Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH3:8].[Cl:9]C1C=C(C)C=CC=1.ClC1C=CC(C)=CC=1>C1(C)C=CC=CC=1>[Cl:9][C:7]1[C:2]([Cl:1])=[C:3]([CH3:8])[CH:4]=[CH:5][CH:6]=1
Reactant: Cc1ccccc1Cl
Reactant: Cc1cccc(Cl)c1
Solvent: Cc1ccc(Cl)cc1
Solvent: Cc1ccccc1
Product: Cc1cccc(Cl)c1Cl
Yield: 4.5 %

Procedure:
The chlorination of toluene in the presence of catalysts is known to produce the ring-chlorinated isomeric o-, m- and p-monochlorotoluenes in a ratio which varies according to the type of catalyst used and the reaction conditions chosen. Thus, for example, the chlorination of toluene at 50° C. in the presence of FeCl3 as catalyst up to a density of 1.043 g/cm3 (20° C.) leads to a product comprising 19% by weight of toluene, 49% by weight of o-chlorotoluene, 2% by weight of m-chlorotoluene and 25.5% by weight of p-chlorotoluene. Apart from these, 4.5% of dichlorotoluene are additionally formed (Ullmanns Encyl. der techn. Chemie [Ullmann's Encyclopedia of Industrial Chemistry] (1975), Volume 9, page 512). The use of TiCl4, SnCl4, WCl6 or ZrCl4 as catalysts at a chlorination temperature of 10°-30° C. increases the o-chlorotoluene content to 75% by weight (U.S. Pat. No. 3,000,975), while the use of disulfide dichloride and the metal chlorides mentioned or of sulfur and SbCl3 shifts the isomeric ratio in favor of p-chlorotoluene (U.S. Pat. No. 1,946,040). There is no successful instance of obtaining a single isomer by a suitable choice of catalyst or reaction conditions. All these processes therefore require a subsequent separation of the reaction mixture into the pure isomers, which separation is customarily carried out in two stages where, in a first working-up stage, which is expensive in outlay and energy, o-chlorotoluene (boiling point 158.5° C.) is separated as top product by distillation, for example in a bubble cap column having over 200 theoretical plates, from a bottom comprising m- and p-chlorotoluene. Due to the small difference in the boiling points of these isomers (161.2° C. and 161.5° C. respectively), it is no longer possible to separate their mixture by distillation. Pure p-chlorotoluene (melting point 7.6° C.) must therefore be separated in a second step by crystallization from the m-isomer, which has a lower melting point (melting point -48.7° C.).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:13]=1[O:14][CH2:15][CH2:16][NH2:17])[C:6]([O:8]CC)=[O:7].[CH3:18][O:19][C:20]1[CH:21]=[C:22]([CH2:37][C:38](O)=[O:39])[CH:23]=[CH:24][C:25]=1[NH:26][C:27]([NH:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[CH3:36])=[O:28].CCN(CC)CC.[OH-].[Na+]>C1COCC1>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][C:13]=1[O:14][CH2:15][CH2:16][NH:17][C:38](=[O:39])[CH2:37][C:22]1[CH:23]=[CH:24][C:25]([NH:26][C:27]([NH:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[CH3:36])=[O:28])=[C:20]([O:19][CH3:18])[CH:21]=1)[C:6]([OH:8])=[O:7]
Reactant: CCOC(=O)c1ccc(OCCN)c(OC)c1
Reactant: COc1cc(CC(=O)O)ccc1NC(=O)Nc1ccccc1C
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: COc1cc(CC(=O)NCCOc2ccc(C(=O)O)cc2OC)ccc1NC(=O)Nc1ccccc1C
Reaction time: 48 h
Yield: 20.8 %

Procedure:
To a stirred solution of ethyl 3-methoxy-4-(2-aminoethoxy)benzoate (250 mg, 1.04 mmol) and pentafluorophenyl ester of 3-methoxy-4-[N′-(2-methylphenyl)ureido]phenylacetic acid (500 mg, 1.04 mmol) was added Et3N (210 μl, 3.01 mmol), and the resulting mixture was stirred for 2 days. 0.25 N NaOH (20 ml) and THF (20 mL) was added to the mixture and the resulting mixture was heated under reflux overnight. After cooling, the mixture was evaporated and the residue was acidified by the addition of 1 N HCl. The mixture was extracted with CHCl3, and the extract was washed with brine, dried over Na2SO4, and evaporated. The obtained crude solid was recrystallized from CHCl3 to give 110 mg (20% for 2 steps) 3-methoxy-4-[2-[3-methoxy-4-[N′-(2-methylphenyl)ureido]phenylacetyl]aminoethoxy]benzoic acid 255 as a white crystalline powder. mp 180-181° C.; IR (KBr) 1687 cm−1; 1H-NMR (DMSO-d6) d 2.24 (s, 3 H), 3.37 (s, 2 H), 3.38 (s, 2 H), 3.41-3.50 (m, 2 H), 3.81 (s, 3 H), 3.83 (s, 3 H), 4.06-4.08 (m, 2 H), 6.76-8.55 (series of m, total 12 H); MS (FAB) m/z 508 (M++1); Anal. Calcd. for C27H29N3O7.1/2H2O: C, 62.78; H, 5.85; N, 8.13. Found: C, 62.46; H, 5.69; N, 8.03.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.Br[CH2:9][C:10]1[CH:28]=[CH:27][C:13]([CH2:14][N:15]2[CH2:19][C@@H:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[O:17][C:16]2=[O:26])=[CH:12][CH:11]=1.[H-].[Na+]>CN(C=O)C.ClCCl>[C:20]1([C@H:18]2[O:17][C:16](=[O:26])[N:15]([CH2:14][C:13]3[CH:12]=[CH:11][C:10]([CH2:9][O:1][C:2]4[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=4)=[CH:28][CH:27]=3)[CH2:19]2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: Oc1cccnc1
Reactant: O=C1O[C@H](c2ccccc2)CN1Cc1ccc(CBr)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C1O[C@H](c2ccccc2)CN1Cc1ccc(COc2cccnc2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 45.8 %

Procedure:
A solution of 3-hydroxypyridine (23 mg, 0.24 mmol) in DMF (1 mL) was added to a suspension of 3-(4-bromomethyl-benzyl)-5-(R)-phenyl-oxazolidin-2-one (70 mg, 0.20 mmol) (synthesized according to procedure 4) and sodium hydride (60%) (9 mg, 0.22 mmol) in DMF (1.5 mL) and the reaction mixture was stirred overnight at RT. It was diluted with dichloromethane (6 mL), washed with water (2×5 mL), dried over anhydrous sodium sulfate and concentrated in vacuo. The product was purified by chromatography on silica gel, eluting with dichloromethane containing 0.25-1% of methyl alcohol, to yield the title compound as a white solid (33 mg, 45%). 1H NMR (300 MHz, CDCl3): δ 8.40 (s, 1H), 8.25 (s, 1H), 7.38 (m, 1H), 5.50 (dd, 1H), 5.11 (s, 2H), 4.59 (d, 1H), 4.43 (d, 1H), 3.80 (t, 1H), 3.34 (dd, 1H).
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([S:12]([CH3:15])(=[O:14])=[O:13])[CH2:9]2)=[CH:4][CH:3]=1.[F:16][C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1.C(=O)([O-])[O-].[K+].[K+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CO.O1CCOCC1.CCOCC.CC([O-])=O.CC([O-])=O.[Pd+2]>[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:2]2[CH:11]=[C:10]3[C:5]([CH2:6][CH2:7][N:8]([S:12]([CH3:15])(=[O:14])=[O:13])[CH2:9]3)=[CH:4][CH:3]=2)=[CH:19][CH:18]=1
Reactant: CS(=O)(=O)N1CCc2ccc(Br)cc2C1
Reactant: OB(O)c1ccc(F)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: CCOCC
Solvent: CO
Solvent: C1COCCO1
Product: CS(=O)(=O)N1CCc2ccc(-c3ccc(F)cc3)cc2C1

Procedure:
A mixture of 7-bromo-2-(methylsulfonyl)-1,2,3,4-tetrahydroisoquinoline (2.90 g, 10.0 mmol), 4-fluorophenylboronic acid (2.10 g, 15.0 mmol), anhydrous potassium carbonate (4.15 g, 30.0 mmol) and triphenylphosphine (525 mg, 2.0 mmol) was prepared in MeOH (20 ml) and 1,4-dioxane (10 ml). Argon was bubbled for 10 min., then Pd(OAc)2 (112 mg, 0.50 mmol) was added. The resulting mixture was refluxed for 5 hours. The reaction mixture was diluted with Et2O (50 ml) and the resulting suspension was filtered trough a pad of Celite. The filtrate was evaporated under reduced pressure. The residue was taken up with Et2O and washed with water (3×) and brine. The organic layer was dried (MgSO4) and the solvent was removed under reduced pressure to give a black oil. After purification by flash chromatography on silica (cHex/EtOAc, gradient from 3/1 to 3/2), the title compound was obtained as a beige solid (2.50 g, 82%). HPLC, Rt: 4.4 min (purity: 98.8%). LC/MS, M+(ESI): 306.2.
Reaction SMILES: [Br:1][C@H:2]1[C@H:7]([OH:8])[C:6]2[CH:9]=[C:10]([C:13]#[N:14])[CH:11]=[CH:12][C:5]=2[O:4][C:3]1([CH3:16])[CH3:15].C(Cl)CCl.[N+:21]([C:24]1[CH:25]=[C:26]([CH:36]=[C:37]([N+:39]([O-:41])=[O:40])[CH:38]=1)[C:27]([S:29][CH2:30][C@H:31]([CH3:35])[C:32](Cl)=[O:33])=[O:28])([O-:23])=[O:22]>N1C=CC=CC=1>[Br:1][C@H:2]1[C@H:7]([O:8][C:32](=[O:33])[C@H:31]([CH3:35])[CH2:30][S:29][C:27](=[O:28])[C:26]2[CH:36]=[C:37]([N+:39]([O-:41])=[O:40])[CH:38]=[C:24]([N+:21]([O-:23])=[O:22])[CH:25]=2)[C:6]2[CH:9]=[C:10]([C:13]#[N:14])[CH:11]=[CH:12][C:5]=2[O:4][C:3]1([CH3:16])[CH3:15]
Reactant: C[C@@H](CSC(=O)c1cc([N+](=O)[O-])cc([N+](=O)[O-])c1)C(=O)Cl
Reactant: CC1(C)Oc2ccc(C#N)cc2[C@@H](O)[C@@H]1Br
Solvent: c1ccncc1
Solvent: ClCCCl
Product: C[C@H](CSC(=O)c1cc([N+](=O)[O-])cc([N+](=O)[O-])c1)C(=O)O[C@@H]1c2cc(C#N)ccc2OC(C)(C)[C@H]1Br
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 93.1 %

Procedure:
To a mixture of 14.5 g of (±)-trans-3-bromo-6-cyano-3,4-dihydro-2,2-dimethyl-4-hydroxy-2H-1-benzopyran, 60 ml of ethylene chloride and 1.6 ml of pyridine was added 5.5 g of (S)-(-)-3-(3,5-dinitrobenzoylthio)-2-methylpropionyl chloride under ice-cooling and was stirred for 1.5 hours under room temperature. The reaction mixture was washed with diluted hydrochloric acid once and 10% aqueous sodium chloride solution twice. The organic layer was separated, dried over magnesium sulfate and concentrated under reduced pressure to give 8.9 g of (±)-trans-3-bromo-6-cyano-3,4-dihydro-2,2-dimethyl-4-[(S)-(-)-3-(3,5-dinitrobenzoylthio)-2-methylpropionyloxy]-2H-1-benzopyran as light yellow semicrystals.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[S:9](Cl)(=[O:11])=[O:10].[NH2:13][C:14]1[C:19]([OH:20])=[CH:18][CH:17]=[CH:16][C:15]=1[CH3:21].C(N(CC)CC)C>C(Cl)Cl>[NH2:13][C:14]1[C:15]([CH3:21])=[CH:16][CH:17]=[CH:18][C:19]=1[O:20][S:9]([C:3]1[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=1[Cl:1])(=[O:11])=[O:10]
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1Cl
Reactant: Cc1cccc(O)c1N
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1cccc(OS(=O)(=O)c2ccc(Cl)cc2Cl)c1N
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a mixture of 2,4-dichlorobenzenesulfonyl chloride (20.2 g, 82.3 mmol) and 2-amino-m-cresol (11 g, 89.4 mmol) in 200 mL of methylene chloride, triethylamine (8.5 g, 83.4 mmol) was added dropwise at 5° C. The mixture was stirred at ambient temperature for 16 hours.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([Cl:15])[CH:9]=2)[CH:4]([C:16](OC)=[O:17])[CH2:3]1.[H-].[Al+3].[Li+].[H-].[H-].[H-].O.[OH-].[Na+]>O1CCCC1>[CH3:1][N:2]1[CH2:7][CH2:6][CH:5]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[C:10]([Cl:15])[CH:9]=2)[CH:4]([CH2:16][OH:17])[CH2:3]1
Reactant: COC(=O)C1CN(C)CCC1c1ccc(Cl)c(Cl)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: CN1CCC(c2ccc(Cl)c(Cl)c2)C(CO)C1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 102.8 %

Procedure:
To a solution of 1-methyl-3-methoxycarbonyl-4-(3,4-dichlorophenyl)piperidine (10 g, 33 mmol) in tetrahydrofuran (100 mL) at −20° C. was added a suspension of lithium aluminium hydride (1.2 g, 32 mmol) in tetrahydrofuran (150 mL) over 35 min. The reaction was heated to 0° C. followed by successive addition of water (1 mL), sodium hydroxide (4 N, 1 mL) and water (10 mL). The reaction was stirred for another 30 min and filtered through celite. Evaporation of the solvent afforded 9.3 g of the title compound as an oil.
Reaction SMILES: [CH3:1][CH:2]1[CH2:5][O:4][CH:3]1CO.[H-].[Na+].[H][H].[Cl-]>C1COCC1>[CH2:3]([O:4][CH2:5][C:2]1([CH3:1])[CH2:3][O:4][CH2:5]1)[CH:2]=[CH2:1]
Reactant: [H][H]
Reactant: CC1COC1CO
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: C=CCOCC1(C)COC1
Reaction time: 3 h
Yield: 160.3 %

Procedure:
The 3-methyl oxetanemethanol (1 mole) is dissolved in THF (500 mL) and fed into 60% sodium hydride dispersion (1.1 mole) in THF (500 mL) at 0° C. Following evolution of hydrogen gas the ally chloride (1.1 mole) is added to the reaction at room temperature. The reaction is aged for 2-4 hrs. The reaction is quenched when GC analysis indicates less than 10% starting alcohol is present. The reaction mass is washed with 10% aqueous sodium chloride solution. The crude reaction mass is purified by fractional distillation affording 114 g of 3-allyloxymethyl-3-methyl-oxetane.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([N:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)[CH:5]=[CH:6][C:7]=1[N+:8]([O-])=O.[H][H]>[Pd].CO>[NH2:1][C:2]1[CH:3]=[C:4]([N:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)[CH:5]=[CH:6][C:7]=1[NH2:8]
Reactant: [H][H]
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc([N+](=O)[O-])c(N)c2)CC1
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCN(c2ccc(N)c(N)c2)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 85.8 %

Procedure:
A 500 ml Parr hydrogenation flask was charged with tert-butyl 4-(3-amino-4-nitrophenyl)piperazine-1-carboxylate (9.0 g), methanol (250 mL) and 10% palladium on carbon (50% w/w water, 2.0 g). The atmosphere of the vessel was replaced by hydrogen gas. The reaction was shaken under a hydrogen atmosphere at 40 psi at room temperature for 1 hour. The reaction mixture was filtered through a plug of Celite, which was washed with additional methanol. The filtrate was concentrated at reduced pressure and the residue was triturated with ether to give 7.0 g of tert-butyl 4-(3,4-diaminophenyl)piperazine-1-carboxylate (yield 85%). 1H-NMR (400 MHz, MeOH-d4): δ 6.65 (d, 1H), 6.47 (s, 1H), 6.30 (d, 1H), 3.52 (s, 4H) 2.90 (s, 4H), 1.48 (s, 9H). MS (EI) for: 293 (MH+).
Reaction SMILES: CCN=C=NCCCN(C)C.Cl.[OH:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.[C:22]1([CH:28]([C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[CH2:29][CH2:30][O:31][C:32]([C:34]2[CH:39]([C:40]3[CH:45]=[CH:44][CH:43]=[C:42]([Cl:46])[CH:41]=3)[C:38]([C:47](O)=[O:48])=[C:37]([CH3:50])[NH:36][C:35]=2[CH3:51])=[O:33])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(=O)([O-])O.[Na+]>ClCCl>[C:22]1([CH:28]([C:52]2[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=2)[CH2:29][CH2:30][O:31][C:32](=[O:33])[C:34]2[C:39]([C:40]3[CH:45]=[CH:44][CH:43]=[C:42]([Cl:46])[CH:41]=3)=[C:38]([C:47]([N:19]3[CH2:20][CH2:21][N:16]([CH2:15][CH2:14][OH:13])[CH2:17][CH2:18]3)=[O:48])[C:37]([CH3:50])=[N:36][C:35]=2[CH3:51])[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: OCCN1CCNCC1
Reactant: CC1=C(C(=O)O)C(c2cccc(Cl)c2)C(C(=O)OCCC(c2ccccc2)c2ccccc2)=C(C)N1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C([O-])O
Solvent: ClCCl
Product: Cc1nc(C)c(C(=O)N2CCN(CCO)CC2)c(-c2cccc(Cl)c2)c1C(=O)OCCC(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
118 mg (0.620 mmol) of WSC hydrochloride and 80 mg (0.610 mmol) of 1-(2-hydroxyethyl) piperazine in the ice bath were added to 252 mg (0.510 mmol) of 4-(3-chlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid mono (3,3-diphenylpropyl) ester in 8 ml of dichloromethane and stirred at room temperature overnight. Saturated aqueous sodium hydrogencarbonate solution was added and the reaction mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was dissolved in 8 ml of dichloromethane. 4 ml of trifluoroacetic acid was added in the ice bath and stirred at room temperature for 9 hours. The reaction mixture was concentrated under reduced pressure, followed by basifying with 1N NaOH aq. After extracting it with ethyl acetate, The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by the basic silica gel chromatography (chloroform/methanol=1000/1) to obtain the title compound.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][N:11]2[CH:15]=[CH:14][N:13]=[CH:12]2)=[CH:4][CH:3]=1.Cl[CH2:17][C:18]1[N:19]=[C:20]([C:23]2[S:24][C:25]([CH3:28])=[CH:26][CH:27]=2)[O:21][CH:22]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[N:11]1([CH2:10][CH2:9][CH2:8][C:5]2[CH:6]=[CH:7][C:2]([O:1][CH2:17][C:18]3[N:19]=[C:20]([C:23]4[S:24][C:25]([CH3:28])=[CH:26][CH:27]=4)[O:21][CH:22]=3)=[CH:3][CH:4]=2)[CH:15]=[CH:14][N:13]=[CH:12]1
Reactant: Oc1ccc(CCCn2ccnc2)cc1
Reactant: Cc1ccc(-c2nc(CCl)co2)s1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ccc(-c2nc(COc3ccc(CCCn4ccnc4)cc3)co2)s1
Temperature: 80 °C
Reaction time: 14 h
Yield: 56.2 %

Procedure:
A mixture of 1-[3-(4-hydroxyphenyl)propyl]imidazole (465 mg), 4-chloromethyl-2-(5-methyl-2-thienyl)oxazole (600 mg), potassium carbonate (315 mg) and N,N-dimethylformamide (15 ml) was stirred at 80° C. for 14 hours. The reaction mixture was poured into water, and extracted with ethyl acetate. The ethyl acetate layer was washed with water, dried (MgSO4), and concentrated under reduced pressure. The residue was subjected to a silica gel column chromatography. From the fraction eluted with ethyl acetate-methanol (20:1, v/v), crystals of 4-[4-[3-(1-imidazolyl)propyl]phenoxymethyl]-2-(5-methyl-2-thienyl)oxazole (490 mg, 56%) was obtained. Recrystallization from ethyl acetate-hexane gave colorless prisms, mp 83-84° C.
Reaction SMILES: CN(C)[CH:3]=[C:4]([C:13]1[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=1)[C:5]([C:7]1[CH:11]=[CH:10][O:9][C:8]=1[CH3:12])=O.Cl.[CH3:21][CH:22]1[CH2:27][CH2:26][CH2:25][N:24]([C:28](=[NH:30])[NH2:29])[CH2:23]1.CC(C)([O-])C.[K+]>C(O)C.O>[CH3:12][C:8]1[O:9][CH:10]=[CH:11][C:7]=1[C:5]1[C:4]([C:13]2[CH:14]=[CH:15][N:16]=[CH:17][CH:18]=2)=[CH:3][N:29]=[C:28]([N:24]2[CH2:25][CH2:26][CH2:27][CH:22]([CH3:21])[CH2:23]2)[N:30]=1
Reactant: Cc1occc1C(=O)C(=CN(C)C)c1ccncc1
Reactant: CC1CCCN(C(=N)N)C1
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CCO
Solvent: O
Product: Cc1occc1-c1nc(N2CCCC(C)C2)ncc1-c1ccncc1
Temperature: 25 °C
Yield: 58.3 %

Procedure:
A mixture of 3-(dimethylamino)-1-(2-methyl-3-furanyl)-2-(4-pyridinyl)-2-propen-1-one (256 mg, 1 mmol) and 3-methyl-1-piperidinecarboximidamide hydrochloride (267 mg, 1.500 mmol) in ethanol (5 ml) was stirred at room temperature. Potassium tert-butoxide (224 mg, 2.000 mmol) was added and the mixture was heated at reflux for 45 minutes. After cooling to room temperature the reaction mixture was diluted with water and extracted with ethyl acetate. The organic extracts were combined, washed with water and brine, dried and evaporated. The residue was purified by silica gel chromatography eluting with 25-50% ethyl acetate and isohexane to give 4-(2-methyl-3-furanyl)-2-(3-methyl-1-piperidinyl)-5-(4-pyridinyl)pyrimidine (195 mg, 58%). A solution of 4-(2-methyl-3-furanyl)-2-(3-methyl-1-piperidinyl)-5-(4-pyridinyl)pyrimidine (167 mg, 0.5 mmol) in dichloromethane (1 ml) was treated with hydrogen chloride (1M in diethyl ether, 0.6 ml). The solvent was evaporated and the residue co-evaporated with diethyl ether (×2). The residue was triturated with diethyl ether and the resulting solid was collected, washed with diethyl ether and dried to give the title compound as a yellow solid (121 mg, 65%). LC/MS [M+H]+=335. 1H NMR (400 MHz, d6-DMSO): δ 8.76 (1H, d), 8.57 (1H, s), 7.80 (2H, d), 7.51 (1H, d), 6.00 (1H, d), 4.67-4.60 (2H, m), 3.06-2.99 (1H, m), 2.67-2.76 (1H, m), 2.37 (3H, s), 1.91-1.19 (5H, m), 0.93 (3H, d).
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH2:9])=[CH:5][CH:4]=1.[CH3:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[S:17](Cl)(=[O:19])=[O:18]>>[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([NH:9][S:17]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[CH3:10])(=[O:19])=[O:18])=[CH:5][CH:4]=1
Reactant: COc1ccc(N)cn1
Reactant: Cc1ccccc1S(=O)(=O)Cl
Product: COc1ccc(NS(=O)(=O)c2ccccc2C)cn1

Procedure:
prepared by reaction of 6-methoxy-pyridin-3-ylamine with 2-methyl-benzenesulfonyl chloride
Reaction SMILES: [CH-:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.[CH-:6]1[CH:10]=[CH:9][CH:8]=[CH:7]1.[Fe+2:11].[CH2:12]([Si:15]([CH3:18])([CH3:17])[Cl:16])[CH:13]=[CH2:14]>>[Cl:16][Si:15]([CH3:18])([CH3:17])[CH2:12][CH:13]([C-:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1)[CH3:14].[CH-:6]1[CH:10]=[CH:9][CH:8]=[CH:7]1.[Fe+2:11]
Reactant: C=CC[Si](C)(C)Cl
Agent: [Fe+2]
Agent: c1cc[cH-]c1
Product: CC(C[Si](C)(C)Cl)[c-]1cccc1
Reaction time: 2 h
Yield: 19.4 %

Procedure:
In the same apparatus and procedures as EXAMPLE 1 above, 0.30 g(1.61 mmol) of ferrocene was reacted with 0.92 mL(6.3 mmol) of allyldimethylchlorosilane under dry nitrogen atmospheric pressure for 2 hrs. After the addition of the catalyst solution, the reaction mixture was stirred for an additional 2 hrs to complete the alkylation. The solvent was distilled off at atmospheric pressure and the products were then extracted with 20.0 ml. of hexane. The reaction products were distilled under vacuum at 200° C. and at 0.5 torr, and produced 0.1 g of (3-chloro-1,3-dimethyl-3-silabutyl)ferrocene (yield; 20%). The remaining products were vacuum distilled at 300° C. and at 0.5 torr, and 0.55 g of bis(3-chloro-1,3-dimethyl-3-silabutyl)ferrocenes(yield; 38%) was obtained.
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.Br[C:13]1[S:21][C:20]2[C:19]([NH:22][C:23]3[CH:24]=[C:25]4[C:29](=[CH:30][CH:31]=3)[NH:28][CH:27]=[CH:26]4)=[N:18][CH:17]=[N:16][C:15]=2[CH:14]=1>>[NH:28]1[C:29]2[C:25](=[CH:24][C:23]([NH:22][C:19]3[C:20]4[S:21][C:13]([C:6]5[CH:7]=[CH:8][C:3]([S:2][CH3:1])=[CH:4][CH:5]=5)=[CH:14][C:15]=4[N:16]=[CH:17][N:18]=3)=[CH:31][CH:30]=2)[CH:26]=[CH:27]1
Reactant: CSc1ccc(B(O)O)cc1
Reactant: Brc1cc2ncnc(Nc3ccc4[nH]ccc4c3)c2s1
Product: CSc1ccc(-c2cc3ncnc(Nc4ccc5[nH]ccc5c4)c3s2)cc1

Procedure:
The title compound was prepared from 4-(methylthio)benzeneboronic acid and (6-bromo-thieno[3,2-d]pyrimidin-4-yl)-(1H-indol-5-yl)-amine by a procedure analogous to example 2. 1H NMR (400 MHz, DMSO) d 11.4 (s, 1H), 11.2 (s, 1H), 8.82 (s, 1H), 7.76 (d, 2H), 7.76 (d, 2H), 7.61 (s, 2H), 7.51 (m, 2H), 7.35 d, 2H), 7.22 (d, 1H), 6.50 (s, 1H), 2.49 (s, 3H), M.P. 163-178° C.; LC-MS 389 (MH+); HPLC RT: 4.73 minutes.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[C:11]#[N:12].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:19]([O:21][C:22](=[O:30])[C:23]1[CH:28]=[CH:27][C:26](F)=[CH:25][CH:24]=1)[CH3:20].O>CN(C)C=O>[CH2:19]([O:21][C:22](=[O:30])[C:23]1[CH:28]=[CH:27][C:26]([N:7]2[C:8]3[C:4](=[CH:3][C:2]([Br:1])=[CH:10][CH:9]=3)[C:5]([C:11]#[N:12])=[CH:6]2)=[CH:25][CH:24]=1)[CH3:20]
Reactant: N#Cc1c[nH]c2ccc(Br)cc12
Reactant: CCOC(=O)c1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)c1ccc(-n2cc(C#N)c3cc(Br)ccc32)cc1
Temperature: 80 °C
Reaction time: 48 h

Procedure:
To a solution of 5-bromo-3-cyanoindole (2.0 g) in N,N-dimethylformamide (50 mL) were added cesium carbonate (7.4 g) and 4-fluorobenzoic acid ethyl ester (3.0 g), and this mixture was stirred at 80° C. for 48 hours. This reaction mixture was poured into water, and the precipitated solid was collected by filtration. This solid was washed with water, dried under reduced pressure at 50° C. to give the title compound (1.8
Reaction SMILES: Cl[CH2:2][C:3]1[C:15]([C:16]([CH3:19])([CH3:18])[CH3:17])=[CH:14][C:13]2[C:12]3[C:7](=[CH:8][CH:9]=[C:10]([C:20]([CH3:23])([CH3:22])[CH3:21])[CH:11]=3)[CH2:6][C:5]=2[CH:4]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[CH3:2][C:3]1[C:15]([C:16]([CH3:18])([CH3:17])[CH3:19])=[CH:14][C:13]2[C:12]3[C:7](=[CH:8][CH:9]=[C:10]([C:20]([CH3:23])([CH3:22])[CH3:21])[CH:11]=3)[CH2:6][C:5]=2[CH:4]=1
Reactant: CC(C)(C)c1ccc2c(c1)-c1cc(C(C)(C)C)c(CCl)cc1C2
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: Cc1cc2c(cc1C(C)(C)C)-c1cc(C(C)(C)C)ccc1C2
Yield: 102.9 %

Procedure:
To a solution of 2-chloromethyl-3,6-di-t-butylfluorene (0.74 g, 2.26 mmol) in THF (15 ml) was added a small portion of LiAlH4 (129 mg, 3.39 mmol) under stirring and the mixture was refluxed for 5 hours. The reaction was quenched with water and NaOH and extracted with ether. The ether solution was evaporated under vacuum to give a white solid yield of 0.68 g. 1H NMR (CDCl3): δ 7.80 and 7.66 (each d, 1H, 4,5-H), 7.45 (d, 1H, J=8.1 Hz, H8), 7.31 (dd, 1H, J=8.1 Hz, J=1.5 Hz, H7), 7.14 (br s, 1H, 1H, H1), 3.69 (s, 2H, H9), 2.40 (s, 3H, Me), 1.41 (s, 18H, t-Bu).