Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:20])[CH:5]([S:12][C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[CH3:2].Br[CH2:22][C:23]#[C:24][CH3:25]>>[CH2:1]([O:3][C:4](=[O:20])[CH:5]([S:12][C:13]1[CH:14]=[CH:15][C:16]([O:19][CH2:22][C:23]#[C:24][CH3:25])=[CH:17][CH:18]=1)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11])[CH3:2]
Reactant: CC#CCBr
Reactant: CCCCCCC(Sc1ccc(O)cc1)C(=O)OCC
Product: CC#CCOc1ccc(SC(CCCCCC)C(=O)OCC)cc1

Procedure:
2-(4-But-2-ynyloxy-phenylsulfanyl)-octanoic acid ethyl ester was prepared according to the general method as outlined in Example 1 (Step 2). Starting from 2-(4-hydroxy-phenylsulfanyl)-octanoic acid ethyl ester 13.6 g, 46 mmol) and 1-bromo-2-butyne(6.23 g, 47mmol). Yield 13.78 g (86%); amber oil; MS: 349.0 (M+H)+
Reaction SMILES: [CH3:1][C:2]1([CH2:7][CH2:8][C:9]#[C:10][CH2:11][CH2:12][CH2:13]Cl)[O:6][CH2:5][CH2:4][O:3]1.[C-:15]#[N:16].[Na+].[Na+].[I-].[C-]#N.[K+]>CCO.O>[CH3:1][C:2]1([CH2:7][CH2:8][C:9]#[C:10][CH2:11][CH2:12][CH2:13][C:15]#[N:16])[O:6][CH2:5][CH2:4][O:3]1
Reactant: [C-]#N
Reactant: CC1(CCC#CCCCCl)OCCO1
Agent: [I-]
Agent: [K+]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CC1(CCC#CCCCC#N)OCCO1
Yield: 96.5 %

Procedure:
2-Methyl-2-(7-chloro-3-heptynyl)-1,3-dioxolane (21.6 g, 0.1 mol) was dissolved in 120 ml EtOH (convenience; dimethylformamide, dimethylsulfoxide, or other polar solvents may be used) and added to a solution of NaCN (9.8 g, 0.2 mol) and NaI (2.0 g, 0.013 mol) in 80 ml H2O. KCN, NH4CN or other cyanide salts may be used. The reaction was concentrated to remove the solvent and was extracted with three 100 ml portions of ether. The combined organic extracts were washed with 2-50 ml portions of water and brine. After drying over anhydrous MgSO4, the solvent was removed to give 20 g of 2-methyl-2-(7-cyano-3-heptynyl)-1,3-dioxolane, pure enough to use directly in the next step. Yield: 20 g, 99%. IR (CHCl3): 3000, 2950, 2890, 2250, 1675 cm-1.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11](=[O:28])[NH:12][CH:13]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=3)[C:14]([F:17])([F:16])[F:15])[NH:8]2)=[CH:4][C:3]=1[CH2:29][NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34].[H-].[Na+].I[CH2:41][CH3:42].O>CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11](=[O:28])[NH:12][CH:13]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:25])([F:27])[F:26])[CH:19]=3)[C:14]([F:16])([F:17])[F:15])[N:8]2[CH2:41][CH3:42])=[CH:4][C:3]=1[CH2:29][NH:30][C:31](=[O:37])[O:32][C:33]([CH3:34])([CH3:36])[CH3:35]
Reactant: CC(C)(C)OC(=O)NCc1cc2cc(C(=O)NC(c3cccc(C(F)(F)F)c3)C(F)(F)F)[nH]c2cc1Cl
Reactant: CCI
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCn1c(C(=O)NC(c2cccc(C(F)(F)F)c2)C(F)(F)F)cc2cc(CNC(=O)OC(C)(C)C)c(Cl)cc21
Yield: 60.1 %

Procedure:
tert-Butyl {[6-chloro-2-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-indol-5-yl]methyl}carbamate (90% pure; 0.74 g, 1.21 mmol) was dissolved under argon at 0° C. in N,N-dimethylformamide (12.5 ml). Sodium hydride (60%; 0.053 g, 1.33 mmol) was added and the mixture was stirred while cooling with ice for 2 h. Subsequently, iodoethane (0.19 g, 1.21 mmol) was added dropwise. The reaction mixture was thawed while stirring within 16 h. Water and ethyl acetate were added and the phases were separated. The organic phase was washed with saturated sodium chloride solution and dried over magnesium sulphate, and the solvent was removed under reduced pressure. The residue was chromatographed with cyclohexane/ethyl acetate (4/1) and gave 0.42 g (60% of theory) of tert-butyl {[6-chloro-1-ethyl-2-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}carbamoyl)-1H-indol-5-yl]methyl}carbamate.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:17][CH3:18])=[C:6]([CH:16]=1)[C:7]([NH:9][C:10]1[S:11][C:12]([CH3:15])=[CH:13][N:14]=1)=[O:8].[H-].[Na+].Br[CH2:22][C:23]1[O:24][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:26][CH:27]=1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:17][CH3:18])=[C:6]([CH:16]=1)[C:7](/[N:9]=[C:10]1\[S:11][C:12]([CH3:15])=[CH:13][N:14]\1[CH2:22][C:23]1[O:24][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:26][CH:27]=1)=[O:8]
Reactant: COc1ccc(Cl)cc1C(=O)Nc1ncc(C)s1
Reactant: FC(F)(F)c1ccc(CBr)o1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc(Cl)cc1C(=O)/N=c1\sc(C)cn1Cc1ccc(C(F)(F)F)o1
Reaction time: 8 h
Yield: 32.2 %

Procedure:
To a solution of Example 340A (0.1 g, 0.36 mmol) in 5 mL DMF was added sodium hydride (0.01 g, 0.39 mmol, 95%). The solution was allowed to stir at ambient temperature for 30 min when 2-(bromomethyl)-5-(trifluoromethyl)furan (0.09 g, 0.39 mmol) was added. The reaction was held at ambient temperature overnight and then quenched with water. The crude was extracted with ethyl acetate and the organics washed with water, then dried over MgSO4, filtered, and concentrated. Flash chromatography over silica gel (50% ethyl acetate/hexane) gave 0.05 g of the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 2.28 (d, J=1.36 Hz, 3H) 3.78 (s, 3H) 5.47 (s, 2H) 6.66 (d, J=2.71 Hz, 1H) 7.11 (d, J=8.81 Hz, 1H) 7.22 (dd, J=3.39, 1.36 Hz, 1H) 7.31-7.39 (m, J=1.36 Hz, 1H) 7.41-7.52 (m, 1H) 7.72 (d, J=2.71 Hz, 1H). m/z 431.0 (M+H)+.
Reaction SMILES: Cl[C:2]1[C:7](Cl)=NC=CN=1.[CH3:9][OH:10].[NH2:11][C:12]1[C:17](Br)=[N:16][C:15]([CH3:19])=[CH:14][N:13]=1>C(O)CC>[NH2:11][C:12]1[C:17]([O:10][CH2:9][CH2:7][CH3:2])=[N:16][C:15]([CH3:19])=[CH:14][N:13]=1
Reactant: Clc1nccnc1Cl
Reactant: Cc1cnc(N)c(Br)n1
Reactant: CO
Solvent: CCCO
Product: CCCOc1nc(C)cnc1N

Procedure:
By replacing the 2,3-dichloropyrazine and anhydrous methanol used in Preparation 43 by equivalent quantities of the product of Step A and n-propanol and following the method described in Preparation 43, 2-amino-3-n-propoxy-5-methylpyrazine is obtained. The 2-amino group can be converted to the 2-hydroxy by the method described by Sharp et al, ibid., (see Route III) which when treated with phosphorus oxychloride by the method of Preparation 13, Step B, provides 2-chloro-3-n-propoxy-5-methylpyrazine.
Reaction SMILES: [CH2:1]([N:5]([CH2:20][CH2:21][CH3:22])[C:6]1[CH:16]=[CH:15][C:9]([C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:8][C:7]=1[N+:17]([O-])=O)[CH:2]([CH3:4])[CH3:3].[H][H]>CCOC(C)=O.[Pd]>[NH2:17][C:7]1[CH:8]=[C:9]([CH:15]=[CH:16][C:6]=1[N:5]([CH2:1][CH:2]([CH3:4])[CH3:3])[CH2:20][CH2:21][CH3:22])[C:10]([O:12][CH2:13][CH3:14])=[O:11]
Reactant: [H][H]
Reactant: CCCN(CC(C)C)c1ccc(C(=O)OCC)cc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CCCN(CC(C)C)c1ccc(C(=O)OCC)cc1N
Yield: 92.6 %

Procedure:
A solution of ethyl 4-[isobutyl(propyl)amino]-3-nitrobenzoate (6 g, 0.0194 mol) in EtOAc (100 mL) was added Pd/C (600 mg). The reaction mixture was hydrogenated with hydrogen gas under 5 kg pressure for 3 h. The reaction mixture was filtered off Pd/C and filtrate was concentrated under reduced pressure to afford the title compound as yellow oil (5 g, 92%). 1H NMR (DMSO-d6, 400 MHz) δ 7.29 (s, 1H), 7.16 (d, 1H), 7.01 (d, 1H), 4.93 (s, 2H), 4.23 (q, 2H), 2.80 (t, 2H), 2.71 (t, 3H), 1.65 (m, 1H) 1.40 (m, 2H), 1.28 (t, 3H), 0.82 (m, 9H). LC/MS (Method A): 279.0 (M+H)+. HPLC (Method B) Rt 3.94 min (purity: 97.9%).
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[CH2:6]Br.[N-:13]=[N+:14]=[N-:15].[Na+].[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[N:25]([CH2:33][CH:34]([OH:39])[C:35]([F:38])([F:37])[F:36])[C:26](=[O:32])[N:27]([CH2:29][C:30]#[CH:31])[N:28]=2)=[CH:20][CH:19]=1>C(#N)C.O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[N:25]([CH2:33][CH:34]([OH:39])[C:35]([F:37])([F:38])[F:36])[C:26](=[O:32])[N:27]([CH2:29][C:30]3[N:13]=[N:14][N:15]([CH2:6][C:5]4[CH:8]=[CH:9][CH:10]=[C:3]([C:2]([F:12])([F:11])[F:1])[CH:4]=4)[CH:31]=3)[N:28]=2)=[CH:20][CH:19]=1
Reactant: C#CCn1nc(-c2ccc(Cl)cc2)n(CC(O)C(F)(F)F)c1=O
Reactant: FC(F)(F)c1cccc(CBr)c1
Reactant: [N-]=[N+]=[N-]
Agent: [Cu+2]
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: O=c1n(Cc2cn(Cc3cccc(C(F)(F)F)c3)nn2)nc(-c2ccc(Cl)cc2)n1CC(O)C(F)(F)F
Temperature: 25 °C
Reaction time: 1 h

Procedure:
29 mg (0.12 mmol) of 3-(trifluoromethyl)benzyl bromide were initially charged in 1 ml of acetonitrile, and 8 mg (0.12 mmol) of sodium azide were added. The mixture was stirred at RT for 1 h. 0.24 mg (0.012 mmol) of copper(II) acetate monohydrate and 50 mg (0.14 mmol) of the compound from Example 13A were then added. The resulting mixture was stirred at room temperature for 11 days. The reaction mixture was then filtered through a little silica gel, the product being eluted with about 10 ml of ethyl acetate, and the filtrate was concentrated under reduced pressure. The crude product was purified chromatographically [Method 19]. This gave 52 mg (65% of theory) of the target compound.
Reaction SMILES: O.C(N)CCCCCCCCCCC.C([O:17][Si:18]([O:25]CC)([O:22]CC)[O:19]CC)C.C(O[Nb:31](OCC)(OCC)(OCC)OCC)C>C(O)C>[Si:18]([O-:25])([O-:22])([O-:19])[O-:17].[Nb+5:31].[Si:18]([O-:25])([O-:22])([O-:19])[O-:17].[Si:18]([O-:25])([O-:22])([O-:19])[O-:17].[Si:18]([O-:25])([O-:22])([O-:19])[O-:17].[Si:18]([O-:25])([O-:22])([O-:19])[O-:17].[Nb+5:31].[Nb+5:31].[Nb+5:31]
Reactant: CCO[Nb](OCC)(OCC)(OCC)OCC
Reactant: CCO[Si](OCC)(OCC)OCC
Agent: CCCCCCCCCCCCN
Solvent: CCO
Solvent: O
Product: [Nb+5]
Product: [O-][Si]([O-])([O-])[O-]
Reaction time: 5 h

Procedure:
150 g of distilled water, 120 g of ethanol and 30 g of dodecylamine were put and dissolved in a 1 L beaker. 62 g of tetraethoxysilane and a solution of pentaethoxyniobium in ethanol (a solution of 9.5 g of pentaethoxyniobium in 5 g of ethanol) were added to the solution while stirring, and the mixture was stirred at room temperature for 22 h. Thereafter, the reaction product was filtrated, washed with water, dried in hot air at 100° C. for 5 h, and thereafter calcined in air at 550° C. for 5 h to decompose and remove the contained dodecylamine, thus obtaining a mesoporous niobium silicate material. The material was found to be a niobium silicate having a Si/Nb molar ratio of about 10 by the X-ray diffractometry. As the results of the pore distribution and specific surface area measurements, the material had a pore peak at the position of about 2.5 nm, a specific surface area of 757 m2/g, a pore volume of 0.63 cm3/g, and the volume occupied by pores of 2 to 50 nm was 0.60 cm3/g. Using 5 g of this material, a mesoporous catalyst with a platinum content of about 2 mass % was synthesized by the method similar to Example 1.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([C:11]([O:13][CH3:14])=[O:12])[N:2]=1.[N+:15]([O-])([O-:17])=[O:16].[Na+]>OS(O)(=O)=O>[N+:15]([C:6]1[CH:7]=[CH:8][CH:9]=[C:10]2[C:5]=1[CH:4]=[C:3]([C:11]([O:13][CH3:14])=[O:12])[N:2]=[CH:1]2)([O-:17])=[O:16]
Reactant: O=[N+]([O-])[O-]
Reactant: COC(=O)c1cc2ccccc2cn1
Agent: O=S(=O)(O)O
Agent: [Na+]
Product: COC(=O)c1cc2c([N+](=O)[O-])cccc2cn1
Temperature: 25 °C
Reaction time: 2 h
Yield: 96.2 %

Procedure:
Methyl isoquinoline-3-carboxylate (9.58 g, 51.2 mmol) in concentrated H2SO4 (100 mL) at 0° C. was treated with sodium nitrate (4.79 g, 56.4 mmol) in small portions such that the temperature was maintained below 5° C. Ten minutes after addition was complete, the reaction mixture was allowed to warm to room temperature and stirred for 2 hours. The mixture was poured over ice and adjusted to pH between 7 and 8 and filtered to afford the title compound as a bright yellow solid (11.44 g, 96%). MS (ESI+) m/z 233 (M+H)−; 1H NMR (DMSO, 300 MHz) δ 3.97 (s, 3H), 8.06 (t, J 8.2, 1H), 8.72 (dt, J 1.0, 8.2, 1H), 8.78 (dd, J 1.0, 7.8, 1H), 9.11 (s, 1H), 9.65 (s, 1H).
Reaction SMILES: O1C=NC=N1.[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]2[C@@H:17]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[CH:19]=3)[C@H:16]([CH2:26][N:27]3[CH:31]=[C:30]([C:32](O)=[O:33])[N:29]=[N:28]3)[O:15][C:14]2=[O:35])=[CH:9][CH:8]=1.[C:36](=[N:39]O)([NH2:38])[CH3:37]>O1CCOCC1.C(#N)C>[Cl:6][C:7]1[CH:8]=[CH:9][C:10]([N:13]2[C@@H:17]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[CH:19]=3)[C@H:16]([CH2:26][N:27]3[CH:31]=[C:30]([C:32]4[O:33][N:39]=[C:36]([CH3:37])[N:38]=4)[N:29]=[N:28]3)[O:15][C:14]2=[O:35])=[CH:11][CH:12]=1
Reactant: COc1cccc([C@H]2[C@H](Cn3cc(C(=O)O)nn3)OC(=O)N2c2ccc(Cl)cc2)c1
Reactant: CC(N)=NO
Agent: c1ncon1
Solvent: CC#N
Solvent: C1COCCO1
Product: COc1cccc([C@H]2[C@H](Cn3cc(-c4nc(C)no4)nn3)OC(=O)N2c2ccc(Cl)cc2)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Reference for 1,2,4-oxadiazole formation: Bioorg. Med. Chem. Lett. 1999, 9, 209. A solution of 1-(((4S,5S)-3-(4-chlorophenyl)-4-(3-methoxyphenyl)-2-oxooxazolidin-5-yl)methyl)-1H-1,2,3-triazole-4-carboxylic acid (32 mg, 0.07 mmol) in dioxane (0.5 mL) is treated with N,N′-carbonyldiimidazole and stirred at room temperature for 30 min. Acetamide oxime (10 mg, 0.13 mmol) is then added and the mixture stirred for 2 h at room temperature then at 100° C. for 18 h. The reaction solution is then diluted with acetonitrile and filtered through a Whatman 0.42 μM and purified by preparative HPLC (C-18, 10-90% ACN/water (0.05% TFA)) HPLC to give the title compound. 1H NMR (acetone-d6, 400 MHz) δ 8.93 (s, 1H), 7.47-7.44 (m, 2H), 7.33-7.28 (m, 3H), 7.05-7.00 (m, 2H), 6.88 (ddd, J=7.9, 2.5, 0.8 Hz, 1H), 5.62 (d, J=5.0 Hz, 1H), 5.25-5.24 (m, 2H), 5.03 (ddd, J=5.7, 5.5, 4.9 Hz, 1H) 3.76 (s, 3H), 2.40 (s, 3H); HPLC-MS calculated C22H19ClN6O4 (M+H+) 467.1, found 467.1.1.
Reaction SMILES: [Br:1][C:2]1[C:3](Cl)=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.O.[NH2:11][NH2:12]>C(O)C>[Br:1][C:2]1[C:3]([NH:11][NH2:12])=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1
Reactant: NN
Reactant: Clc1ncc(Br)c(Cl)n1
Solvent: CCO
Solvent: O
Product: NNc1nc(Cl)ncc1Br

Procedure:
A 500 mL round bottom flask was charged with 5-bromo-2,4-dichloropyrimidine (13.5 g, 59.2 mmol), hydrazine hydrate (8.8 mL, 181 mmol) and absolute ethanol (300 mL). The resulting solution was refluxed under N2 for 12 h. Work-up: the resulting crystalline solid was collected by filtration. The solid was washed with ethanol (100 mL), and dried to afford 17 g (quantitative) of the product as a yellow solid, which was used in the next step without further purification.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([O:11][C:12]2[CH:13]=[C:14]([N+:18]([O-])=O)[CH:15]=[CH:16][CH:17]=2)[CH:8]=[CH:9][CH:10]=1)([O:3][CH3:4])=[O:2]>CO.[Pd]>[C:1]([C:5]1[CH:6]=[C:7]([O:11][C:12]2[CH:13]=[C:14]([NH2:18])[CH:15]=[CH:16][CH:17]=2)[CH:8]=[CH:9][CH:10]=1)([O:3][CH3:4])=[O:2]
Reactant: COC(=O)c1cccc(Oc2cccc([N+](=O)[O-])c2)c1
Agent: [Pd]
Solvent: CO
Product: COC(=O)c1cccc(Oc2cccc(N)c2)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 41 (440 mg) in 30 mL of methanol under a nitrogen atmosphere was added 10% Pd/C (30 mg). The solution was purged with H2 gas, then stirred at room temperature under a balloon atmosphere of H2. After 8 h, the reaction was flushed with nitrogen and filtered through celite to remove the catalyst, then concentrated in vacuo. The resulting brown oil was used without further purification.
Reaction SMILES: [I-].[C:2]([C:4]1[CH:13]=[C:12]2[C:7]([CH:8]=[CH:9][CH:10]=[N+:11]2[CH2:14][CH:15]=[CH2:16])=[CH:6][CH:5]=1)#[N:3].[OH-:17].[K+].O>O1CCOCC1.O.[Fe-3](C#N)(C#N)(C#N)(C#N)(C#N)C#N.[K+].[K+].[K+]>[O:17]=[C:10]1[CH:9]=[CH:8][C:7]2[C:12](=[CH:13][C:4]([C:2]#[N:3])=[CH:5][CH:6]=2)[N:11]1[CH2:14][CH:15]=[CH2:16]
Reactant: C=CC[n+]1cccc2ccc(C#N)cc21
Reactant: [OH-]
Agent: N#C[Fe-3](C#N)(C#N)(C#N)(C#N)C#N
Agent: [I-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: C=CCn1c(=O)ccc2ccc(C#N)cc21
Temperature: 25 °C
Reaction time: 2 h
Yield: 52.9 %

Procedure:
A mixture of 7-cyano-1-(2-propen-1-yl)quinolinium iodide (1.75 g, 5.4 mmol), potassium hydroxide (1.33 g, 23.76 mmol) and potassium ferricyanide (3.9 g, 11.9 mmol) in 50% 1,4-dioxane/water was stirred at rt for 2 h. Water (50 ml) was then added and the organic phase was extracted with 10% methanol/DCM (2×100 ml). The combined organic phases were washed with water (100 ml) then dried and evaporated. The residue was chromatographed on silica gel, eluting with 0-5% methanol-DCM to afford the desired compound (0.6 g, 55%).
Reaction SMILES: [C:1]([O:4][CH2:5][C:6]([CH3:12])([CH3:11])[C:7]([O:9]C)=[O:8])(=[O:3])[CH3:2].I[Si](C)(C)C.O.C>C(Cl)(Cl)(Cl)Cl.C(OCC)(=O)C>[C:1]([O:4][CH2:5][C:6]([CH3:12])([CH3:11])[C:7]([OH:9])=[O:8])(=[O:3])[CH3:2]
Reactant: COC(=O)C(C)(C)COC(C)=O
Agent: C[Si](C)(C)I
Solvent: CCOC(C)=O
Solvent: ClC(Cl)(Cl)Cl
Solvent: O
Product: CC(=O)OCC(C)(C)C(=O)O
Temperature: 25 °C
Reaction time: 60 h
Yield: 40.7 %

Procedure:
To a stirred solution of 4.0 grams (0.023 mole) of methyl 3-acetoxy-2,2-dimethylpropionate in 50 ml of carbon tetrachloride under an argon atmosphere was added slowly via a syringe 9.2 grams (0.046 mole) of iodotrimethylsilane. Upon completion of addition the reaction mixture was stirred at ambient temperature for 60 hours. The reaction mixture was then heated at 50° for 1.5 hours, and at 65° for 18 hours. Nuclear magnetic resonance spectroscopy indicated the reaction had not gone to completion. The reaction mixture was heated at 65° for six days, then poured into 100 ml water. The mixture was stirred for 20 minutes and the carbon tetrachloride layer separated. The water layer was extracted with three portions of 50 ml each of methylene chloride. The methylene chloride extracts and the carbon tetrachloride layer were combined. The combination was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to give a semi-solid residue. The semi-solid was dissolved in hot ethyl acetate and treated with decolorizing charcoal. The mixture was filtered and the filtrate concentrated under reduced pressure to give a solid residue. The solid was recrystallized from hexane to give 1.5 grams of 3-acetoxy-2,2-dimethylpropionic acid; mp 56°-59°.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)=[CH:8][C:9]=1[NH2:10])=[O:4].CO[CH:20]([N:23]([CH3:25])[CH3:24])OC>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)=[CH:8][C:9]=1[N:10]=[CH:20][N:23]([CH3:25])[CH3:24])=[O:4]
Reactant: COC(OC)N(C)C
Reactant: COC(=O)c1sc(-c2ccc(Cl)cc2)cc1N
Solvent: CN(C)C=O
Product: COC(=O)c1sc(-c2ccc(Cl)cc2)cc1N=CN(C)C
Reaction time: 36 h

Procedure:
A solution of 3-amino-5-(4-chlorophenyl)thiophene-2-carboxylic acid methyl ester (5.0 g) in DMF (30 μL) was mixed with dimethoxymethyldimethylamine (5 mL) and stirred for 36 hours. The reaction solution was partitioned between water and ethyl acetate. The organic phase was dried over magnesium sulfate and concentrated. The product with the molecular weight of 322.82 (C15H15ClN2O2S) was obtained in this way; MS (ESI): 323 (M+H+).
Reaction SMILES: CS(O[CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:15][CH2:16][CH:17]([CH3:19])[CH3:18])(=O)=O.[Cl:20]C1C=C2C(=CC=1)NC=C2CC(N)(C)C.[NH2:35][C:36]([C:38]1[NH:39][C:40]2[C:45]([C:46]=1[CH2:47][C:48]([NH2:51])([CH3:50])[CH3:49])=[CH:44][CH:43]=[CH:42][CH:41]=2)=[O:37]>>[ClH:20].[NH2:35][C:36]([C:38]1[NH:39][C:40]2[C:45]([C:46]=1[CH2:47][C:48]([NH:51][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:15][CH2:16][CH:17]([CH3:18])[CH3:19])([CH3:49])[CH3:50])=[CH:44][CH:43]=[CH:42][CH:41]=2)=[O:37]
Reactant: CC(C)(N)Cc1c[nH]c2ccc(Cl)cc12
Reactant: CC(C)COc1ccccc1OCCOS(C)(=O)=O
Reactant: CC(C)(N)Cc1c(C(N)=O)[nH]c2ccccc12
Product: CC(C)COc1ccccc1OCCNC(C)(C)Cc1c(C(N)=O)[nH]c2ccccc12
Product: Cl

Procedure:
Proceeding as an Example 3, but replacing 2-[2-(cyclopropylmethyloxy)phenoxy]ethyl methanesulfonate with 2-[2-(2-methylprop-1-yloxy)phenoxy]ethyl methanesulfonate and [2-(5-chloro-1H-indol-3-yl)-1,1-dimethylethyl]amine with [2-(2-aminocarbonyl-1H-indol-3-yl)-1,1-dimethylethyl]amine, gave [2-(2-aminocarbonyl-1H-indol-3-yl)-1,1-dimethylethyl]{2-[2-(2-methylprop-1-yloxy)phenoxy]ethyl}amine hydrochloride, m.p. 154°-156° C.
Reaction SMILES: [C:1]([C:3]1[S:4][C:5]([CH2:8]Br)=[CH:6][CH:7]=1)#[N:2].[N-:10]=[N+:11]=[N-:12].[Na+].C(OCC)(=O)C>CN(C=O)C.CCCCCC>[C:1]([C:3]1[S:4][C:5]([CH2:8][N:10]=[N+:11]=[N-:12])=[CH:6][CH:7]=1)#[N:2]
Reactant: [N-]=[N+]=[N-]
Reactant: N#Cc1ccc(CBr)s1
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CCCCCC
Product: N#Cc1ccc(CN=[N+]=[N-])s1
Yield: 82.7 %

Procedure:
A solution of 2-cyano-5-(bromomethyl)thiophene (compound 24, 3.5 g, 17.3 mmol) and sodium azide (Aldrich, 1.7 g, 26 mmol) in DMF (Aldrich, 60 ml) was stirred at ambient temperature for 10 hours. Flash column chromatography (20% ethyl acetate in hexane) resulted the title compound (2.35 g, 83%). TLC: Rf 0.48 (20% of ethyl acetate in hexane); 1H NMR (CDCl3): δ 4.56 (s, 2H), 7.01 (d, 1H, J=3.7 Hz), 7.55 (d, 1H, J=3.7 Hz).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9](=[O:16])[CH2:10][CH:11]([CH3:15])[C:12]([OH:14])=[O:13])=[CH:5][CH:4]=1.Br.[CH3:18][C:19](O)=O>>[CH2:18]([O:13][C:12](=[O:14])[CH:11]([CH3:15])[CH2:10][C:9]([C:6]1[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=1)=[O:16])[CH3:19]
Reactant: COc1ccc(C(=O)CC(C)C(=O)O)cc1
Reactant: CC(=O)O
Agent: Br
Product: CCOC(=O)C(C)CC(=O)c1ccc(OC)cc1
Yield: 93 %

Procedure:
A solution of 4-(4-methoxyphenyl)-2-methyl-4-oxobutyric acid (10 g, 45 mmol) and 150 mL of 48% HBr in 20 mL of AcOH was heated to 100° C. for 48 h. The solvent was evaporated and EtOH (3×30 mL) was added and evaporated to give 4-(4-methoxyphenyl)-2-methyl-4-oxobutyric acid ethyl ester (9.96 g, 93%); MS m/z 259 (M+23).
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[CH:14][C:13]2[S:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5](=O)[C:4]=2[CH:3]=1.ClC1C=CC(S)=CC=1.ClC1C=CC=CC=1C#[N:29]>>[Cl:1][C:2]1[CH:15]=[CH:14][C:13]([S:12][C:11]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[C:5]#[N:29])=[CH:4][CH:3]=1
Reactant: O=c1c2ccccc2sc2ccc(Cl)cc12
Reactant: N#Cc1ccccc1Cl
Agent: Sc1ccc(Cl)cc1
Product: N#Cc1ccccc1Sc1ccc(Cl)cc1

Procedure:
Method of preparing 2-chloro-thioxanthone which comprises reacting an alkali metal derivative of 4-chloro-thiophenol with 2-chloro-benzonitrile in an organic solvent to form 2-(4'-chloro-phenylthio)-benzonitrile, hydrolyzing said 2-(4'-chloro-phenylthio)-benzonitrile to form 2-(4'l -chloro-phenylthio)-benzoic acid and cyclising said 2-(4'-chloro-phenylthio)-benzoic acid by dehydration to produce 2-cloro-thioxanthone.
Reaction SMILES: [CH3:1][Ge:2]([CH3:20])([CH3:19])[C:3]1[CH:4]=[C:5]([C:13]2([CH3:18])OCC[O:14]2)[CH:6]=[C:7]([Ge:9]([CH3:12])([CH3:11])[CH3:10])[CH:8]=1.CC1C=CC(S([O-])(=O)=O)=CC=1.C1C=C[NH+]=CC=1.O>CC(C)=O>[CH3:11][Ge:9]([CH3:10])([CH3:12])[C:7]1[CH:6]=[C:5]([C:13](=[O:14])[CH3:18])[CH:4]=[C:3]([Ge:2]([CH3:19])([CH3:1])[CH3:20])[CH:8]=1
Reactant: CC1(c2cc([Ge](C)(C)C)cc([Ge](C)(C)C)c2)OCCO1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: c1cc[nH+]cc1
Solvent: CC(C)=O
Solvent: O
Product: CC(=O)c1cc([Ge](C)(C)C)cc([Ge](C)(C)C)c1
Yield: 98 %

Procedure:
A mixture of 240 mg (0.60 mmol) of 2-[3,5-bis(trimethylgermyl)phenyl]-2-methyl-1,3-dioxolane, 23 mg (0.090 mmol) of PPTS, 10.6 ml of acetone (excess) and 540 mg (30 mmol) of water was refluxed for 2.5 hours. The reaction mixture was evaporated and extracted with ether. The extract was evaporated to give 208 mg of pale yellow crystals, which were sublimed at 70° C., 0.5 mmHg to give 189 mg of white prisms, m.p. 56° C. (yield 89%).