Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:14]=[CH:13][C:5]([C:6]([O:8][C:9](C)(C)[CH3:10])=[O:7])=[CH:4][CH:3]=1.[CH3:15][Si:16](C#C)([CH3:18])[CH3:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(N(CC)CC)C.C(Cl)Cl.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:15][Si:16]([C:10]#[C:9][O:8][C:6](=[O:7])[C:5]1[CH:13]=[CH:14][CH:2]=[CH:3][CH:4]=1)([CH3:18])[CH3:17]
Reactant: CC(C)(C)OC(=O)c1ccc(Br)cc1
Reactant: C#C[Si](C)(C)C
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C[Si](C)(C)C#COC(=O)c1ccccc1
Temperature: 100 °C

Procedure:
A mixture containing 1.31 g of tert.-butyl 4-bromobenzoate, 1.0 g of trimethylsilylacetylene, 10 mg of palladium acetate and 15.6 mg of triphenylphosphine in 15 ml of anhydrous triethylamine is heated in a sealed container to 100° C. for 16 hours. After cooling to room temperature, the reaction mixture is diluted with methylene chloride and extracted with water. The organic solution is dried over anhydrous sodium sulfate and the solvent removed under reduced pressure. The dark residue is chromatographed a a column of flash silica gel using a 10% ethyl acetate-hexanes mixture as the eluent to give tert.-butyl 4-(trimethylsilylethynylbenzoate as a dark oil: NMR (CDCl3, 300 MHz) delta 0.26 (s, 9H), 1.59 (s, 9H), 7.49 (d, 2H, J=8.23 Hz), 7.91 (d, 2H, J=8.23 Hz). This is dissolved in 20 ml of anhydrous methanol, and then treated with 0.1 g of anhydrous potassium carbonate. The mixture is allowed to stir at room temperature under nitrogen for 3 hours. The reaction mixture is diluted with methylene chloride, extracted with water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue is distilled under reduced pressure (60°-70° C./0.1 mm to give 0.75 g (73% over 2 steps) of tert.-butyl 4-ethynylbenzoate as a white solid: m.p. 71.5°-72° C.; NMR (CDCl3 , 80 MHz) delta 1.62 (s, 9H), 3.23 (s, 1H), 7.55 (d, 2H, J=8.11 Hz), 7.96 (d, 2H, J=8.11 Hz); IR (KBr) 3240, 2970, 2100, 1700, 1600, 1450, 1365, 1300, 1250, 1160, 1115, 1015, 845 and 765 cm-1 ; M/S 202M+), 187, 157, 146, 129, 101, 75 and 57.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][S:9]([CH2:12][C:13]2[CH:18]=[CH:17][C:16](Cl)=[C:15]([N+:20]([O-:22])=[O:21])[CH:14]=2)(=[O:11])=[O:10])=[CH:4][C:3]=1[N+:23]([O-:25])=[O:24].[OH-:26].[Na+].S(=O)(=O)(O)[OH:29]>O>[OH:26][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][S:9]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([OH:29])=[C:15]([N+:20]([O-:22])=[O:21])[CH:14]=2)(=[O:11])=[O:10])=[CH:4][C:3]=1[N+:23]([O-:25])=[O:24]
Reactant: O=S(=O)(O)O
Reactant: [OH-]
Reactant: O=[N+]([O-])c1cc(CS(=O)(=O)Cc2ccc(Cl)c([N+](=O)[O-])c2)ccc1Cl
Agent: [Na+]
Solvent: O
Product: O=[N+]([O-])c1cc(CS(=O)(=O)Cc2ccc(O)c([N+](=O)[O-])c2)ccc1O
Temperature: 90 °C
Reaction time: 3.5 h

Procedure:
25.6 kg of 4-chloro-3-nitrophenylmethylsulfone are stirred slowly into 4 kg of 30% aqueous sodium hydroxide and the mixture is diluted continuously with water to a volume of about 50 liters. The reaction mixture is heated to 90° C. and then a further 29 kg of 30% aqueous sodium hydroxide are added, with stirring, over 3 to 4 hours. The mixture is then heated for 90 minutes to 103° C. After it has cooled to about 60° C., the solution is adjusted with 16% sulfuric acid to a pH value of about 1.5, whereupon the product precipitates. The precipitate is isolated by filtration, washed and recrystallised from ethanol. Yield: 24 kg of colourless crystals with a melting point of 166°-168° C.
Reaction SMILES: Br[CH2:2][CH2:3][O:4][C:5](=[O:7])[CH3:6].C(=O)([O-])[O-].[K+].[K+].[CH3:14][N:15]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]1>O1CCCC1>[CH2:3]([O:4][C:5](=[O:7])[CH2:6][N:18]1[CH2:19][CH2:20][N:15]([CH3:14])[CH2:16][CH2:17]1)[CH3:2]
Reactant: CC(=O)OCCBr
Reactant: CN1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: CCOC(=O)CN1CCN(C)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 22 %

Procedure:
To a solution of bromoethylacetate, 3.3 g (30.0 mmol) in 100 mL of tetrahydrofuran was added 4.14 g (30.0 mmol) of potassium carbonate and 3.3 mL (30.0 mmol) of 4-methylpiperazine. The reaction mixture stirred overnight at rt. and was concentrated to dryness. The residue was partitioned between 20% isopropanol/chloroform and saturated aqueous NaHCO3. The mixture was washed with saturated NaHCO3, washed with brine, dried over Na2SO4, filtered and concentrated to dryness to give 1.23 g (22%) of the desired product as a tan oil. MS (ion spray) 187.1 (M+).
Reaction SMILES: N.Cl[C:3]1[NH:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]2[C:13](=[O:26])[N:14]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH3:25])=[CH:19][CH:18]=3)[C:15](=[O:16])[C:4]=12>C1COCC1>[CH2:24]([O:23][C:20]1[CH:19]=[CH:18][C:17]([N:14]2[C:15](=[O:16])[C:4]3=[CH:3][NH:12][C:11]4[C:6]([N:5]3[C:13]2=[O:26])=[CH:7][CH:8]=[CH:9][CH:10]=4)=[CH:22][CH:21]=1)[CH3:25]
Reactant: CCOc1ccc(-n2c(=O)c3c(Cl)[nH]c4ccccc4n-3c2=O)cc1
Agent: N
Solvent: C1CCOC1
Product: CCOc1ccc(-n2c(=O)c3c[nH]c4ccccc4n-3c2=O)cc1
Temperature: 25 °C

Procedure:
A solution of THF (10 mL), ammonia (10 mL) and 4-Chloro-2-(4-ethoxyphenyl)-imidazo[1,5,a]quinoxaline-1,3(2H,5H)-dione (100 mg) was heated to 100IC in a sealed tube for 4 hours. After cooling to room temperature the solvent was removed in vacuo. The solid was slurried in 50% EtOH—H2O and filtered to yield 4-Amino-2-(4-ethoxyphenyl-imidazo[1,5,a]quinoxaline-1,3(2H,5H)-dione (Compound 37).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([O:9]C)=[C:4]([CH:11]([CH3:13])[CH3:12])[CH:3]=1.B(Br)(Br)Br>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([OH:9])=[C:4]([CH:11]([CH3:13])[CH3:12])[CH:3]=1
Reactant: COc1c(F)cc(Br)cc1C(C)C
Agent: BrB(Br)Br
Solvent: ClCCl
Product: CC(C)c1cc(Br)cc(F)c1O
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 104.4 %

Procedure:
To a solution of 4-bromo-6-fluoro-2-iso-propylanisole (0.92 g, 3.70 mmol) in CH2Cl2 (10.0 mL) at −78° C. was added BBr3 (5.5 mL, 5.5 mmol, 1.0 M in CH2Cl2). After 5 min, the reaction mixture was stirred at room temperature for 16 h, poured into ice (50 g) and extracted with ethyl acetate (20.0 mL). The organic layer was separated, dried over MgSO4 and filtered. The solvent was removed under reduced pressure to afford 4-bromo-6-fluoro-2-iso-propylphenol (0.90 g, 100%) as a dark oil, which was used for the next step without further purification: 1H NMR (300 MHz, CD3OD): δ 7.26 (d, J=10.5 Hz, 1H), 6.92 (d, J=10.5 Hz, 1H), 3.30 (m, 1H), 1.23 (d, J=6.6 Hz, 6H); TLC conditions: Uniplate silica gel, 250 microns; Mobile phase=ethyl acetate-hexanes (1:9); Rf=0.40.
Reaction SMILES: Br[C:2]1[N:7]=[N:6][C:5]([NH2:8])=[N:4][C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[Cl:15][C:16]1[CH:17]=[CH:18][C:19]([O:25][CH3:26])=[C:20](B(O)O)[CH:21]=1>>[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([O:25][CH3:26])=[C:18]([C:2]2[N:7]=[N:6][C:5]([NH2:8])=[N:4][C:3]=2[C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:17]=1
Reactant: COc1ccc(Cl)cc1B(O)O
Reactant: Nc1nnc(Br)c(-c2ccccc2)n1
Product: COc1ccc(Cl)cc1-c1nnc(N)nc1-c1ccccc1
Yield: 22.8 %

Procedure:
6-(5-Chloro-2-methoxyphenyl)-5-phenyl-1,2,4-triazin-3-amine (57 mg, 22%) was prepared from 6-bromo-5-phenyl-1,2,4-triazin-3-amine (0.21 g, 0.80 mmol) and 5-chloro-2-methoxyphenylboronic acid (0.15 g, 0.80 mmol) according to the general procedure of Example 1.
Reaction SMILES: P(Br)(Br)[Br:2].[C:5]([C:9]1[CH:10]=[C:11]([CH:38]=[C:39]([C:41]([CH3:44])([CH3:43])[CH3:42])[CH:40]=1)[CH:12]=[CH:13][C:14]1[CH:15]=[C:16]([CH:19]=[C:20]([CH:22]=[CH:23][C:24]2[CH:29]=[C:28]([C:30]([CH3:33])([CH3:32])[CH3:31])[CH:27]=[C:26]([C:34]([CH3:37])([CH3:36])[CH3:35])[CH:25]=2)[CH:21]=1)[CH2:17]O)([CH3:8])([CH3:7])[CH3:6].CC(O)C>ClCCl>[C:5]([C:9]1[CH:10]=[C:11]([CH:38]=[C:39]([C:41]([CH3:44])([CH3:43])[CH3:42])[CH:40]=1)[CH:12]=[CH:13][C:14]1[CH:15]=[C:16]([CH:19]=[C:20]([CH:22]=[CH:23][C:24]2[CH:29]=[C:28]([C:30]([CH3:33])([CH3:32])[CH3:31])[CH:27]=[C:26]([C:34]([CH3:37])([CH3:36])[CH3:35])[CH:25]=2)[CH:21]=1)[CH2:17][Br:2])([CH3:8])([CH3:7])[CH3:6]
Reactant: CC(C)(C)c1cc(C=Cc2cc(C=Cc3cc(C(C)(C)C)cc(C(C)(C)C)c3)cc(CO)c2)cc(C(C)(C)C)c1
Reactant: BrP(Br)Br
Solvent: ClCCl
Solvent: CC(C)O
Product: CC(C)(C)c1cc(C=Cc2cc(C=Cc3cc(C(C)(C)C)cc(C(C)(C)C)c3)cc(CBr)c2)cc(C(C)(C)C)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 84.5 %

Procedure:
Phosphorus tribromide (2.8 cm3, 30 mmol) was added to a solution of 3,5-bis(3′,5′-di-tert-butylstyryl)benzyl alcohol (1.60 g, 3.0 mmol) in dichloromethane (50 cm3) and the mixture stirred at room temperature for 3 h. Propan-2-ol (14 cm3) was added slowly and the solvent was completely removed. The residue was purified by column chromatography over silica, eluting with dichloromethane-light petroleum (40-60) (1:9), giving 3,5-bis(3′,5′-di-tert-butylstyryl)benzyl bromide (1.52 g, 85%). A sample for analysis was recrystallised from a dichloromethane-light petroleum (60-80) mixture, mp 222-223° C. (Found: C, 77.75; H, 8.72. C39H51Br requires C, 78.11; H, 8.57%); νmax(CHCl3)/cm−1 1596s (C═C) and 964s (C═C—H trans); λmax(CHCl3)/nm (log ε) 315 (4.82); δH(400 MHz, CDCl3) 1.38 (36 H, s, t-Bu), 4.55 (2 H, s, CH2), 7.12 and 7.24 (4 H, d, J 16, 7′,8′-H), 7.39 (2 H, dd, J 1.5, 4′-H), 7.41 (4 H, d, J 1.5, 2′,6′-H), 7.47 (2 H, d, J 1, 2,6-H) and 7.63 (1 H, m, 4-H); m/z (APCI+) 521 ((M-Br)+, 100%) and 599 (M+, 40%).
Reaction SMILES: C1(CCC[NH2:10])C=CC=CC=1.[CH2:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:13][N:12]1[C:20]([NH:22][CH2:23][CH2:24][C:25]([OH:27])=O)=[O:21].[CH2:28]1[C:36]2[C:31](=CC=CC=2)[CH2:30][N:29]1[C:37]([NH:39][C:40]1[CH:48]=[CH:47][C:43](C(O)=O)=CC=1)=O>>[O:27]=[C:25]([N:10]1[CH2:36][CH2:28][N:29]([C:37]2[CH:43]=[CH:47][CH:48]=[CH:40][N:39]=2)[CH2:30][CH2:31]1)[CH2:24][CH2:23][NH:22][C:20]([N:12]1[CH2:11][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:13]1)=[O:21]
Reactant: NCCCc1ccccc1
Reactant: O=C(O)c1ccc(NC(=O)N2Cc3ccccc3C2)cc1
Reactant: O=C(O)CCNC(=O)N1Cc2ccccc2C1
Product: O=C(CCNC(=O)N1Cc2ccccc2C1)N1CCN(c2ccccn2)CC1

Procedure:
The title compound was prepared as described in Example 1C, substituting 1-(pyridin-2-yl)piperazine for 3-phenylpropan-1-amine and 3-(isoindoline-2-carboxamido)propanoic acid for 4-(isoindoline-2-carboxamido)benzoic acid. 1H NMR (300 MHz, DMSO-d6) δ ppm 8.11 (ddd, J=4.9, 2.0, 0.8 Hz, 1H), 7.53 (ddd, J=8.7, 7.0, 1.9 Hz, 1H), 7.25-7.34 (m, 4H), 6.83 (d, J=8.6 Hz, 1H), 6.65 (ddd, J=7.1, 4.9, 0.8 Hz, 1H), 6.37 (t, J=5.6 Hz, 1H), 4.57 (s, 4H), 3.44-3.61 (m, 8H), 3.28-3.37 (m, 2H), 2.54-2.61 (m, 2H); MS (ESI(+)) m/e 380 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:29]([O:30][CH3:31])=[CH:28][C:6]2[CH2:7][CH2:8][N:9]([C:12](=[O:27])[CH2:13][CH2:14][N:15]([CH2:17][CH:18]3[CH2:25][C:24]4[C:19]3=[CH:20][CH:21]=[C:22]([OH:26])[CH:23]=4)[CH3:16])[CH2:10][CH2:11][C:5]=2[CH:4]=1.C(N(CC)CC)C.[CH3:39][N:40]([CH3:44])[C:41]([Cl:43])=[O:42]>N1C=CC=CC=1>[ClH:43].[CH3:39][N:40]([CH3:44])[C:41](=[O:42])[O:26][C:22]1[CH:23]=[C:24]2[C:19](=[CH:20][CH:21]=1)[CH:18]([CH2:17][N:15]([CH2:14][CH2:13][C:12]([N:9]1[CH2:10][CH2:11][C:5]3[CH:4]=[C:3]([O:2][CH3:1])[C:29]([O:30][CH3:31])=[CH:28][C:6]=3[CH2:7][CH2:8]1)=[O:27])[CH3:16])[CH2:25]2
Reactant: CN(C)C(=O)Cl
Reactant: COc1cc2c(cc1OC)CCN(C(=O)CCN(C)CC1Cc3cc(O)ccc31)CC2
Solvent: c1ccncc1
Solvent: CCN(CC)CC
Product: COc1cc2c(cc1OC)CCN(C(=O)CCN(C)CC1Cc3cc(OC(=O)N(C)C)ccc31)CC2
Product: Cl
Reaction time: 8 h

Procedure:
At ambient temperature, to 0.7 g (1.65 mmol) of the compound of Example 43 in 5 ml of pyridine, there are added, all at once, 0.3 mL (2.06 mmol/1.25 eq.) of triethylamine and then, dropwise, 0.2 mL (2.06 mmol/1.25 eq.) of dimethylcarbamoyl chloride. Stirring is carried out at ambient temperature overnight and the mixture is then concentrated. The residue is chromatographed over 130 g of silica (eluant: dichloromethane/ethanol/ammonia: 95/5/0.5) to yield the expected product in the form of the base. It is dissolved in 7 mL of ethanol and treated with 0.5 mL of 3N ethanolic HCl to yield the hydrochloride.
Reaction SMILES: [Cl:1][C:2]1[N:11]=[C:10](Cl)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[CH2:13]([NH2:16])[CH2:14][CH3:15].C(N(CC)CC)C>C(#N)C.C(OCC)(=O)C>[Cl:1][C:2]1[N:11]=[C:10]([NH:16][CH2:13][CH2:14][CH3:15])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1
Reactant: CCCN
Reactant: Clc1nc(Cl)c2ccccc2n1
Solvent: CCOC(C)=O
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCCNc1nc(Cl)nc2ccccc12
Temperature: 25 °C

Procedure:
2,4-Dichloroquinazoline (600 mg, 3.01 mmol) was dissolved in acetonitrile (10 mL). Propylamine (200 mg, 3.3 mmol) and triethylamine (2.1 mL, 15 mmol) were added. The mixture was stirred at room temperature over-night. Filtration and evaporation of the filtrate gave a yellow solid, which was dissolved in ethyl acetate and washed three times with water. Drying (magnesium sulphate), filtration and evaporation gave (2-chloro-quinazolin-4-yl)-propylamine as a yellow solid.
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[NH:10][C:11]1[CH:19]=[CH:18][CH:17]=[CH:16][C:12]=1[C:13]([OH:15])=O.[C:20](C1NC=CN=1)(C1NC=CN=1)=O.C(OC(=O)CC(O)=O)C.O.FC(F)(F)C(O)=O>C1COCC1>[Cl:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[NH:10][C:11]1[CH:19]=[CH:18][CH:17]=[CH:16][C:12]=1[C:13](=[O:15])[CH3:20]
Reactant: O=C(c1ncc[nH]1)c1ncc[nH]1
Reactant: Cc1ccc(Cl)c(Nc2ccccc2C(=O)O)c1Cl
Agent: CCOC(=O)CC(=O)O
Solvent: C1CCOC1
Solvent: O=C(O)C(F)(F)F
Solvent: O
Product: CC(=O)c1ccccc1Nc1c(Cl)ccc(C)c1Cl
Yield: 77.5 %

Procedure:
2-[(2,6-Dichloro-3-methylphenyl)amino]benzoic acid (8.4 g, 28.5 mmol) and carbonyl diimidazole (6.9 g, 42.7 mmol) are stirred in 300 ml THF under argon for two hours. Malonic acid monoethyl ester, magnesium salt (24.0 g, 85.4 mmol) is added and the reaction mixture is warmed to reflux for 15 hours. The solvent is evaporated, and the residue partitioned between ethyl acetate and lN HCl. The pH of the aqueous layer is adjusted to pH=1 with concentrated HCl. The aqueous layer is extracted with ethyl acetate. The organic layer is washed with 1N HCl, and with saturated sodium bicarbonate, and then dried over magnesium sulfate and evaporated. The solid remaining is taken up in ethyl acetate and adsorbed onto a silica gel pad. The pad is washed with chloroform. Evaporation of the chloroform gives crude β-keto ester which is treated with 30% water/trifluoroacetic acid at reflux for two hours. The trifluoroacetic acid is evaporated, and the residue is taken up in diethyl ether. The ether solution is washed with 100 ml of saturated sodium bicarbonate three times. It is dried over magnesium sulfate, and evaporated. The remaining solid is taken up in methylene chloride and adsorbed onto a silica gel pad. This pad is washed with methylene chloride. Evaporation of the solvent gives a yellow solid. Recrystallization from methylene chloride/hexane gives 6.5 g (42%) of 1-[2-[(2,6-dichloro-3-methylphenyl) amino]phenyl]ethanone; mp 130°- 132° C.
Reaction SMILES: [Si:1]([O:18][CH2:19][C@H:20]1[O:24][C@@H:23]([N:25]2[C:34]3[N:33]=[CH:32][N:31]=[C:29]([NH2:30])[C:28]=3[N:27]=[CH:26]2)[C@H:22]([O:35][CH2:36][CH2:37][OH:38])[C@@H:21]1[OH:39])([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.C[Si](C)(C)Cl.[C:45](Cl)(=[O:52])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1.[NH4+].[OH-]>N1C=CC=CC=1.CCOC(C)=O.O>[Si:1]([O:18][CH2:19][C@H:20]1[O:24][C@@H:23]([N:25]2[C:34]3[N:33]=[CH:32][N:31]=[C:29]([NH:30][C:45](=[O:52])[C:46]4[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=4)[C:28]=3[N:27]=[CH:26]2)[C@H:22]([O:35][CH2:36][CH2:37][OH:38])[C@@H:21]1[OH:39])([C:14]([CH3:15])([CH3:17])[CH3:16])([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: CC(C)(C)[Si](OC[C@H]1O[C@@H](n2cnc3c(N)ncnc32)[C@H](OCCO)[C@@H]1O)(c1ccccc1)c1ccccc1
Reactant: O=C(Cl)c1ccccc1
Agent: C[Si](C)(C)Cl
Agent: [NH4+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: O
Solvent: c1ccncc1
Product: CC(C)(C)[Si](OC[C@H]1O[C@@H](n2cnc3c(NC(=O)c4ccccc4)ncnc32)[C@H](OCCO)[C@@H]1O)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 83.2 %

Procedure:
Dried 5′-O-t-butyldiphenylsilyl-2′-O-(hydroxyethyl)-adenosine (24 g, 43.7 mmol) was dissolved in anhydrous pyridine (500 mL) under inert atmosphere, and trimethylchlorosilane (27.7 mL, 218 mmol) was added at 0° C. The reaction was allowed to warm to ambient temperature, stirred for 1 hour, then cooled to 0° C. Benzoyl chloride (25.3 mL, 218 mmol) was added dropwise, then the reaction was allowed to warm to ambient temperature and stirred for 4 hours after which it was cooled to 0° C. and water (100 mL) was added. After stirring for 10 minutes aqueous 30% NH4OH (100 mL) was added, and the reaction was stirred at 0° C. for 1 hour. The solvent was evaporated in vacuo to give a residue which was dissolved in EtOAc (1 L), and the resulting solution was washed with water (200 mL) twice, then with brine (100 mL). The organic solution was dried with MgSO4, and the solvent was evaporated in vacuo to give a residue. The residue was purified by column chromatography using CH2Cl2-EtOAc-MeOH, 70:27:3, to give the title compound as a solid (23.77 g, 83%).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[NH:9][C:10]2[C:15]([CH:16]=1)=[CH:14][CH:13]=[CH:12][CH:11]=2.C(O)(=O)C.[NH:21]1[CH2:26][CH2:25][C:24](=O)[CH2:23][CH2:22]1.O.Cl.[NH4+].[OH-]>C(O)C>[NH:21]1[CH2:26][CH2:25][C:24]2([C:16]3=[C:15]4[C:10](=[N:9][C:8]3=[C:3]3[C:2](=[CH:7][CH:6]=[CH:5][CH2:4]3)[NH:1]2)[CH:11]=[CH:12][CH:13]=[CH:14]4)[CH2:23][CH2:22]1
Reactant: Nc1ccccc1-c1cc2ccccc2[nH]1
Reactant: O=C1CCNCC1
Agent: Cl
Agent: [NH4+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CCO
Solvent: O
Product: C1=CCC2=C3N=c4ccccc4=C3C3(CCNCC3)NC2=C1
Temperature: 25 °C
Yield: 53.6 %

Procedure:
To a mixture prepared from 8 g of 2-(2-aminophenyl)indole, 2.5 ml of acetic acid and 100 ml of ethanol was added 6.5 g of 4-piperidone·H2O·HCl. The mixture was refluxed for 6 hours and thereafter cooled to room temperature. The resultant mixture was treated with dilute NH4OH and the resultant solid was collected, washed with water and dried. The crude product (9.15 g) was flash chromatographed using CH3OH as an eluent, and thereafter converted to the HCl salt. This salt was converted back to the free base using CH2Cl2 /dilute NH4OH to give 5.96 g of solid, m.p. 257°-259° dec.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([C:13]2[O:14]C=CC=2)=[CH:11][C:10]([C:18]([O:20][CH3:21])=[O:19])=[N:9]1.O.C(Cl)(Cl)(Cl)Cl.I([O-])(=O)(=O)=[O:29].[Na+]>C(#N)C.[Ru](Cl)(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]1[C:12]([C:13]([OH:14])=[O:29])=[CH:11][C:10]([C:18]([O:20][CH3:21])=[O:19])=[N:9]1
Reactant: [O-][I+3]([O-])([O-])[O-]
Reactant: COC(=O)c1cc(-c2ccco2)n(-c2ccccc2Cl)n1
Agent: Cl[Ru](Cl)Cl
Agent: [Na+]
Solvent: O
Solvent: CC#N
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)c1cc(C(=O)O)n(-c2ccccc2Cl)n1
Temperature: 25 °C
Reaction time: 72 h
Yield: 43.2 %

Procedure:
To a stirred mixture of compound 6 (3.0 g, 9.9 mmol) in a mixture of acetonitrile (60 mL), water (80 mL) and carbon tetrachloride (60 mL) was added sodium periodate (8.3 g, 39 mmol) and ruthenium chloride (125 mg, 0.03 mmol) and the reaction mixture was stirred at room temperature for 72 h. On completion, solvent was removed, crude mass was dissolved in saturated sodium bicarbonate solution, extracted with ether (50 ml×3). Aqueous layer was acidified with 1N HCl and extracted with ethyl acetate (60 mL×4). The combined ethyl acetate layer was washed with brine, dried over sodium sulphate and concentrated to afford the title compound 7 (1.2 g, 44%) which was used for further reaction.
Reaction SMILES: [NH:1]1[C:5]([CH2:6][C:7]2[CH:8]=[CH:9][C:10]3[O:14][CH:13]=[C:12]([C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)[C:11]=3[CH:21]=2)=[N:4][N:3]=[N:2]1.C(Cl)(Cl)Cl.[Br:26]Br>O1CCOCC1>[Br:26][C:13]1[O:14][C:10]2[CH:9]=[CH:8][C:7]([CH2:6][C:5]3[NH:1][N:2]=[N:3][N:4]=3)=[CH:21][C:11]=2[C:12]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: c1ccc(-c2coc3ccc(Cc4nnn[nH]4)cc23)cc1
Reactant: BrBr
Solvent: C1COCCO1
Solvent: ClC(Cl)Cl
Product: Brc1oc2ccc(Cc3nnn[nH]3)cc2c1-c1ccccc1
Temperature: 0 °C

Procedure:
To a stirred solution of 2.8 g. (0.01 mole) of 5-tetrazolylmethyl-3-phenylbenzofuran in 100 ml. of chloroform and 20 ml. of dioxane is added dropwise 1.6 g. (0.01 mole) of bromine. After 45 minutes the mixture is cooled to 0° C., then the product is separated by filtration and washed with chloroform. Recrystallization from aqueous ethanol provides 2-bromo-3-phenyl-5-(1H-tetrazol-5yl)methylbenzofuran m.p. 215°-217° C.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.Br.Br.[C:13]([N:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1)([CH3:16])([CH3:15])[CH3:14].C(N(CC)CC)C>C(#N)C.O>[C:13]([N:17]1[CH2:22][CH2:21][N:20]([C:2]2[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=2)[CH2:19][CH2:18]1)([CH3:16])([CH3:15])[CH3:14]
Reactant: CC(C)(C)N1CCNCC1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Agent: Br
Solvent: CCN(CC)CC
Solvent: CC#N
Solvent: O
Product: CC(C)(C)N1CCN(c2ccc([N+](=O)[O-])cc2)CC1
Temperature: 25 °C
Yield: 272.1 %

Procedure:
A solution of 800 mg (5.67 mmol) of 1-fluoro-4-nitrobenzene, 2.07 g (1.2 mmol) of 1-tert-butylpiperazine dihydrobromide and 3.2 mL (20.41 mmol) of triethylamine, in 22 mL of acetonitrile, was refluxed for 10 hours. The mixture was cooled to room temperature, diluted with water and extracted with dichloromethane. The organic layer was washed with water and brine, dried over Na2SO4 and evaporated. Purification by flash chromatography (eluant dichloromethane/methanol 7/3) yielded 860 mg of the title compound as yellow solid.
Reaction SMILES: [F:1][C:2]([S:5][C:6]1[CH:13]=[CH:12][C:9]([CH:10]=O)=[CH:8][CH:7]=1)([F:4])[F:3].C(O)(=O)[CH2:15][C:16]([OH:18])=[O:17].N1CCCCC1.C(=O)=O.Cl>N1C=CC=CC=1>[F:1][C:2]([S:5][C:6]1[CH:13]=[CH:12][C:9]([CH:10]=[CH:15][C:16]([OH:18])=[O:17])=[CH:8][CH:7]=1)([F:4])[F:3]
Reactant: O=C(O)CC(=O)O
Reactant: O=Cc1ccc(SC(F)(F)F)cc1
Agent: Cl
Agent: O=C=O
Solvent: c1ccncc1
Solvent: C1CCNCC1
Product: O=C(O)C=Cc1ccc(SC(F)(F)F)cc1
Temperature: 0 °C

Procedure:
A mixture of 5.42 g (26.3 mmol) 4-trifluoromethylsulfanyl-benzaldehyde, 3.12 g (30.0 mmol) malonic acid, 0.26 g (3.0 mmol) piperidine and 12.0 ml pyridine was kept at reflux temperature until carbon dioxide development ceased (5 h). The reaction mixture was poured into a solution of 50 ml ice water and 15 ml 6N HCl. The precipitate was isolated, washed with water, then with n-heptane and dried at 50° C. Yield: 5.9 g (85%) 3-(4-Trifluoromethylsulfanyl-phenyl)-acrylic acid.