Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CS(O[CH2:6][CH2:7][CH:8]([NH:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=1)(=O)=O.C1COCC1.[CH3:29][NH:30][CH3:31]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[Cl:15][C:12]1[CH:13]=[CH:14][C:9]([CH:8]([NH:16][C:17](=[O:18])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:7][CH2:6][N:30]([CH3:31])[CH3:29])=[CH:10][CH:11]=1
Reactant: CC(C)(C)OC(=O)NC(CCOS(C)(=O)=O)c1ccc(Cl)cc1
Reactant: CNC
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [I-]
Solvent: C1CCOC1
Product: CN(C)CCC(NC(=O)OC(C)(C)C)c1ccc(Cl)cc1
Temperature: 150 °C
Yield: 84 %

Procedure:
3-(tert-Butoxycarbonylamino)-3-(4-chlorophenyl)propyl methanesulfonate (Intermediate 31) (0.075 g, 0.21 mmol) and tetrabutylammonium iodide (0.015 g, 0.04 mmol) were dissolved in a solution of dimethylamine in THF (2M, 5.153 mL, 10.31 mmol) and sealed into a microwave tube. The reaction was heated to 150° C. for 30 minutes in the microwave reactor and cooled to ambient temperature. The reaction mixture was concentrated, diluted with DCM (25 mL) and washed with water (25 mL). The organic layer was filtered through a phase-separating filter paper and evaporated. The crude product was purified by flash silica chromatography, elution gradient 4 to 8% (10:1 MeOH/conc. NH3 (aq)) in DCM. Pure fractions were evaporated to dryness to afford tert-butyl 1-(4-chlorophenyl)-3-(dimethylamino)propylcarbamate (0.054 mg, 84%) as a colourless oil.
Reaction SMILES: C[C:2]1[CH:6]=C(C)[N:4]([C:8](=[NH:19])[NH:9][S:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)(=[O:12])=[O:11])[N:3]=1.CS(O)(=O)=O.NN1CC[O:29][CH2:28][CH2:27]1>>[NH2:19][C:8]([NH:4][N:3]1[CH2:2][CH2:6][O:29][CH2:28][CH2:27]1)=[N:9][S:10]([C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1)(=[O:11])=[O:12]
Reactant: NN1CCOCC1
Reactant: Cc1cc(C)n(C(=N)NS(=O)(=O)c2ccccc2)n1
Agent: CS(=O)(=O)O
Product: NC(=NS(=O)(=O)c1ccccc1)NN1CCOCC1

Procedure:
The compound of Example 29 was prepared according to the accompanying synthesis procedure from 0.5 ml of N-[(3,5-dimethylpyrazol-1-yl)-iminomethyl]-benzenesulfonamide solution (0.2 M, acetonitrile) with 19 mg of methanesulfonic acid and 0.5 ml of N-aminomorpholine solution (1.0 M, acetonitrile) and filed in a substance databank. Calculated mol. wt. 284.34; found mol. wt. (M+H) 285.3; 569.1 (Dimer)
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[N:22]1[CH2:26][CH2:25][C@@H:24]([OH:27])[CH2:23]1)[C:5]([NH:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=1)=[O:6].[CH3:28][C:29]1[N:34]=[CH:33][C:32](B(O)O)=[CH:31][CH:30]=1>>[OH:27][C@@H:24]1[CH2:25][CH2:26][N:22]([C:21]2[CH:20]=[CH:19][C:4]([C:5]([NH:7][C:8]3[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=3)=[O:6])=[CH:3][C:2]=2[C:32]2[CH:33]=[N:34][C:29]([CH3:28])=[CH:30][CH:31]=2)[CH2:23]1
Reactant: Cc1ccc(B(O)O)cn1
Reactant: O=C(Nc1ccc(OC(F)(F)F)cc1)c1ccc(N2CC[C@@H](O)C2)c(Br)c1
Product: Cc1ccc(-c2cc(C(=O)Nc3ccc(OC(F)(F)F)cc3)ccc2N2CC[C@@H](O)C2)cn1

Procedure:
The title compound was prepared in an analogous fashion to that described in Example 1 using (R)-3-bromo-4-(3-hydroxypyrrolidin-1-yl)-N-(4-(trifluoromethoxy)phenyl)benzamide (Stage 2.1) and (6-methylpyridin-3-yl)boronic acid to afford a white solid. UPLC-MS (condition 1) tR=1.92, m/z=458.1-459.1 [M+H]+, m/z=456.2-457.3 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.69-1.78 (m, 1H) 1.81-1.91 (m, 1H) 2.53 (s, 3H) 2.67 (d, J=10.27 Hz, 1H) 3.00-3.08 (m, 2H) 3.18-3.28 (m, 1H) 4.16-4.21 (m, 1H) 4.83 (d, J=3.42 Hz, 1H) 6.93 (d, J=9.05 Hz, 1H) 7.30-7.36 (m, 3H) 7.68 (dd, J=7.95, 2.32 Hz, 1H) 7.77 (d, J=2.20 Hz, 1H) 7.84-7.92 (m, 3H) 8.48 (d, J=1.96 Hz, 1H) 10.09 (s, 1H).
Reaction SMILES: [C:1]([O:20][CH2:21][CH:22]([CH2:30][O:31][C:32](=[O:50])[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39]/[CH:40]=[CH:41]\[CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49])[O:23][C:24](=[O:29])[NH:25][CH2:26][CH2:27]Br)(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[CH3:51][NH:52][CH2:53][CH2:54][OH:55].C(N(C(C)C)CC)(C)C>C(Cl)(Cl)Cl>[CH3:51][N:52]([CH2:27][CH2:26][NH:25][C:24]([O:23][CH:22]([CH2:30][O:31][C:32](=[O:50])[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39]/[CH:40]=[CH:41]\[CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH3:49])[CH2:21][O:20][C:1](=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[O:29])[CH2:53][CH2:54][OH:55]
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)OCC(COC(=O)CCCCCCC/C=C\CCCCCCCC)OC(=O)NCCBr
Reactant: CNCCO
Solvent: ClC(Cl)Cl
Solvent: CCN(C(C)C)C(C)C
Product: CCCCCCCC/C=C\CCCCCCCC(=O)OCC(COC(=O)CCCCCCC/C=C\CCCCCCCC)OC(=O)NCCN(C)CCO
Temperature: 80 °C
Yield: 74.7 %

Procedure:
In 10 ml of chloroform was dissolved 173 mg (0.224 mmol) of 1,3-O-dioleoyl-2-O-(2-bromoethyl)carbamoylglycerol followed by addition of 543 mg (7.228 mmol) of 2-(methylamino)ethanol and 27 mg (0.209 mmol of diisopropylethylamine and the mixture was refluxed at 80° C. overnight. The reaction mixture was then washed with 5% sodium dihydrogen phosphate-H2O, dried, and concentrated. The residue was subjected to column chromatography (silica gel/methylene chloride-methanol) to provide 128 mg (74.3%) of the title compound of the invention.
Reaction SMILES: C[O:2][C:3](=[O:33])/[CH:4]=[C:5](\[O:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([O:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH2:28][CH2:29][CH3:30])[C:12]=1[CH2:31][CH3:32])/[C:6]([O:8]C)=[O:7].[OH-].[Na+].CO.Cl>C(Cl)(Cl)Cl>[CH2:31]([C:12]1[C:13]([O:17][CH2:18][CH2:19][CH2:20][O:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[CH2:28][CH2:29][CH3:30])=[CH:14][CH:15]=[CH:16][C:11]=1[O:10]/[C:5](=[CH:4]\[C:3]([OH:33])=[O:2])/[C:6]([OH:8])=[O:7])[CH3:32]
Reactant: CCCc1ccccc1OCCCOc1cccc(O/C(=C\C(=O)OC)C(=O)OC)c1CC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: ClC(Cl)Cl
Product: CCCc1ccccc1OCCCOc1cccc(O/C(=C\C(=O)O)C(=O)O)c1CC

Procedure:
A solution of 42.0 parts of dimethyl 2-ethyl-3-(3-[2-propylphenoxy]propoxy)phenoxyfumaric acid and 7.36 parts of sodium hydroxide in 50% v/v aqueous methanol was refluxed for four hours. The reaction mixture was cooled, acidified with excess 2N hydrochloric acid and extracted with chloroform. Evaporation of the chloroform and trituration of the residue with 40/60 light petroleum ether gave an oily solid. This solid was dissolved in hot chloroform and addition of 40/60 light petroleum ether to the solution gave 33.8 parts of 2-ethyl-3-(3-[2-propylphenoxy]propoxy)phenoxyfumaric acid, m.pt. 104°-105°.
Reaction SMILES: [CH3:1][C:2]([CH3:23])([O:4][C:5]([NH:7][C@@H:8]([C:12]12[CH2:21][CH:16]3[CH2:17][CH:18]([CH2:20][C:14]([OH:22])([CH2:15]3)[CH2:13]1)[CH2:19]2)[C:9](O)=[O:10])=[O:6])[CH3:3].CS(Cl)(=O)=O.C(N(C(C)C)CC)(C)C.Cl.[C@H:39]12[CH2:44][C@H:43]1[CH2:42][C@@H:41]([C:45]([NH2:47])=[O:46])[NH:40]2.OC1C2N=NNC=2C=CC=1>C1COCC1>[CH3:3][C:2]([CH3:23])([O:4][C:5]([NH:7][C@@H:8]([C:12]12[CH2:19][CH:18]3[CH2:17][CH:16]([CH2:15][C:14]([OH:22])([CH2:20]3)[CH2:13]1)[CH2:21]2)[C:9]([N:40]1[C@H:41]([C:45]([NH2:47])=[O:46])[CH2:42][C@H:43]2[C@@H:39]1[CH2:44]2)=[O:10])=[O:6])[CH3:1]
Reactant: CC(C)(C)OC(=O)N[C@H](C(=O)O)C12CC3CC(CC(O)(C3)C1)C2
Reactant: NC(=O)[C@@H]1C[C@@H]2C[C@@H]2N1
Agent: CS(=O)(=O)Cl
Agent: Cl
Agent: Oc1cccc2[nH]nnc12
Solvent: C1CCOC1
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N[C@H](C(=O)N1[C@H](C(N)=O)C[C@@H]2C[C@@H]21)C12CC3CC(CC(O)(C3)C1)C2
Temperature: -6 °C
Reaction time: 8 h

Procedure:
A 2 L three-necked flask equipped with a thermometer, a mechanical stirrer and a gas inlet was charged with (S)-α[[(1,1-dimethylethoxy)carbonyl]amino]-3-hydroxytricyclo[3.3.1.13,7]decane-1-acetic acid (Formula VI) (50 grams, 153.8 mmol). THF (200 ml) was added and stirred to produce a clear solution. The solution was cooled to −6° C. in an acetone-dry ice-water bath. Methanesulfonyl chloride (Mes-Cl)(13.1 ml, 169 mmol, 1.1 equivalents) was then added as a single portion followed by diisopropylethylamine (94 ml, 539 mmol, 1.1 equivalents). The diisopropylethylamine was added slowly over a period of about 4 minutes to keep the internal temperature below 8° C. The reaction mixture was stirred at 0° C. until all acid was converted to mixed anhydride. (1S,3S,5S)-2-azabicyclo[3.1.0]hexane-3-carboxamide hydrochloride salt (32.5 grams, 200 mmol, 1.1 equivalents) and hydroxybenzotriazole (HOBT) (1.04 grams, 7.6 mmol, 0.05 equivalents) were then added in a single portion and the flask was removed from the cooling bath. The reaction mixture was stirred at room temperature for 2 hours and then left overnight at room temperature.
Reaction SMILES: [CH:1]1([C:4]2[C:12]3[CH2:11][CH:10]([C:13]([O:15]C)=[O:14])[CH2:9][CH2:8][C:7]=3[NH:6][N:5]=2)[CH2:3][CH2:2]1.O[Li].O>CO.O>[CH:1]1([C:4]2[C:12]3[CH2:11][CH:10]([C:13]([OH:15])=[O:14])[CH2:9][CH2:8][C:7]=3[NH:6][N:5]=2)[CH2:2][CH2:3]1
Reactant: COC(=O)C1CCc2[nH]nc(C3CC3)c2C1
Agent: [Li]O
Solvent: CO
Solvent: O
Product: O=C(O)C1CCc2[nH]nc(C3CC3)c2C1
Temperature: 25 °C
Reaction time: 18 h
Yield: 76.3 %

Procedure:
To a solution methyl 3-cyclopropyl-4,5,6,7-tetrahydro-1H-indazole-5-carboxylate (35.0 g) in MeOH (300 mL) was added a solution of LiOH.H2O (10.8 g, 0.26 mol) in H2O (200 mL) at 0° C. After stirring 18 h at rt the solvent was removed in vacuum. To the residue water (200 mL) was added and aqueous solution was acidified to pH=4-5 with 10% HCl. The precipitate was collected by filtration to give 3-cyclopropyl-4,5,6,7-tetrahydro-1H-indazole-5-carboxylic acid (25.0 g, 80% yield for 2 steps).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]3[C:17]([CH3:18])=[C:16]([C:19]([O:21][CH3:22])=[O:20])[S:15][C:11]=3[N:12]=[CH:13][N:14]=2)=[C:4]([OH:23])[CH:3]=1.Br[CH2:25][CH:26]1[CH2:31][CH2:30][O:29][CH2:28][CH2:27]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCOC(C)=O>[CH3:22][O:21][C:19]([C:16]1[S:15][C:11]2[N:12]=[CH:13][N:14]=[C:9]([NH:8][C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=3[O:23][CH2:25][CH:26]3[CH2:31][CH2:30][O:29][CH2:28][CH2:27]3)[C:10]=2[C:17]=1[CH3:18])=[O:20]
Reactant: BrCC1CCOCC1
Reactant: COC(=O)c1sc2ncnc(Nc3ccc(F)cc3O)c2c1C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: COC(=O)c1sc2ncnc(Nc3ccc(F)cc3OCC3CCOCC3)c2c1C
Temperature: 60 °C
Reaction time: 8 h

Procedure:
Methyl 4-(4-fluoro-2-hydroxyphenylamino)-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylate (100 mg) was dissolved in DMF (2 ml), 4-bromomethyltetrahydropyran (107 mg) and potassium carbonate (83 mg) were added. The reaction was stirred at 60° C. overnight. Then the reaction mixture was diluted with EtOAc and washed with water and brine. The solvent was removed in vacuo and the residue triturated with Et2O.
Reaction SMILES: [C:1]1([CH3:39])[CH:6]=[CH:5][C:4]([S:7]([N:10]2[CH2:18][CH2:17][N:16](S(C3C=CC(C)=CC=3)(=O)=O)[CH2:15][CH2:14][N:13](S(C3C=CC(C)=CC=3)(=O)=O)[CH2:12][CH2:11]2)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[Br:40]C(Br)C.[BrH:44].C(O)(=O)C>>[BrH:40].[BrH:44].[C:1]1([CH3:39])[CH:2]=[CH:3][C:4]([S:7]([N:10]2[CH2:11][CH2:12][NH:13][CH2:14][CH2:15][NH:16][CH2:17][CH2:18]2)(=[O:8])=[O:9])=[CH:5][CH:6]=1
Reactant: CC(Br)Br
Reactant: Cc1ccc(S(=O)(=O)N2CCN(S(=O)(=O)c3ccc(C)cc3)CCN(S(=O)(=O)c3ccc(C)cc3)CC2)cc1
Agent: Br
Solvent: CC(=O)O
Product: Cc1ccc(S(=O)(=O)N2CCNCCNCC2)cc1

Procedure:
From N,N′,N″-Tris(p-toluenesulfonyl)-1,4,7-triazacyclononane (1.3.13.31) prepared from 1.3.13.18, dibromoethane and base) and HBr/acetic acid.
Reaction SMILES: [CH3:1][N:2]([CH3:7])[CH2:3][CH2:4][CH2:5][NH2:6].Cl[C:9]1[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][C:10]=1[N+:16]([O-:18])=[O:17]>C(OCC)(=O)C>[Cl:15][C:12]1[CH:13]=[CH:14][C:9]([NH:6][CH2:5][CH2:4][CH2:3][N:2]([CH3:7])[CH3:1])=[C:10]([N+:16]([O-:18])=[O:17])[CH:11]=1
Reactant: O=[N+]([O-])c1cc(Cl)ccc1Cl
Reactant: CN(C)CCCN
Solvent: CCOC(C)=O
Product: CN(C)CCCNc1ccc(Cl)cc1[N+](=O)[O-]
Temperature: 125 °C
Reaction time: 14 h

Procedure:
N,N-Dimethyl-1,3-propanediamine (2.92 ml) was added to 2,5-dichloronitrobenzene (2.23 g) and stirred for 14 hours at 125° C. The reaction mixture, with ethyl acetate added thereto, was washed with 1N sodium hydroxide aqueous solution, water and saturated brine successively, dried over sodium sulfate anhydride, and concentrated, thereby yielding the entitled compound (2.99 g) as brown oil.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:25])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15]CC2C=CC=CC=2)=[CH:11][C:10]=1[CH:23]=[O:24])([CH3:7])[CH3:6])[CH3:2].[H][H]>C(O)C.[Pd]>[CH2:1]([O:3][C:4](=[O:25])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=1[CH2:23][OH:24])([CH3:7])[CH3:6])[CH3:2]
Reactant: CCOC(=O)C(C)(C)Oc1ccc(OCc2ccccc2)cc1C=O
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)C(C)(C)Oc1ccc(O)cc1CO
Yield: 84.5 %

Procedure:
2-(4-Benzyloxy-2-formyl-phenoxy)-2-methyl-propionic acid ethyl ester (185 g, 540 mmol) in ethanol (700 mL) was treated with 10% Pd/C (205 g) and hydrogen (60 psi) at 50° C. for 2 d. The mixture was filtered through Celite, washed with ethanol (1.5 L), and concentrated. The residue was recrystallized from EtOAc/hexanes to give the title compound (116 g). 1H NMR (400 MHz, CDCl3) δ 1.26 (t, 3H, J=7.3 Hz), 1.52 (s, 6H), 2.14 (s, 3H), 4.23 (q, 2H, J=7.3 Hz), 4.59 (brs, 2H), 6.61-6.68 (m, 2H), 6.77 (d, 1H, J=2.8 Hz).
Reaction SMILES: [CH2:1]([CH:3]([C:24]([OH:26])=[O:25])[N:4]([CH2:13][CH2:14][CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([NH2:23])=[CH:19][CH:18]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]#[N:12])[CH:6]=1)[CH3:2].[N+]([O-])(O)=O.C[C:32]1C=C(C)[N:34](C(N)=N)[N:33]=1>N1C=CC=CC=1>[CH2:1]([CH:3]([C:24]([OH:26])=[O:25])[N:4]([CH2:13][CH2:14][CH2:15][CH2:16][C:17]1[CH:18]=[CH:19][C:20]([NH:23][CH:32]=[N:33][NH2:34])=[CH:21][CH:22]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([C:11]#[N:12])[CH:6]=1)[CH3:2]
Reactant: CCC(C(=O)O)N(CCCCc1ccc(N)cc1)c1cccc(C#N)c1
Reactant: Cc1cc(C)n(C(=N)N)n1
Solvent: O=[N+]([O-])O
Solvent: c1ccncc1
Product: CCC(C(=O)O)N(CCCCc1ccc(NC=NN)cc1)c1cccc(C#N)c1
Yield: 58.3 %

Procedure:
Part E. A solution of ethyl N-[4-[4-aminophenyl]butyl]-N-[3-cyanophenyl]glycine (0.12 gm, 0.34 mmol) and 3,5-dimethylpyrazole-1-carboxamidine nitrate (0.103 gm, 0.51 mmol) in 10 mL pyridine was heated to 100° C. under a nitrogen atmosphere for 3 hrs. The reaction mixture was allowed to cool and was partitioned between ethyl acetate and water. The combined organic layer was washed with water, brine, dried over magnesium sulfate and concentrated to give the crude product. The product was purified by flash chromatography on silica gel eluting chloroform:methanol (v:v, 80:20) to give ethyl N-[4-[4-[(aminoiminomethyl)amino]phenyl]butyl]-N-[3-cyanophenyl]glycine 0.078 gm (58%) MS 394(M+H)+ 1 H NMR (CDCl3): 7.0(m, 10H), 6.8(m, 2H), 4.2(q, 2H), 4.0(s, 2H), 3.4(m, 2H), 2.7(m, 2H), 1.2(t, 3H).
Reaction SMILES: C([O-])([O-])=O.[K+].[K+].[CH2:7]([SH:9])[CH3:8].Cl[C:11]1[C:20]([N:21]2[C:29](=[O:30])[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]2=[O:31])=[C:19]([CH3:32])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]=1>CN(C=O)C.O>[CH2:7]([S:9][C:11]1[C:20]([N:21]2[C:29](=[O:30])[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[C:22]2=[O:31])=[C:19]([CH3:32])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[N:12]=1)[CH3:8]
Reactant: CCS
Reactant: Cc1c(N2C(=O)c3ccccc3C2=O)c(Cl)nc2ccccc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCSc1nc2ccccc2c(C)c1N1C(=O)c2ccccc2C1=O
Temperature: 60 °C
Yield: 78.4 %

Procedure:
2.1 g (15.4 mmol) of K2CO3 and 760 μl (10.3 mmol) of ethanethiol were added in succession to a solution of 2.1 g (5.1 mmol) of 2-(2-chloro-4-methylquinolin-3-yl)isoindoline-1,3-dione in DMF (36 ml). The mixture was then heated for 16 h at 60° C. A further 2.1 g (15.4 mmol) of K2CO3 and 760 μl (10.3 mmol) of ethanethiol were then added, and the mixture was again heated for 16 h at 50° C. After cooling to RT, the mixture was diluted with water and extracted twice with EA. The combined organic phases were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. There were obtained as residue 1.7 g (4.0 mmol, 78%) of 2-(2-(ethylthio)-4-methylquinolin-3-yl)isoindoline-1,3-dione, which was reacted further without additional purification.
Reaction SMILES: [C:1]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]1[C:13](=[O:20])[CH2:14][C:15](=[O:19])[C:16]=1[O:17][CH3:18])([O:3][CH2:4][CH3:5])=[O:2].CO.C(CCCCCCC1C(=O)CC(=O)C=1OC)(OC)=O>C(O)(C)C>[C:1]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]1[C:13](=[O:20])[CH2:14][CH:15]([OH:19])[C:16]=1[O:17][CH3:18])([O:3][CH2:4][CH3:5])=[O:2]
Reactant: CCOC(=O)CCCCCCC1=C(OC)C(=O)CC1=O
Agent: COC(=O)CCCCCCC1=C(OC)C(=O)CC1=O
Solvent: CC(C)O
Solvent: CO
Product: CCOC(=O)CCCCCCC1=C(OC)C(O)CC1=O
Yield: 98.6 %

Procedure:
The procedure similar to that of Step 2 of Example 1 was repeated except that 2.82 g of 2-(6'-carbethoxyhexyl)-3-methoxy-4-oxo-2-cyclopenten-1-one and 35 ml of methanol were used instead of 24 g of 2-(6'-carbomethoxyhexyl)-3-methoxy-4-oxo-2-cyclopenten-1-one and isopropanol respectively to provide 2.8 g of 2-(6'-carboethoxyhexyl)-3-methoxy-4-hydroxy-2-cyclopenten-1-one as an oily product.
Reaction SMILES: [OH:1][CH:2]1[CH2:6][N:5]([C@@H](C2C=CC=CC=2)C)[CH2:4][C@@:3]1([CH3:22])[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16].Cl.C(=O)([O-])O.[Na+].[CH2:29]([O:36][C:37](Cl)=[O:38])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>C(O)C.C(OCC)C>[CH2:29]([O:36][C:37]([N:5]1[CH2:6][CH:2]([OH:1])[C@:3]([CH3:22])([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:4]1)=[O:38])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: C[C@H](c1ccccc1)N1CC(O)[C@](C)(C(=O)OC(C)(C)C)C1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: CCOCC
Product: CC(C)(C)OC(=O)[C@]1(C)CN(C(=O)OCc2ccccc2)CC1O
Reaction time: 0.17 h
Yield: 91 %

Procedure:
To a solution of tert-butyl(3R)-4-hydroxy-3-methyl-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylate (2.00 g, 6.55 mmol) in ethanol (10 mL), 1N hydrochloric acid (6.88 mL, 6.88 mmol) was added at room temperature, and the mixture was stirred for 10 minutes. After concentrating the reaction mixture under reduced pressure and dissolving the residue in ethanol (50 mL), 10% palladium-carbon catalyst (200 mg) was added, and the suspension was stirred in an oil bath at 50° C. for 14 hours in hydrogen atmosphere. After filtering the reaction mixture, the filtrate was concentrated, and the diethylether (30 mL) and saturated sodium hydrogencarbonate (30 mL) were added to the residue, and benzyloxycarbonyl chloride (982 μl, 6.88 mmol) was added in an ice bath. The mixture was stirred at room temperature for 3 hours, and the reaction mixture was extracted with ethyl acetate (100 mL×2). The organic layer was washed with saturated aqueous solution of sodium chloride (20 mL), and dried with anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1→1:2) to obtain 2.00 g (91.1%) of the title compound as a colorless oily substance.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([S:8][CH3:9])=[CH:4][N:3]=1.C(N(CC)CC)C.[CH2:17]([O:19]C([Sn](CCCC)(CCCC)CCCC)=C)[CH3:18]>O1CCOCC1>[CH3:9][S:8][C:5]1[CH:6]=[CH:7][C:2]([C:17](=[O:19])[CH3:18])=[N:3][CH:4]=1
Reactant: CSc1ccc(Br)nc1
Reactant: C=C(OCC)[Sn](CCCC)(CCCC)CCCC
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Product: CSc1ccc(C(C)=O)nc1

Procedure:
To a stirring solution of 2-bromo 5-methylsulfanyl pyridine (3.05 g 14.9 mmol), triethylamine (2.10 mL, 14.9 mmol) and (1-ethoxyvinyl)tributyl tin (10.1 mL, 29.8 mmol) in anhydrous 1,4-dioxane (100 mL), was added dichlorobis(triphenylphosphine) palladium (II) (5 mol %, 0.524 g) and the reaction heated to reflux under nitrogen for 18 hours. After cooling, dichlorobis(triphenylphosphine) palladium (II) was added and the reaction heated under nitrogen for a further 18 hours. The reaction was allowed to cool and-the reaction mixture partitioned between saturated aqueous potassium fluoride solution (250 mL) and diethyl ether (250 mL). The ether layer was separated and 2N hydrochloric acid (250 mL) added. The acid layer was separated and sodium carbonate added portionwise until the solution reached pH 8. The solution was extracted with dichloromethane (3×200 mL). The organic extracts were combined and the solvent removed. The residue was partitioned between cyclohexane (60 ml) and acetonitrile (60 mL). The acetonitrile layer was separated and the solvent removed to yield a brown solid. The crude product was purified by flash column chromatography (cyclohexane:ethyl acetate, 95:5) to afford the title compound as a white solid:
Reaction SMILES: C=C.[CH2:3]1[CH:7]2[C@@H:8]3[CH:12]=[CH:11][C@H:10]([CH:6]2[CH:5]=[CH:4]1)[CH2:9]3>C1(C)C=CC=CC=1>[CH2:3]=[CH2:4].[CH2:3]1[CH:7]2[CH:8]3[CH:12]=[CH:11][CH:10]([CH:6]2[CH:5]=[CH:4]1)[CH2:9]3
Reactant: C1=CC2C(C1)[C@@H]1C=C[C@H]2C1
Agent: C=C
Solvent: Cc1ccccc1
Product: C1=CC2C3C=CC(C3)C2C1

Procedure:
In this example, η5-cyclopentadienyl(2,6-di-tert-butyl-4-methylphenoxy)titanium(IV) dichloride was used again to polymerize ethylene and DCPD in toluene as in Example 1 except during this experiment 110 grams of 91.5% by weight DCPD in toluene were added to the reactor. 26.3 grams of an ethylene/dicyclopentadiene polymer mixture were obtained. The ethylene/dicyclopentadiene polymer mixture was washed with 1% by weight HCl, then washed with water, and finally the ethylene/dicyclopentadiene polymer was washed with acetone. The ethylene/dicyclopentadiene polymer was dried in a vacuum oven to a dry weight of 2.9 grams yielding an activity of 290 grams of ethylene/dicyclopentadiene polymer per gram of η5-cyclopentadienyl(2,6-di-tert-butyl-4-methylphenoxy)titanium(IV) dichloride per hour.
Reaction SMILES: Br[CH:2]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[C:3]([O:5][CH3:6])=[O:4].[NH:13]1[CH:17]=[CH:16][N:15]=[CH:14]1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[N:13]1([CH:2]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]([O:5][CH3:6])=[O:4])[CH:17]=[CH:16][N:15]=[CH:14]1
Reactant: COC(=O)C(Br)c1ccccc1
Reactant: c1c[nH]cn1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: COC(=O)C(c1ccccc1)n1ccnc1
Yield: 81.4 %

Procedure:
(RS) Methyl 2-bromo-2-phenylacetate (171.75 g), imidazole (102 g) and potassium carbonate (227.7 g) were stirred in acetone (1.75 liters for 60 hours. After settling, the supernatant was decanted off and the residue washed thoroughly with acetone. The acetone was evaporated under reduced pressure and the residue in ethyl acetate was washed with water and extracted twice with 2M hydrochloric acid. The combined acid extracts, after washing once with ether, were basified with solid potassium carbonate and extracted with toluene containing 10% ethyl acetate. The organic extracts were dried over magnesium sulphate and evaporated under reduced pressure to give the title compound as a yellow oil (132 g, 8i%).