Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:7][CH2:8][C@@H:9]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[C:10]1[C:18]([CH3:19])=[CH:17][C:13]2[N:14]=[CH:15][S:16][C:12]=2[C:11]=1[C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=1)(=O)C(C)(C)C.[OH-].[Na+]>CO.C1COCC1.C(OCC)(=O)C>[C:28]([O:27][C@@H:9]([C:10]1[C:18]([CH3:19])=[CH:17][C:13]2[N:14]=[CH:15][S:16][C:12]=2[C:11]=1[C:20]1[CH:21]=[CH:22][C:23]([Cl:26])=[CH:24][CH:25]=1)[CH2:8][OH:7])([CH3:31])([CH3:29])[CH3:30]
Reactant: Cc1cc2ncsc2c(-c2ccc(Cl)cc2)c1[C@@H](COC(=O)C(C)(C)C)OC(C)(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CO
Solvent: C1CCOC1
Product: Cc1cc2ncsc2c(-c2ccc(Cl)cc2)c1[C@@H](CO)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of (S)-2-tert-butoxy-2-(7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)ethyl pivalate (5J) (8 mg, 0.0174 mmol) in MeOH (0.5 mL) and THF (1 mL) was added sodium hydroxide (2 M, 0.1 mL, 0.2 mmol) and the reaction mixture was stirred at room temperature overnight. Reaction mixture diluted with ethyl acetate and washed with saturated sodium bicarbonate solution. Aqueous layer back-extracted with ethyl acetate and combined organic layer was dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 0 to 50% ethyl acetate/hexanes). LCMS-ESI+: calc'd for C20H22ClNO2S: 376.1 (M+H+). Found: 376.1 (M+H+).
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[CH:15]=[CH:14][C:13]([N:16]4[C:20]([CH2:21][C@@H:22]5[CH2:26][CH2:25][N:24]([C:27]([CH:29]6[CH2:31][CH2:30]6)=[O:28])[CH2:23]5)=[N:19][NH:18][C:17]4=[O:32])=[CH:12][CH:11]=3)=[CH:9][C:4]=2[CH:3]=[CH:2]1.C(=O)([O-])[O-].[K+].[K+].Cl[CH2:40][C:41]([CH3:44])([OH:43])[CH3:42].ClCCl>CN(C)C=O.O>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[CH:11]=[CH:12][C:13]([N:16]4[C:20]([CH2:21][C@@H:22]5[CH2:26][CH2:25][N:24]([C:27]([CH:29]6[CH2:30][CH2:31]6)=[O:28])[CH2:23]5)=[N:19][N:18]([CH2:40][C:41]([OH:43])([CH3:44])[CH3:42])[C:17]4=[O:32])=[CH:14][CH:15]=3)=[CH:9][C:4]=2[CH:3]=[CH:2]1
Reactant: O=C(C1CC1)N1CC[C@@H](Cc2n[nH]c(=O)n2-c2ccc(-c3ccc4occc4c3)cc2)C1
Reactant: CC(C)(O)CCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Solvent: ClCCl
Product: CC(C)(O)Cn1nc(C[C@@H]2CCN(C(=O)C3CC3)C2)n(-c2ccc(-c3ccc4occc4c3)cc2)c1=O
Temperature: 80 °C
Reaction time: 16 h
Yield: 48 %

Procedure:
To a solution of 4-[4-(1-benzofuran-5-yl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (100 mg, 0.233 mmol) in N,N-dimethylformamide (1 mL) in a 5 mL microwaveable vial was added potassium carbonate (100 mg, 0.724 mmol, 3.1 eq) and 1-chloro-2-methyl-2-propanol (50 mg, 0.461 mmol, 2 eq). The vial was capped and purged with nitrogen gas, and the reaction mixture was stirred for 16 h at 80° C. Analysis by LC/MS displayed no reaction. The solution was then irradiated in the microwave at 185° C. for 60 min. Analysis by LC/MS displayed the reaction was complete. The reaction mixture was poured into a mixture of dichloromethane and water. The organic layer was separated. The aqueous layer was washed with dichloromethane. The organic extractions were combined and washed 3× with a dilute brine solution. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 25-55% acetonitrile w/0.1% TFA/water w/0.1% TFA). The product fractions were neutralized with the addition of saturated aq sodium bicarbonate, combined, and extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to afford the title compound (56 mg, 48%). MS(ES)+ m/e 501.1 [M+H]+.
Reaction SMILES: [S-:1][C:2]#[N:3].[NH4+:4].C(Cl)(=O)C1C=CC=CC=1.[Cl:14][C:15]1[CH:24]=[C:23]2[C:18]([C:19]([NH:25][C@H:26]3[CH2:31][CH2:30][C@@H:29](NC4C5C(=CC(Cl)=CC=5)N=CC=4)[CH2:28][CH2:27]3)=[CH:20][CH:21]=[N:22]2)=[CH:17][CH:16]=1.O>CC(C)=O>[Cl:14][C:15]1[CH:24]=[C:23]2[C:18]([C:19]([NH:25][CH:26]3[CH2:31][CH2:30][CH:29]([NH:3][C:2]([NH2:4])=[S:1])[CH2:28][CH2:27]3)=[CH:20][CH:21]=[N:22]2)=[CH:17][CH:16]=1
Reactant: N#C[S-]
Reactant: [NH4+]
Reactant: Clc1ccc2c(N[C@H]3CC[C@@H](Nc4ccnc5cc(Cl)ccc45)CC3)ccnc2c1
Solvent: CC(C)=O
Solvent: O
Solvent: O=C(Cl)c1ccccc1
Product: NC(=S)NC1CCC(Nc2ccnc3cc(Cl)ccc23)CC1
Yield: 47 %

Procedure:
Ammonium thiocyanate (320 mg, 4.2 mmol) was dissolved in 85 mL dry acetone. A solution of benzoyl chloride (590 mg, 4.2 mmol) in 10 mL dry acetone was added dropwise and heated at reflux for 30 minutes. A solution of 23A cis-N,N′-bis(7-chloroquinolin-4-yl)cyclohexane-1,4-diamine (1 g, 3.6 mmol) in 10 mL dry acetone was added dropwise to the refluxing solution. After the addition, the solution was poured into 100 mL of water. The resulting solid was filtered and heated in 30 mL of 10% sodium hydroxide until dissolved. The solution was then allowed to cool and was placed in the freezer overnight. The white solid was filtered and dried under vacumn to give 565 mg, 47% yield. MS ESI(+)Q1MS m/z 334 (M+H)+; 1 H NMR (300 MHz, DMSO) δ ppm 8.38-8.42 (m, 2 H), 8.78 (d, 1 H), 7.44 (dd, 1 H), 6.66-6.69 (m, 2 H), 6.53 (d, 1 H), 4.17 (m, 1 H), 3.61 (m, 1 H), 1.96-2.06 (m, 4H), 1.65-1.84 (m, 8 H).
Reaction SMILES: [Cr](O)(O)(=O)=O.[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[C:13]1[N:17]2[NH:18][C:19](=[O:27])[C:20]([CH:22]3[CH2:25][CH:24]([OH:26])[CH2:23]3)=[CH:21][C:16]2=[N:15][N:14]=1.[CH:28](O)([CH3:30])C.O>CC(C)=O>[F:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[C:13]1[N:17]2[N:18]=[C:19]([O:27][CH2:30][C:28]3[N:15]([CH3:16])[N:14]=[CH:13][N:17]=3)[C:20]([CH:22]3[CH2:23][C:24](=[O:26])[CH2:25]3)=[CH:21][C:16]2=[N:15][N:14]=1
Reactant: CC(C)O
Reactant: O=c1[nH]n2c(-c3ccccc3F)nnc2cc1C1CC(O)C1
Agent: O=[Cr](=O)(O)O
Solvent: CC(C)=O
Solvent: O
Product: Cn1ncnc1COc1nn2c(-c3ccccc3F)nnc2cc1C1CC(=O)C1

Procedure:
8N Chromic acid was added to a solution of 3-(2-fluorophenyl)-7-(3-hydroxycyclobutyl)-1,2,4-triazolo[4,3-b]pyridazin-6-one (0.36 g, 1.2 mmol) in acetone (50 ml) dropwise, until excess was present (red colour remained). The reaction was then stirred for 2 hours before isopropanol was added until the blue colour remained and no excess chromic acid was present. Water (50 ml) was added and the aqueous layer extracted with ethyl acetate (4×50 ml), organic layers were combined, washed with brine (50 ml), dried (MgSO4), filtered and concentrated to give the desired product as a white solid. Data for the title compound: 1H NMR (360 MHz, DMSO) δ3.41 (2H, s), 3.43 (2H, s), 3.73-3.78 (1H, m), 7.42-7.50 (2H, m), 7.64-7.72 (1H, m), 7.83-7.88 (1H, m), 8.38 (1H, s); MS (ES+) m/e 299 [MH]+.
Reaction SMILES: C(=O)(O)[O-].[Na+].Cl[CH2:7][C:8]1[C@H:9]2[CH2:14][CH:11]([CH2:12][CH:13]=1)[C:10]2([CH3:16])[CH3:15].[O:17]=[C:18]1[NH:24][C:23]2[CH:25]=[CH:26][CH:27]=[CH:28][C:22]=2[NH:21][CH2:20][C@H:19]1[NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31]>CO>[O:17]=[C:18]1[NH:24][C:23]2[CH:25]=[CH:26][CH:27]=[CH:28][C:22]=2[N:21]([CH2:7][C:8]2[C@H:9]3[CH2:14][CH:11]([CH2:12][CH:13]=2)[C:10]3([CH3:16])[CH3:15])[CH2:20][C@H:19]1[NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31]
Reactant: CC1(C)C2CC=C(CCl)[C@H]1C2
Reactant: CC(C)(C)OC(=O)N[C@@H]1CNc2ccccc2NC1=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Product: CC(C)(C)OC(=O)N[C@@H]1CN(CC2=CCC3C[C@H]2C3(C)C)c2ccccc2NC1=O
Yield: 61.6 %

Procedure:
Sodium bicarbonate (2.02 g) and (1s)-10-chloro-2-pinene (4.1 g) were added to a solution of (R)-2-oxo-3-tert-butoxycarbonylamino-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (2.22 g) in anhydrous methanol (40 ml), and the mixture was refluxed overnight. The reaction mixture was concentrated under reduced pressure, water (200 ml) was added, and extracted with ethyl acetate (200 ml) twice. The organic layer was washed with saturated brine, dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, the residue was purified by silica gel column chromatography(n-hexane:ethyl acetate=4:1), to thereby obtain 2.03 g of the titled compound.
Reaction SMILES: [O:1]1[CH:6]([C:7]([OH:9])=[O:8])[CH:2]1[C:3]([OH:5])=O.[C:10]1([K])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(Cl)(=O)C(Cl)=O.[NH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>>[C:24]1([NH:23][C:3](=[O:5])[CH:2]2[O:1][CH:6]2[C:7]([O:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[O:8])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: Nc1ccccc1
Reactant: [K]c1ccccc1
Reactant: O=C(O)C1OC1C(=O)O
Agent: O=C(Cl)C(=O)Cl
Product: O=C(Nc1ccccc1)C1OC1C(=O)Oc1ccccc1
Yield: 19.7 %

Procedure:
Following the procedure of Example 1, monophenyl potassium epoxysuccinate (3.64 g) was successively treated with oxalyl chloride (2.10 g) and aniline (1.4 g) to give 0.82 g of phenyl N-phenyl-2,3-epoxysuccinamate (Compound No. 28) as colorless needles melting at 121° C.
Reaction SMILES: [N:1]([O-:3])=O.[Na+].[Cl:5][C:6]1[CH:11]=[C:10]([CH2:12][C:13]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)=[O:14])[CH:9]=[CH:8][N:7]=1>O.C(O)(=O)C>[Cl:5][C:6]1[CH:11]=[C:10]([C:12](=[N:1][OH:3])[C:13]([C:15]2[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=2)=[O:14])[CH:9]=[CH:8][N:7]=1
Reactant: O=N[O-]
Reactant: O=C(Cc1ccnc(Cl)c1)c1ccc(F)cc1
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: O=C(C(=NO)c1ccnc(Cl)c1)c1ccc(F)cc1
Temperature: 10 °C
Reaction time: 3 h

Procedure:
With stirring and cooling in a water bath (about 10° C.), a solution of NaNO2 (0.85 g; 12.3 mmol) in H2O (10 ml) was added dropwise over a period of 2.5 min to a solution of 21a (3.0 g; 12 mmol) in glacial acetic acid. After the addition had ended, the reaction mixture was stirred at room temperature for 0.5 h, H2O (60 ml) was added and stirring at room temperature was continued for 3 h. The light-beige precipitate was filtered off, washed with water and dried under reduced pressure over CaCl2.
Reaction SMILES: S(Cl)(Cl)=O.[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:13]=[CH:14][C:15]([C:18]#[C:19][C:20]3[CH:21]=[C:22]4[C:27](=[CH:28][CH:29]=3)[N:26]=[C:25]([CH2:30]O)[CH:24]=[C:23]4[CH3:32])=[N:16][CH:17]=2)=[CH:8][CH:7]=1.N1C=CC=CC=1.[CH3:39][CH:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1>C(Cl)Cl>[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:13]=[CH:14][C:15]([C:18]#[C:19][C:20]3[CH:21]=[C:22]4[C:27](=[CH:28][CH:29]=3)[N:26]=[C:25]([CH2:30][N:43]3[CH2:44][CH2:45][CH:40]([CH3:39])[CH2:41][CH2:42]3)[CH:24]=[C:23]4[CH3:32])=[N:16][CH:17]=2)=[CH:8][CH:7]=1
Reactant: CC1CCNCC1
Reactant: Cc1cc(CO)nc2ccc(C#Cc3ccc(-c4ccc(Cl)cc4)cn3)cc12
Solvent: ClCCl
Solvent: c1ccncc1
Solvent: O=S(Cl)Cl
Product: Cc1cc(CN2CCC(C)CC2)nc2ccc(C#Cc3ccc(-c4ccc(Cl)cc4)cn3)cc12
Temperature: 25 °C
Reaction time: 2 h

Procedure:
16 μL (0.20 mmol) of thionyl chloride was added at RT to a solution of 50 mg (0.13 mmol) of {6-[5-(4-chlorophenyl)pyridin-2-ylethynyl]-4-methylquinolin-2-yl}methanol and 52 μL (0.65 mmol) of pyridine in 3 mL of DCM and the mixture was stirred for 2 hours at RT. The reaction mixture was diluted with DCM, and the organic phase was washed with saturated aqueous sodium bicarbonate solution, dried over magnesium sulfate, and evaporated down in vacuo. The residue was taken up in 3 mL of DMF, combined with 60 μL (0.51 mmol) of 4-methylpiperidine and stirred for 16 hours at RT. The reaction mixture was evaporated down in vacuo, diluted with DCM, and the organic phase was washed with saturated aqueous sodium bicarbonate solution, dried over magnesium sulfate and evaporated down in vacuo. The crude product was purified by column chromatography (silica gel, gradient DCM/MeOH/sat. aqueous ammonia 100:0:0 95:5:0.5) and HPLC-MS (Zorbax Bonus C18 amide-phase 5 μm, gradient 0.15% formic acid in water/acetonitrile 10/90→90/10 v/v). Yield: 4 mg (7% of theoretical); C30H28ClN3 (M=466.016); calc.: molpeak (M+H)+: 466/468 (Cl); found: molpeak (M+H)+: 466/468 (Cl); Rf value: 0.38 (silica gel, DCM/MeOH/sat. aqueous ammonia 9:1:0.1).
Reaction SMILES: [PH2](O)=O.C(N1CCCCC1)C.[CH2:12]=[CH:13][S:14]([O:17][C:18]1[C:23]([F:24])=[C:22]([F:25])[C:21]([F:26])=[C:20]([F:27])[C:19]=1[F:28])(=[O:16])=[O:15].I[CH:30]1[CH2:35][CH2:34][CH2:33][N:32]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:31]1.C(B(CC)CC)C>C(Cl)Cl>[F:24][C:23]1[C:22]([F:25])=[C:21]([F:26])[C:20]([F:27])=[C:19]([F:28])[C:18]=1[O:17][S:14]([CH2:13][CH2:12][CH:34]1[CH2:35][CH2:30][CH2:31][N:32]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:33]1)(=[O:16])=[O:15]
Reactant: CC(C)(C)OC(=O)N1CCCC(I)C1
Reactant: C=CS(=O)(=O)Oc1c(F)c(F)c(F)c(F)c1F
Agent: CCB(CC)CC
Agent: CCN1CCCCC1
Agent: O=[PH2]O
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCCC(CCS(=O)(=O)Oc2c(F)c(F)c(F)c(F)c2F)C1
Temperature: 0 °C
Reaction time: 0 h

Procedure:
1-Ethylpiperidine hypophosphite (7.49 g, 41.8 mmol) were weighed into the reaction flask under an inert gas, and methylene chloride (38 ml) was added. The solution was cooled with ice-water, and 2,3,4,5,6-pentafluorophenyl 1-ethylenesulfonate (1.38 g, 5.02 mmol) [Org. Lett.; 2002; 4(15); 2549-2551] and tert-butyl 3-iodopiperidine-1-carboxylate (1.3 g, 4.18 mmol) was added at 0° C. Triethylborane solution (0.21 ml, 1 mol/l) was added to the reaction mixture and compressed air was then passed through the mixture for 10 sec. After stirring for 5 min the addition of triethylborane solution-compressed air was repeated with the same amount. Stir for 5 min, the addition of triethylborane solution-compressed air was then repeated with the same amount. The reaction mixture was washed with water (20 ml), sodium bicarbonate solution (20 ml, saturated 50% diluted) and saturated sodium chloride solution (20 ml), dried over sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (silica gel) with hexane/diethyl ether (3:1). Yield: 0.5 g (26%)
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([O:14][CH2:15][CH2:16][NH2:17])[CH:7]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:9]=1)([O-:3])=[O:2].N1C=CC=CC=1.[S:24](Cl)([CH3:27])(=[O:26])=[O:25]>C(Cl)Cl>[N+:1]([C:4]1[CH:5]=[C:6]([O:14][CH2:15][CH2:16][NH:17][S:24]([CH3:27])(=[O:26])=[O:25])[CH:7]=[C:8]([C:10]([F:11])([F:12])[F:13])[CH:9]=1)([O-:3])=[O:2]
Reactant: CS(=O)(=O)Cl
Reactant: NCCOc1cc([N+](=O)[O-])cc(C(F)(F)F)c1
Solvent: ClCCl
Solvent: c1ccncc1
Product: CS(=O)(=O)NCCOc1cc([N+](=O)[O-])cc(C(F)(F)F)c1
Temperature: 0 °C
Reaction time: 18 h

Procedure:
2-((3-Nitro-5-(trifluoromethyl)phenyl)oxy)ethylamine (4.05 g, 16.2 mmols, 1 eq) was dissolved in 100 mL of CH2Cl2. The solution was cooled to 0° C. Pyridine (2.6 mL, 32.4 mmols, 2 eq) was added followed by mesyl chloride (1.25 mL, 16.2 mmols, 1 eq). The reaction was stirred for 18 h during which time it was warmed slowly to RT. The solvent was removed in vacuo, and the residue dissolved in EtOAc. The resulting solution was washed twice with 2 N HCl, once with water, and 3× with brine. After being dried over Na2SO4 the solution was filtered and concentrated. The crude was purified by silica gel chromatography eluting with 50% to 60% EtOAc:hexane to yield the desired compound.
Reaction SMILES: [CH2:1]([CH:7]([CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH2:8]O)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[BrH:18]>>[Br:18][CH2:8][CH:7]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH3:17]
Reactant: CCCCCCCCC(CO)CCCCCC
Reactant: Br
Product: CCCCCCCCC(CBr)CCCCCC

Procedure:
1-Bromo-2-hexyldecane was prepared by reacting 2-hexyldecanol with hydrogen bromide gas, or with 47% aqueous hydrogen bromide, according to well known procedures. The crude product was purified by distillation, b.p. 152°-154° at 18 mm of mercury.
Reaction SMILES: [H-].C([Al+]CC(C)C)C(C)C.[CH:11]#[C:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[CH:19]([C:21]1[C:30]([CH3:31])=[C:29]([O:32][C:33](=[O:35])[CH3:34])[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:22]=1)=[O:20].Cl>CCCCCC.O1CCCC1.O>[OH:20][CH:19]([C:21]1[C:30]([CH3:31])=[C:29]([O:32][C:33](=[O:35])[CH3:34])[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:22]=1)/[CH:11]=[CH:12]/[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: C#CCCCCCC
Reactant: CC(=O)Oc1c(C)c(C=O)nc2ccccc12
Agent: CC(C)C[Al+]CC(C)C
Agent: Cl
Agent: [H-]
Solvent: O
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCCCCC/C=C/C(O)c1nc2ccccc2c(OC(C)=O)c1C
Temperature: 50 °C
Reaction time: 2 h
Yield: 398.2 %

Procedure:
13.9 ml of an n-hexane solution of 13.9 mmols of diisobutylaluminium hydride was added to a solution of 1.68 g (1.53 mmols) of 1-octyne in 20 ml of n-hexane in an atmosphere of nitrogen at 0° C. and stirred at 50° C. for 2 hours. After removal of the solvent by distillation under reduced pressure, 20 ml of tetrahydrofuran was added, followed by further addition of a solution, in 15 ml of tetrahydrofuran, of 2.66 g (11.6 mmols) of 2-formyl-3-methyl 4-acetoxyquinoline at -78° C. The reaction temperature was raised from -78° C. to room temperature and the reaction solution was stirred at room temperature for 15 minutes. The solution was added to a solution of 15 ml of 1N hydrochloric acid and 100 ml of water and filtered through Celite, followed by extraction with ethyl acetate, washing with water and then with a saturated sodium chloride aqueous solution, and drying with sodium sulfate. The solvent was distilled off under reduced pressure and the resultant residue was purified by silica gel column chromatography (solvent: n-hexane : ethyl acetate=15:1) to obtain 2.08 g (yield 52%) of 2-(trans-1-hydroxy-2-nonenyl)-3-methyl-4-acetoxyquinoline.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].C(=O)([O-])[O-].[K+].[K+].[CH2:17]([N:24]1[CH2:29][CH2:28][C:27]([NH2:31])([CH3:30])[CH2:26][CH2:25]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CS(C)=O.O>[CH2:17]([N:24]1[CH2:29][CH2:28][C:27]([NH:31][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[N+:8]([O-:10])=[O:9])([CH3:30])[CH2:26][CH2:25]1)[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: CC1(N)CCN(Cc2ccccc2)CC1
Reactant: O=[N+]([O-])c1ccccc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: CC1(Nc2ccccc2[N+](=O)[O-])CCN(Cc2ccccc2)CC1
Temperature: 150 °C
Yield: 71.1 %

Procedure:
3.6 g 1-fluor-2-nitrobenzene and 82.7 g potassiumcarbonate were added to 5.3 g 1-benzyl-4-methyl-piperidin-4-ylamine in 50 mL DMSO and the mixture was stirred at 150° C. 24 h. The reaction was diluted with water and the aqueous layer was extracted with ethylacetate. The organic layer was evaporated and the residue purified by column chromatographie on silica gel (heptane/ethylacetate:9/1) to give 5.9 g of the desired product.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([O:8][CH2:9][CH3:10])[CH:7]=1.C1C=C(Cl)C=C(C(OO)=[O:19])C=1>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[N+:4]([O-:19])[CH:5]=[C:6]([O:8][CH2:9][CH3:10])[CH:7]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: CCOc1cncc(Br)c1
Solvent: ClCCl
Product: CCOc1cc(Br)c[n+]([O-])c1
Reaction time: 15 h
Yield: 63 %

Procedure:
To a solution of 3-bromo-5-ethoxypyridine (53 g, 262 mmol) in DCM (600 mL) at 0° C. was slowly added m-CPBA (67.9 g, 393 mmol) over 30 min. After the resulting solution was stirred for 15 h, the mixture was washed with Na2S2O3 solution and extracted with DCM (600 mL×2). The combined organic layer was washed with saturated NaHCO3 (300 mL), brine (300 mL), dried over Na2SO4, filtered, and concentrated to give 3-bromo-5-ethoxypyridine-1-oxide (40 g, 165 mmol, 63% yield): 1HNMR (400 MHz, CD3OD) δ 8.19-8.18 (m, 1H), 8.08-8.07 (m, 1H), 7.50-7.49 (m, 1H), 4.17-4.15 (d, J=8.8 Hz, 2H), 1.43 (t, J=7.0 Hz, 3H); ES-LCMS m/z 217 (M+H).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[CH3:9][N:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1>CCO>[Cl:1][C:2]1[N:7]=[C:6]([N:13]2[CH2:14][CH2:15][N:10]([CH3:9])[CH2:11][CH2:12]2)[CH:5]=[CH:4][N:3]=1
Reactant: CN1CCNCC1
Reactant: Clc1ccnc(Cl)n1
Solvent: CCO
Product: CN1CCN(c2ccnc(Cl)n2)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 2,4-dichloropyrimidine (740 mg, 5 mmol) in EtOH (15 mL) was slowly added 1-methylpiperazine (550 mg, 5.5 mmol). The resulting mixture was stirred at room temperature overnight, then was concentrated, diluted with water, and extracted with CH2Cl2. The organic layer was dried and concentrated to yield 2-chloro-4-(4-methyl-piperazin-1-yl)-pyrimidine.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:16])[CH2:5][NH:6][CH2:7][C:8]1[C:13]([CH3:14])=[CH:12][CH:11]=[CH:10][C:9]=1[NH2:15])[CH3:2].[C:17](Cl)(Cl)=[S:18]>O1CCCC1>[CH3:14][C:13]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:8]=1[CH2:7][N:6]([CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:16])[C:17](=[S:18])[NH:15]2
Reactant: S=C(Cl)Cl
Reactant: CCOC(=O)CNCc1c(C)cccc1N
Solvent: C1CCOC1
Product: CCOC(=O)CN1Cc2c(C)cccc2NC1=S
Temperature: 25 °C

Procedure:
To a cooled solution of compound (10b) (15 g., 67 mmole) in 300 ml of anhydrous tetrahydrofuran under a nitrogen atmosphere, is added 72 mmole of thiophosgene at about room temperature. Upon completion of the addition, the solution was refluxed for 10 hours, cooled to room temperature and the tetrahydrofuran removed in vacuo. The residue is dissolved in methylene chloride, washed with 5% aqueous hydrochloric acid, then water. The methylene chloride solution is dried over sodium sulfate, filtered and the solvent removed in vacuo to produce the title product.
Reaction SMILES: [Br:1][C:2]1[CH:35]=[CH:34][C:5]([CH2:6][C:7]2[N:8]([C:20]3[CH:25]=[CH:24][C:23]([N:26]4[S:30](=[O:32])(=[O:31])[NH:29][C:28](=[O:33])[CH2:27]4)=[CH:22][CH:21]=3)[CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=3[Cl:19])[N:11]=2)=[CH:4][CH:3]=1.[CH3:36][Si:37]([CH3:44])([CH3:43])[CH2:38][CH2:39][O:40][CH2:41]Cl>>[Br:1][C:2]1[CH:35]=[CH:34][C:5]([CH2:6][C:7]2[N:8]([C:20]3[CH:21]=[CH:22][C:23]([N:26]4[S:30](=[O:32])(=[O:31])[N:29]([CH2:41][O:40][CH2:39][CH2:38][Si:37]([CH3:44])([CH3:43])[CH3:36])[C:28](=[O:33])[CH2:27]4)=[CH:24][CH:25]=3)[CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][C:13]=3[Cl:19])[N:11]=2)=[CH:4][CH:3]=1
Reactant: C[Si](C)(C)CCOCCl
Reactant: O=C1CN(c2ccc(-n3cc(-c4ccc(Cl)cc4Cl)nc3Cc3ccc(Br)cc3)cc2)S(=O)(=O)N1
Product: C[Si](C)(C)CCOCN1C(=O)CN(c2ccc(-n3cc(-c4ccc(Cl)cc4Cl)nc3Cc3ccc(Br)cc3)cc2)S1(=O)=O

Procedure:
5-{4-[2-(4-Bromo-benzyl)-4-(2,4-dichloro-phenyl)-imidazol-1-yl]-phenyl}-1,2,5-thiadiazolidine-3-one-1,1-dioxide (1.19 g, 2 mmol) was treated as described in general procedure L using 2-(trimethylsilyl)ethoxymethyl chloride (708 μL, 4 mmol) to give 5-{4-[2-(4-bromo-benzyl)-4-(2,4-dichloro-phenyl)-imidazol-1-yl]-phenyl}-1,1-dioxo-2-(2-trimethylsilanyl-ethoxymethyl)-[1,2,5]thiadiazolidin-3-one, which was then treated according to general procedure AD to give 5-(4-{4-(2,4-dichloro-phenyl)-2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl]-imidazol-1-yl}-phenyl)-1,1-dioxo-2-(2-trimethylsilanyl-ethoxymethyl)-[1,2,5]thiadiazolidin-3-one.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]([N+:10]([O-])=O)=[C:6]([CH:9]=1)[C:7]#[N:8].[O:13]1[CH2:18][CH2:17][N:16]([CH:19]2[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]2)[CH2:15][CH2:14]1>>[NH2:10][C:5]1[CH:4]=[CH:3][C:2]([N:22]2[CH2:23][CH2:24][CH:19]([N:16]3[CH2:17][CH2:18][O:13][CH2:14][CH2:15]3)[CH2:20][CH2:21]2)=[CH:9][C:6]=1[C:7]#[N:8]
Reactant: C1CC(N2CCOCC2)CCN1
Reactant: N#Cc1cc(Cl)ccc1[N+](=O)[O-]
Product: N#Cc1cc(N2CCC(N3CCOCC3)CC2)ccc1N

Procedure:
By the reaction and treatment in the same manner as in Starting Material Synthesis Example 40 using 5-chloro-2-nitrobenzonitrile and 4-morpholinopiperidine, the title compound was obtained, melting point: 178–180° C.