Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CO[C:3]1[CH:4]=[CH:5][C:6]2[NH:12][C:11](=[O:13])[CH2:10][N:9]=[C:8]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:7]=2[CH:20]=1.[C:21]1(=O)OCC[O:22]1.I[CH3:28]>>[CH3:21][O:22][C:4]1[CH:3]=[CH:20][C:7]2[C:8]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)=[N:9][CH2:10][C:11](=[O:13])[N:12]([CH3:28])[C:6]=2[CH:5]=1
Reactant: O=C1OCCO1
Reactant: CI
Reactant: COc1ccc2c(c1)C(c1ccccc1)=NCC(=O)N2
Product: COc1ccc2c(c1)N(C)C(=O)CN=C2c1ccccc1
Yield: 76 %

Procedure:
By replacing 7,8-dimethoxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one (XXIIaa) in the example by 7-methoxy-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one (XXIIan), and ethylene carbonate by iodomethane, and proceeding in the same manner, the abovenamed product is obtained. Yield: 76%. M: 114–116° C. 1H-NMR (CDCl3, 300 MHz): d 3.41 (s, 3H, NCH3), 3.90 (s, 3H, OCH3), 4.29 (AB system, ? d=0.99, JAB=10.6, 2H, —CH2), 6.71–6.75 (m, 1H Ar), 6.81–6.82 (m, 1H Ar), 7.22–7.25 (m, 1H Ar), 7.36–7.42 (m, 3H Ar), 7.50–7.62 (m, 2H Ar).
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4](C)[C:5](=O)OC(C)(C)C.[F:13][C:14]1[CH:22]=[CH:21][C:17]([C:18]([Cl:20])=[O:19])=[CH:16][CH:15]=1.N1C=CC=CC=1>C(OCC)(=O)C>[ClH:20].[F:13][C:14]1[CH:22]=[CH:21][C:17]([C:18]([O:1][CH2:2][CH2:3][NH:4][CH3:5])=[O:19])=[CH:16][CH:15]=1
Reactant: CN(CCO)C(=O)OC(C)(C)C
Reactant: O=C(Cl)c1ccc(F)cc1
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: CNCCOC(=O)c1ccc(F)cc1
Product: Cl
Temperature: 25 °C
Reaction time: 6.5 h
Yield: 81 %

Procedure:
To a mixture of tert-butyl 2-hydroxyethyl(methyl)carbamate (1.75 g) obtained in Reference Example 1 and ethyl acetate (10 mL) were added 4-fluorobenzoyl chloride (1.74 g) and pyridine (0.97 mL). The mixture was stirred at room temperature for 6.5 hrs. Ethyl acetate (80 mL) was added to the reaction mixture, and the mixture was washed with water (30 mL), a saturated aqueous sodium hydrogen carbonate solution (30 mL), water (30 mL) and saturated brine (30 mL), and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, a 4N hydrogen chloride—ethyl acetate solution (10 mL) was added to the residue. After stirring at room temperature for 1 hr., the precipitated solid was collected by filtration. The solid was washed twice with ethyl acetate (15 mL) and dried under reduced pressure at 60° C. to give the title compound (1.89 g) as a white solid.
Reaction SMILES: [CH3:1][C:2]1([CH3:20])[CH2:11][CH:10]=[C:9]([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)[C:8]2[CH:7]=[C:6]([C:17]([OH:19])=[O:18])[CH:5]=[CH:4][C:3]1=2.O[C:22]1[CH:36]=[CH:35][C:25]([C:26]([O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])=[O:27])=[CH:24][CH:23]=1.Cl.CN(C)CCCN=C=NCC.CCOCC>CN(C=O)C>[CH3:32][Si:31]([CH3:34])([CH3:33])[CH2:30][CH2:29][O:28][C:26](=[O:27])[C:25]1[CH:35]=[CH:36][C:22]([O:18][C:17]([C:6]2[CH:5]=[CH:4][C:3]3[C:2]([CH3:20])([CH3:1])[CH2:11][CH:10]=[C:9]([C:12]4[S:13][CH:14]=[CH:15][CH:16]=4)[C:8]=3[CH:7]=2)=[O:19])=[CH:23][CH:24]=1
Reactant: C[Si](C)(C)CCOC(=O)c1ccc(O)cc1
Reactant: CC1(C)CC=C(c2cccs2)c2cc(C(=O)O)ccc21
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CCOCC
Solvent: CN(C)C=O
Product: CC1(C)CC=C(c2cccs2)c2cc(C(=O)Oc3ccc(C(=O)OCC[Si](C)(C)C)cc3)ccc21

Procedure:
A solution of 5,5-dimethyl-5,6-dihydro-8-(2-thienyl)-naphthalene-2-carboxylic acid (Compound E6, 79.0 mg, 0.280 mmol), 2-trimethylsilylethyl 4-hydroxybenzoate (73.3 mg, 0.308 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (70.0 mg, 0.364 mmol), and 4-N,N-dimethylaminopyridine (44.5 mg, 0.364 mmol) in 2.0 mL DMF was stirred overnight at room temperature. Et2O (100 mL) was added and the solution washed with H2O, 5% HCl, saturated aqueous NaCO3, and saturated aqueous NaCl before being dried over MgSO4. Removal of the sovents under reduced pressure and column chromatography (10% EtOAc-hexanes) of the residual oil afforded the title compound as a colorless solid.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([C:16]3[C:21]([CH3:22])=[CH:20][C:19]([CH:23]4[CH2:25][CH2:24]4)=[CH:18][N:17]=3)[CH2:12][CH2:11]2)=[O:9])=[CH:4][CH:3]=1.[CH3:26][N:27]1[C:31](=[O:32])[CH:30]([CH3:33])[NH:29][C:28]1=[O:34]>>[CH:23]1([C:19]2[CH:20]=[C:21]([CH3:22])[C:16]([N:13]3[CH2:14][CH2:15][N:10]([C:8]([C:5]4[CH:6]=[CH:7][C:2]([N:29]5[CH:30]([CH3:33])[C:31](=[O:32])[N:27]([CH3:26])[C:28]5=[O:34])=[CH:3][CH:4]=4)=[O:9])[CH2:11][CH2:12]3)=[N:17][CH:18]=2)[CH2:25][CH2:24]1
Reactant: CC1NC(=O)N(C)C1=O
Reactant: Cc1cc(C2CC2)cnc1N1CCN(C(=O)c2ccc(Br)cc2)CC1
Product: Cc1cc(C2CC2)cnc1N1CCN(C(=O)c2ccc(N3C(=O)N(C)C(=O)C3C)cc2)CC1
Yield: 11.2 %

Procedure:
Using (4-bromophenyl) [4-(5-cyclopropyl-3-methylpyridin-2-yl)piperazin-1-yl]methanone (160 mg) described in Preparation Example 185 and 3,5-dimethylimidazolidine-2,4-dione (51 mg) described in Preparation Example 217 and by the reaction and treatment in the same manner as in Example 536, the title compound (20 mg) was obtained.
Reaction SMILES: [CH2:1]([N:3]([CH2:11][CH2:12][OH:13])[C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH3:10])[CH:5]=1)[CH3:2].[S:14](=[O:18])(=[O:17])([OH:16])[OH:15].[N:19](OC(C)C)=O.[H][H]>[C].[Pd].C(O)(C)C>[S:14]([OH:18])([OH:17])(=[O:16])=[O:15].[NH2:19][C:7]1[CH:8]=[CH:9][C:4]([N:3]([CH2:1][CH3:2])[CH2:11][CH2:12][OH:13])=[CH:5][C:6]=1[CH3:10]
Reactant: CCN(CCO)c1cccc(C)c1
Reactant: CC(C)ON=O
Reactant: [H][H]
Agent: [Pd]
Agent: O=S(=O)(O)O
Solvent: CC(C)O
Product: CCN(CCO)c1ccc(N)c(C)c1
Temperature: 10 °C
Reaction time: 3 h
Yield: 182.4 %

Procedure:
With 89.6 g (0.5 mole) of N-ethyl-N-(β-hydroxyethyl)-m-toluidine was mixed 270 ml of 50% v/v isopropanol, and 24.5 g (0.25 mole) of sulfuric acid was added with cooling and stirring at 10° C. or lower. After 49.0 g (0.55 mole) of isopropyl nitrite was added dropwise at 10° C. or lower, the reaction was carried out at 2°-5° C. for another 3 hours. After completion of the reaction, hydrogenation was carried out at 40°-45° C. and at a hydrogen pressure of 3-5 kg/cm2 while adding the nitrosation reaction mixture to 270 ml of 50% v/v isopropanol containing 6.5 g of 5% palladium-carbon over a period of 2 hours. After completion of the hydrogenation, the catalyst was filtered off and the filtrate was concentrated to dryness to remove the solvent. The residue was dissolved in 270 ml of 90% v/v ethanol with heating and 24.5 g (0.25 mole) of sulfuric acid was added at 45°-50° C. Then, the resulting mixture was cooled for 2 hours to carry out crystallization, and the crystals thus formed were collected by filtration at 3° C., washed with 100 ml of cold ethanol, and then dried to obtain 133.3 g of 4-amino-3-methyl-N-ethyl-N-(β-hydroxyethyl)aniline sulfate as white powder. Yield: 91.2%. Melting point: 154.6° C. The purity of 4-amino-3-methyl-N-ethyl-N-(β-hydroxyethyl)aniline sulfate was 100% as measured by HPLC, namely, no impurity was detected at all.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12].ClC1C=CC=C(C(OO)=[O:24])C=1>C(OCC)(=O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][NH+:8]([O-:24])[C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13]
Reactant: CC(C)(C)OC(=O)NCc1ccccn1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)[NH+]([O-])Cc1ccccn1
Temperature: 25 °C
Reaction time: 15 h
Yield: 91.7 %

Procedure:
tert-Butyl 2-pyridylmethylcarbamate (11.4 g, 54 mmol) and 3-chloroperbenzoic acid (77%, 5.9 g, 71 mmol) were dissolved in ethyl acetate (150 ml), and the mixture was stirred at room temperature for 15 hrs. The solvent was evaporated, and the residue was subjected to a silica gel column chromatography. The fractions eluted with methanol-ethyl acetate (1:5, v/v) were collected and concentrated to give the titled compound (11.1 g, 90%).
Reaction SMILES: [CH:1]1[CH:2]=[CH:3][C:4]2[NH:13][C:12]3[CH:11]=[N:10][CH:9]=[CH:8][C:7]=3[C:5]=2[CH:6]=1.[ClH:14].[Cl:15]N1C(=O)CCC1=O>O>[Cl:14][C:2]1[CH:3]=[C:4]2[C:5]([C:7]3[CH:8]=[CH:9][N:10]=[CH:11][C:12]=3[N:13]2[Cl:15])=[CH:6][CH:1]=1
Reactant: Cl
Reactant: O=C1CCC(=O)N1Cl
Reactant: c1ccc2c(c1)[nH]c1cnccc12
Solvent: O
Product: Clc1ccc2c3ccncc3n(Cl)c2c1
Reaction time: 3 h
Yield: 20.2 %

Procedure:
To a suspension of norharmane (84 mg, 0.50 mmol) in water (3 ml) at RT was added 1M aqueous HCl (1.1 ml, 1.1 mmol). To this homogenous solution was added N-chlorosuccinimide (747 mg, 5.58 mmol) portionwise and the resulting solution was stirred at 60° C. to 70° C. for 3 h. The reaction was partitioned in EtOAc and saturated aqueous NaHCO3 and the organic layer was dried (brine; MgSO4) and then concentrated. The residue was chromatographed (2:3 THF-hexane) on silica gel to give 24 mg of 7,9-dichloro-β-carboline after triturating with (1:1) methylene chloride-hexane, then with hexane.
Reaction SMILES: C(O[CH:4](OCC)[C:5]#[C:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][C:11](=[O:16])[CH2:10]2)C.[C:20]1([NH:26][NH2:27])[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.S(=O)(=O)(O)O.C([O-])(O)=O.[Na+]>C(#N)C.O>[C:20]1([N:26]2[C:6]([C:7]3[CH:8]=[C:9]4[C:13](=[CH:14][CH:15]=3)[NH:12][C:11](=[O:16])[CH2:10]4)=[CH:5][CH:4]=[N:27]2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: NNc1ccccc1
Reactant: CCOC(C#Cc1ccc2c(c1)CC(=O)N2)OCC
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Solvent: CC#N
Product: O=C1Cc2cc(-c3ccnn3-c3ccccc3)ccc2N1
Temperature: 25 °C
Reaction time: 3 h
Yield: 42.1 %

Procedure:
To a solution of 5-(3,3-diethoxyprop-1-ynyl)indolin-2-one (100 mg, 0.39 mmol) in acetonitrile (5 ml) were added phenyl hydrazine (38 μL, 0.38 mmol) and sulfuric acid (52 μL, 0.98 mmol), and the mixture was stirred for 3 h at room temperature, then the mixture was stirred for 2 h at 50° C. The reaction mixture was poured into water (50 mL), and the resulting precipitate was filtered and dried. The precipitated was dissolved in acetonitrile (5 mL), then water (52 μL, 3.9 mmol) and sulfuric acid (93 μL, 1.75 mmol) were added. The mixture was heated at 80 C for 4 h. The mixture was cooled to room temperature, and then neutralized with sat. NaHCO3. The mixture was extracted with CHCl3/EtOAc 3 times. The combined organic extracts were washed with sat. NaCl, dried over Na2SO4, and evaporated in vacuo. The residue purified by column chromatography (EtOAc/n-hexane) to give the title compound as a brown solid (44 mg, 41%).
Reaction SMILES: [CH3:1][C:2]1[CH:20]=[CH:19][C:5]([CH2:6][C:7]2[CH:8]=[CH:9][C:10]3[O:14][C:13](B(O)O)=[CH:12][C:11]=3[CH:18]=2)=[CH:4][CH:3]=1.Br[C:22]1[CH:36]=[CH:35][C:25]([CH2:26][N:27]2[CH2:30][CH:29]([C:31]([O:33][CH3:34])=[O:32])[CH2:28]2)=[CH:24][C:23]=1[F:37]>>[F:37][C:23]1[CH:24]=[C:25]([CH:35]=[CH:36][C:22]=1[C:13]1[O:14][C:10]2[CH:9]=[CH:8][C:7]([CH2:6][C:5]3[CH:19]=[CH:20][C:2]([CH3:1])=[CH:3][CH:4]=3)=[CH:18][C:11]=2[CH:12]=1)[CH2:26][N:27]1[CH2:28][CH:29]([C:31]([O:33][CH3:34])=[O:32])[CH2:30]1
Reactant: COC(=O)C1CN(Cc2ccc(Br)c(F)c2)C1
Reactant: Cc1ccc(Cc2ccc3oc(B(O)O)cc3c2)cc1
Product: COC(=O)C1CN(Cc2ccc(-c3cc4cc(Cc5ccc(C)cc5)ccc4o3)c(F)c2)C1

Procedure:
In a similar manner as described in general procedure D, 5-(4-methylbenzyl)-benzofuran-2-ylboronic acid (150 mg, 0.56 mmol) was reacted with methyl 1-(4-bromo-3-fluorobenzyl)azetidine-3-carboxylate (155 mg, 0.51 mmol) to give methyl 1-(3-fluoro-4-(5-(4-methylbenzyl)benzofuran-2-yl)benzyl)azetidine-3-carboxylate as white solid: MS (ESI) m/z: Calculated: 443.51; Observed: 444.0 (M++1).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.O[C@@H:10]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:11][N:12]1[CH2:17][CH2:16][CH:15]([C:18]2[CH:19]=[C:20]([NH:24][C:25](=[O:29])[CH:26]([CH3:28])[CH3:27])[CH:21]=[CH:22][CH:23]=2)[CH2:14][CH2:13]1>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C@H:10]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH2:11][N:12]2[CH2:17][CH2:16][CH:15]([C:18]3[CH:19]=[C:20]([NH:24][C:25](=[O:29])[CH:26]([CH3:28])[CH3:27])[CH:21]=[CH:22][CH:23]=3)[CH2:14][CH2:13]2)=[CH:4][CH:3]=1
Reactant: Oc1ccc(F)cc1
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(C[C@@H](O)c3ccccc3)CC2)c1
Product: CC(C)C(=O)Nc1cccc(C2CCN(C[C@H](Oc3ccc(F)cc3)c3ccccc3)CC2)c1

Procedure:
Prepared by Procedure B and Scheme B1 using 4-fluorophenol and N-(3-{1-[(2S)-2-hydroxy-2-phenylethyl]-4-piperidinyl}phenyl)-2-methylpropanamide: ESMS m/e: 461.2 (M+H)+.
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:11]=[C:12]3[CH:18]=[C:17]([C:19]([O-:21])=O)[NH:16][C:13]3=[N:14][CH:15]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[Li+].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.[F:45][C:46]1[CH:53]=[CH:52][C:49]([CH2:50][NH2:51])=[CH:48][CH:47]=1.C(N(CC)C(C)C)(C)C>>[F:45][C:46]1[CH:53]=[CH:52][C:49]([CH2:50][NH:51][C:19]([C:17]2[NH:16][C:13]3=[N:14][CH:15]=[C:10]([O:9][CH2:8][CH2:7][CH2:6][N:1]4[CH2:2][CH2:3][CH2:4][CH2:5]4)[CH:11]=[C:12]3[CH:18]=2)=[O:21])=[CH:48][CH:47]=1
Reactant: O=C([O-])c1cc2cc(OCCCN3CCCC3)cnc2[nH]1
Reactant: NCc1ccc(F)cc1
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Agent: [Li+]
Solvent: CCN(C(C)C)C(C)C
Product: O=C(NCc1ccc(F)cc1)c1cc2cc(OCCCN3CCCC3)cnc2[nH]1
Yield: 29 %

Procedure:
The title compound was synthesized in analogy to example 1 from lithium 5-(3-pyrrolidin-1-yl-propoxy)-1H-pyrrolo[2,3-b]pyridine-2-carboxylate, O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate, 4-fluorobenzylamine and N,N-diisopropylethylamine to give the desired product as a light yellow solid (29%).
Reaction SMILES: Br[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][C:9]=2[O:11][C:12]2[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:21])[CH3:20])=[CH:14][C:13]=2[F:22])[N:4]([S:23]([C:26]2[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=2)(=[O:25])=[O:24])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH:39]1(B(O)O)[CH2:41][CH2:40]1>CN(C=O)C.ClCCl.CO>[CH:39]1([C:2]2[C:10]3[C:5](=[N:6][CH:7]=[CH:8][C:9]=3[O:11][C:12]3[CH:17]=[CH:16][C:15]([NH:18][C:19](=[O:21])[CH3:20])=[CH:14][C:13]=3[F:22])[N:4]([S:23]([C:26]3[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=3)(=[O:25])=[O:24])[CH:3]=2)[CH2:41][CH2:40]1
Reactant: CC(=O)Nc1ccc(Oc2ccnc3c2c(Br)cn3S(=O)(=O)c2ccc(C)cc2)c(F)c1
Reactant: OB(O)C1CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CO
Solvent: ClCCl
Product: CC(=O)Nc1ccc(Oc2ccnc3c2c(C2CC2)cn3S(=O)(=O)c2ccc(C)cc2)c(F)c1
Temperature: 110 °C

Procedure:
500 mg (0.96 mmol) of N-[4-({3-bromo-1-[(4-methylphenyl)sulfonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}oxy)-3-fluorophenyl]acetamide and 400 mg (2.89 mmol) of potassium carbonate are suspended in DMF (5 ml). The solution is degassed and vented with argon. 39 mg (0.05 mmol) of [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride/methylene dichloride complex and 207 mg (2.41 mmol) of cyclopropylboronic acid (Wallace, Debra J.; Chen, Cheng-yl; Tetrahedron Lett. 2002, 43(39), 6987-6990) are then added. The mixture is heated at 110° C. overnight. The reaction mixture is then dissolved in dichloromethane/methanol 10:1 and filtered through an Extrelut cartridge. The filtrate is concentrated under reduced pressure and the crude product is purified by preparative HPLC.
Reaction SMILES: Cl.Cl.[CH3:3][O:4][CH2:5][CH:6]1[CH2:11][NH:10][CH2:9][CH2:8][NH:7]1.C(N(CC)CC)C.[C:19]1([C:25](Cl)([C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C(Cl)Cl>[CH3:3][O:4][CH2:5][CH:6]1[CH2:11][N:10]([C:25]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[CH2:9][CH2:8][NH:7]1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: COCC1CNCCN1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COCC1CN(C(c2ccccc2)(c2ccccc2)c2ccccc2)CCN1
Temperature: 25 °C
Reaction time: 16 h
Yield: 101.2 %

Procedure:
Compound 12 (2.14 g, 10.5 mmol) was dissolved in dry CH2Cl2 (60 ml), in the presence of dry triethylamine (5.9 ml, 42.3 mmol). The solution was cooled (0° C.) and triphenylmethyl chloride (2.94 g, 10.6 mmol) in dry CH2Cl2 (10 ml) was added drop-wise. Once the addition was complete the reaction was warmed to room temperature and stirred for 16 h. The reaction mixture was washed with saturated NaHCO3 (75 mL), water (75 mL), and brine (75 mL). The organic portion was dried (K2CO3), and concentrated in vacuo to give 13 as an amorphous foam (3.96 g, 99% yield). 1H NMR (400 MHz, CDCl3): δ 1.3 (m, 3H), 1.9 (s, 3H), 3.0 (m, 3H), 3.2 (m, 1H), 3.3 (s, 3H), 7.16 (m, 4H), 7.27 (m, 7H), 7.49 (m, 4H).
Reaction SMILES: [NH2:1][C:2]1[C:3]([CH3:8])=[CH:4][CH:5]=[CH:6][CH:7]=1.[CH2:9]([N:12]=[C:13]=[O:14])[CH2:10][CH3:11]>C1(C)C=CC=CC=1>[CH3:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[NH:1][C:13]([NH:12][CH2:9][CH2:10][CH3:11])=[O:14]
Reactant: Cc1ccccc1N
Reactant: CCCN=C=O
Solvent: Cc1ccccc1
Product: CCCNC(=O)Nc1ccccc1C
Reaction time: 6 h
Yield: 64.1 %

Procedure:
2-Toluidine (32.1 g) was dissolved in toluene (500 ml) and propyl isocyanate (25.2 g) was added in one portion with stirring. The mixture was stirred for 1 h and then allowed to stand at room temperature for 6 h. The solid was collected by filtration and washed with toluene to provide the title compound (36.5 g).
Reaction SMILES: O.O.O.C([O-])(=[O:6])C.[Na+].[CH3:9][O:10][C:11]1[CH:12]=[C:13]([C:17]2[CH2:21][CH2:20][CH2:19][CH:18]=2)[CH:14]=[CH:15][CH:16]=1>C(OO)(=O)C.ClCCl>[CH3:9][O:10][C:11]1[CH:12]=[C:13]([C:17]23[O:6][CH:21]2[CH2:20][CH2:19][CH2:18]3)[CH:14]=[CH:15][CH:16]=1
Reactant: CC(=O)[O-]
Reactant: COc1cccc(C2=CCCC2)c1
Agent: CC(=O)OO
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: COc1cccc(C23CCCC2O3)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 298 %

Procedure:
A solution of sodium acetate trihydrate (6 g) in peracetic acid (38 ml) was added dropwise to a stirred solution of 1-(3-methoxyphenyl) cyclopentene (33.5 g) in dichloromethane (200 ml), maintaining the temperature in the range 0°-10°. The solution was stirred for 3 hours at room temperature and then washed with 8% aqueous sodium bicarbonate (700 ml) and 8% sodium thiosulphate solution (400 ml). The organic phase was separated, dried and evaporated and the residue was distilled in vacuo to give the title compound as a colourless oil (25 g) b.p. 89°-92° (0.01 mm).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[C:9]1([C@H:19]([NH2:21])[CH3:20])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=[CH:11][CH:10]=1.[Cl:22][CH:23]=[CH:24][CH2:25]Cl>C(#N)C.O>[ClH:22].[Cl:22][CH:23]=[CH:24][CH2:25][NH:21][C@@H:19]([C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=[CH:11][CH:10]=1)[CH3:20]
Reactant: ClC=CCCl
Reactant: C[C@@H](N)c1cccc2ccccc12
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: O
Solvent: CC#N
Product: C[C@@H](NCC=CCl)c1cccc2ccccc12
Product: Cl
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
Potassium carbonate (161.2 g) and potassium iodide (5 g) were added to a solution of (R)-1(1-naphthyl)ethylamine (100 g) and 1,3-dichloropropene (97.3 g) in acetonitrile (1 L) at room temperature. The reaction mixture was refluxed at 80° C. to 85° C. for 4 hours. After the completion of the reaction, the mixture was cooled to room temperature and de-ionized water (500 mL) was added. The solution was stirred for 15 minutes and layers were separated. The organic layer was concentrated under vacuum at 55° C. to 60° C. till about 100 to 150 mL of residue was left. Toluene (500 mL) was added to the residue and the organic layer was washed twice with de-ionized water (2×250 mL). The organic layer was concentrated under vacuum at 55° C. to 60° C. Isopropyl alcohol was added to the residue and stirred for 10 minutes at room temperature. The pH of the solution was adjusted to 0.5 to 1.0 using concentrated hydrochloric acid (35 mL) and stirred for one hour at room temperature. The solid was filtered, washed with isopropyl alcohol (2×100 mL) and dried under vacuum at 45° C. to 50° C.
Reaction SMILES: [NH2:1][C:2]1[CH2:7][CH2:6][CH2:5][C:4](=[O:8])[CH:3]=1.Cl.CN(C)[CH2:12][CH2:13][C:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=O.C(=O)([O-])[O-].[Na+].[Na+]>C(O)(=O)C>[C:16]1([C:14]2[CH:13]=[CH:12][C:3]3[C:4](=[O:8])[CH2:5][CH2:6][CH2:7][C:2]=3[N:1]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: NC1=CC(=O)CCC1
Reactant: CN(C)CCC(=O)c1ccccc1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: O=C1CCCc2nc(-c3ccccc3)ccc21
Temperature: 25 °C
Yield: 26.4 %

Procedure:
3-Aminocyclohexenone (5.55 g, 50 mmol) and 3-dimethylaminopropiophenone hydrochloride (10.65 g, 50 mmol) were suspended in glacial acetic acid (15 mL) and heated at reflux for 1 h. The mixture was cooled to room temperature and cautiously poured into 20% aqueous sodium carbonate. After gas evolution ceased the residue was extracted with chloroform, dried over anhydrous sodium carbonate, filtered and evaporated. Purification by chromatography on silica gel using 1:1 chloroform/dichloromethane as eluant provided 2.95 g (26%) of 2-phenyl-7,8-dihydroquinolin-5(6H)-one as an off-white solid, mp 128°-130° C.; 1H NMR (CDCl3) δ 8.32 (d, 1H), 8.05 (dd, 2H), 7.66 (d, 2H), 7.55-7.42 (m, 3H), 3.21 (t, 2H), 2.72 (t, 2H), 2.22 (m, 2H).
Reaction SMILES: Cl[C:2]([O:4][CH3:5])=[O:3].[Br:6][C:7]1[CH:15]=[CH:14][C:10]([CH2:11][CH2:12][NH2:13])=[CH:9][CH:8]=1.C([O-])([O-])=O.[Na+].[Na+].O>CC(C)=O>[Br:6][C:7]1[CH:15]=[CH:14][C:10]([CH2:11][CH2:12][NH:13][C:2]([O:4][CH3:5])=[O:3])=[CH:9][CH:8]=1
Reactant: COC(=O)Cl
Reactant: NCCc1ccc(Br)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: O
Product: COC(=O)NCCc1ccc(Br)cc1
Temperature: 25 °C
Yield: 110.7 %

Procedure:
Into a 50 mL-single neck flask, 260 mg of methyl chloroformate in acetone (5 mL) was added dropwise to 500 mg of 4-bromophenethyl amine and 291 mg of Na2CO3 in acetone (20 mL) while stirring at room temperature under a nitrogen atmosphere. The reaction was then stirred overnight at this temperature. In the morning, the mixture was poured into H2O and the desired product was extracted with ethyl acetate. This organic layer was washed with H2O, dried over Na2SO4, and concentrated under reduced vacuum to yield the intermediate title compound (714 mg) as a white solid. This material was taken to the next reaction without further purification. Ion spray M.S. 259.2 (M*+1).
Reaction SMILES: [CH:1]1([CH2:4][N:5]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([O:14][CH2:15][CH3:16])[CH:12]=3)[CH:7]=[C:6]2[C:17]2[CH:22]=[CH:21][C:20]([N+:23]([O-:25])=[O:24])=[CH:19][CH:18]=2)[CH2:3][CH2:2]1.[I:26]N1C(=O)CCC1=O>CN(C=O)C.O>[CH:1]1([CH2:4][N:5]2[C:13]3[C:8](=[CH:9][CH:10]=[C:11]([O:14][CH2:15][CH3:16])[CH:12]=3)[C:7]([I:26])=[C:6]2[C:17]2[CH:18]=[CH:19][C:20]([N+:23]([O-:25])=[O:24])=[CH:21][CH:22]=2)[CH2:3][CH2:2]1
Reactant: O=C1CCC(=O)N1I
Reactant: CCOc1ccc2cc(-c3ccc([N+](=O)[O-])cc3)n(CC3CC3)c2c1
Solvent: O
Solvent: CN(C)C=O
Product: CCOc1ccc2c(I)c(-c3ccc([N+](=O)[O-])cc3)n(CC3CC3)c2c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 96.4 %

Procedure:
To 1-cyclopropylmethyl-6-ethoxy-2-(4-nitro-phenyl)-1H-indole (800 mg, 2.38 mmol) in DMF (8.6 mL) at room temperature was added a solution of N-iodosuccinimide (585 mg, 2.6 mmol) in DMF (5.6 mL) dropwise. The reaction mixture was stirred at room temperature for 2 h, diluted with H2O and extracted with EtOAc. The organic layer was washed with H2O, and then with sat. aq. NaHCO3 and then dried and concentrated. The residue was triturated with hexane to provide 1-cyclopropylmethyl-6-ethoxy-3-iodo-2-(4-nitro-phenyl)-1H-indole (1.061 g, 96%) as an orange solid.
Reaction SMILES: Cl.[NH:2]1[CH2:7][CH:6]([C:8]([OH:10])=[O:9])[CH2:5][N:4]=[CH:3]1.S(Cl)([Cl:13])=O.[CH2:15](O)[CH3:16]>>[ClH:13].[CH2:15]([O:9][C:8]([CH:6]1[CH2:7][NH:2][CH:3]=[N:4][CH2:5]1)=[O:10])[CH3:16]
Reactant: O=C(O)C1CN=CNC1
Reactant: O=S(Cl)Cl
Reactant: CCO
Agent: Cl
Product: CCOC(=O)C1CN=CNC1
Yield: 63 %

Procedure:
1,4,5,6-Tetrahydropyrimidine-5-carboxylic acid hydrochloride (1.5 g, 9.12 mmol) was dissolved in absolute ethanol (40 ml) by heating. The thionyl chloride (1.1 g, 9.16 mmol) was added dropwise with stirring. The resulting solution was refluxed 20 h and then evaporated to dryness in vacuo. The residue was taken up in absolute methanol (5 ml) and dry THF (10 ml) was added to induce crystallization, giving 1.1 g (63%) product as white crystals, mp 125°-127° C. 300 MHz nmr confirmed the product. Microanalysis calc.: C 43.64, H 6.75, N 14.55; found: C, 43.43, H 6.58, N 14.40.