Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][C:7]1[N:15]=[C:14]([C:16]([F:19])([F:18])[F:17])[CH:13]=[CH:12][C:8]=1[C:9]([OH:11])=O.C(N(CC)CC)C.[CH3:27][N:28]1[C:32](=[O:33])[CH2:31][C:30]([CH3:34])=[N:29]1.CC(C)(O)C#N>C(Cl)(=O)C(Cl)=O>[OH:33][C:32]1[N:28]([CH3:27])[N:29]=[C:30]([CH3:34])[C:31]=1[C:9]([C:8]1[C:7]([CH2:6][O:5][CH2:4][CH2:3][O:2][CH3:1])=[N:15][C:14]([C:16]([F:19])([F:18])[F:17])=[CH:13][CH:12]=1)=[O:11]
Reactant: COCCOCc1nc(C(F)(F)F)ccc1C(=O)O
Reactant: CC1=NN(C)C(=O)C1
Agent: CC(C)(O)C#N
Agent: O=C(Cl)C(=O)Cl
Solvent: CCN(CC)CC
Product: COCCOCc1nc(C(F)(F)F)ccc1C(=O)c1c(C)nn(C)c1O
Temperature: 25 °C
Reaction time: 1 h
Yield: 62.3 %

Procedure:
1.0 g (0.004 mol) of 2-(2-methoxyethoxymethyl)-6-trifluoromethylnicotinic acid is dissolved in 10 ml of oxalyl chloride. Three drops of dimnethylformamide are added, and the mixture is stirred at room temperature for 1 hour. The mixture is then concentrated using a rotary evaporator, and the residue (2-(2-methoxyethoxymethyl)-6-trifluoromethylnicotinoyl chloride) is taken up in 10 ml of methylene chloride. At a temperature of 0° C., 0.84 ml (0.006 mol) of triethylamine and 0.45 g (0.004 mol) of 2,5dimethyl-2,4-dihydropyrazol-3one are added. After 2 hours at a temperature of 22° C., the solvent is removed using a vacuum rotary evaporator, and the residue that remains is dissolved in 10 ml of acetonitrile and, to rearrange the intermediate (2,5-dimethyl-2H-pyrazol-3-yl 2-(2-methoxyethoxymethyl)-6-trifluoromethylnicotinate), admixed with 0.1 ml of acetone cyanohydrin and 1.13 ml (0.008 mol) of triethylamine. The reaction solution is stirred at room temperature for four hours and then concentrated. The syrup that remains is chromatographed on silica gel. The viscous oil obtained by eluting with a mixture of toluene, ethyl alcohol, dioxane, triethylamine and water (100:40:20:20:5 parts by volume) is dissolved in ethyl acetate and washed successively with 10% hydrochloric acid and water. The organic solution is dried over Na2SO4 and concentrated, giving 0.93 g of (5-hydroxy-1,3-dimethyl-1H-pyrazol-4yl)-[2-(2-methoxyethoxymethyl)-6-trifluoromethylpyridin-3-yl]methanone in the form of a viscous oil.
Reaction SMILES: N[C:2]1[CH:3]=[C:4]([F:16])[CH:5]=[C:6]([C:8]2[C:9]([C:14]#[N:15])=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:7]=1.N([O-])=O.[Na+].[BrH:21]>O1CCOCC1.O.[Cu]Br>[Br:21][C:2]1[CH:3]=[C:4]([F:16])[CH:5]=[C:6]([C:8]2[C:9]([C:14]#[N:15])=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:7]=1
Reactant: N#Cc1ccccc1-c1cc(N)cc(F)c1
Reactant: Br
Agent: [Cu]Br
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: N#Cc1ccccc1-c1cc(F)cc(Br)c1
Temperature: 3 °C
Reaction time: 2 h
Yield: 94 %

Procedure:
A warm solution of 5′-amino-3′-fluorobiphenyl-2-carbonitrile (4.5 g, 21 mmol) in 1,4-dioxane (20 ml) was treated with 48% hydrobromic acid (100 ml) and the resulting suspension stirred and cooled to 3° C. (internal temperature). A solution of sodium nitrite (1.7 g, 24 mmol) in water (4 ml) was then added dropwise over 20 min keeping the internal temperature <5° C. Stirring at <5° C. was continued for 2 h before adding a cooled (5° C.) solution of copper(I) bromide (9.1 g, 3 mmol) in 48% hydrobromic acid (30 ml). The resulting purple reaction mixture was stirred at 5° C. for 10 min then warmed to 50° C. for 20 min. The reaction was diluted with ice-cold water (500 ml) and extracted with ethyl acetate (2×200 ml). The organics were combined, washed with 5% aqueous sodium sulphite and saturated aqueous ammonium chloride, dried over anhydrous magnesium sulfate, filtered and pre-adsorbed onto silica. Purification on silica, eluting with isohexane (containing 1% methanol) on a gradient of ethyl acetate (5-15%) afforded 5′-bromo-3′-fluorobiphenyl-2-carbonitrile as a white solid (5.52 g, 94%).
Reaction SMILES: [OH:1][C@@H:2]1[C@H:7]2[C@H:8]3[C@H:18]([CH2:19][CH2:20][C@:5]2([CH3:6])[C:4](=[O:22])[CH2:3]1)[C@:16]1([CH3:17])[C:11](=[CH:12][C:13](=[O:21])[CH2:14][CH2:15]1)[CH2:10][CH2:9]3.[C:23](OC(=O)C)(=[O:25])[CH3:24]>N1C=CC=CC=1.C(Cl)Cl>[C:23]([O:1][C@@H:2]1[C@H:7]2[C@H:8]3[C@H:18]([CH2:19][CH2:20][C@:5]2([CH3:6])[C:4](=[O:22])[CH2:3]1)[C@:16]1([CH3:17])[C:11](=[CH:12][C:13](=[O:21])[CH2:14][CH2:15]1)[CH2:10][CH2:9]3)(=[O:25])[CH3:24]
Reactant: C[C@]12CCC(=O)C=C1CC[C@H]1[C@@H]3[C@@H](O)CC(=O)[C@@]3(C)CC[C@@H]12
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Solvent: ClCCl
Product: CC(=O)O[C@H]1CC(=O)[C@@]2(C)CC[C@H]3[C@@H](CCC4=CC(=O)CC[C@@]43C)[C@H]12
Temperature: 0 °C
Reaction time: 1.5 h

Procedure:
168 g of 15α-hydroxy-4-androstene-3,17-dione in 250 ml of pyridine and 125 ml of acetic anhydride are heated on a steam bath. After 90 minutes, the reaction mixture is stirred into ice/water. The thus-precipitated product is suctioned off, taken up in methylene chloride, washed with water, and dried over sodium sulfate. After recrystallization from ethyl acetate, 120 g of 15α-acetoxy-4-androstene-3,17-dione is obtained, mp 145° C.
Reaction SMILES: [C:1]1([CH2:7][C:8]([NH:10][C@H:11]([C:13]([OH:15])=O)[CH3:12])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[CH3:17][O:18][C:19](=[O:22])[CH2:20][NH2:21]>>[CH3:17][O:18][C:19](=[O:22])[CH2:20][NH:21][C:13](=[O:15])[C@H:11]([CH3:12])[NH:10][C:8](=[O:9])[CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: C[C@H](NC(=O)Cc1ccccc1)C(=O)O
Reactant: COC(=O)CN
Agent: Cl
Product: COC(=O)CNC(=O)[C@H](C)NC(=O)Cc1ccccc1

Procedure:
Following General Procedure A and using N-(phenylacetyl)-L-alanine (from Example B1 above) and glycine methyl ester hydrochloride (Aldrich), the title compound was prepared as a solid (mp=152-153.5° C.). The reaction was monitored by tlc (Rf=0.10 in 50% EtOAc/hexanes).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7](=[O:20])[C:8]2[CH:13]=[N:12][C:11](OC)=[N:10][C:9]=2[N:16]([CH2:18][CH3:19])[CH:17]=1)=[O:5])[CH3:2].[NH:21]1[CH2:25][CH2:24][CH2:23][CH2:22]1.C1(C)C=CC=CC=1>O>[CH2:1]([O:3][C:4]([C:6]1[C:7](=[O:20])[C:8]2[CH:13]=[N:12][C:11]([N:21]3[CH2:25][CH2:24][CH2:23][CH2:22]3)=[N:10][C:9]=2[N:16]([CH2:18][CH3:19])[CH:17]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1cn(CC)c2nc(OC)ncc2c1=O
Reactant: C1CCNC1
Solvent: O
Solvent: Cc1ccccc1
Product: CCOC(=O)c1cn(CC)c2nc(N3CCCC3)ncc2c1=O

Procedure:
5.9 g of 6-ethoxycarbonyl-8-ethyl-2-methoxy-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine, 4.6 g. of pyrrolidine and 12 g of toluene are heated for 2 hours at 90° C. After cooling, 100 cm3 of water are added to the mixture. The precipitate is filtered off and washed with water. After drying, 5.5 g of 6-ethoxycarbonyl-8-ethyl-5-oxo-2-pyrrolidino-5,8-dihydro-pyrido[2,3-d]pyrimidine are obtained. After recrystallisation from ethanol, it melts at 202° C and is identical to the product described in the literature.
Reaction SMILES: [S:1]([C:5]1[CH:23]=[CH:22][C:8]([N:9]=[CH:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[O:18][CH:19]=[CH:20][CH:21]=3)=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)(=[O:4])(=[O:3])[NH2:2].C[Si]([C:28]#[N:29])(C)C.O>C1COCC1.[Cl-].[Zn+2].[Cl-]>[S:1]([C:5]1[CH:23]=[CH:22][C:8]([NH:9][CH:10]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3[O:18][CH:19]=[CH:20][CH:21]=3)=[CH:13][CH:12]=2)[C:28]#[N:29])=[CH:7][CH:6]=1)(=[O:4])(=[O:3])[NH2:2]
Reactant: NS(=O)(=O)c1ccc(N=Cc2ccc(-c3ccco3)cc2)cc1
Reactant: C[Si](C)(C)C#N
Agent: [Cl-]
Agent: [Zn+2]
Solvent: C1CCOC1
Solvent: O
Product: N#CC(Nc1ccc(S(N)(=O)=O)cc1)c1ccc(-c2ccco2)cc1
Reaction time: 8 h
Yield: 72.1 %

Procedure:
To a suspension of 4-sulfamoyl-N-[4-(2-furyl)benzylidene]aniline (0.37 g, 1.13 mmol) in anhydrous THF (5 mL) at 0° C. was added trimethylsilyl cyanide (0.135 g, 1.36 mmol), zinc chloride (1.36 mL, 1.0 M solution in ether, 1.36 mmol). The temperature of the reaction mixture was then allowed to return to room temperature, and the mixture was stirred overnight. The reaction mixture was poured into water and the whole was extracted with ethyl acetate (20 mL×2). The organic layer was washed with brine, dried over Na2SO4, and concentrated to give the subtitle compound (0.288 g). 1H-NMR (DMSO-d6) δ: 7.84-7.78 (m, 3H), 7.65-7.60 (m, 4H), 7.39 (d, J=9 Hz, 1H), 7.04-7.01 (m, 3H), 6.91 (d, J=9 Hz, 2H), 6.62 (dd, J=3, 2 Hz, 1H), 6.16 (d, J=9 Hz, 1H). MS (EI) m/z 353 (M+)
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:3][CH2:2]1.Cl[CH2:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH3:22][O:21][C:18]1[CH:19]=[CH:20][C:15]([CH2:14][CH2:13][N:1]2[CH2:6][CH2:5][CH:4]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:3][CH2:2]2)=[CH:16][CH:17]=1
Reactant: CCOC(=O)C1CCNCC1
Reactant: COc1ccc(CCCl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)C1CCN(CCc2ccc(OC)cc2)CC1
Temperature: 70 °C
Yield: 25.7 %

Procedure:
A stirred mixture of 5.0 grams (0.032 mole) of ethyl piperidin-4-ylcarboxylate, 5.4 grams (0.032 mole) of 1-(2-chloroethyl)-4-methoxybenzene and 4.4 grams (0.032 mole) of potassium carbonate in 50 mL of dried N,N-dimethylformamide was heated at 70° C. for about 16 hours. After this time the reaction mixture was cooled and partitioned between diethyl ether and water. The organic layer was separated and washed with water and then with an aqueous solution saturated with sodium chloride. The organic layer was dried with magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to a residue, which was subjected to column chromatography on silica gel, with diethyl ether/hexane mixtures as eluants. The product-containing fractions were combined and concentrated under reduced pressure, yielding 2.4 grams of ethyl N-[2-(4-methoxyphenyl)ethyl]piperidin-4-ylcarboxylate. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: [NH2:1][C:2]1[C:3]2[N:4]([C:8]([CH:12]=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:5]=[CH:6][CH:7]=1.[C:14]([O:18][C:19]([NH:21][C:22]1[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[C:23]=1[CH2:24]Cl)=[O:20])([CH3:17])([CH3:16])[CH3:15].[I-].[Na+].C(=O)([O-])[O-].[Na+].[Na+]>CC(C)=O>[C:14]([O:18][C:19]([NH:21][C:22]1[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[C:23]=1[CH2:24][NH:1][C:2]1[C:3]2[N:4]([C:8]([CH:12]=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:5]=[CH:6][CH:7]=1)=[O:20])([CH3:17])([CH3:16])[CH3:15]
Reactant: Cc1cccc(NC(=O)OC(C)(C)C)c1CCl
Reactant: Cc1nc2c(N)cccn2c1C=O
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Product: Cc1cccc(NC(=O)OC(C)(C)C)c1CNc1cccn2c(C=O)c(C)nc12

Procedure:
Starting from 8-amino-3-formyl-2-methylimidazo[1,2-a]pyridine (4.0 g), 2-tert-butoxycarbonylamino-6-methylbenzyl chloride (7.0 g), sodium iodide (4.1 g) and sodium carbonate (6.1 g) in acetone (250 ml) analogously using the process of Example B1 gives, after chromatography on silica gel (eluent toluene/dioxane 9:1) and recrystallization from diisopropyl ether, 7.3 g (81%) of the title compound of m.p. 210-212° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][NH:13][C:14](=[O:23])[C:15]1[CH:20]=[CH:19][C:18]([CH2:21]Cl)=[CH:17][CH:16]=1.[NH:24]1[CH:28]=[CH:27][CH:26]=[N:25]1.[I-].[Na+]>C1COCC1>[N:24]1([CH2:21][C:18]2[CH:19]=[CH:20][C:15]([C:14]([NH:13][CH2:12][CH2:11][C:5]3[C:4]4[C:8](=[CH:9][CH:10]=[C:2]([Cl:1])[CH:3]=4)[NH:7][CH:6]=3)=[O:23])=[CH:16][CH:17]=2)[CH:28]=[CH:27][CH:26]=[N:25]1
Reactant: c1cn[nH]c1
Reactant: O=C(NCCc1c[nH]c2ccc(Cl)cc12)c1ccc(CCl)cc1
Agent: [I-]
Agent: [Na+]
Solvent: C1CCOC1
Product: O=C(NCCc1c[nH]c2ccc(Cl)cc12)c1ccc(Cn2cccn2)cc1
Yield: 84.9 %

Procedure:
4-((1H-Pyrazol-1-yl)methyl)-N-(2-(5-Chloro-1H-indol-3-yl)ethyl)benzamide was prepared following Method C starting from N-(2-(5-chloro-1H-indol-3-yl)ethyl)-4-(chloromethyl)benzamide (0.069 g; 0.199 mmol), pyrazole (0.062 g; 0.893 mmol) and sodium iodide (0.150 g; 0.994 mmol) in THF (3 mL), under a microwave irradiation at 150° C. for 20 minutes. Flash chromatography on silica gel (eluent 7 to 60% ethyl acetate in dichloromethane) furnished 0.064 g (85%) of the title compound as a white solid.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[Li+].CC([N-]C(C)C)C.[CH2:21]([N:23]1[C:31]2[C:26](=[CH:27][CH:28]=[C:29]([O:32][CH3:33])[CH:30]=2)[C:25]([C:34]#[N:35])=[CH:24]1)[CH3:22].[CH2:36]([Sn:40](I)([CH2:45][CH2:46][CH2:47][CH3:48])[CH2:41][CH2:42][CH2:43][CH3:44])[CH2:37][CH2:38][CH3:39]>C1COCC1>[CH2:21]([N:23]1[C:31]2[C:26](=[CH:27][CH:28]=[C:29]([O:32][CH3:33])[CH:30]=2)[C:25]([C:34]#[N:35])=[C:24]1[Sn:40]([CH2:41][CH2:42][CH2:43][CH3:44])([CH2:45][CH2:46][CH2:47][CH3:48])[CH2:36][CH2:37][CH2:38][CH3:39])[CH3:22]
Reactant: CCCC[Sn](I)(CCCC)CCCC
Reactant: CCn1cc(C#N)c2ccc(OC)cc21
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: CCCC[Sn](CCCC)(CCCC)c1c(C#N)c2ccc(OC)cc2n1CC
Temperature: -78 °C
Reaction time: 0.33 h
Yield: 98.5 %

Procedure:
A solution of THF (60 mL) and diisopropylamine (5.5 mL, 39 mmol) is cooled to −78° C. n-Butyllithium (14.5 mL, 2.5M in hexanes, 36.2 mmol) is added dropwise over 5 minutes. The LDA mixture is stirred at −78° C. for 10 minutes, and then at 0° C. for 20 minutes. The solution is re-cooled to −78° C. 1-ethyl-6-methoxy-1H-indole-3-carbonitrile (5.0 g, 25 mmol), prepared as in example 1A, is taken up in THF (30 mL) and added dropwise to the LDA mixture over 15 minutes. The reaction is stirred at −78° C. for 10 minutes, and at 0° C. for 30 minutes. Once again, the reaction mixture is cooled to −78° C. Tributyltin iodide (10 mL, 35 mmol) is added dropwise. This is stirred at −78° C. for 15 minutes, and then at 0° C. for 30 minutes. The reaction mixture is absorbed onto silica gel and concentrated. Purification by chromatography (CH2Cl2) yields 1-ethyl-6-methoxy-2-tributylstannanyl-1H-indole-3-carbonitrile (12.05 g, 98%).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:16])[CH2:12][C:13](=O)[CH3:14])=[CH:6][CH:5]=1)([O-:3])=[O:2].[NH:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1>C1C=CC=CC=1>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:16])[CH:12]=[C:13]([N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)[CH3:14])=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: CC(=O)CC(=O)Nc1ccc([N+](=O)[O-])cc1
Reactant: C1CCNC1
Solvent: c1ccccc1
Product: CC(=CC(=O)Nc1ccc([N+](=O)[O-])cc1)N1CCCC1
Yield: 93.6 %

Procedure:
A mixture of 11.10 g (50 mmol) of N-(4-nitrophenyl)-3-oxobutanamide and 4.26 g (60 mmol) of pyrrolidine in 125 ml of benzene was refluxed for one hour using a Dean-Stark trap to separate water. The reaction was cooled to give 12.89 g (94% yield) of N-(4-nitrophenyl)-3-pyrrolidyl-2-butenamide as a yellow solid.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[C:10]([SH:12])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:20][C:21]([O:23][CH3:24])=[O:22].O>CN(C)C=O>[CH3:1][C:2]1[CH:11]=[C:10]([S:12][CH2:20][C:21]([O:23][CH3:24])=[O:22])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1
Reactant: Cc1cc(S)c2ccccc2n1
Reactant: COC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)CSc1cc(C)nc2ccccc12
Reaction time: 0.25 h
Yield: 88.5 %

Procedure:
2-methylquinoline-4-thiol 5a (1.00 g, 5.71 mmol, 1.00 eq.) was dissolved in dimethylformamide (10 mL) at room temperature. Potassium carbonate (0.87 g, 6.28 mmol, 1.10 eq.) was added and the mixture was stirred for 15 minutes. Methyl bromoacetate (921 mg, 6.02 mmol, 1.05 eq.) was added dropwise to the solution, and the reaction was stirred at room temperature for 2.5 hours. Water (20 mL) was added to the reaction mixture, and the aqueous layer was extracted with ethyl acetate (30 mL). The aqueous layer was further extracted with ethyl acetate (3×50 mL), and the combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo. The resulting residue was dried on high vacuum to yield 5b as a brown solid (1.25 g, 88%).
Reaction SMILES: [OH:1][CH:2]1[CH:7]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[O:26][CH3:27])=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4]([C:28]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:29])[CH2:3]1.Br[CH2:39][C:40]1[CH:41]=[CH:42][CH:43]=[C:44]2[C:48]=1[N:47]([CH2:49][O:50][CH2:51][CH2:52][Si:53]([CH3:56])([CH3:55])[CH3:54])[C:46](=[O:57])[C:45]2([CH3:59])[CH3:58]>>[CH3:58][C:45]1([CH3:59])[C:44]2[C:48](=[C:40]([CH2:39][O:1][CH:2]3[CH:7]([C:8]4[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][O:18][CH2:19][C:20]5[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=5[O:26][CH3:27])=[CH:10][CH:9]=4)[CH2:6][CH2:5][N:4]([C:28]([O:30][CH2:31][C:32]4[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=4)=[O:29])[CH2:3]3)[CH:41]=[CH:42][CH:43]=2)[N:47]([CH2:49][O:50][CH2:51][CH2:52][Si:53]([CH3:54])([CH3:56])[CH3:55])[C:46]1=[O:57]
Reactant: CC1(C)C(=O)N(COCC[Si](C)(C)C)c2c(CBr)cccc21
Reactant: COc1ccccc1COCCCOc1ccc(C2CCN(C(=O)OCc3ccccc3)CC2O)cc1
Product: COc1ccccc1COCCCOc1ccc(C2CCN(C(=O)OCc3ccccc3)CC2OCc2cccc3c2N(COCC[Si](C)(C)C)C(=O)C3(C)C)cc1

Procedure:
Analogously to Method D, 0.600 g of benzyl 3-hydroxy-4-{4-[3-(2-methoxybenzyloxy)-propoxy]phenyl}piperidine-1-carboxylate (Example 10f) and 0.574 g of 7-bromomethyl-3,3-dimethyl-1-(2-trimethylsilanylethoxymethyl)-1,3-dihydroindol-2-one are reacted. The title compound is obtained as a slightly yellowish oil. Rf=0.16 (1:2 EtOAc-heptane); Rt=6.79.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[CH:11]=[CH:10][NH:9][C:5]2=[N+:6]([O-])[CH:7]=1.C(=O)([O-])O.[Na+].P(Cl)(Cl)([Cl:19])=O>>[Cl:19][C:3]1[C:2]([F:1])=[CH:7][N:6]=[C:5]2[NH:9][CH:10]=[CH:11][C:4]=12
Reactant: [O-][n+]1cc(F)cc2cc[nH]c21
Reactant: O=P(Cl)(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Product: Fc1cnc2[nH]ccc2c1Cl

Procedure:
A solution of 1.7 g of 5-fluoro-1H-pyrrolo[2,3-b]pyridine-7-oxide in 10 cm3 of phosphorus oxychloride is maintained at the reflux point of the POCl3 for 8 hours. After distilling off the POCl3 under vacuum, the residue is treated with 50 g of ice, and the pH of the solution obtained is brought in the region of 8-9 by addition of sodium hydrogen carbonate. The aqueous phase is extracted with five times 80 cm3 of ethyl acetate. The combined organic phases are then dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (13 kPa). 1.3 g of 4-chloro-5-fluoro-1H-pyrrolo[2,3-b]pyridine are thus obtained in the form of a solid, the characteristics of which are as follows:
Reaction SMILES: [CH2:1]([O:4][C:5]([C:7]1[C:12]2[C:13]([C:17](Cl)=[O:18])=[C:14]([CH3:16])[O:15][C:11]=2[CH:10]=[CH:9][C:8]=1[O:20][C:21]1[N:26]=[C:25]([O:27][CH3:28])[CH:24]=[C:23]([O:29][CH3:30])[N:22]=1)=[O:6])[CH:2]=[CH2:3].[CH3:31][NH:32][CH3:33].O>ClCCl>[CH3:30][O:29][C:23]1[CH:24]=[C:25]([O:27][CH3:28])[N:26]=[C:21]([O:20][C:8]2[C:7]([C:5]([O:4][CH2:1][CH:2]=[CH2:3])=[O:6])=[C:12]3[C:13]([C:17](=[O:18])[N:32]([CH3:33])[CH3:31])=[C:14]([CH3:16])[O:15][C:11]3=[CH:10][CH:9]=2)[N:22]=1
Reactant: CNC
Reactant: C=CCOC(=O)c1c(Oc2nc(OC)cc(OC)n2)ccc2oc(C)c(C(=O)Cl)c12
Solvent: ClCCl
Solvent: O
Product: C=CCOC(=O)c1c(Oc2nc(OC)cc(OC)n2)ccc2oc(C)c(C(=O)N(C)C)c12
Reaction time: 0.5 h
Yield: 60 %

Procedure:
3.0 g of 4-allyloxycarbonyl-5-(4,6-dimethoxypyrimidin-2-yl)oxy-2-methylbenzofuran-3-carbonyl chloride was dissolved in 13 ml of dichloromethane, and 1.5 g of a 50% dimethylamine aqueous solution was dropwise added thereto under cooling with ice. After stirring for 30 minutes, the reaction solution was poured into water and extracted with dichloromethane. The organic layer was washed with water and then dried over anhydrous sodium sulfate. The oily substance obtained by concentration under reduced pressure, was purified by silica gel column chromatography (n-hexane/ethyl acetate=4/1) to obtain 1.84 g (yield: 60%) of the desired compound.
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([S:10]([NH2:13])(=[O:12])=[O:11])=[CH:9][C:4]=2[O:3][CH2:2]1.[OH-].[Na+].[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]=[C:24]=[O:25])=[CH:19][CH:18]=1.O>CC(C)=O>[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([NH:23][C:24]([NH:13][S:10]([C:8]2[CH:7]=[CH:6][C:5]3[O:1][CH2:2][O:3][C:4]=3[CH:9]=2)(=[O:12])=[O:11])=[O:25])=[CH:19][CH:18]=1
Reactant: NS(=O)(=O)c1ccc2c(c1)OCO2
Reactant: O=C=Nc1ccc(Cl)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(C)=O
Product: O=C(Nc1ccc(Cl)cc1)NS(=O)(=O)c1ccc2c(c1)OCO2
Yield: 75 %

Procedure:
To a solution of 26.9 g of 1,3-benzodioxole-5-sulfonamide in 100 ml of acetone was added 150 ml of a 1N sodium hydroxide solution. A solution of 26.4 g of 4-chlorophenylisocyanate in 85 ml of acetone was added to the reaction mixture with stirring. After stirring at room temperature for 18 hours, the reaction mixture was filtered and 150 ml of 1N hydrochloric acid were added to the filtrate, thereby providing a precipitate. One liter of water was added, and the solid was recovered by filtration to provide the desired title product in 75% yield.
Reaction SMILES: [CH:1](=O)[C:2]1[C:3]([O:8][CH3:9])=[CH:4][CH:5]=[CH:6][CH:7]=1.C(S)CCS.S1CCCCS1.[Li]CCCC.[C:27](OC)(=[O:36])[CH:28]=[CH:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.CN1CCN(C)C1=O>C(Cl)Cl>[CH3:9][O:8][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:2]=1[CH2:1][CH:29]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:28][C:27]2=[O:36]
Reactant: COC(=O)C=Cc1ccccc1
Reactant: COc1ccccc1C=O
Agent: C1CCSSC1
Agent: SCCCS
Agent: [Li]CCCC
Solvent: ClCCl
Solvent: CN1CCN(C)C1=O
Product: COc1cccc2c1CC(c1ccccc1)CC2=O

Procedure:
o- Anisaldehyde (20.5 g) was treated with 1,3-propanedithiol (24 ml) in the presence of BF. etherate (4 ml) and CH2Cl2 (300 ml). This dithiane derivative (4.7 g) was reacted with n-BuLi (2.5 M hexane solution) (7.3 ml), methyl cinnamate (3.4 g) and 1,3-dimethyl-2-imidazolidone (4.6 ml) affording the desired product (M+H)+ 389. Desulfurization was accomplished with Raney Nickel and EtOH, followed by hydrolysis to the desired carboxylic acid. Cyclization to the desired 5-methoxy-3-phenyl-1-tetralone was accomplished by heating with polyphosphoric acid, (M+H)+ 253.
Reaction SMILES: [CH2:1]([CH:3]([CH2:6][CH3:7])[CH:4]=[CH2:5])[CH3:2].[N+:8]([O-])([OH:10])=[O:9]>>[CH2:4]([C:3]([CH2:6][CH3:7])=[CH:1][CH2:2][N+:8]([O-:10])=[O:9])[CH3:5]
Reactant: C=CC(CC)CC
Reactant: O=[N+]([O-])O
Product: CCC(=CC[N+](=O)[O-])CC
Temperature: 70 °C
Reaction time: 0.5 h
Yield: 12 %

Procedure:
3-Ethyl-1-pentene (15 mL, 0.11 moles) and concentrated nitric acid (9.6 mL, 0.15 moles) were mixed together at room temperature then with rapid stirring, heated to 70° C. for 4 hours. Heat was removed and stirring continued an additional 30 min. The organic layer was separated and washed with a saturated sodium chloride solution (3×15 mL) then dried over magnesium sulfate. After filtering, vacuum distillation (20 Torr, 28° C.) removed unreacted 3-ethyl-1-pentene. The remaining yellow oil contains 3-ethyl-1-nitro-2-pentene (12% yield) and a small amount of 3-ethyl-2-pentylnitrate. This was confirmed by IR and GC analysis.
Reaction SMILES: Br[CH2:2][CH2:3][N:4]1[C:8]([CH2:9]Br)=[CH:7][C:6]([N+:11]([O-:13])=[O:12])=[N:5]1.[CH:14]1([NH2:17])[CH2:16][CH2:15]1>C1COCC1>[CH:14]1([N:17]2[CH2:2][CH2:3][N:4]3[N:5]=[C:6]([N+:11]([O-:13])=[O:12])[CH:7]=[C:8]3[CH2:9]2)[CH2:16][CH2:15]1
Reactant: O=[N+]([O-])c1cc(CBr)n(CCBr)n1
Reactant: NC1CC1
Solvent: C1CCOC1
Product: O=[N+]([O-])c1cc2n(n1)CCN(C1CC1)C2
Temperature: 30 °C
Reaction time: 8 h
Yield: 99.8 %

Procedure:
A mixture of 1-(2-bromoethyl)-5-(bromomethyl)-3-nitro-1H-pyrazole 113c (4 g, 12.9 mmol) and cyclopropanamine (7.35 g, 129 mmol) in THF (40 mL) was stirred at 30° C. overnight. After the completion of the reaction, the mixture was filtered and the solid was washed with THF (100 mL). The filtrate was concentrated under reduced pressure to give 128a (2.68 g, 99%). MS: [M+H]+ 209.