Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[N:2]1.[H-].[Na+].I[CH2:13][C:14]1[N:18](S(C)(=O)=O)[C:17]2[CH:23]=[CH:24][CH:25]=[CH:26][C:16]=2[N:15]=1>CN(C)C=O.O>[NH:15]1[C:16]2[CH:26]=[CH:25][CH:24]=[CH:23][C:17]=2[N:18]=[C:14]1[CH2:13][N:2]1[N:3]=[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]2=[N:1]1.[N:15]1[C:16]2[CH:26]=[CH:25][CH:24]=[CH:23][C:17]=2[NH:18][C:14]=1[CH2:13][N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[N:2]1
Reactant: CS(=O)(=O)n1c(CI)nc2ccccc21
Reactant: c1ccc2[nH]nnc2c1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: c1ccc2[nH]c(Cn3nnc4ccccc43)nc2c1
Product: c1ccc2nn(Cc3nc4ccccc4[nH]3)nc2c1
Reaction time: 1 h
Yield: 5 %
Yield: 48 %

Procedure:
Benzotriazole (238 mg, 2 mmol) in 4 mL of anhydrous N,N-dimethylformamide was added sodium hydride (60% in mineral oil, 88 mg, 2.2 mmol). After stirring for 1 hour, 2-iodomethyl-1-methanesulfonyl benzimidazole (740 mg, 2.2 mmol) was added. The resulting solution was stirred for 6 hours, diluted with water, and extracted with diethyl ether. The combined extracts were dried over magnesium sulfate, and evaporated. To the residue was added 5 mL of methanol and hydrazine (0.5 mL), and stirred at 65° C. overnight. The solvent was evaporated and the residue was diluted with water and extracted with ethyl acetate. The combined extracts were dried over magnesium sulfate, and evaporated. The residue was purified by flash chromatography (EtOAc: hexane=1:1 to 2:1) to give 24 mg (5%) of 2-(1H-benzimidazol-2-ylmethyl)-2H-benzotriazole (IV), and 240 mg (48%) of 1-(1-benzimidazol-2-ylmethyl)-1H-benzotriazole (III) as solids.
Reaction SMILES: [F:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][CH2:7][CH:8]2[O:12][C:11]([NH2:13])=[N:10][CH2:9]2)=[CH:4][CH:3]=1.[C:16](OCC)(=[O:19])[C:17]#[CH:18]>C(O)C>[F:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][CH2:7][CH:8]2[O:12][C:11]3=[N:13][C:16](=[O:19])[CH:17]=[CH:18][N:10]3[CH2:9]2)=[CH:4][CH:3]=1
Reactant: C#CC(=O)OCC
Reactant: NC1=NCC(COc2ccc(F)cc2)O1
Solvent: CCO
Product: O=c1ccn2c(n1)OC(COc1ccc(F)cc1)C2
Temperature: 25 °C
Yield: 43.9 %

Procedure:
To a solution of 5-(4-fluoro-phenoxymethyl)-4,5-dihydro-oxazol-2-ylamine (4.20 g, 2.00 mmol) in ethanol (8 mL) was added ethyl propiolate (0.25 g, 2.60 mmol). The reaction mixture was stirred at reflux for 6 hours. The mixture was stirred at 30° C. for a few minutes after which it was cooled to room temperature. The resulting crystals were collected and washed twice with hexane. The solid was dried under high vacuum at 65° C. for 18 hours to afford 0.23 g (50%) of 2-(4-fluorophenoxymethyl)-2,3-dihydro-oxazolo[3,2-a]pyrimidin-7-one.
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[CH:5]1[CH:6]=[CH:7][C:8]2[O:14][C:12](=[O:13])[NH:11][C:9]=2[CH:10]=1.[Cl:15][CH2:16][CH2:17][C:18](Cl)=[O:19]>CN(C)C=O>[Cl:15][CH2:16][CH2:17][C:18]([C:6]1[CH:5]=[CH:10][C:9]2[NH:11][C:12](=[O:13])[O:14][C:8]=2[CH:7]=1)=[O:19]
Reactant: O=C(Cl)CCCl
Reactant: O=c1[nH]c2ccccc2o1
Agent: [Al+3]
Agent: [Cl-]
Solvent: CN(C)C=O
Product: O=C(CCCl)c1ccc2[nH]c(=O)oc2c1

Procedure:
56.1 g (0.42 mole) of aluminum chloride are weighed into a ground-necked flask, 10 cm3 of dimethylformamide are then added using a dropping funnel and the mixture is left stirring until it becomes homogeneous. 8.1 g (0.06 mole) of benzoxazolinone are then added and the mixture is left stirring for 10 minutes before adding 7 cm3 (0.072 mole) of 3-chloropropionic acid chloride. This mixture is maintained in an oil bath at 80°-85° C. for approximately 2 hours 30 minutes. After cooling, the reaction mixture is poured into ice-cold water. The precipitate is drained and washed with water to neutrality. The product is recrystallized in ethanol.
Reaction SMILES: [F:1][C:2]([F:20])([F:19])[C:3]1[CH:18]=[CH:17][C:6]2[S:7][C:8](=[N:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[S:9][C:5]=2[CH:4]=1.[CH3:21][I:22]>C1C=CC=CC=1>[I-:22].[CH3:21][N+:10](=[C:8]1[S:7][C:6]2[CH:17]=[CH:18][C:3]([C:2]([F:1])([F:19])[F:20])=[CH:4][C:5]=2[S:9]1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: FC(F)(F)c1ccc2sc(=Nc3ccccc3)sc2c1
Reactant: CI
Solvent: c1ccccc1
Product: C[N+](c1ccccc1)=c1sc2ccc(C(F)(F)F)cc2s1
Product: [I-]
Reaction time: 72 h

Procedure:
A solution of N-[5-(trifluoromethyl)-1,3-benzodithiol-2-ylidene]benzenamine (2.4 g) and methyl iodide (20 ml, excess) in 100 ml of benzene is heated at reflux for 2.5 weeks. The reaction mixture is filtered and recharged with methyl iodide every three days. The combined precipitates (3.3g) are recrystallized from acetonitrile/benzene. The recrystallized product is dried in vacuo at 100° C for 3 days to yield 3.0g of the title compound, melting point 161°-164° C.
Reaction SMILES: [C:1]([C:5]1[CH:12]=[CH:11][C:8]([CH2:9]Br)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1>C1COCC1>[C:1]([C:5]1[CH:12]=[CH:11][C:8]([CH2:9][N:13]2[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)c1ccc(CBr)cc1
Reactant: C1CNCCN1
Solvent: C1CCOC1
Product: CC(C)(C)c1ccc(CN2CCNCC2)cc1

Procedure:
Synthesized according to General Procedure A: 4-tert-butylbenzyl bromide (4{20}, 4.05 mL, 22.0 mmol, 1 equiv.), piperazine (11.4 g, 132.1 mmol, 6 equiv.), THF (48.1 mL). Purification with flash column chromatography on silica gel (4:1 EtOAc:MeOH) afforded 5{20} (3.75 g, 73%) as a beige solid. 1H-NMR (500 MHz, CDCl3): δ 7.30 (d, 2H, J=8.5 Hz), 7.22 (d, 2H, J=8.5 Hz), 3.44 (s, 2H), 2.85 (t, 4H, J=5.0 Hz), 2.38 (br s, 4H), 1.54 (br s, 1H), 1.29 (s, 9H). 13C-NMR (125 MHz, CDCl3): δ 149.6, 134.7, 128.7, 124.8, 63.1, 54.3, 45.9, 34.2, 31.2.
Reaction SMILES: [S:1]1[CH:5]=[C:4]([C:6]2[CH:13]=[CH:12][C:9]([CH:10]=O)=[CH:8][CH:7]=2)[N:3]=[N:2]1.[CH3:14][CH:15]([CH3:31])[C:16]([NH:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([CH:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[CH:20]=1)=[O:17]>>[CH3:14][CH:15]([CH3:31])[C:16]([NH:18][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([CH:25]2[CH2:30][CH2:29][N:28]([CH2:10][C:9]3[CH:12]=[CH:13][C:6]([C:4]4[N:3]=[N:2][S:1][CH:5]=4)=[CH:7][CH:8]=3)[CH2:27][CH2:26]2)[CH:20]=1)=[O:17]
Reactant: CC(C)C(=O)Nc1cccc(C2CCNCC2)c1
Reactant: O=Cc1ccc(-c2csnn2)cc1
Product: CC(C)C(=O)Nc1cccc(C2CCN(Cc3ccc(-c4csnn4)cc3)CC2)c1

Procedure:
Prepared by Procedure F and Scheme R using 4-(1,2,3-thiadiazol-4-yl)benzaldehyde and 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide: ESMS m/e: 421.1 (M+H)+.
Reaction SMILES: [Cl-].[CH3:2][C:3]1[N:8]2[N:9]=[C:10]([CH2:12][P+](C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[N:11]=[C:7]2[C:6]([CH3:32])=[N:5][CH:4]=1.[CH:33]1([N:36]([CH3:45])[C:37]2[N:41]=[C:40]([CH:42]=O)[N:39]([CH3:44])[N:38]=2)[CH2:35][CH2:34]1>>[CH:33]1([N:36]([C:37]2[N:41]=[C:40]([CH:42]=[CH:12][C:10]3[N:11]=[C:7]4[C:6]([CH3:32])=[N:5][CH:4]=[C:3]([CH3:2])[N:8]4[N:9]=3)[N:39]([CH3:44])[N:38]=2)[CH3:45])[CH2:34][CH2:35]1
Reactant: CN(c1nc(C=O)n(C)n1)C1CC1
Reactant: Cc1ncc(C)n2nc(C[P+](c3ccccc3)(c3ccccc3)c3ccccc3)nc12
Agent: [Cl-]
Product: Cc1ncc(C)n2nc(C=Cc3nc(N(C)C4CC4)nn3C)nc12
Yield: 33.4 %

Procedure:
Was prepared in the same manner as described in General Procedure Example 1g) using ((5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)methyl)triphenylphosphonium chloride (127 mg, 277 μmol, Eq: 1.00) and 3-(cyclopropyl(methyl)amino)-1-methyl-1H-1,2,4-triazole-5-carbaldehyde (50 mg, 277 μmol, Eq: 1.00) as starting materials. Chromatography afforded Cyclopropyl-{5-[2-(5,8-dimethyl-[1,2,4]triazolo[1,5-a]pyrazin-2-yl)-vinyl]-1-methyl-1H-[1,2,4]triazol-3-yl}-methyl-amine (30 mg, 33.3%) as light yellow waxy solid. MS: m/z=325.5 (M+H+)
Reaction SMILES: [CH3:1][Si:2]([CH3:32])([CH3:31])[O:3][CH:4]1[CH2:12][CH2:11][CH2:10][C@@:9]2([CH3:13])[CH:5]1[CH2:6][CH2:7][C@@H:8]2[C@H:14]([CH3:30])[CH:15]=[CH:16][CH:17]([C@@:19]1([CH3:29])[O:23][C@H:22]([C:24]([CH3:27])([CH3:26])[CH3:25])[O:21][C:20]1=[O:28])[OH:18].Cl[C:34]([O:36][CH3:37])=[O:35].C(OCC)(=O)C.O>CN(C)C1C=CN=CC=1.ClCCl>[CH3:32][Si:2]([CH3:1])([CH3:31])[O:3][CH:4]1[CH2:12][CH2:11][CH2:10][C@@:9]2([CH3:13])[CH:5]1[CH2:6][CH2:7][C@@H:8]2[C@H:14]([CH3:30])[CH:15]=[CH:16][CH:17]([C@@:19]1([CH3:29])[O:23][C@H:22]([C:24]([CH3:26])([CH3:25])[CH3:27])[O:21][C:20]1=[O:28])[O:18][C:34]([O:36][CH3:37])=[O:35]
Reactant: COC(=O)Cl
Reactant: C[C@H](C=CC(O)[C@@]1(C)O[C@H](C(C)(C)C)OC1=O)[C@H]1CCC2C(O[Si](C)(C)C)CCC[C@@]21C
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: O
Product: COC(=O)OC(C=C[C@@H](C)[C@H]1CCC2C(O[Si](C)(C)C)CCC[C@@]21C)[C@@]1(C)O[C@H](C(C)(C)C)OC1=O

Procedure:
A 1.24 g amount of (5R,2S)-5-{(4R)-4-[(1R, 7aR)-octahydro-4-trimethylsilyloxy-7a-methyl-1H-inden-1-yl]-1-hydroxy-2-penten-1-yl}-5-methyl-2-t-butyl-1, 3-dioxolan-4-one and 1.0 g of 4-dimethylaminopyridine were dissolved in 15 ml of dichloromethane in a 50 ml eggplant-shaped flask. The solution was stirred under ice-cooling while slowly adding 315 μl of methyl chloroformate, then was stirred at the same temperature for 15 minutes and at room temperature for 1.5 hours. A 100 ml amount of ethyl acetate and 30 ml of water were added for separation, and extraction was performed from the aqueous layer by 50 ml of ethyl acetate. The organic layer was washed by a saturated aqueous solution of potassium hydrogensulfate, a saturated aqueous solution of sodium hydrogencarbonate, and saturated saline and was dried over anhydrous magnesium sulfate. The desiccant was filtered out, then the filtrate was concentrated under reduced pressure to obtain a crude product in an amount of 3.61 g. This was purified by a silica column (hexane/ethyl acetate=19/1 to 9/1) to obtain (5R,2S)-5-{(4R)-4-[(1R,7aR)-octahydro-4-trimethylsilyloxy-7a-methyl-1H-inden-1-yl]-1-methoxycarbonyloxy-2-penten-1-yl}-5-methyl-2-t-butyl-1,3-dioxolan-4-one in an amount of 1.388 g (98%).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:13])[CH2:5][S:6][CH2:7][C:8]1[O:12][CH:11]=[CH:10][CH:9]=1)[CH3:2].I([O-])(=O)(=O)=[O:15].[Na+]>CO.O>[CH2:1]([O:3][C:4](=[O:13])[CH2:5][S:6]([CH2:7][C:8]1[O:12][CH:11]=[CH:10][CH:9]=1)=[O:15])[CH3:2]
Reactant: CCOC(=O)CSCc1ccco1
Reactant: [O-][I+3]([O-])([O-])[O-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CCOC(=O)CS(=O)Cc1ccco1

Procedure:
2.00 g of ethyl-2-(furfurylthio)acetate was dissolved in 40 ml of methanol, and stirred under cooling in an ice bath. 2.50 g of sodium metaperiodate dissolved in 20 ml of water was added dropwise, and stirred overnight at room temperature. The reaction product was extracted by adding 100 ml of dichloromethane, and washed with water. Dichloromethane was evaporated in vacuo, and the residue was purified by column chromatography using benzene:ethyl acetate=4:1 as developing solvent to obtain the captioned ethyl-2-(furfurylsulfinyl)acetate. Yield: 1.93 g.
Reaction SMILES: [CH3:1][NH:2][N:3]=[C:4]([CH3:10])[CH2:5][S:6]([CH3:9])(=[O:8])=[O:7].O1CCCC1.[CH3:16][N:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:19]([C:26](=[O:30])[C:27](Cl)=[O:28])=[CH:18]1>O>[CH3:1][N:2]([C:27](=[O:28])[C:26]([C:19]1[C:20]2[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=2)[N:17]([CH3:16])[CH:18]=1)=[O:30])[N:3]=[C:4]([CH3:10])[CH2:5][S:6]([CH3:9])(=[O:8])=[O:7]
Reactant: Cn1cc(C(=O)C(=O)Cl)c2ccccc21
Reactant: CNN=C(C)CS(C)(=O)=O
Solvent: C1CCOC1
Solvent: O
Product: CC(CS(C)(=O)=O)=NN(C)C(=O)C(=O)c1cn(C)c2ccccc12
Reaction time: 2 h
Yield: 72 %

Procedure:
To a 50 ml volume three-necked flask, 1-methyl-2-(1-methylsulfonyl-2-propylidene)hydrazine (5-2-1) (2.22 g) and tetrahydrofuran (anhydrous) (10 ml) were added under a nitrogen atmosphere. To the mixture, 2-(1-methyl-1H-indol-3-yl)-2-oxoacetyl chloride (26-a) (3.0 g) was added dropwise under ice-cooling, and stirred for 2 hours. The reaction mixture was added to iced water, and the precipitated solids were collected by filtration, washed with water and hexane, and dried under reduced pressure to give 3.4 g of 1-methyl-1-[2(1-methyl-1H-indol-3-yl)-2-oxoacetyl]-2-(1-methylsulfonyl-2-propylidene)hydrazine ((4-203-(13)28).
Reaction SMILES: [C:1]([O-:9])(=[O:8])[C:2]1C=[CH:6][CH:5]=[CH:4][CH:3]=1.[Na+].CN(C)C=[O:14]>>[C@@H:1]12[O:9][CH2:6][C@@H:5]([O:8]1)[CH:4]=[CH:3][C@H:2]2[OH:14]
Reactant: O=C([O-])c1ccccc1
Reactant: CN(C)C=O
Agent: [Na+]
Product: O[C@@H]1C=C[C@H]2CO[C@@H]1O2
Temperature: 25 °C
Reaction time: 0.42 h

Procedure:
10.5 g of 1,6-anhydro-3,4-dideoxy-2-O-(p-toluene)sulfonyl-β-D-threo-hex-3-enopyranose obtained in the above reaction, was dissolved in 100 ml of dried dimethylformamide, and 6 g of sodium benzoate was added thereto. The mixture was refluxed under heating for 30 minutes. The solvent was distilled off under reduced pressure, and 200 ml of water was added to the residue. The mixture was extracted with 300 ml of chloroform. The organic layer was washed once with 200 ml of a saturated sodium hydrogencarbonate aqueous solution and then washed twice with 200 ml of a saturated sodium chloride aqueous solution. Then, the organic layer was dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then the obtained syrup crude product was dissolved in 100 ml of dry methanol. Then, 2 ml of a methanol solution of sodium methoxide (28 wt %) was added thereto. The mixture was stirred for 25 minutes at room temperature. The reaction solution was neutralyzed with a 20% citric acid aqueous solution and then filtered through Celite® to remove the precipitate. The filtrate was concentrated under reduced pressure, and the obtained crude product was purified by silica gel column chromatography (ethyl acetate: hexane=1:2) to obtain 1.1 g of the desired product (Compound No. 103). The NMR analytical data of this product are as follows.
Reaction SMILES: [C:1]([CH2:3][C:4]1[CH:9]=[C:8]([CH3:10])[CH:7]=[C:6]([O:11][CH3:12])[CH:5]=1)#N.[OH-:13].[Na+].[OH2:15]>C(O)C>[CH3:12][O:11][C:6]1[CH:5]=[C:4]([CH2:3][C:1]([OH:15])=[O:13])[CH:9]=[C:8]([CH3:10])[CH:7]=1
Reactant: O
Reactant: [OH-]
Reactant: COc1cc(C)cc(CC#N)c1
Agent: [Na+]
Solvent: CCO
Product: COc1cc(C)cc(CC(=O)O)c1
Yield: 62 %

Procedure:
A solution of 1-bromomethyl-3-methoxy-5-methyl-benzene (1.66 g, 7.7 mmol) and sodium cyanide (1.89 g, 38.5 mmol) in ethanol (15 mL) and water (5 mL) was warmed to 60° C. for 2 hrs. The reaction mixture was cooled, concentrated in vacuo, diluted with water (100 mL), and extracted with methylene chloride (3×20 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo to afford 1.16 g of a light yellow oil. The crude 1-cyanomethyl-3-methoxy-5-methyl-benzene (1.16 g, 7.1 mmol) and sodium hydroxide (1.44 g, 35.9 mmol) in ethanol (20 mL) and water (10 mL) was refluxed overnight. The reaction mixture was cooled, concentrated in vacuo, diluted with water, and extracted with methylene chloride (3×10 mL). The aqueous layer was acidified to pH 2 with 6N hydrochloric acid and extracted with methylene chloride (3×20 mL). The combined organic layers were dried over magnesium sulfate, filtered and concentrated in vacuo to afford 0.86 g (62% for 2 steps) of (3-methoxy-5-methyl-phenyl)-acetic acid as an off white solid. This material was used without further purification: 1H NMR (300 MHz) compatible.
Reaction SMILES: [CH3:1][O-:2].[Na+].C(C1[C:10]2[CH:11]=[CH:12][C:13](OCCCBr)=[C:14]([CH2:15][CH2:16]C)[C:9]=2ON=1)C.[CH3:23][OH:24]>>[CH3:1][O:2][C:23](=[O:24])[CH:15]([C:14]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1)[CH3:16]
Reactant: CCCc1c(OCCCBr)ccc2c(CC)noc12
Reactant: C[O-]
Reactant: CO
Agent: [Na+]
Product: COC(=O)C(C)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 2-(3-chloro-4-dimethylcarbamoylthio)phenyl propionic acid methyl ester (0.106 g; 0.352 mmol) in dry methanol (1.42 mL) was treated with a solution of sodium methoxide in methanol (4.37 M; 0.113 mL; 0.493 mmol). The solution was refluxed for 4 hours and then cooled to room temperature. 3-ethyl-6-(3-bromopropyl)oxy-7-propyl-benz[4,5]isox-azole (0.096 grams; 0.293 mmol) was added and the reaction stirred for 1 hour. The reaction mixture was partitioned between isopropyl acetate and pH 4.0 buffer. The organic layer was dried over magnesium sulfate, filtered and evaporated. Silica gel chromatography afforded the title compound.
Reaction SMILES: [H-].[Na+].[OH:3][CH2:4][C@@H:5]1[CH2:10][C:9]([C:11]2[N:12]=[C:13]([SH:16])[S:14][CH:15]=2)=[CH:8][CH2:7][N:6]1[C:17]([O:19][CH2:20][CH:21]=[CH2:22])=[O:18].O(P(OC1C=CC=CC=1)O[C:32]1[C@H:38]([CH3:39])[C@H:37]2[N:34]([C:35](=[O:47])[C@@H:36]2[C@H:40]([O:42][Si](C)(C)C)[CH3:41])[C:33]=1[C:48]([O:50][CH2:51][CH:52]=[CH2:53])=[O:49])C1C=CC=CC=1.C(#N)C.Cl>C1COCC1.CN(C=O)C>[CH2:20]([O:19][C:17]([N:6]1[CH2:7][CH:8]=[C:9]([C:11]2[N:12]=[C:13]([S:16][C:32]3[C@H:38]([CH3:39])[C@H:37]4[N:34]([C:35](=[O:47])[C@@H:36]4[C@H:40]([OH:42])[CH3:41])[C:33]=3[C:48]([O:50][CH2:51][CH:52]=[CH2:53])=[O:49])[S:14][CH:15]=2)[CH2:10][C@H:5]1[CH2:4][OH:3])=[O:18])[CH:21]=[CH2:22]
Reactant: C=CCOC(=O)C1=C(OP(Oc2ccccc2)Oc2ccccc2)[C@H](C)[C@@H]2[C@@H]([C@@H](C)O[Si](C)(C)C)C(=O)N12
Reactant: C=CCOC(=O)N1CC=C(c2csc(S)n2)C[C@H]1CO
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CC#N
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: C=CCOC(=O)C1=C(Sc2nc(C3=CCN(C(=O)OCC=C)[C@H](CO)C3)cs2)[C@H](C)[C@@H]2[C@@H]([C@@H](C)O)C(=O)N12
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 46 %

Procedure:
Sodium hydride (60 w/w %, 13.3 mg, 0.33 mmol) was added at 0–5° C. to a solution of allyl (2S)-2-(hydroxymethyl)-4-(2-mercapto-1,3-thiazol-4-yl)-3,6-dihydro-1(2 H)-pyridinecarboxylate (purity 70%, 139 mg, 0.33 mmol) in a mixture of THF (11.0 ml) and DMF(0.5 ml) and the mixture was stirred for 10 minutes. To the reaction solution was added at 0° C. a solution of allyl (4R,5R,6S)-3-[(diphenoxyphosphino)oxy]-4-methyl-7-oxo-6-{(1R)-1-[(trimethylsilyl)oxy]ethyl}-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate in acetonitrile (30%, 1.27 g, 0.67 mmol) and the solution was allowed to stand in a refrigerator for 16 hours. To the reaction solution was added ice water and the solution was adjusted to pH 3 at 0–5° C. with 1N hydrochloric acid. After the mixture was stirred for 30 minutes, the reaction mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution and dried over anhydrous sodium sulfate. After removal of the solvent in vacuo, the residue was purified with thin layer chromatography (10% methanol in chloroform) to give allyl (4R,5S,6S)-3-({4-[(2S)-1-[(allyloxy)carbonyl]-2-(hydroxymethyl)-1,2,3,6-tetrahydro-4-pyridinyl]-1,3-thiazol-2-yl}sulfanyl)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (87 mg, 46%).
Reaction SMILES: [OH:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[S:4][C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19].C(N(CC)CC)C.[C:27](OC(=O)C)(=[O:29])[CH3:28]>C(#N)C.CN(C)C1C=CN=CC=1>[C:27]([O:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[S:4][C:3]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19])(=[O:29])[CH3:28]
Reactant: Cc1ccccc1-c1sc(-c2ccccc2)cc1O
Reactant: CC(=O)OC(C)=O
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CC(=O)Oc1cc(-c2ccccc2)sc1-c1ccccc1C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
3-Hydroxy-2-(2-methylphenyl)-5-phenylthiophene (537 mg, 2.02 mmol) was dissolved in acetonitrile (4.0 mL), and 4-dimethylaminopyridine (15 mg, 0.12 mmol) and triethylamine (0.65 mL, 470 mg, 6.9 mmol) were added followed by acetic anhydride (0.65 mL, 700 mg, 6.9 mmol). The reaction was stirred overnight at 25° C. The reaction mixture was evaporated and the residue was chromatographed on 30 g of silica gel eluting with 700 mL of 15% ethyl acetate in hexane. 3-Acetoxy-2-(2'-methylphenyl)-5-phenylthiophene was isolated as 370 mg of viscous oil. The product could be distilled bulb-to-bulb, bp (0.4 mm) 140°-150° C.
Reaction SMILES: [CH2:1]([NH2:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].Cl[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[N+:27]([O-:29])=[O:28]>CCCCCC>[N+:27]([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[NH:19][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])([O-:29])=[O:28]
Reactant: O=[N+]([O-])c1ccccc1Cl
Reactant: CCCCCCCCCCCCCCCCCCN
Solvent: CCCCCC
Product: CCCCCCCCCCCCCCCCCCNc1ccccc1[N+](=O)[O-]
Temperature: 125 °C
Reaction time: 17.5 h
Yield: 97.8 %

Procedure:
Octadecylamine (11.858 g) was added to 2-chloronitrobenzene (3.151 g) and the mixture was stirred for 17.5 hours at 125° C. After n-hexane was added to the reaction mixture, solid materials were crushed well and removed out by filtration. The filtrate was concentrated and the residue (9.13 g) was purified by silica gel column chromatography (silica gel 90 g, n-hexane:ethyl acetate=50:1), thereby yielding the entitled compound (7.642 g) as yellow solid.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([S:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]2[CH:16]=[C:17]([CH3:28])[C:18]3[NH:23][C:22](=[O:24])[O:21][C:20]([CH3:26])([CH3:25])[C:19]=3[CH:27]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].[OH:29]O>>[Cl:1][C:2]1[CH:3]=[C:4]([S:9]([CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]2[CH:16]=[C:17]([CH3:28])[C:18]3[NH:23][C:22](=[O:24])[O:21][C:20]([CH3:25])([CH3:26])[C:19]=3[CH:27]=2)=[O:29])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: Cc1cc(OCCCCSc2ccc(Cl)c(Cl)c2)cc2c1NC(=O)OC2(C)C
Reactant: OO
Product: Cc1cc(OCCCCS(=O)c2ccc(Cl)c(Cl)c2)cc2c1NC(=O)OC2(C)C

Procedure:
Prepared analogously to Example 2 from 6-[4-(3,4-dichloro-phenylmercapto)-butoxy]-4,4,8-trimethyl-4H-3,1-benzoxazin-2-one and hydrogen peroxide.
Reaction SMILES: [CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[CH:9][C:10]([C:23]([O:25][CH3:26])=[O:24])=[C:11]3[C:16]=2[O:15][CH2:14][CH:13]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[NH:12]3)=[C:5]([CH3:27])[O:4][N:3]=1.Cl.[N:29]([O-])=[O:30].[Na+]>C(OCC)(=O)C.O>[CH3:1][C:2]1[C:6]([C:7]2[CH:8]=[CH:9][C:10]([C:23]([O:25][CH3:26])=[O:24])=[C:11]3[C:16]=2[O:15][CH2:14][CH:13]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:12]3[N:29]=[O:30])=[C:5]([CH3:27])[O:4][N:3]=1
Reactant: COC(=O)c1ccc(-c2c(C)noc2C)c2c1NC(c1ccccc1)CO2
Reactant: O=N[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Product: COC(=O)c1ccc(-c2c(C)noc2C)c2c1N(N=O)C(c1ccccc1)CO2
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 91.9 %

Procedure:
A suspension of methyl 8-(3,5-dimethylisoxazol-4-yl)-3-phenyl-3,4-dihydro-2H-1,4-benzoxazine-5-carboxylate (0.230 g, 0.631 mmol) in ethyl acetate (6.13 mL) was cooled to 0° C. and treated with 6.0 M hydrogen chloride in water (0.789 mL, 4.73 mmol) and water (0.460 mL) followed by sodium nitrite (0.0871 g, 1.26 mmol) in water (0.690 mL) dropwise. The reaction mixture was stirred at 0° C. for 15 min, the ice bath was removed, and stirred for 30 min which gave a biphasic solution. After another 30 min a suspension was present. The reaction mixture was diluted with EtOAc (40 mL) and water (20 mL). The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated to give a crude tan solid. Purification by flash column chromatography (100% hexanes to 50% EtOAc/hexanes) gave the desired product (0.228 g, 92%) as a yellow solid. LCMS calculated for C21H20N2O4 ([M−NO]+H)+: m/z=364.1. found: 364.1.
Reaction SMILES: C1(C)[CH:6]=[CH:5][C:4]([S:7](O)(=O)=O)=CC=1.[CH2:12]([SH:16])[CH:13]([SH:15])C.[CH3:17]CC=S>C1CCCCC1>[CH3:6][CH:5]1[CH2:4][S:7][CH:13]([CH2:12][S:16][CH3:17])[S:15]1
Reactant: CCC=S
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: CC(S)CS
Solvent: C1CCCCC1
Product: CSCC1SCC(C)S1
Reaction time: 1 h

Procedure:
Into a 100 ml reaction flask equipped with reflux condensor, heating mantle, hot plate equipped with magnetic stirring apparatus and magnetic stirring bar is placed 10 ml cyclohexane, 0.5 grams of para toluene sulfonic acid and 10.8 grams (0.1 mole) of 1,2-propanedithiol. Over a period of one hour, 9 grams (0.1 mole) of methylthioacetaldehyde is added to the reaction mass. The reaction mass is then heated to reflux and maintained at reflux for a period of eight hours. At the end of the eight hour period the reaction mass is transferred to a separatory funnel and washed with one 50 ml portion of a saturated aqueous sodium chloride solution, then dried over anhydrous sodium sulfate, filtered and distilled. The distillation takes place on a micro vigreux column yielding the following fractions: