Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]([C:14]([CH3:17])([CH3:16])[CH3:15])[C:11](Cl)=[O:12])=[CH:6][C:5]=1[F:18])[CH3:2].[F:19][C:20]([F:24])([F:23])[CH2:21][OH:22]>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]([C:14]([CH3:17])([CH3:16])[CH3:15])[C:11]([O:22][CH2:21][C:20]([F:24])([F:23])[F:19])=[O:12])=[CH:6][C:5]=1[F:18])[CH3:2]
Reactant: CCOc1ccc(C(C(=O)Cl)C(C)(C)C)cc1F
Reactant: OCC(F)(F)F
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Product: CCOc1ccc(C(C(=O)OCC(F)(F)F)C(C)(C)C)cc1F
Temperature: 25 °C
Reaction time: 2 h

Procedure:
3.0 g (0.011 mol) 2-(4-Ethoxy-3-fluorophenyl)-3,3-dimethylbutyryl chloride was added dropwise to a solution of 1.12 g (0.0121 mol) 2,2,2-trifluoroethanol and 100 mg 4-dimethylaminopyridine in 15 ml pyridine at 0° C. After stirring for two hours at room temperature, tlc showed complete reaction. The mixture was added to ice/water, made weakly acidic, extracted with ether, the extract dried over magnesium sulphate and evaporated under reduced pressure. After silica gel chromatography, 2.80 g (=75.6% of theory) of a pale yellow oil was obtained. nD20 : 1.4783
Reaction SMILES: [NH2:1][CH2:2][CH:3]([C:9]1([CH3:14])[O:13][CH2:12][CH2:11][O:10]1)[C:4]([O:6][CH2:7][CH3:8])=[O:5].[Br:15][C:16]1[CH:17]=[C:18]2[C:23](=O)[O:22][C:20](=[O:21])[C:19]2=[CH:25][CH:26]=1>>[Br:15][C:16]1[CH:17]=[C:18]2[C:19](=[CH:25][CH:26]=1)[C:20](=[O:21])[N:1]([CH2:2][CH:3]([C:9]1([CH3:14])[O:10][CH2:11][CH2:12][O:13]1)[C:4]([O:6][CH2:7][CH3:8])=[O:5])[C:23]2=[O:22]
Reactant: CCOC(=O)C(CN)C1(C)OCCO1
Reactant: O=C1OC(=O)c2cc(Br)ccc21
Product: CCOC(=O)C(CN1C(=O)c2ccc(Br)cc2C1=O)C1(C)OCCO1

Procedure:
Ethyl 3-(5-bromo-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-2-(2-methyl-[1,3]dioxolan-2-yl)propionate was prepared (0.42 g, 52%) in the same manner as described in the above example 5 (20) from ethyl 3-amino-2-(2-methyl-[1,3]dioxolan-2-yl)propionate (0.40 g, 1.97 mmol) and 4-bromophthalic anhydride (0.58 g, 2.56 mmol), and the obtained product was identified with the following NMR data.
Reaction SMILES: [CH3:1][C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][C:3]=1[C:11]([OH:13])=[O:12].C([N-]C(C)C)(C)C.[Li+].[CH2:22](Br)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.Cl>C1COCC1.CCCCCCC.C1COCC1.C(C1C=CC=CC=1)C>[CH2:1]([C:2]1[C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][C:3]=1[C:11]([OH:13])=[O:12])[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: Cc1c(C(=O)O)oc2ccccc12
Reactant: BrCc1ccccc1
Agent: CC(C)[N-]C(C)C
Agent: Cl
Agent: [Li+]
Solvent: CCCCCCC
Solvent: C1CCOC1
Solvent: CCc1ccccc1
Product: O=C(O)c1oc2ccccc2c1CCc1ccccc1
Temperature: -10 °C
Reaction time: 0.17 h
Yield: 10.7 %

Procedure:
3-Methyl-benzofuran-2-carboxylic acid (9.99 g, 56.7 mmol) in 150 mL of anhydrous THF was added under nitrogen dropwise to a solution of lithium diisopropylamide (60 mL of a 2.0 M solution in heptane/THF/ethylbenzene; 120 mmol) in 350 mL of anhydrous THF at −10° C. After the addition was complete the reaction was stirred at −10° C. for approximately 10 minutes. Benzyl bromide (13.5 mL, 113 mmol) was then added dropwise to the reaction. After the addition the reaction was allowed to warm to room temperature and then stirred at room temperature for 2 h. The reaction was acidified by the addition of 1 N HCl and then concentrated under reduced pressure to remove the THF. The residue was partitioned between 1 N HCl and methylene chloride. The aqueous layer was separated and extracted two times with methylene chloride. The combined extracts were dried (MgSO4) and the solvent removed under reduced pressure. The residue was recrystallized from ethyl acetate to give 3-phenethyl-benzofuran-2-carboxylic acid (1.62 g, 11%) as a white solid, mp 169-172° C.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH:10]([O:12][C:13]([NH:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:14])[CH3:11])([O-:3])=[O:2].[H-].[Na+].[CH3:24]I>CN(C)C=O>[N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[CH:10]([O:12][C:13]([N:15]([CH3:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:14])[CH3:11])([O-:3])=[O:2]
Reactant: CC(OC(=O)Nc1ccccc1)c1ccccc1[N+](=O)[O-]
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(OC(=O)N(C)c1ccccc1)c1ccccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 86 %

Procedure:
N-[1-(2-Nitrophenyl)-1-ethoxycarbonyl]-N-phenylamine Ia (1.0 g; 3.4 mmol) in dry dimethylformamide (10 ml) was added to a slurry of sodium hydride (80% w/w; 0.19 g; 3.5 mmol) in dry dimethylformamide (20 ml) under an inert atmosphere. The mixture was stirred at room temperature for 15 min and then methyl iodide (2.1 ml; 34.9 mmol) was added over a period of 10 min. The reaction mixture was warmed to 50° C. and at this temperature for a further 30 min. The precipitate of sodium iodide was filtered off and the solvent was removed by evaporation under vacuum to give a viscous oil, which was purified by flash chromatography on silica, eluting with dichloromethane, to afford the required compound as a colourless solid. Recrystallization from toluene gave colourless crystals (0.9 g; 86% yield), mp 62-63° C.
Reaction SMILES: Cl.Cl.[C:3]1([CH:9]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:10]2[CH2:13][CH:12]([NH:14][NH2:15])[CH2:11]2)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[Cl:22][C:23]1[CH:24]=[CH:25][C:26]([OH:36])=[C:27]([C:29](=O)/[CH:30]=[CH:31]/N(C)C)[CH:28]=1>C(O)C.C(O)(=O)C.COC(C)(C)C>[Cl:22][C:23]1[CH:24]=[CH:25][C:26]([OH:36])=[C:27]([C:29]2[N:14]([CH:12]3[CH2:13][N:10]([CH:9]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=4)[C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[CH2:11]3)[N:15]=[CH:31][CH:30]=2)[CH:28]=1
Reactant: CN(C)/C=C/C(=O)c1cc(Cl)ccc1O
Reactant: NNC1CN(C(c2ccccc2)c2ccccc2)C1
Agent: Cl
Solvent: CCO
Solvent: CC(=O)O
Solvent: COC(C)(C)C
Product: Oc1ccc(Cl)cc1-c1ccnn1C1CN(C(c2ccccc2)c2ccccc2)C1
Temperature: 25 °C
Yield: 42 %

Procedure:
1-(diphenylmethyl)-3-hydrazinoazetidine dihydrochloride (Preparation 690, 1.00 g, 3.06 mmol) was added to an ice cold, stirred suspension of (2E)-1-(5-chloro-2-hydroxyphenyl)-3-(dimethylamino)prop-2-en-1-one (Preparation 759, 700 mg, 3.1 mmol) in ethanol (5 ml) and acetic acid (5 ml), stirred at 0° C. for 2 hours then allowed to warm up to room temperature over 2 hours. The solvents were removed in vacuo and the residue partitioned between ethyl acetate (80 ml) and saturated aqueous sodium hydrogencarbonate solution (50 ml). The organic layer was separated and dried over sodium sulphate, filtered and the solvents removed in vacuo to give a yellow gum. This was dissolved in warm methyl-t-butyl ether (20 ml) and allowed to crystallize to give the title compound as a pale yellow powder, 541 mg, yield 42%.
Reaction SMILES: [F:1][CH:2]([C:7]([O:9]C)=O)[C:3](OC)=[O:4].Cl.[NH2:12][C:13]([NH2:15])=[NH:14]>>[OH:9][C:7]1[C:2]([F:1])=[C:3]([OH:4])[N:14]=[C:13]([NH2:15])[N:12]=1
Reactant: N=C(N)N
Reactant: COC(=O)C(F)C(=O)OC
Agent: Cl
Product: Nc1nc(O)c(F)c(O)n1

Procedure:
Commercially available dimethyl fluoromalonate (1) (or the diethyl ester) is condensed with guanidine hydrochloride (2) to yield 4,6-dihydroxy-5-fluoro-2-pyrimidineamine (3). This product (3) was converted to the dichloride (4) with POCl3 /2-picoline. Introduction of the 4-amino group was carried out undersealed tube conditions to give (5). Oxidation of (5) with MCPBA formed the N-oxide (6) which was smoothly converted to the 5-fluoro minoxidil with piperidine in refluxing ethanol.
Reaction SMILES: [ClH:1].[NH2:2][C:3]1[NH:4][CH2:5][C:6]([CH3:10])([CH3:9])[CH2:7][N:8]=1.[NH3:11]>>[ClH:1].[NH:2]([C:3]1[NH:8][CH2:7][C:6]([CH3:10])([CH3:9])[CH2:5][N:4]=1)[NH2:11]
Reactant: CC1(C)CN=C(N)NC1
Reactant: N
Agent: Cl
Product: CC1(C)CN=C(NN)NC1
Reaction time: 8 h

Procedure:
The product (2.60 parts) of Example 1 above, 2-amino-5,5-dimethyl-1,4,5,6-tetrahydropyrimidine hydrochloride, is added to a suitable flask equipped with condenser and magnetic stirring bar, and flushed with argon. There is next added 1.19 parts, 1.5 equivalents, of hydrazine hydrate, and the mixture is stirred until a clear solution is obtained. The flask is then placed in an oil bath preheated to 115° C. Ammonia is evolved almost immediately. The reaction is maintained at 115°-120° C. under a stream of argon for twelve hours. After sitting overnight at room temperature, the flask contains a white, crystalline solid and a small amount of clear, colorless liquid. The liquid is evaporated at room temperature. Resultant yield of 2-hydrazino-5,5-dimethyl-1,4,5,6-tetrahydropyrimidine hydrochloride which is found to be 97% pure is almost quantitative.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[CH:9]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[Cl:18])[CH2:10][OH:11].C(O)(=O)C.[CH:23](=O)[C:24]([CH3:27])([CH3:26])[CH3:25].C([BH3-])#N.[Na+]>CO>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][CH2:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[C:3]([CH:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[Cl:18])[CH2:10][OH:11])[CH:4]=1
Reactant: Nc1ccc(Cl)cc1C(CO)c1ccccc1Cl
Reactant: CC(C)(C)C=O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: CC(=O)O
Product: CC(C)(C)CNc1ccc(Cl)cc1C(CO)c1ccccc1Cl
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 99.2 %

Procedure:
To a solution of 2-(2-amino-5-chlorophenyl)-2-(2-chlorophenyl)ethanol (4.44 g) in methanol (50 ml) were added acetic acid (1.4 ml) and pivalaldehyde (2.0 g). The mixture was stirred for 30 minutes at room temperature. To the solution was added sodium cyano borohydride (1.5 g), and the mixture was stirred for one hour at room temperature. The reaction mixture was then processed in substantially the same manner as in Example 52-(7) to give 5.5 g of an oily compound.
Reaction SMILES: [CH3:1][C:2]1[C:3]([N+:16]([O-:18])=[O:17])=[C:4]([NH:12]C(=O)C)[C:5]([CH3:11])=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].S(=O)(=O)(O)O.O>C(O)C>[CH3:1][C:2]1[C:3]([N+:16]([O-:18])=[O:17])=[C:4]([NH2:12])[C:5]([CH3:11])=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9]
Reactant: CC(=O)Nc1c(C)cc([N+](=O)[O-])c(C)c1[N+](=O)[O-]
Agent: O=S(=O)(O)O
Solvent: O
Solvent: CCO
Product: Cc1cc([N+](=O)[O-])c(C)c([N+](=O)[O-])c1N
Yield: 85.8 %

Procedure:
A mixture of N-(3,6-dimethyl-2,4-dinitro-phenyl)-acetamide (14.4 g, from above), concentrated sulfuric acid (15 mL), water (30 mL) and ethanol (150 mL) was heated at reflux for 24 hr. The precipitated product was filtered, washed with little ethanol and dried to afford 3,6-dimethyl-2.4-dinitro-phenylamine (10.3 g).
Reaction SMILES: [NH2:1][CH:2]([CH2:4][CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([N+:12]([O-:14])=[O:13])[CH:7]=1)[CH3:3].[CH3:15][C:16]1([CH3:28])[CH2:25][CH:24]([CH:26]=O)[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[O:17]1.B([O-])=O.[Na+]>CO>[N+:12]([C:8]1[CH:7]=[C:6]([CH2:5][CH2:4][CH:2]([NH:1][CH2:26][CH:24]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[O:17][C:16]([CH3:15])([CH3:28])[CH2:25]2)[CH3:3])[CH:11]=[CH:10][CH:9]=1)([O-:14])=[O:13]
Reactant: CC1(C)CC(C=O)c2ccccc2O1
Reactant: CC(N)CCc1cccc([N+](=O)[O-])c1
Agent: O=B[O-]
Agent: [Na+]
Solvent: CO
Product: CC(CCc1cccc([N+](=O)[O-])c1)NCC1CC(C)(C)Oc2ccccc21
Reaction time: 24 h

Procedure:
12.1 g (0.1 mol) of 2-amino-4-(3-nitrophenyl)butane are added to 19.0 g (0.1 mol) of 2,2-dimethyl-4-formyl-chroman in 100 ml of methanol at 20° C., with stirring and slight cooling, and the mixture is stirred for 1.5 hours. Thereafter, 4.5 g of sodium boranate are added, and stirring is continued for 1 day, and the mixture is evaporated down and worked up with ethyl acetate/water. The ethyl acetate phase is washed with water, dried and evaporated down. Distillation gives 4-{N-[4-(3-nitrophenyl)-2-butyl]-aminomethyl}-2,2-dimethylchroman. B.p.: 225°-235° C./0.04 mmHg.
Reaction SMILES: [C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([N+:26]([O-])=O)[C:18]([NH:19][CH:20]4[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]4)=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1COCC1>[Pd].C(O)C>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([NH2:26])[C:18]([NH:19][CH:20]4[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]4)=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=[N+]([O-])c1cnc2c(ccn2S(=O)(=O)c2ccccc2)c1NC1CCCCC1
Agent: [Pd]
Solvent: CCO
Solvent: C1CCOC1
Product: Nc1cnc2c(ccn2S(=O)(=O)c2ccccc2)c1NC1CCCCC1
Temperature: 50 °C
Reaction time: 13 h
Yield: 103.8 %

Procedure:
A suspension of (1-benzenesulfonyl-5-nitro-1H-pyrrolo[2,3-b]pyridin-4-yl)-cyclohexyl-amine (10 g, 25.0 mmol) and palladium on carbon (2.7 g, 10%, wet, Degussa, E101 NE/W) in a 3:1 mixture of THF and ethanol (200 ml) was stirred under a hydrogen atmosphere (2-3 balloons) at 50° C. for 13 h. The reaction mixture was cooled to 25° C. then was filtered through Celite. The filtrate was concentrated under reduced pressure to afford crude 1-benzenesulfonyl-N-4-cyclohexyl-1H-pyrrolo[2,3-b]pyridine-4,5-diamine (9.61 g, 100%) as a rose foam. LCMS (Method G, ESI): RT=0.83 min, m+H=371.2. This material was used in subsequent reactions without additional purification or characterization.
Reaction SMILES: [Li][CH2:2][CH2:3][CH2:4][CH3:5].[N:6]1[C:15]2[CH2:14][CH2:13][CH2:12][CH2:11][C:10]=2[CH:9]=[CH:8][CH:7]=1.C(Br)(CC)C>C1COCC1>[CH:3]([CH:14]1[C:15]2[N:6]=[CH:7][CH:8]=[CH:9][C:10]=2[CH2:11][CH2:12][CH2:13]1)([CH2:4][CH3:5])[CH3:2]
Reactant: [Li]CCCC
Reactant: c1cnc2c(c1)CCCC2
Solvent: C1CCOC1
Solvent: CCC(C)Br
Product: CCC(C)C1CCCc2cccnc21
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 89 %

Procedure:
A solution of BuLi (6.8 ml, 1.6 M in hexane) was added dropwise to a cold (−78° C.) solution of 5,6,7,8-tetrahydroquinoline (1.33 g, 10 mmol) in THF (20 ml). The mixture was stirred for 10 min at −78° C. and sec-butyl bromide (1.51 g, 11 mmol) was added dropwise. The mixture was allowed to warm up to room temperature during 1 h, was then carefully quenched with water and extracted with MTBE (3×50 ml). The combined organic phases were washed with water and brine, dried (MgSO4) and concentrated in vacuo. The brown residue was distilled bulb-to-bulb to yield 1.69 g (89%) of the title compound as a colorless oil. This is a general synthetic procedure and the other compounds exemplified were made according to this procedure, duly modified to employ the appropriate alkyl halide alkylating agent in order to add the correct alkyl group at the 8-position.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][CH:7]=[C:6]2[CH2:12][CH2:13][CH2:14][CH2:15][N:16]1[CH2:21][CH2:20][N:19]([C:22]2[CH:23]=[CH:24][C:25]3[O:29][C:28]([C:30]([O:32]C)=O)=[CH:27][C:26]=3[CH:34]=2)[CH2:18][CH2:17]1)#[N:2].[NH3:35]>>[CH:11]1[C:3]([C:1]#[N:2])=[CH:4][C:5]2[C:6]([CH2:12][CH2:13][CH2:14][CH2:15][N:16]3[CH2:21][CH2:20][N:19]([C:22]4[CH:23]=[CH:24][C:25]5[O:29][C:28]([C:30]([NH2:35])=[O:32])=[CH:27][C:26]=5[CH:34]=4)[CH2:18][CH2:17]3)=[CH:7][NH:8][C:9]=2[CH:10]=1
Reactant: N
Reactant: COC(=O)c1cc2cc(N3CCN(CCCCc4c[nH]c5ccc(C#N)cc45)CC3)ccc2o1
Product: N#Cc1ccc2[nH]cc(CCCCN3CCN(c4ccc5oc(C(N)=O)cc5c4)CC3)c2c1
Temperature: 27.5 °C

Procedure:
Methyl 5-[4-[4-(5-cyanoindol-3-yl)butyl]piperazin-1-yl]benzofuran-2-carboxylate (41 g) was added to saturated methanolic ammonia solution (8200 ml) under stirring at 25-30° C., the resulting mixture was stirred for 3 to 4 hours at the same temperature to form a clear solution. The reaction mass was stirred for 24 hours at 25-30° C., followed by filtration of the separated solid and then dried to produce 28 g of vilazodone. The mother liquors were taken and the solvent was distilled off under vacuum until the solvent quantity reaches around 1200 ml of the initial volume. The resulting mass was cooled to 25-30° C., followed by filtration and then drying to produce 11 g of Vilazodone (Purity by HPLC: 99.5%; Yield: 98.5%).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([N:8]=[C:9]=[O:10])[CH:5]=[CH:6][CH:7]=1.[NH2:11][CH2:12][C:13]([N:15]([CH2:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[C:16]1[CH:21]=[CH:20][C:19]([N:22]([CH3:24])[CH3:23])=[CH:18][CH:17]=1)=[O:14]>O1CCCC1>[CH3:23][N:22]([CH3:24])[C:19]1[CH:18]=[CH:17][C:16]([N:15]([CH2:25][C:26]([O:28][C:29]([CH3:31])([CH3:30])[CH3:32])=[O:27])[C:13](=[O:14])[CH2:12][NH:11][C:9]([NH:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[CH:3]=2)=[O:10])=[CH:21][CH:20]=1
Reactant: Cc1cccc(N=C=O)c1
Reactant: CN(C)c1ccc(N(CC(=O)OC(C)(C)C)C(=O)CN)cc1
Solvent: C1CCOC1
Product: Cc1cccc(NC(=O)NCC(=O)N(CC(=O)OC(C)(C)C)c2ccc(N(C)C)cc2)c1
Temperature: 20 °C
Reaction time: 3 h
Yield: 697.8 %

Procedure:
3-Methylphenyl isocyanate (0.35 g) is added at a temperature in the region of 20° C. to a solution of tert-butyl 2-[2-amino-N-(4-dimethylaminophenyl)acetamido]acetate (0.7 g) in anhydrous tetrahydrofuran (15 cc). The solution obtained is stirred for 3 hours at a temperature in the region of 20° C. and then concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. After recrystallisation of the residual solid in ethyl acetate, tert-butyl 2-{N-(4-dimethylaminophenyl)-2-[3-(3-methylphenyl)ureido]acetamido}acetate (0 7 g), m.p 105° C., is obtained.
Reaction SMILES: C([O:4][CH2:5][CH2:6][CH:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1)[O:8]C(=O)C)(=O)C.C(=O)([O-])[O-].[K+].[K+]>CO.O>[N:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[CH:7]([OH:8])[CH2:6][CH2:5][OH:4]
Reactant: CC(=O)OCCC(OC(C)=O)c1ccccn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CO
Product: OCCC(O)c1ccccn1

Procedure:
A solution of 3-(2-pyridyl)-1,3-propanediol diacetate (1 mmole) in methanol-water (3:1) was treated with potassium carbonate (5 mmole) at 25° C. for 3 h. Evaporation and chromatography gave 3-(2-pyridyl)-1,3-propanediol as a solid.
Reaction SMILES: [CH2:1]([Li])CCC.C(NC(C)C)(C)C.[N:13]1([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:18][CH2:17][CH2:16][CH:15]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:14]1.CI>C1COCC1>[CH3:1][C:15]1([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:16][CH2:17][CH2:18][N:13]([C:24]([O:26][C:27]([CH3:29])([CH3:28])[CH3:30])=[O:25])[CH2:14]1
Reactant: [Li]CCCC
Reactant: CCOC(=O)C1CCCN(C(=O)OC(C)(C)C)C1
Solvent: CC(C)NC(C)C
Solvent: CI
Solvent: C1CCOC1
Product: CCOC(=O)C1(C)CCCN(C(=O)OC(C)(C)C)C1
Temperature: -30 °C
Reaction time: 1 h
Yield: 90.1 %

Procedure:
To a flame-dried round bottom flask under Argon atmosphere was added THF (100 mL), then it was cooled to −30° C. To this cold solvent were added n-butyllithium (40.1 ml, 64.1 mmol), and diisopropylamine (10.80 ml, 76 mmol) drop wise. The resultant solution was stirred at −25° C. for 1 hour. To the above solution 1-tert-butyl 3-ethyl piperidine-1,3-dicarboxylate (15 g, 58.3 mmol) in THF (20 mL) was added drop wise at −78° C. (maintain temperature <−70° C.). After the addition, the reaction was stirred at −70° C. for 1 h, and then methyl iodide (4.74 mL, 76 mmol) was added drop wise. This reaction mixture was stirred at same temperature for 1 h, then slowly warmed to RT and stirred for 16 h. The reaction mixture was quenched with sat. aq. NH4Cl (50 mL), extracted with EtOAc (2×200 mL), the combined organics extracts was washed with sat. NH4Cl (100 mL), brine (50 mL), dried (Na2SO4) and concentrated to get crude compound. The crude residue was purified by ELSD ISCO on 120 g silica column, eluted the compound around 20% ethyl acetate in hexanes, the pure fractions were collected and concentrated to give desired product 1-tert-butyl 3-ethyl 3-methylpiperidine-1,3-dicarboxylate (15.14 g, 52.5 mmol, 90% yield) as a colorless oil. Anal. Calcd. for C14H25NO4 m/z 271.3, found: 172.2 (M-Boc+H)+; 1H NMR (400 MHz, CDCl3) δ ppm 4.13 (q, J=7.0 Hz, 2 H), 3.82 (d, J=13.5 Hz, 1 H), 3.46-3.38 (m, 1 H), 3.32-3.19 (m, 1 H) 3.13 (d, J=13.2 Hz, 1 H) 2.07-1.97 (m, 1 H) 1.60-1.50 (m, 2 H) 1.48-1.40 (m, 10 H), 1.25 (t, J=7.15 Hz, 3 H), 1.15 (s, 3 H)
Reaction SMILES: [CH2:1]([CH:3]([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:4][NH2:5])[CH3:2].[C:10]1(=[O:15])[O:14][CH2:13][CH2:12][CH2:11]1>>[CH2:1]([CH:3]([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:4][NH:5][C:13](=[O:14])[CH2:12][CH2:11][CH2:10][OH:15])[CH3:2]
Reactant: O=C1CCCO1
Reactant: CCCCC(CC)CN
Product: CCCCC(CC)CNC(=O)CCCO
Temperature: 100 °C
Reaction time: 1 h

Procedure:
In a glass reaction vessel 12.9 grams of 2-ethylhexylamine were admixed with 8.6 grams of butyrolactone and the mixture heated to 100° C. on a steam bath until reaction was completed in a period of one hour. A conversion of greater than 95%, based on butyrolactone, was achieved. The product upon cooling to room temperature was a colorless, clear, moderately viscous liquid. IR=6.09 mu.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][C:9]2[NH:10][C:11]3[C:16]([C:17]=2[C:18]=1[CH3:19])=[CH:15][CH:14]=[CH:13][CH:12]=3)=[O:5])[CH3:2].C(Cl)(Cl)[Cl:21]>ClCl>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[CH:8][C:9]2[NH:10][C:11]3[C:16]([C:17]=2[C:18]=1[CH3:19])=[CH:15][C:14]([Cl:21])=[CH:13][CH:12]=3)=[O:5])[CH3:2]
Reactant: ClC(Cl)Cl
Reactant: CCOC(=O)c1ncc2[nH]c3ccccc3c2c1C
Agent: ClCl
Product: CCOC(=O)c1ncc2[nH]c3ccc(Cl)cc3c2c1C
Reaction time: 3 h

Procedure:
1 g of 4-methyl-β-carbolin-3-carboxylic acid ethyl ester is dissolved in 120 ml of chloroform saturated at 0° C. with chlorine gas and stirred for 3 hours while cooling with ice. The excess chlorine and part of the chloroform are then distilled with suction in vacuo, the crystalline precipitate is filtered off, suspended in 50 ml of ethyl acetate, and aqueous ammonia (5%, 10 ml) is added thereto. After 10 minutes, the crystalline product had dissolved. After separating off the aqueous phase and washing the organic phase with water, the residue is dried with sodium sulphate, filtered, and the solvent is distilled off in vacuo. The residue is crystallized from ethyl acetate. 0.73 g of 6-chloro-4-methyl-β-carbolin-3-carboxylic acid ethyl ester of melting point 225°-228° C. is obtained.
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6]([CH2:9][CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:5][CH:4]=1.[CH:16](OCC)=[O:17].[H-].[Na+]>COCCOC>[CH:16]([CH:10]([CH2:9][C:6]1[CH:7]=[N:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1)[C:11]([O:13][CH2:14][CH3:15])=[O:12])=[O:17]
Reactant: CCOC=O
Reactant: CCOC(=O)CCc1ccc(OC)nc1
Agent: [H-]
Agent: [Na+]
Solvent: COCCOC
Product: CCOC(=O)C(C=O)Cc1ccc(OC)nc1
Reaction time: 8 h
Yield: 69.8 %

Procedure:
A mixture of ethyl 3-(6-methoxy-3-pyridyl)propionate (32.74 g) and ethyl formate (17.22 g) was added dropwise over 1.5 hours to a stirred suspension of sodium hydride in oil (50%, 9.38 g) in 1,2-dimethoxyethane (50 ml) cooled to -2°, allowed to stand overnight at room temperature and was poured on to ice. The mixture was extracted with ether (discarded), and the aqueous phase was adjusted to pH 5 with 2N sulphuric acid. An oil was precipitated and crystallised on standing to give ethyl 2-formyl-3-(6-methoxy-3-pyridyl)propionate (25.9 g, 70%) m.p. 91.5°-94°. A sample recrystallised from aqueous ethanol had m.p. 93°-94°.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([CH2:8][OH:9])[CH:5]=[CH:4][N:3]=1.[Si:10](Cl)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11].N1C=CN=C1.C(OCC)(=O)C>ClCCl>[Si:10]([O:9][CH2:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([F:1])[CH:7]=1)([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]
Reactant: OCc1ccnc(F)c1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)OCc1ccnc(F)c1
Yield: 81.3 %

Procedure:
2-Fluoro-4-pyridinemethanol (508.5 mg, 4.00 mmol), t-butyldimethylsilylchloride (1.21 g, 8.00 mmol) and imidazole (1.09 g, 16.00 mmol) were stirred in dichloromethane (10 mL) at room temperature for an hour. After completion of the reaction, the reaction solution was mixed with ethyl acetate, and the resulting organic layer was washed with saturated aqueous ammonium chloride, dried over anhydrous sodium sulfate and evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate=10/1) to give the desired product (785.2 mg, 81% yield).