Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([Li])CCC.[CH:6](=[N:13][CH2:14][C:15]#[C:16][Si:17]([CH3:20])([CH3:19])[CH3:18])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[C:21]([O:25][CH3:26])(=[O:24])[CH:22]=[CH2:23].O>CCCCCC.O1CCCC1>[CH3:20][Si:17]([CH3:19])([CH3:18])[C:16]#[C:15][CH:14]([N:13]=[CH:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH2:23][CH2:22][C:21]([O:25][CH3:26])=[O:24]
Reactant: C=CC(=O)OC
Reactant: C[Si](C)(C)C#CCN=Cc1ccccc1
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Solvent: CCCCCC
Product: COC(=O)CCC(C#C[Si](C)(C)C)N=Cc1ccccc1
Temperature: -70 °C
Reaction time: 0.33 h

Procedure:
53.6 ml of a 1.6M solution of n-butyllithium in hexane was added drop-by-drop over 20 minutes to a solution of 18.0 g of 1B in 700 ml of dry tetrahydrofuran at -70° C. The resulting mixture was stirred for 20 minutes at -70° C., when 7.2 g of freshly distilled methyl acrylate was added over 14 minutes. The resulting mixture was stirred for 30 minutes at -70° C., when 16.5 ml of water was added drop-by-drop. The resulting mixture was allowed to warm slowly to room temperature; the solvent was evaporated; the residue was diluted with water and the resulting mixture was extracted with ether. The ether extract was washed with brine, dried (Na2SO4), filtered and the solvent was evaporated. The residue (a dark thick oil) was distilled in a Kugelrohr apparatus to give methyl 6-(trimethylsilyl)-4-(benzylideneamino)-5-hexynoate (3A), b.p.: 140°-142° C. (0.01 Torr.).
Reaction SMILES: Cl.[NH2:2][C:3]1[CH:4]=[C:5]([CH:21]=[CH:22][CH:23]=1)[CH2:6][NH:7][C:8]1[C:17]2[C:12](=[C:13]([C:18]([NH2:20])=[O:19])[CH:14]=[CH:15][CH:16]=2)[N:11]=[CH:10][N:9]=1.Br[C:25]1[N:30]=[CH:29][C:28]([CH2:31][C:32]#[N:33])=[CH:27][CH:26]=1>>[C:32]([CH2:31][C:28]1[CH:27]=[CH:26][C:25]([NH:2][C:3]2[CH:4]=[C:5]([CH:21]=[CH:22][CH:23]=2)[CH2:6][NH:7][C:8]2[C:17]3[C:12](=[C:13]([C:18]([NH2:20])=[O:19])[CH:14]=[CH:15][CH:16]=3)[N:11]=[CH:10][N:9]=2)=[N:30][CH:29]=1)#[N:33]
Reactant: NC(=O)c1cccc2c(NCc3cccc(N)c3)ncnc12
Reactant: N#CCc1ccc(Br)nc1
Agent: Cl
Product: N#CCc1ccc(Nc2cccc(CNc3ncnc4c(C(N)=O)cccc34)c2)nc1

Procedure:
The title compound was prepared according to Example 616 starting 4-(3-Amino-benzylamino)-quinazoline-8-carboxylic acid amide hydrochloride and (6-Bromo-pyridin-3-yl)-acetonitrile.
Reaction SMILES: FC(F)(F)C(O)=O.[CH3:8][C:9]1([CH3:23])[C:14](=[O:15])[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10]1>ClCCl>[CH3:8][C:9]1([CH3:23])[C:14](=[O:15])[CH2:13][CH2:12][NH:11][CH2:10]1
Reactant: CC(C)(C)OC(=O)N1CCC(=O)C(C)(C)C1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC1(C)CNCCC1=O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Trifluoroactic acid (4 mL, 51.92 mmol) was added to a solution of tert-butyl 3,3-dimethyl-4-oxopiperidine-1-carboxylate (2.0588 g, 9.06 mmol) in dichloromethane (12 mL). The reaction was stirred at RT for 2 h and the solution was concentrated to remove the solvent. The residue as the product was directly used in the next step without further purification. m/z 128.
Reaction SMILES: [NH2:1][C:2]1[CH2:7][CH2:6][CH2:5][C:4](=[O:8])[CH:3]=1.[C:9](OC)(=[O:12])[C:10]#[CH:11]>>[NH:1]1[C:2]2[CH2:7][CH2:6][CH2:5][C:4](=[O:8])[C:3]=2[CH:11]=[CH:10][C:9]1=[O:12]
Reactant: C#CC(=O)OC
Reactant: NC1=CC(=O)CCC1
Product: O=C1CCCc2[nH]c(=O)ccc21

Procedure:
3-Aminocyclohex-2-enone (ex Aldrich) was reacted with methyl propiolate (ex Lancaster) to give 7,8-dihydro-2,5-quinoline-dione according to Speckamp et al J. Trav. Chem. Pays. bas., 91 157 (1972). The latter was converted to 2-chloro-7,8-dihydro-5-quinolinone by analogy with Example VI. The latter compound (2 g) was dissolved in chloroform (200 ml) and treated with bromine (0.53 ml) dropwise at room temperature. After 30 min solid potassium carbonate was added, the mixture was stirred for 1 hour, filtered and solvent removed to give 2-chloro-6-bromo-7,8-dihydro-5-quinolinone (2.86 g). This compound was heated at 110° C. with anhydrous lithium chloride (1.4 g) and dimethylformamide (45 ml) for 3 hours. The mixture was diluted with water, worked-up in conventional fashion and purified by column chromatography on silica (eluting with ether-hexane) to give 2-chloro-5-hydroxyquinoline (0.77 g).
Reaction SMILES: [CH2:1]([NH2:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[Li]CCCC.C([O:21][C:22](=O)[C:23]1[CH:28]=[C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[CH:30]=2)[C:26]([O:36][CH2:37][CH2:38][OH:39])=[C:25]([C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([Cl:46])[CH:41]=2)[CH:24]=1)C>C1COCC1>[CH2:1]([NH:13][C:22](=[O:21])[C:23]1[CH:24]=[C:25]([C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([Cl:46])[CH:41]=2)[C:26]([O:36][CH2:37][CH2:38][OH:39])=[C:27]([C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([Cl:35])[CH:30]=2)[CH:28]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCCCN
Reactant: CCOC(=O)c1cc(-c2cccc(Cl)c2)c(OCCO)c(-c2cccc(Cl)c2)c1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCCCCCCCCCCCNC(=O)c1cc(-c2cccc(Cl)c2)c(OCCO)c(-c2cccc(Cl)c2)c1
Temperature: 0 °C
Reaction time: 0.67 h
Yield: 71.6 %

Procedure:
To a flamed dried round bottom flask with dodecyl amine (0.519 g, 2.80 mmol) and THF (8 mL) cooled to 0° C. was added n-BuLi (1.12 mL, 2.5 M in hexane, 2.80 mmol) dropwise over a 5 min. period. The resulting solution was stirred at this temperature for 40 min. and then cooled to −45° C. To this solution was added dropwise a solution (at 0° C.) of 3,5-bis-(m-chlorophenyl)-4-(2-hydroxyethoxy)benzoic acid ethyl ester (0.302 g, 0.700 mmol) in THF (8 mL) over 5 min. This final mixture was stirred and warmed to room temperature over 30 min. At this point, the reaction mixture was quenched with H2O (3 mL) and diluted with EtOAc (40 mL). The organic layer was washed with 1 N HCl (3×7 mL), brine (7 mL), and H2O:brine (1:1, 14 mL) and then dried (Na2SO4). After concentration, the residue was purified by flash chromatography (0 to 15% EtOAc/hexane gradient) to afford the product (0.286 g, 72%) as an oily white solid; 1H NMR (DMSO-d6) δ 0.86 (t, J=7.7 Hz, 3H), 1.20-1.37 (m, 18H), 1.46-1.57 (m, 2H), 3.13 (dd, J=6.9, 11.5 Hz, 2H), 3.20-3.33 (m, 4H), 4.46 (t, J=6.2 Hz, 1H), 7.43-7.57 (m, 4H), 7.59-7.63 (m, 2H), 7.68-7.73 (m, 2H), 7.89 (s, 2H), 8.67 (t, J=6.2 Hz, 1H); mass spectrum [(+) APCI], m/z 570 (M+H)+.
Reaction SMILES: C[O:2][C:3](=[O:33])[C@@H:4]([O:30][CH2:31][CH3:32])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[N:15]=[C:16]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[C:22]([CH3:27])[CH:21]=3)[O:17][C:18]=2[CH3:19])=[CH:8][C:7]=1[CH2:28][CH3:29].[Li+].[OH-]>>[CH2:31]([O:30][C@@H:4]([CH2:5][C:6]1[CH:11]=[CH:10][C:9]([O:12][CH2:13][C:14]2[N:15]=[C:16]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[C:22]([CH3:27])[CH:21]=3)[O:17][C:18]=2[CH3:19])=[CH:8][C:7]=1[CH2:28][CH3:29])[C:3]([OH:33])=[O:2])[CH3:32]
Reactant: CCO[C@@H](Cc1ccc(OCc2nc(-c3ccc(F)c(C)c3)oc2C)cc1CC)C(=O)OC
Agent: [Li+]
Agent: [OH-]
Product: CCO[C@@H](Cc1ccc(OCc2nc(-c3ccc(F)c(C)c3)oc2C)cc1CC)C(=O)O

Procedure:
In analogy to the procedure described in example 1 g], (S)-2-ethoxy-3-{2-ethyl-4-[2-(4-fluoro-3-methyl-phenyl)-5-methyl-oxazol-4-ylmethoxy]-phenyl}-propionic acid methyl ester was treated with LiOH to obtain (S)-2-ethoxy-3-{2-ethyl-4-[2-(4-fluoro-3-methyl-phenyl)-5-methyl-oxazol-4-ylmethoxy]-phenyl}-propionic acid as colorless solid.
Reaction SMILES: C([O:8][CH2:9][CH:10]1[O:24][C:14]2=[C:15]3[C:20](=[CH:21][CH:22]=[C:13]2[O:12][CH2:11]1)[N:19]=[C:18]([CH3:23])[CH:17]=[CH:16]3)C1C=CC=CC=1.C1CCCCC=1>CCO.[Pd]>[CH3:23][C:18]1[CH:17]=[CH:16][C:15]2[C:20](=[CH:21][CH:22]=[C:13]3[O:12][CH2:11][C@H:10]([CH2:9][OH:8])[O:24][C:14]3=2)[N:19]=1
Reactant: Cc1ccc2c3c(ccc2n1)OCC(COCc1ccccc1)O3
Agent: [Pd]
Solvent: C1=CCCCC1
Solvent: CCO
Product: Cc1ccc2c3c(ccc2n1)OC[C@H](CO)O3
Yield: 97.7 %

Procedure:
To a solution of (2S)-2[(benzyloxy)methyl-8-methyl-2,3-dihydro[1,4]dioxino[2,3-f]quinoline (0.16 g, 0.5 mmol) in EtOH (1 mL) was added cyclohexene (0.5 mL) then 10% Pd/C (0.016 g, 10 mol %). The mixture was heated to reflux under N2 for 18 hours then cooled and filtered. The catalyst was rinsed with methanol and the filtrate was concentrated in vacuo to afford 0.113 g (98%) of the title alcohol as an off-white solid: 1H NMR (CD3OD) δ 8.46 (m, 1H), 7.47 (m, 1H), 7.38–7.31 (m, 2H), 4.40 (m, 1H), 4.36 (m, 1H), 4.18 (m, 1H), 3.91 (m, 2H), 2.68 (s, 3H).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:22]=[CH:23][CH:24]=1)[CH2:7][N:8]1[CH2:13][CH2:12][CH:11]([NH:14]C(=O)OC(C)(C)C)[CH2:10][CH2:9]1)([O-:3])=[O:2]>C(O)(C(F)(F)F)=O.C(Cl)Cl>[N+:1]([C:4]1[CH:5]=[C:6]([CH:22]=[CH:23][CH:24]=1)[CH2:7][N:8]1[CH2:9][CH2:10][CH:11]([NH2:14])[CH2:12][CH2:13]1)([O-:3])=[O:2]
Reactant: CC(C)(C)OC(=O)NC1CCN(Cc2cccc([N+](=O)[O-])c2)CC1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: NC1CCN(Cc2cccc([N+](=O)[O-])c2)CC1
Temperature: 30 °C
Reaction time: 8 h
Yield: 156.7 %

Procedure:
Tert-butyl N-{1-(3-nitrobenzyl)piperidin-4-yl}carbamate (30.0 g, 89.5 mmol, 1.0 eq)) was dissolved in 300 mL of TFA:DCM (1:10) and the resulting solution stirred at 30° C. overnight. The reaction mixture was then concentrated under vacuum to provide crude 1-(3-nitrobenzyl)piperidin-4-amine (33 g, TFA salt) as a white solid.
Reaction SMILES: Br[C:2]1[C:6]([CH3:7])=[C:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=2)[S:4][C:3]=1[CH:16]1[O:20][CH2:19][CH2:18][O:17]1.[CH3:21][O:22][C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][CH:28]=1.C([O-])([O-])=O.[K+].[K+].C(OCC)(=O)C.CCCCCC>C(COC)OC.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:21][O:22][C:23]1[CH:28]=[C:27]([C:2]2[C:6]([CH3:7])=[C:5]([C:8]3[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=3)[S:4][C:3]=2[CH:16]2[O:20][CH2:19][CH2:18][O:17]2)[CH:26]=[CH:25][CH:24]=1
Reactant: COc1cccc(B(O)O)c1
Reactant: COc1ccc(-c2sc(C3OCCO3)c(Br)c2C)cc1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: CCCCCC
Solvent: COCCOC
Solvent: CCOC(C)=O
Product: COc1ccc(-c2sc(C3OCCO3)c(-c3cccc(OC)c3)c2C)cc1
Temperature: 75 °C
Reaction time: 8 h
Yield: 94.1 %

Procedure:
2-[3-Bromo-5-(4-methoxyphenyl)-4-methylthien-2-yl]-1,3-dioxolane (7.0 g, 20 mmol), 3-methoxyphenylboronic acid (3.3 g, 22 mmol), K2CO3 (9.1 g, 66 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium [II] (0.8 g, 1 mmol) were combined in 20% aqueous dimethoxyethane (80 mL) and heated at 75° C. After 8 h, the cooled mixture was filtered through Celite and washed with ethyl acetate (200 mL). The filtrate was washed with 1 N aqueous NaOH and brine (200 mL each), dried (K2CO3) and concentrated in vacuo to give the crude product (8.4 g) as a dark oil which was pre-adsorbed on silica gel (15 g). Flash chromatography (105 g silica, gradient 5%-10%-20% ethyl acetate-hexane) gave the title compound (7.2 g, 95%) as a clear, colorless oil.
Reaction SMILES: [CH3:1][C:2]1([CH3:33])[C:6]2[C:7]([O:11][C:12]3[N:17]=[CH:16][C:15]([NH:18][C:19]([C@H:21]([NH:25]C(=O)OC(C)(C)C)[CH:22]([CH3:24])[CH3:23])=[O:20])=[CH:14][N:13]=3)=[CH:8][CH:9]=[CH:10][C:5]=2[O:4][CH2:3]1.C(O)(C(F)(F)F)=O>ClCCl>[NH2:25][C@H:21]([CH:22]([CH3:24])[CH3:23])[C:19]([NH:18][C:15]1[CH:14]=[N:13][C:12]([O:11][C:7]2[C:6]3[C:2]([CH3:1])([CH3:33])[CH2:3][O:4][C:5]=3[CH:10]=[CH:9][CH:8]=2)=[N:17][CH:16]=1)=[O:20]
Reactant: CC(C)[C@@H](NC(=O)OC(C)(C)C)C(=O)Nc1cnc(Oc2cccc3c2C(C)(C)CO3)nc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC(C)[C@@H](N)C(=O)Nc1cnc(Oc2cccc3c2C(C)(C)CO3)nc1
Reaction time: 1 h
Yield: 98.4 %

Procedure:
To a solution of 1,1-dimethylethyl {(1R)-1-[({2-[(3,3-dimethyl-2,3-dihydro-1-benzofuran-4-yl)oxy]-5-pyrimidinyl}amino)carbonyl]-2-methylpropyl}carbamate (Intermediate 144, 52 mg, 0.114 mmol) in dry Dichloromethane (DCM) (2 mL) at 0° C. TFA (0.5 ml, 6.49 mmol) was slowly added and the reaction mixture was stirred for 1 h at the same temperature. The solvent and the excess of TFA were evaporated end the residue was dissolved in DCM (5 ml) and an aqueous saturated solution of NaHCO3 was added while the pH was allowed to reach ˜8-9. Two phases were separated and the organic layer was dried (Na2SO4), filtered and evaporated affording the title compound (40 mg) as a white solid.
Reaction SMILES: [CH3:1][C:2]1[S:11][C:10]2[NH:9][C:8]3[CH:12]=[CH:13][C:14]([C:16]#[N:17])=[CH:15][C:7]=3[N:6]=[C:5]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[C:4]=2[CH:3]=1.Cl>CO.[Pd]>[CH3:1][C:2]1[S:11][C:10]2[NH:9][C:8]3[CH:12]=[CH:13][C:14]([CH2:16][NH2:17])=[CH:15][C:7]=3[N:6]=[C:5]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[C:4]=2[CH:3]=1
Reactant: Cc1cc2c(s1)Nc1ccc(C#N)cc1N=C2N1CCN(C)CC1
Agent: [Pd]
Agent: Cl
Solvent: CO
Product: Cc1cc2c(s1)Nc1ccc(CN)cc1N=C2N1CCN(C)CC1
Reaction time: 1 h

Procedure:
To a solution of 2-Methyl-10-(4-methyl-piperazin-1-yl)-4H-3-thia-4,9-diaza-benzo[f]azulene-7-carbonitrile, prepared as described in the previous step, (0.25 g) in methanol (90 mL) was added concentrated HCl (0.4 mL) and Pd black (57 mg). Hydrogenation was carried out at 50 psi for 1 h. More Pd black (147 mg) was added. The mixture was shaken at 50 psi for 22 h. The catalyst was filtered and washed with methanol. The filtrate was concentrated, treated with saturated sodium bicarbonate solution (5 mL), and concentrated to dryness. The product was purified by silica column. LC-MS: m/z 342 (M+1). 1H NMR (CD3OD, 400 MHz): δ (ppm) 6.89-6.85 (m, 2H), 6.64 (d, 1H), 6.34 (d, 1H), 3.66 (s, 2H), 3.46 (m, 4H), 2.54 (m, 4H), 2.34 (s, 3H), 2.30 (d, 3H).
Reaction SMILES: [C:1]([C:3]1[CH2:20][CH2:19][C@@:18]2([CH3:21])[C:5](=[CH:6][CH2:7][C@@H:8]3[C@@H:17]2[CH2:16][CH2:15][C@@:13]2([CH3:14])[C@H:9]3[CH2:10][CH2:11][C@@H:12]2[C:22](O)=[O:23])[CH:4]=1)#[N:2].[CH3:25][C:26]([NH2:34])([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH3:27]>>[CH3:25][C:26]([NH:34][C:22]([C@H:12]1[CH2:11][CH2:10][C@H:9]2[C@H:8]3[C@H:17]([CH2:16][CH2:15][C@:13]12[CH3:14])[C@:18]1([CH3:21])[C:5]([CH:4]=[C:3]([C:1]#[N:2])[CH2:20][CH2:19]1)=[CH:6][CH2:7]3)=[O:23])([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[CH3:27]
Reactant: CC(C)(N)c1ccccc1
Reactant: C[C@]12CC[C@H]3[C@@H](CC=C4C=C(C#N)CC[C@@]43C)[C@@H]1CC[C@@H]2C(=O)O
Product: CC(C)(NC(=O)[C@H]1CC[C@H]2[C@@H]3CC=C4C=C(C#N)CC[C@]4(C)[C@H]3CC[C@]12C)c1ccccc1
Yield: 74 %

Procedure:
Following a procedure similar to that described in Preparation 16a, but using 3-cyanoandrosta-3,5-diene-17β-carboxylic acid [prepared as described in Example 1(b)] and 1-methyl-1-phenylethylamine as starting materials, in relative proportions similar to those used in that Preparation, the title compound was obtained in a yield of 74%.
Reaction SMILES: [CH:1]1([C:5]2[C:6]([O:14][CH2:15][C:16]([F:19])([F:18])[F:17])=[CH:7][C:8]([C:11]([OH:13])=O)=[N:9][CH:10]=2)[CH2:4][CH2:3][CH2:2]1.[NH2:20][C:21]1([CH2:27][C:28]([NH2:30])=[O:29])[CH2:24][S:23](=[O:26])(=[O:25])[CH2:22]1>>[NH2:30][C:28](=[O:29])[CH2:27][C:21]1([NH:20][C:11]([C:8]2[CH:7]=[C:6]([O:14][CH2:15][C:16]([F:19])([F:18])[F:17])[C:5]([CH:1]3[CH2:2][CH2:3][CH2:4]3)=[CH:10][N:9]=2)=[O:13])[CH2:22][S:23](=[O:25])(=[O:26])[CH2:24]1
Reactant: NC(=O)CC1(N)CS(=O)(=O)C1
Reactant: O=C(O)c1cc(OCC(F)(F)F)c(C2CCC2)cn1
Product: NC(=O)CC1(NC(=O)c2cc(OCC(F)(F)F)c(C3CCC3)cn2)CS(=O)(=O)C1

Procedure:
The title compound was synthesized in analogy to Example 112e, using 5-Cyclobutyl-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (example 108f) and 2-(3-amino-1,1-dioxo-thietan-3-yl)acetamide (example 160d) as starting materials and isolated (16.5 mg, 21%); MS (ESI, m/z): 436.3 (M+H+).
Reaction SMILES: [S:1]1[C:10]2[CH2:9][CH2:8][C:7]3[CH:11]=[CH:12][CH:13]=[CH:14][C:6]=3[C:5](=[CH:15][C:16]3[CH:17]=[C:18]([NH2:22])[CH:19]=[CH:20][CH:21]=3)[C:4]=2[CH:3]=[CH:2]1.[Cl:23]C(Cl)(Cl)C(Cl)(Cl)Cl>C1COCC1>[Cl:23][C:2]1[S:1][C:10]2[CH2:9][CH2:8][C:7]3[CH:11]=[CH:12][CH:13]=[CH:14][C:6]=3[C:5](=[CH:15][C:16]3[CH:17]=[C:18]([NH2:22])[CH:19]=[CH:20][CH:21]=3)[C:4]=2[CH:3]=1
Reactant: ClC(Cl)(Cl)C(Cl)(Cl)Cl
Reactant: Nc1cccc(C=C2c3ccccc3CCc3sccc32)c1
Solvent: C1CCOC1
Product: Nc1cccc(C=C2c3ccccc3CCc3sc(Cl)cc32)c1
Reaction time: 1 h
Yield: 22 %

Procedure:
Add 2.2 equiv of n-BuLi-hexanes dropwise to a solution of 3-(9,10-dihydro-1-thia-benzo[f]azulen-4-ylidenemethyl)-phenylamine in THF (0.1 M) at 0° C. under Ar. Stir the resultant dark solution for 1 h before adding 2.5 equiv of hexachloroethane in THF. Stir for 2 h, quench with excess water, and acidify to neutral pH. Extract the aqueous layer with diethyl ether (3×) and then dry (MgSO4) and concentrate the combined organic layers under reduced pressure. Purify the crude residue by column chromatography (0% to 2% to 20% EtOAc:hexanes) to give title compound as an oil (22%) along with recovered starting material: HPLC (ISO80-20A) t=1.903 (90%). MS (APCI): 338 (M+1).
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([CH3:12])=[CH:8][N+:7]=1[O-:13].C(=O)([O-])[O-].[Na+].[Na+]>S(=O)(=O)(O)O>[Cl:5][C:6]1[CH:11]=[C:10]([N+:1]([O-:4])=[O:2])[C:9]([CH3:12])=[CH:8][N+:7]=1[O-:13]
Reactant: Cc1ccc(Cl)[n+]([O-])c1
Reactant: O=[N+]([O-])O
Agent: O=C([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Product: Cc1c[n+]([O-])c(Cl)cc1[N+](=O)[O-]
Temperature: 100 °C
Reaction time: 2 h
Yield: 80 %

Procedure:
To a mixture of 165 mL of nitric acid and 209 mL of sulfuric acid was slowly added 56.4 g of 2-chloro-5-methylpyridine-1-oxide. The reaction mixture was stirred at 100° C. for two hours, cooled to room temperature, and added to ice. Sodium carbonate was added to adjust the pH to about pH 2 to pH 3. The resulting yellow solid was separated by filtration and washed with ice-water. The combined filtrates were extracted with hot chloroform. The extracts were combined, dried over sodium sulfate, and concentrated to give 59.1 g of 2-chloro-5-methyl-4-nitropyridine-1-oxide (80%). Mass Spec. M+H=189.
Reaction SMILES: [CH3:1]I.[NH:3]1[CH2:8][CH2:7][CH:6]([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH2:11][C:12](=[O:18])[NH:13]3)[CH2:5][CH2:4]1>C(#N)C.CO>[CH3:1][N:3]1[CH2:4][CH2:5][CH:6]([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH2:11][C:12](=[O:18])[NH:13]3)[CH2:7][CH2:8]1
Reactant: CI
Reactant: O=C1Cc2c(cccc2C2CCNCC2)N1
Solvent: CO
Solvent: CC#N
Product: CN1CCC(c2cccc3c2CC(=O)N3)CC1
Temperature: 25 °C
Reaction time: 48 h
Yield: 70.8 %

Procedure:
Methyl iodide (130.6 mg, 0.92 mmol) was added to a solution of 4-piperidin-4-yl-1,3-dihydroindol-2-one (199 mg, 0.92 mmol) in acetonitrile (10 mL) and methanol (1 mL). The reaction was stirred at room temperature under nitrogen for 2 days. The solvents were removed and the residue was purified on a silica gel column to give 150 mg (70%) of 4-(1-methylpiperidin-4-yl)-1,3-dihydroindol-2-one as a tan solid.
Reaction SMILES: [OH:1][C:2]1[C:7]2[C:8]([CH3:19])=[C:9]([C:11](=O)[C:12]3[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=3)[O:10][C:6]=2[CH:5]=[CH:4][C:3]=1[CH2:20][CH2:21][CH3:22].[OH-].[K+].NN.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(O)CO>[OH:1][C:2]1[C:7]2[C:8]([CH3:19])=[C:9]([CH2:11][C:12]3[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=3)[O:10][C:6]=2[CH:5]=[CH:4][C:3]=1[CH2:20][CH2:21][CH3:22]
Reactant: CCCc1ccc2oc(C(=O)c3ccncc3)c(C)c2c1O
Agent: NN
Agent: O=C(O)CC(O)(CC(=O)O)C(=O)O
Agent: [K+]
Solvent: OCCO
Product: CCCc1ccc2oc(Cc3ccncc3)c(C)c2c1O
Temperature: 155 °C
Reaction time: 2 h
Yield: 68.4 %

Procedure:
A mixture of 4 hydroxy 3 methyl 5 propyl-2 -(isonicotinoyl)-benzofuran (1.5 g; 5.2mmoles), potassium hydroxide pellets (2 g; 37mmoles), ethylene glycol (25 ml) and 99% hydrazine (0.8 ml) was heated with stirring at 130° C. for 1 hour and at 155° C. for 2 hours. The mixture was cooled and acidified with 20% citric acid solution. The mixture was extracted using 20% ethyl acetate in diethyl ether. The organic layer was dried (Na2SO4), filtered, concentrated, and chromatographed to obtain 1 g of the title compound which was then recrystallized from ethyl acetate.
Reaction SMILES: [C:1]([N:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)(=[O:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]=[CH2:11].[C:19]([O:25][CH2:26][CH3:27])(=[O:24])[CH2:20][C:21]([CH3:23])=[O:22]>[60Co]>[C:21]([CH:20]([C:19]([O:25][CH2:26][CH3:27])=[O:24])[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][C:1]([N:13]1[CH2:14][CH2:15][O:16][CH2:17][CH2:18]1)=[O:12])(=[O:22])[CH3:23]
Reactant: CCOC(=O)CC(C)=O
Reactant: C=CCCCCCCCCC(=O)N1CCOCC1
Agent: [60Co]
Product: CCOC(=O)C(CCCCCCCCCCC(=O)N1CCOCC1)C(C)=O

Procedure:
Samples of 2 grams (.0078 mole) of 10-undecenoylmorpholine and 30.9 grams (0.237 mole) of ethyl acetoacetate were placed in a flask, mixed well, and exposed to a cobalt-60 (γ-radiation) source to initiate free radical chain reaction. After irradiating for 17 hours, the mixture was removed from the irradiation source and stripped under reduced pressure. Analysis of the product, N-(12-acetyl-12-carboethoxydodecanoyl) morpholine: % G 65.78 (theory 65.76); % H, 9.87 (theory 9.73); % N, 3.68 (theory 3.65).
Reaction SMILES: [N+](C1C=CC(N=[N:11][C:12]2[C:13]([CH3:32])=[C:14]([CH3:31])[C:15]3[O:19][C:18]([CH3:21])([CH3:20])[CH:17]([C:22]4[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=4)[C:16]=3[C:29]=2[CH3:30])=CC=1)([O-])=O.S(S([O-])=O)([O-])=O.[Na+].[Na+].CO.[OH-].[Na+]>C1(C)C=CC=CC=1.O>[CH3:20][C:18]1([CH3:21])[CH:17]([C:22]2[CH:23]=[CH:24][C:25]([CH3:28])=[CH:26][CH:27]=2)[C:16]2[C:29]([CH3:30])=[C:12]([NH2:11])[C:13]([CH3:32])=[C:14]([CH3:31])[C:15]=2[O:19]1
Reactant: Cc1ccc(C2c3c(C)c(N=Nc4ccc([N+](=O)[O-])cc4)c(C)c(C)c3OC2(C)C)cc1
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Solvent: Cc1ccccc1
Product: Cc1ccc(C2c3c(C)c(N)c(C)c(C)c3OC2(C)C)cc1
Temperature: 67.5 °C
Reaction time: 2 h
Yield: 84.8 %

Procedure:
The above-obtained 1-(4-nitrophenyl)-2-[2,2,4,6,7-pentamethyl-3-(4-methylphenyl)-2,3-dihydro-1-benzofuran-5-yl]diazene (6.0 g) and sodium dithionite (14.6 g) were added to a mixture of methanol (30 mL) and water (30 mL), and the mixture was stirred at 65 to 70° C. for 2 hours under a nitrogen atmosphere. The mixture was cooled to room temperature, and further stirred at 0 to 5° C. for one hour. Precipitated crystals were collected by filtration, and washed with a mixture of methanol and water again to obtained wetted crystals. The wetted crystals were added to a mixture of toluene and 2N aqueous sodium hydroxide. An organic layer was separated and concentrated. The concentrate was recrystallized from a mixture of water and methanol, and the resultant crystals were dried under reduced pressure to obtain the title compound (3.5 g., yield 86%).
Reaction SMILES: [I-].CS[C:4]1[S:5][CH2:6][C@@H:7]2[CH2:16][C:15]3[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=3[CH2:9][N+:8]=12.[NH2:17][C:18]1[CH:27]=[CH:26][CH:25]=[C:24]2[C:19]=1[CH:20]=[C:21]([CH2:28][CH2:29][CH2:30][CH3:31])[N:22]=[CH:23]2>N1C=CC=CC=1>[CH2:28]([C:21]1[N:22]=[CH:23][C:24]2[C:19]([CH:20]=1)=[C:18]([N:17]=[C:4]1[N:8]3[CH2:9][C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][C:15]=4[CH2:16][C@H:7]3[CH2:6][S:5]1)[CH:27]=[CH:26][CH:25]=2)[CH2:29][CH2:30][CH3:31]
Reactant: CSC1=[N+]2Cc3ccccc3C[C@H]2CS1
Reactant: CCCCc1cc2c(N)cccc2cn1
Agent: [I-]
Solvent: c1ccncc1
Product: CCCCc1cc2c(N=C3SC[C@@H]4Cc5ccccc5CN34)cccc2cn1
Reaction time: 96 h
Yield: 54.5 %

Procedure:
(S)-3-Methylthio-1,5,10,10a-tetrahydrothiazolo-[3,4-b]isoquinolinium iodide (5.25 g) is added to a solution of 5-amino-3-butylisoquinoline (3 g) in pyridine (100 cc). The suspension obtained dissolves gradually. After 4 days at a temperature of about 20° C., the mixture is concentrated to dryness under reduced pressure (25 mm Hg) at 50° C. The residue is dissolved in chloroform (200 cc). This solution is washed with N aqueous sodium hydroxide solution (3×100 cc) and then with water (2×50 cc), dried over sodium sulphate, filtered and the filtrate is then concentrated to dryness under reduced pressure (40 mm Hg) at 40° C. The residue obtained is recrystallised from diisopropyl ether (50 cc). (S)-3-[(3-Butylisoquinol-5-yl)imino]-1,5,10,10a-tetrahydrothiazolo[3,4-b]-isoquinoline (3.05 g), which melts at 82° C., is thus obtained.