Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3]([C:5]1[C:13]2[N:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:11]([C@@H:20]([NH:22][C:23]3[N:31]=[CH:30][N:29]=[C:28]4[C:24]=3[N:25]=[CH:26][N:27]4[CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][O:33]3)[CH3:21])=[N:10][C:9]=2[CH:8]=[CH:7][C:6]=1[F:38])=[O:4].O.[OH-].[Li+]>CO.O>[F:38][C:6]1[CH:7]=[CH:8][C:9]2[N:10]=[C:11]([C@@H:20]([NH:22][C:23]3[N:31]=[CH:30][N:29]=[C:28]4[C:24]=3[N:25]=[CH:26][N:27]4[CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][O:33]3)[CH3:21])[N:12]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:13]=2[C:5]=1[C:3]([OH:4])=[O:2]
Reactant: COC(=O)c1c(F)ccc2nc([C@H](C)Nc3ncnc4c3ncn4C3CCCCO3)n(-c3ccccc3)c12
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: C[C@H](Nc1ncnc2c1ncn2C1CCCCO1)c1nc2ccc(F)c(C(=O)O)c2n1-c1ccccc1
Temperature: 80 °C

Procedure:
To a solution of 5-fluoro-3-phenyl-2-{(S)-1-[9-(tetrahydro-pyran-2-yl)-9H-purin-6-ylamino]ethyl}-3H-benzoimidazole-4-carboxylic acid methyl ester (1.34 g, 2.66 mmol) in methanol (40 mL) and water (4 mL) was added lithium hydroxide monohydrate (0.166 g, 15. 9 mmol) and the reaction mixture heated at 80° C. for 16 h. The reaction mixture was concentrated in vacuo to remove methanol and the residual aqueous solution acidified to ph˜4 by addition of HCl (1 M) causing a precipitate to form. The product was collected by filtration and dried in vacuo to give the title compound as an off white solid (564 mg, 43%). LCMS (Method C): RT=2.44 min, [M+H]+=502.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][C:6]([NH:10][CH:11]3[CH2:16][CH2:15][C:14](=O)[CH2:13][CH2:12]3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1.[CH2:18]([NH2:21])[CH2:19][CH3:20].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].Cl.CO>CO>[NH:1]1[C:9]2[C:4](=[CH:5][C:6]([NH:10][CH:11]3[CH2:16][CH2:15][CH:14]([NH:21][CH2:18][CH2:19][CH3:20])[CH2:13][CH2:12]3)=[CH:7][CH:8]=2)[CH:3]=[N:2]1
Reactant: O=C1CCC(Nc2ccc3[nH]ncc3c2)CC1
Reactant: CCCN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: CCCNC1CCC(Nc2ccc3[nH]ncc3c2)CC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 7.4 %

Procedure:
4-(1H-5-Indazolylamino)-1-cyclohexanone (intermediate 3) (57 mg) and propylamine (30 mg) were dissolved in methanol (1 ml), and sodium triacetoxyborohydride (105 mg) was added by portions to the solution at room temperature. The reaction mixture was stirred at room temperature for 18 hr. Hydrochloric acid-methanol was then added thereto, and the mixture was stirred and was then concentrated. The residue was purified by HPLC [0.5% aqueous trifluoroacetic acid solution/acetonitrile]. A saturated aqueous sodium hydrogencarbonate solution (2 ml) was added to fractions containing respective compounds, followed by extraction with chloroform-propanol (3/1). The organic layers were dried over anhydrous sodium sulfate, and the solvent was removed by distillation under the reduced pressure to give an anti-form compound (5 mg) and a syn-form compound (5 mg).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[NH:7][C:6](=O)[CH2:5]2.B.CO.Cl>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[NH:7][CH2:6][CH2:5]2
Reactant: O=C1Cc2cc(F)c(F)cc2N1
Agent: B
Agent: Cl
Solvent: C1CCOC1
Solvent: CO
Product: Fc1cc2c(cc1F)NCC2
Temperature: 70 °C

Procedure:
Under an argon atmosphere 0.30 g (1.8 mmol) 5,6-difluoroxindole were dissolved in 10 mL THF and 3.0 mL of a 1 molar borane solution in THF were added dropwise. Then the reaction mixture was heated to 70° C. for 2 h and then cooled. After mixing with 3 mL MeOH another 5 mL of a 4N aqueous hydrochloric acid solution were added and the mixture was refluxed for 1 h. The organic phase was evaporated down, the aqueous phase was washed with DCM and then made alkaline with a 4N aqueous sodium hydroxide solution and extracted several times with EtOAc. The combined organic phases were dried on sodium sulphate, filtered and evaporated down.
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:4][C:3]=1[C:18]([NH:20][C:21]1[CH:26]=[N:25][CH:24]=[CH:23][N:22]=1)=[O:19]>C(Cl)(Cl)Cl.[O-2].[O-2].[Mn+4]>[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:4]=[C:3]1[C:18]([NH:20][C:21]1[CH:26]=[N:25][CH:24]=[CH:23][N:22]=1)=[O:19]
Reactant: O=C(Nc1cnccn1)C1=C(O)c2ccccc2N(c2ccccc2)C1
Agent: [Mn+4]
Agent: [O-2]
Solvent: ClC(Cl)Cl
Product: O=C(Nc1cnccn1)c1cn(-c2ccccc2)c2ccccc2c1=O
Temperature: 25 °C
Reaction time: 6 h
Yield: 68.7 %

Procedure:
A solution of 8.0 g of 1,2-dihydro-4-hydroxy-1-phenyl-N-(2-pyrazinyl)-3-quinolinecarboxamide in 250 ml of chloroform was treated with 33.0 g of activated manganese dioxide and stirred for six hours at room temperature. The slurry was filtered and evaporated. Recrystallization of the residue from chloroform yielded 5.46 g (90%) of 1,4-dihydro-4-oxo-1-phenyl-N-(2-pyrazinyl)-3-quinolinecarboxamide, m.p. 298°-300° C.
Reaction SMILES: [CH2:1]([C:3]1[CH:4]=[N:5][C:6]([NH:9][CH2:10][CH2:11][CH2:12][C:13]2[CH:18]=[CH:17][C:16]([O:19]C)=[CH:15][CH:14]=2)=[N:7][CH:8]=1)[CH3:2].[F:21][C:22]([F:33])([F:32])[O:23][C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=1)[CH2:27]Br>>[CH2:1]([C:3]1[CH:8]=[N:7][C:6]([N:9]([CH2:27][C:26]2[CH:29]=[CH:30][CH:31]=[C:24]([O:23][C:22]([F:21])([F:32])[F:33])[CH:25]=2)[CH2:10][CH2:11][CH2:12][C:13]2[CH:14]=[CH:15][C:16]([OH:19])=[CH:17][CH:18]=2)=[N:5][CH:4]=1)[CH3:2]
Reactant: FC(F)(F)Oc1cccc(CBr)c1
Reactant: CCc1cnc(NCCCc2ccc(OC)cc2)nc1
Product: CCc1cnc(N(CCCc2ccc(O)cc2)Cc2cccc(OC(F)(F)F)c2)nc1

Procedure:
Similarly prepared from 5-ethyl-N-[3-(4-methoxyphenyl)propyl]pyrimidin-2-amine and 3-trifluoromethoxy benzyl bromide.
Reaction SMILES: [NH3:1].Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([CH2:13][Cl:14])=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1>>[NH2:1][C:3]1[C:12]2[C:7](=[CH:8][C:9]([CH2:13][Cl:14])=[CH:10][CH:11]=2)[N:6]=[CH:5][N:4]=1
Reactant: N
Reactant: ClCc1ccc2c(Cl)ncnc2c1
Product: Nc1ncnc2cc(CCl)ccc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 77 %

Procedure:
To 15 ml of a saturated ethanolic ammonia solution is added 1.0 g (4.7 mmole) of 4-chloro-7-chloromethylquinazoline. The mixture is stirred at room temperature overnight. The precipitate which forms is collected to give 0.7 g of the title intermediate product, mp>300° C.; 77% yield. 1H NMR (d6-DMSO, 300 MHz) δ 8.38 (s, 1H), 8.20 (d, 1H), 7.78 (bs, 2H), 7.70 (s, 1H), 7.51 (d, 1H), 4.92 (s, 2H). EI MS, [M]+=193, 195 (Cl pattern).
Reaction SMILES: C(OC([NH:11][C@H:12]1[CH2:16][CH2:15][N:14]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][C:18]2([CH3:31])[CH3:30])[C:13]1=[O:32])=O)C1C=CC=CC=1>CO>[NH2:11][C@H:12]1[CH2:16][CH2:15][N:14]([CH:17]2[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:28])([CH3:27])[CH3:29])=[O:24])[CH2:19][C:18]2([CH3:31])[CH3:30])[C:13]1=[O:32]
Reactant: CC(C)(C)OC(=O)N1CCC(N2CC[C@H](NC(=O)OCc3ccccc3)C2=O)C(C)(C)C1
Solvent: CO
Product: CC(C)(C)OC(=O)N1CCC(N2CC[C@H](N)C2=O)C(C)(C)C1
Yield: 105.6 %

Procedure:
tert-Butyl 4-((S)-3-(benzyloxycarbonylamino)-2-oxopyrrolidin-1-yl)-3,3-dimethylpiperidine-1-carboxylate (0.81 g, 1.8 mmol) was dissolved in methanol (20 mL) and the mixture was purged with N2 by three vacuum pump/N2 balloon cycles. 10% Palladium on carbon (dry basis, wet, Degussa type, 0.5 g) was added and the system was purged with 1 atm H2 by three vacuum pump/H2 balloon cycles. The reaction was stirred under the H2 atmosphere until the starting material was consumed. The mixture was filtered through Celite® and concentrated to afford tert-butyl 4-((S)-3-amino-2-oxopyrrolidin-1-yl)-3,3-dimethylpiperidine-1-carboxylate (0.59 g, 1.9 mmol, 100% yield) as a white solid.
Reaction SMILES: C1(C=CC=C(O)C=1)[OH:2].[Br:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][O:20][C:21]1[CH:28]=[CH:27][C:24]([CH:25]=[O:26])=[CH:23][CH:22]=1.[O-]Cl=O.[Na+]>C(O)(C)(C)C.O>[Br:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][O:20][C:21]1[CH:22]=[CH:23][C:24]([C:25]([OH:2])=[O:26])=[CH:27][CH:28]=1
Reactant: O=Cc1ccc(OCCCCCCCCCCBr)cc1
Reactant: Oc1cccc(O)c1
Agent: [Na+]
Agent: [O-][Cl+][O-]
Solvent: O
Solvent: CC(C)(C)O
Product: O=C(O)c1ccc(OCCCCCCCCCCBr)cc1
Temperature: 70 °C
Reaction time: 8 h

Procedure:
Resorcinol (4.16 g, 38 mmol) and 5 (10.0 g, 29 mmol) were dissolved in t-butanol (600 mL) through gentle heating to 70° C. The solution was cooled to room temperature, and a solution of NaH2PO4·H2O (13.7 g, 88 mmol) and NaClO2 (15.3 g, 170 mmol) in deionized H2O (100 mL) was added dropwise to the flask over a period of 10 minutes. The purple-red mixture was stirred overnight, following which it faded to a pale yellow colour. Volatile components were removed, and the residue was taken in hexane (200 mL) and 1 M HCl (200 mL). The white precipitate was filtered and washed profusely with distilled H2and hexane. Yield 10.5 g (quant.). 1H NMR: δH (CDCl3; 300 MHz): 1.26-1.55 (12 H, m, CH2), 1.86 (4 H, m, O—CH2—CH2/Br—CH2—CH2), 3.44 (2 H, t, 3J=6.8 Hz, Br—CH2), 4.04 (2 H, t, 3J=6.5 Hz, O—CH2), 6.95 (2 H, d, 3J=8.9 Hz, Ar—H), 8.07 (2 H, d, 3J=8.9 Hz, Ar—H). 13C NMR: δC (CDCl3; 75 MHz): 26.0, 28.1, 28.7, 29.0, 29.3, 29.4, 32.8, 34.0, 68.3, 114.2, 121.4, 132.3, 163.7, 171.5.
Reaction SMILES: [CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[C:4]([CH3:9])[C:3]=1[OH:10].[N+]([O-])(O)=[O:12]>C(O)(=O)C.N([O-])=O.[Na+]>[CH3:9][C:4]1[C:3](=[O:10])[C:2]([CH3:1])=[C:7]([CH3:8])[C:6](=[O:12])[CH:5]=1
Reactant: O=[N+]([O-])O
Reactant: Cc1ccc(C)c(O)c1C
Agent: O=N[O-]
Agent: [Na+]
Solvent: CC(=O)O
Product: CC1=CC(=O)C(C)=C(C)C1=O
Yield: 69.6 %

Procedure:
Also, in the process described in Japanese Pat. Publication No. 38063/70 (German Pat. OLS No. 1,814,652), 2,3,6-trimethylphenol is dissolved in acetic acid and oxidized with a dilute nitric acid using sodium nitrite as a catalyst to obtain trimethyl-p-benzoquinone in maximum yield of 69.6 percent. This process is simple and is considered to be a good one. However, the yield is a little low.
Reaction SMILES: [N+]([C:4]1[NH:5][CH:6]=[C:7]([N+:9]([O-:11])=[O:10])[N:8]=1)([O-])=O.[O:12]1[CH2:14][CH:13]1[CH2:15][NH:16][C:17](=[O:25])[O:18][C:19]1C=CC=C[CH:20]=1.C([O-])(=O)C.[Na+].C(=O)([O-])O.[Na+]>C(O)C.C(Cl)Cl>[N+:9]([C:7]1[N:8]=[C:4]2[N:5]([CH:6]=1)[CH2:14][CH:13]([CH2:15][NH:16][C:17](=[O:25])[O:18][CH2:19][CH3:20])[O:12]2)([O-:11])=[O:10]
Reactant: O=C(NCC1CO1)Oc1ccccc1
Reactant: O=[N+]([O-])c1c[nH]c([N+](=O)[O-])n1
Agent: CC(=O)[O-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: ClCCl
Product: CCOC(=O)NCC1Cn2cc([N+](=O)[O-])nc2O1
Yield: 11.5 %

Procedure:
2,4-Dinitro-1H-imidazole (0.678 g, 3.92 mmol) and phenyl oxiran-2-ylmethylcarbamate (1.04 g, 5.87 mmol) were dissolved in ethanol (20 ml). To the solution, sodium acetate (0.386 g, 4.70 mmol) was added followed by stirring under reflux overnight. To the reaction mixture, a saturated sodium hydrogencarbonate solution and methylene chloride were added, and the solution was extracted with methylene chloride. The organic phase was dried over sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (methylene chloride/methanol=50/1) and treated with diisopropyl ether to afford ethyl (6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)carbamate (0.116 g, yield 11.6%) as a light brown solid.
Reaction SMILES: [CH3:1][N:2]1[C@@H:18]2[CH2:19][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][C@H:13]5[C:14]([O:20]C)=[CH:15][CH:16]=[C:17]2[C@:5]5([C:6]=34)[CH2:4][CH2:3]1.C(O)(=O)C.[K+].[Br-]>CO.[Hg](Br)Br>[CH3:1][N:2]1[C@@H:18]2[CH2:19][C:7]3[CH:8]=[CH:9][C:10]([O:22][CH3:23])=[C:11]4[O:12][C@H:13]5[C:14]([CH2:15][CH:16]=[C:17]2[C@:5]5([C:6]=34)[CH2:4][CH2:3]1)=[O:20]
Reactant: COC1=CC=C2[C@H]3Cc4ccc(OC)c5c4[C@@]2(CCN3C)[C@H]1O5
Agent: Br[Hg]Br
Agent: [Br-]
Agent: [K+]
Solvent: CC(=O)O
Solvent: CO
Product: COc1ccc2c3c1O[C@H]1C(=O)CC=C4[C@@H](C2)N(C)CC[C@]431
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A solution of thebaine (1.00 g., 3.22 mmol) in methanol (40 ml.) was added to a stirred suspension of mercuric acetate (1.54 g., 4.82 mmol, 150 mol%) in methanol (30 ml.) at reflux for 50 min. under N2. After reflux, the mixture was filtered and the solvent evaporated in vacuo to give 2.67 g. of residue. This residue was taken up in 100 ml. of 3N acetic acid (17 ml. glacial HOAc diluted to 100 ml. H2O) and stirred at room temperature under N2 for 100 min. at which time 70 ml. of sat. aq. KBr was added to ppt. HgBr2. The precipitated mercury salts were filtered off through filter-aid after stirring for about 1 hour. The filtrate was cooled to 0° C. and 50 ml. of chloroform was added. The aqueous phase was basified to pH 12 with concentrated aq. NaOH. The chloroform layer was separated and the aqueous layer extracted with several portions of chloroform. All of the chloroform extracts were combined, washed with water, dried over Na2SO4, filtered and evaporated in vacuo to give crystalline neopinone; 0.995 g. (100%).
Reaction SMILES: Cl[CH2:2][C:3]([N:5]([CH:27]1[CH2:32][C:31]([CH3:34])([CH3:33])[NH:30][C:29]([CH3:36])([CH3:35])[CH2:28]1)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][N:12]([C:23](=[O:26])[CH2:24]Cl)[CH:13]1[CH2:18][C:17]([CH3:20])([CH3:19])[NH:16][C:15]([CH3:22])([CH3:21])[CH2:14]1)=[O:4].[CH3:37][N:38]1[C:43]([CH3:45])([CH3:44])[CH2:42][CH:41]([OH:46])[CH2:40][C:39]1([CH3:48])[CH3:47].[Na]>C1(C)C(C)=CC=CC=1>[CH3:37][N:38]1[C:43]([CH3:44])([CH3:45])[CH2:42][CH:41]([O:46][CH2:2][C:3]([N:5]([CH:27]2[CH2:32][C:31]([CH3:34])([CH3:33])[NH:30][C:29]([CH3:36])([CH3:35])[CH2:28]2)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][N:12]([C:23](=[O:26])[CH2:24][O:46][CH:41]2[CH2:40][C:39]([CH3:47])([CH3:48])[N:38]([CH3:37])[C:43]([CH3:45])([CH3:44])[CH2:42]2)[CH:13]2[CH2:18][C:17]([CH3:20])([CH3:19])[NH:16][C:15]([CH3:22])([CH3:21])[CH2:14]2)=[O:4])[CH2:40][C:39]1([CH3:48])[CH3:47]
Reactant: CC1(C)CC(N(CCCCCCN(C(=O)CCl)C2CC(C)(C)NC(C)(C)C2)C(=O)CCl)CC(C)(C)N1
Reactant: CN1C(C)(C)CC(O)CC1(C)C
Agent: [Na]
Solvent: Cc1ccccc1C
Product: CN1C(C)(C)CC(OCC(=O)N(CCCCCCN(C(=O)COC2CC(C)(C)N(C)C(C)(C)C2)C2CC(C)(C)NC(C)(C)C2)C2CC(C)(C)NC(C)(C)C2)CC1(C)C

Procedure:
38.29 g (0.07 mol) of N,N'-bis-(2-chloroacetyl)-N,N'-bis-(2,2,6,6-tetramethyl-piperidin-4-yl)-1,6-diaminohexane are dissolved in 100 ml of anhydrous xylene. The solution thus obtained is cooled to 0°-10° C.; the solution of 29.72 g (0.154 mol) of the sodium alcoholate of 1,2,2,6,6-pentamethyl-piperidin-4-ol in 120 ml of xylene (obtained beforehand by reacting 3.54 g (0.154 mol) of sodium with 26.38 g (0.154 mol) of 1,2,2,6,6-pentamethyl-piperidin-4-ol in 120 ml of anhydrous xylene) is then added slowly with continuous stirring.
Reaction SMILES: Br[CH:2]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:3](=O)[C:4]([O:6][CH2:7][CH3:8])=[O:5].[F:17][C:18]1[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:19]=1[C:20](=[S:22])[NH2:21]>CO>[CH2:10]([C:2]1[S:22][C:20]([C:19]2[CH:23]=[C:24]([F:27])[CH:25]=[CH:26][C:18]=2[F:17])=[N:21][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: NC(=S)c1cc(F)ccc1F
Reactant: CCOC(=O)C(=O)C(Br)Cc1ccccc1
Solvent: CO
Product: CCOC(=O)c1nc(-c2cc(F)ccc2F)sc1Cc1ccccc1
Yield: 60.4 %

Procedure:
To a solution of ethyl 3-bromo-2-oxo-4-phenylbutanoate (13.8 g, 48.4 mmol) in MeOH (161 mL) was slowly added 2,5-difluorobenzothioamide (8.38 g, 48.4 mmol) at room temperature. The reaction mixture was then refluxed for overnight. After cooled down, white precipitate was filtered, washed by cold ethanol and dried. A mixture of methyl 5-benzyl-2-(2,5-difluorophenyl)thiazole-4-carboxylate and ethyl 5-benzyl-2-(2,5-difluorophenyl)thiazole-4-carboxylate (10.5 g, 61%) was obtained as white solid. LC/MS (uplc): MW 346.1, 1.21 min for methyl ester; 360.1, 1.27 min for ethyl ester.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH:9]1[CH2:14][CH2:13][C:12](=[O:15])[CH:11]=[CH:10]1>[Pd].C(OC(=O)C)C>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH:9]1[CH2:14][CH2:13][C:12](=[O:15])[CH2:11][CH2:10]1
Reactant: COc1ccccc1C1C=CC(=O)CC1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: COc1ccccc1C1CCC(=O)CC1
Reaction time: 6.5 h

Procedure:
To a suspension of palladium on carbon (3.75 g, 25% wt) in 200 mL ethylacetate was added a 1:2 mixture of 4-(2-Melhoxy-phenyl)-cyclohex-3-enone and 4-(2-Methoxy-phenyl)-cyclohex-2-enone (15 g, 75.0 mmol) under argon. The suspension was stirred under a hydrogen at 1 atm. for 6.5 h, filtered through celite,concentrated in vacuo, and crystallized from ethylacetate to give 4-(2-Methoxy-phenyl)-cyclohexanone.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][CH:3]=1.[CH3:9][C@H:10]1[CH2:15][NH:14][CH2:13][C@@H:12]([CH3:16])[NH:11]1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([N:14]2[CH2:13][C@H:12]([CH3:16])[NH:11][C@H:10]([CH3:9])[CH2:15]2)=[CH:3][CH:4]=1
Reactant: C[C@@H]1CNC[C@H](C)N1
Reactant: Clc1ccc(Br)cc1
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: Cc1ccccc1
Product: C[C@@H]1CN(c2ccc(Cl)cc2)C[C@H](C)N1
Temperature: 100 °C
Yield: 98 %

Procedure:
A mixture of 4-bromochlorobenzene (1.0 g), cis-2,6-dimethylpiperazine (716 mg), sodium tert-butoxide (728 mg), (S)-(−)-BINAP (97.6 mg), and tris(dibenzylideneacetone)dipalladium(0) (71.6 mg) in anhydrous toluene (50 ml) was heated at 100° C. under a nitrogen atmosphere for 3 hours. The dark colored reaction mixture was filtered through celite and the celite was washed with chloroform. The filtrate was concentrated, and the residue was purified by silica gel column chromatography (chloroform-methanol 60:1) to give the title compound as a yellow powder (1.15 g).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]2[C:11]([NH2:16])=[CH:12][CH:13]=[CH:14][CH:15]=2)=[CH:4][CH:3]=1.[F:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][N:25]2[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=3[N:27]=[C:26]2[NH:34][CH:35]2[CH2:40][CH2:39][N:38]([CH2:41][CH2:42][N:43]=[C:44]=[S:45])[CH2:37][CH2:36]2)=[CH:20][CH:19]=1>O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][NH:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[NH:16][C:44]([NH:43][CH2:42][CH2:41][N:38]2[CH2:39][CH2:40][CH:35]([NH:34][C:26]3[N:25]([CH2:24][C:21]4[CH:20]=[CH:19][C:18]([F:17])=[CH:23][CH:22]=4)[C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=4[N:27]=3)[CH2:36][CH2:37]2)=[S:45])=[CH:6][CH:7]=1
Reactant: Nc1ccccc1NCc1ccc(F)cc1
Reactant: Fc1ccc(Cn2c(NC3CCN(CCN=C=S)CC3)nc3ccccc32)cc1
Solvent: C1CCOC1
Product: Fc1ccc(CNc2ccccc2NC(=S)NCCN2CCC(Nc3nc4ccccc4n3Cc3ccc(F)cc3)CC2)cc1
Yield: 100 %

Procedure:
A mixture of 2.1 parts of N-(4-fluorophenylmethyl)-1,2-benzenediamine, 4 parts of 1-(4-fluorophenylmethyl)-N-[1-(2-isothiocyanatoethyl)-4-piperidinyl]-1H-benzimidazol-2-amine and 90 parts of tetrahydrofuran is stirred and refluxed for 2 hours. The reaction mixture is evaporated, yielding 6 parts (100%) of N-{2-[(4-fluorophenylmethyl)amino]phenyl}-N'-[2-{4-[1-(4-fluorophenylmethyl)-1H-benzimidazol-2-ylamino]-1-piperidinyl}-ethyl]thiourea as a residue.
Reaction SMILES: [C:1]1([C:7](=O)[CH2:8][C:9](=O)[C:10]([F:13])([F:12])[F:11])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(C1C=CC=CC=1)(=O)C.[NH2:25][C:26]1[N:27]=[CH:28][NH:29][C:30]=1[C:31]#[N:32]>>[C:1]1([C:7]2[CH:8]=[C:9]([C:10]([F:13])([F:12])[F:11])[N:27]3[CH:28]=[N:29][C:30]([C:31]#[N:32])=[C:26]3[N:25]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: N#Cc1[nH]cnc1N
Reactant: O=C(CC(=O)C(F)(F)F)c1ccccc1
Solvent: CC(=O)c1ccccc1
Product: N#Cc1ncn2c(C(F)(F)F)cc(-c3ccccc3)nc12
Yield: 37.1 %

Procedure:
Reaction of 1-phenyl-4,4,4-trifluoro-butane-1,3-dione (216 mg, 1.0 mmol), prepared from commercially available acetophenone according to general procedure A, and 4-amino-5-cyano-1H-imidazole (108 mg, 1.0 mmol) according to general procedure B yielded the title compound as a yellow solid (107 mg, 37%). MS (ISP) 289.0 [(M+H)+]; mp 202° C.
Reaction SMILES: [C:1]12([C:11]([NH:13][NH:14][C:15]([NH:17][CH2:18][CH2:19][CH2:20][CH2:21][OH:22])=[S:16])=O)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[OH-].[Na+].N#N.Cl>>[C:1]12([C:11]3[N:17]([CH2:18][CH2:19][CH2:20][CH2:21][OH:22])[C:15]([SH:16])=[N:14][N:13]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2
Reactant: O=C(NNC(=S)NCCCCO)C12CC3CC(CC(C3)C1)C2
Agent: Cl
Agent: N#N
Agent: [Na+]
Product: OCCCCn1c(S)nnc1C12CC3CC(CC(C3)C1)C2

Procedure:
A mixture of 1-(1-adamantylcarbonyl)-4-(4-hydroxybutyl) thiosemicarbazide (H) (471 mg, 1.45 mmol) and 2 N NaOH (12 mL) was heated under reflux in a N2 atmosphere for 1.5 h. The cooled reaction was acidified with conc. HCl to pH 4. The precipitated solid was filtered, washed with water and dried to give 4-[3-(1-adamantyl)-5-mercapto-4H-1,2,4-triazol-4-yl] butan-1-ol (3-36).
Reaction SMILES: [C:1]([O:9][CH3:10])(=[O:8])/[CH:2]=[CH:3]\[C:4]([O:6][CH3:7])=[O:5].C([O:13][C:14]1O[C:17]([CH:19]=[CH2:20])=[N:16][C:15]=1[CH3:21])C.Cl.C(=O)(O)[O-].[Na+]>CO.O.CCOCC>[CH3:21][C:15]1[C:14]([OH:13])=[C:3]([C:4]([O:6][CH3:7])=[O:5])[C:2]([C:1]([O:9][CH3:10])=[O:8])=[C:17]([CH:19]=[CH2:20])[N:16]=1
Reactant: COC(=O)/C=C\C(=O)OC
Reactant: C=Cc1nc(C)c(OCC)o1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CO
Solvent: CCOCC
Product: C=Cc1nc(C)c(O)c(C(=O)OC)c1C(=O)OC

Procedure:
A mixture of 0.2 mole of dimethyl maleate and 0.1 mole of 5-ethoxy-4-methyl-2-vinyloxazole are heated at 110°-115° C. for 4 hours. The reaction mixture is cooled and 20 ml. of a 25% solution of hydrogen chloride (dry) in absolute methanol added. Addition of ether to the cooled reaction mixture precipitates the hydrochloride salt of the product. The free base is obtained by dissolving the hydrochloride salt in a minimum volume of water, adding solid sodium bicarbonate to pH 6.5 to 7.0 and extracting with chloroform. The combined chloroform extracts are dried over sodium sulfate and concentrated in vacuo to give dimethyl 2-methyl-3-hydroxy-6-vinyl-pyridine 4,5-dicarboxylate.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][OH:5].C(N(CC)CC)C.[C:13]1([CH3:23])[CH:18]=[CH:17][C:16]([S:19](Cl)(=[O:21])=[O:20])=[CH:15][CH:14]=1.C(Cl)(Cl)Cl>ClCCl>[S:19]([C:16]1[CH:17]=[CH:18][C:13]([CH3:23])=[CH:14][CH:15]=1)([O:5][CH2:4][CH2:3][O:2][CH3:1])(=[O:21])=[O:20]
Reactant: COCCO
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: ClC(Cl)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COCCOS(=O)(=O)c1ccc(C)cc1
Temperature: 0 °C
Reaction time: 8 h
Yield: 92.5 %

Procedure:
2-methoxyethanol (0.989 g, 13 mmol) was dissolved in 30 ml dichloromethane, and triethylamine (2.53 g, 25 mmol) was added to the solution. The reaction mixture was set to stir in an ice-water bath, and p-toluenesulfonyl chloride (3.22 g, 17 mmol) was added all at once. The ice was allowed to melt, and the reaction was continued overnight. The reaction mixture was then filtered, to remove all of the triethylamine hydrochloride, and the filtrate was washed with ml saturated NaHCO3(aq), then 30 ml 1N KHSO4(aq), then 30 ml saturated NaHCO3(aq). The organic layer was dried over anhydrous magnesium sulfate, and the solvent was removed by distillation. The colorless oily residue was chromatographed on silica gel in 1:5 ethyl acetate:chloroform, to yield 2.77 g (92% yield) of 2-methoxyethyl tosylate as a viscous liquid.