, 7.8 mmol) in 0.5 M diazomethane in Et2O, was added palladium(II) acetate by portionwise addition (4 portions of 5 mg each were added in 15 min intervals). A total of 4 portions were added. The reaction mixture was filtered on a pad of celite and concentrated under 60 mm Hg with gentle warming. This crude product was treated a second time with diazomethane and palladium(II) acetate, filtered and concentrated. The resulting oil was filtered on a pad of florisil (60–100 mesh), washed with Et2O (2×10 mL), concentrated under 60 mm Hg to give ethyl 3-(1-methylcyclopropyl)propanoate as a colorless oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:9][CH3:10])=[C:6]([CH:8]=1)[NH2:7].[I:11][C:12]1[CH:17]=[CH:16][C:15]([S:18](Cl)(=[O:20])=[O:19])=[CH:14][CH:13]=1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:9][CH3:10])=[C:6]([NH:7][S:18]([C:15]2[CH:16]=[CH:17][C:12]([I:11])=[CH:13][CH:14]=2)(=[O:20])=[O:19])[CH:8]=1
Reactant: O=S(=O)(Cl)c1ccc(I)cc1
Reactant: CSc1ccc(Cl)cc1N
Product: CSc1ccc(Cl)cc1NS(=O)(=O)c1ccc(I)cc1

Procedure:
Following General Procedure B, the title compound was prepared from 5-chloro-2-(methylthio)aniline and 4-iodo-benzenesulfonyl chloride.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][NH:13][C:14](=[O:33])/[C:15](/[Sn](CCCC)(CCCC)CCCC)=[CH:16]\[CH:17]([CH3:19])[CH3:18])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].[Cl:34][C:35]1[CH:40]=[CH:39][C:38](I)=[CH:37][CH:36]=1.O>CN(C)C=O.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.[Cu]I>[Cl:34][C:35]1[CH:40]=[CH:39][C:38](/[C:15](=[CH:16]/[CH:17]([CH3:18])[CH3:19])/[C:14]([NH:13][CH2:12][CH2:11][C:5]2[CH:6]=[CH:7][C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=2)=[O:33])=[CH:37][CH:36]=1
Reactant: CCCC[Sn](CCCC)(CCCC)/C(=C/C(C)C)C(=O)NCCc1ccc(OC)c(OC)c1
Reactant: Clc1ccc(I)cc1
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc(CCNC(=O)/C(=C\C(C)C)c2ccc(Cl)cc2)cc1OC
Temperature: 22.5 °C
Reaction time: 14 h
Yield: 85 %

Procedure:
A solution of 10 g (17.6 mmol) of (2E)-N-[2-(3,4-dimethoxyphenyl)ethyl]-4-methyl-2-(tributylstannyl)-2-pentenamide (5) in 15 ml of dimethylformamide (DMF) was mixed with 4.2 g (17.7 mmol) of 4-chloroiodobenzene, 0.5 g of Pd(PPh3)4 and 0.5 g of copper(I) iodide. After stirring for approximately 14 hours at 20 to 25° C., the reaction solution was poured into water and extracted with MTBE. The organic phases were washed with water, dried and freed from the solvent. After chromatographing on silica gel (cyclohexane:MTBE [7:1 to 1:1]), 5.8 g of the title compound were obtained.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]1[C:13]([N+:14]([O-])=O)=[CH:12][CH:11]=[CH:10][N:9]=1.[H][H]>C(O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]1[C:13]([NH2:14])=[CH:12][CH:11]=[CH:10][N:9]=1
Reactant: O=[N+]([O-])c1cccnc1Nc1ccccn1
Reactant: [H][H]
Solvent: CCO
Product: Nc1cccnc1Nc1ccccn1
Yield: 100.2 %

Procedure:
A solution of 18.3 g of the product of Step A in 550 ml of 95% ethanol containing 1.6 g of 10% palladized carbon was hydrogenated at atmosphere pressure at room temperature until 6.3 liters of hydrogen were absorbed (about one hour) and the mixture was filtered to remove the catalyst. The filtrate was evaporated to dryness under reduced pressure and the 15.8 g of residue (98.6% yield) which was easily changed in air was used for the next step immediately.