Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9]([CH:11]1[CH2:14][CH:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:12]1)=O>C(O)(=O)C>[CH2:16]([O:15][CH:13]1[CH2:14][CH:11]([C:9]2[NH:8][C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[N:1]=2)[CH2:12]1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: Nc1ccccc1NC(=O)C1CC(OCc2ccccc2)C1
Solvent: CC(=O)O
Product: c1ccc(COC2CC(c3nc4ccccc4[nH]3)C2)cc1
Temperature: 25 °C

Procedure:
A solution of N-(2-aminophenyl)-3-(benzyloxy)cyclobutanecarboxamide (1.78 g, 6.01 mmol) in acetic acid was heated to 100° C. for 1 h, then cooled to RT. The acetic acid was removed in vacuo and ethyl acetate was added to the resulting oil. The resulting suspension was filtered and the collected solid was air dried to give 2-(3-(Benzyloxy)cyclobutyl)-1H-benzo[d]imidazole. The filtrate was concentrated in vacuo to give another suspension, which was filtered, air dried, and added to the first crop of product to give a total of 0.96 g (3.43 mmol, 57% yield) of 2-(3-(Benzyloxy)cyclobutyl)-1H-benzo[d]imidazole as a white solid.
Reaction SMILES: Br[C:2]1[S:24][C:5]2=[N:6][C:7]([Cl:23])=[C:8]([CH:10]([N:12]3[C:20](=[O:21])[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[C:13]3=[O:22])[CH3:11])[CH:9]=[C:4]2[CH:3]=1>[Pd]>[Cl:23][C:7]1[N:6]=[C:5]2[S:24][CH:2]=[CH:3][C:4]2=[CH:9][C:8]=1[CH:10]([N:12]1[C:13](=[O:22])[C:14]2[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:20]1=[O:21])[CH3:11]
Reactant: CC(c1cc2cc(Br)sc2nc1Cl)N1C(=O)c2ccccc2C1=O
Agent: [Pd]
Product: CC(c1cc2ccsc2nc1Cl)N1C(=O)c2ccccc2C1=O
Reaction time: 96 h

Procedure:
In a hydrogenation apparatus, 2-(1-(2-bromo-6-chlorothieno[2,3-b]pyridin-5-yl)ethyl)isoindoline-1,3-dione (800 mg, 1.9 mmol) and 5% palladium on carbon (151 mg) were combined. The reaction vessel was purged with nitrogen and 60 mL ethyl acetate, 15 mL ethanol, and 15 drops of concentrated HCl were added. The reaction vessel was pressurized with hydrogen gas to 50 psi. After 4 days, the apparatus was purged with nitrogen and the contents were filtered through celite. The Celite™ pad was washed with ethyl acetate to afford an orange solution. The solvent was removed on the rotovap and redissolved in dichloromethane. Silica gel (3.2 g) was added to the dichloromethane solution and the solvent was removed on the rotovap. The silica gel was transferred to the head of a chromatography column and eluted with 15% ethyl acetate in hexanes to afford 2-(1-(6-chlorothieno[2,3-b]pyridin-5-yl)ethyl)isoindoline-1,3-dione and recovered 2-(1-(2-bromo-6-chlorothieno[2,3-b]pyridin-5-yl)ethyl)isoindoline-1,3-dione. LC/MS (M+1, found=343.0). 1H NMR (400 MHz, CDCl3) δ 8.52 (s, 1H), 7.82 (m, 2H), 7.72 (m, 2H), 7.54 (d, J=5.9 Hz, 1H), 7.32 (d, J=5.9 Hz, 1H), 5.95 (q, J=7.0 Hz, 1H), 1.95 (d, J=7.0 Hz, 3H) ppm.
Reaction SMILES: C(O[C:4](=[O:20])[C:5](=[CH:11][NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH3:19])[N:14]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7])C.C1(OC2C=CC=CC=2)C=CC=CC=1>CCCCCC.C(OCC)(=O)C>[CH2:9]([O:8][C:6]([C:5]1[C:4](=[O:20])[C:18]2[C:13](=[N:14][C:15]([CH3:19])=[CH:16][CH:17]=2)[NH:12][CH:11]=1)=[O:7])[CH3:10]
Reactant: CCOC(=O)C(=CNc1cccc(C)n1)C(=O)OCC
Solvent: CCCCCC
Solvent: CCOC(C)=O
Solvent: c1ccc(Oc2ccccc2)cc1
Product: CCOC(=O)c1c[nH]c2nc(C)ccc2c1=O
Temperature: 25 °C
Yield: 67.6 %

Procedure:
Add 2-[(6-methyl-pyridin-2-ylamino)-methylene]-malonic acid diethyl ester (14.8 g) to the refluxing phenyl ether (100 ml) over a period of 5 min under nitrogen. After the addition is complete, keep the reaction under reflux for 3 h. Cool it to room temperature, and then pour the reaction mixture into 1:1 hexane/ethyl acetate (2000 ml). Collect the brown precipitate by filtration to obtain 7-methyl-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid ethyl ester (8.35 g, 72% for two steps). MS (ES+): 233 (M+H); (ES−): 231 (M−H).
Reaction SMILES: C([Li])CCC.[CH3:6][S:7][CH2:8][P:9](=[O:16])([O:13][CH2:14][CH3:15])[O:10][CH2:11][CH3:12].[CH2:17]([C:21]1[CH:26]=[C:25](Cl)[N:24]2[N:28]=[CH:29][CH:30]=[C:23]2[N:22]=1)[CH2:18][CH2:19][CH3:20]>C1COCC1.C(OCC)(=O)C>[CH2:17]([C:21]1[CH:26]=[C:25]([CH2:6][S:7][CH2:8][P:9](=[O:16])([O:13][CH2:14][CH3:15])[O:10][CH2:11][CH3:12])[N:24]2[N:28]=[CH:29][CH:30]=[C:23]2[N:22]=1)[CH2:18][CH2:19][CH3:20]
Reactant: CCCCc1cc(Cl)n2nccc2n1
Reactant: CCOP(=O)(CSC)OCC
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CCCCc1cc(CSCP(=O)(OCC)OCC)n2nccc2n1
Temperature: -78 °C
Reaction time: 1 h
Yield: 66.6 %

Procedure:
30.7 ml of n-butyl lithium (1.63 M, n-hexane solution) was diluted with 35 ml of THF, and the diluted solution was cooled to −78° C. in an atmosphere of argon. Thereto was added a solution of 10.4 g of diethyl methylthiomethylphosphonate in 10 ml of THF, followed by stirring at −78° C. for 1 hour. Thereto was added dropwise a solution of 5 g of 5-n-butyl-7-chloropyrazolo[1,5-a]pyrimidine in 5 ml of THF, followed by stirring at −78° C. for 1 hour. The reaction mixture was diluted with ethyl acetate and washed sequentially with aqueous ammonium chloride solution, water and saturated saline and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; ethyl acetate:n-hexane=1:3→1:1). As a result, 5.9 g of diethyl (5-n-butylpyrazolo[1,5-a]pyrimidin-7-yl)methylthiomethylphosphonate was obtained as an oily product.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]([O:13]C)=[O:12])=[C:8]([CH3:15])[C:7]=2[CH:16]=1)#[N:2].O1CCCC1.O.O.[OH-].[Li+]>CO>[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]([OH:13])=[O:12])=[C:8]([CH3:15])[C:7]=2[CH:16]=1)#[N:2]
Reactant: COC(=O)c1oc2ccc(C#N)cc2c1C
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Solvent: O
Product: Cc1c(C(=O)O)oc2ccc(C#N)cc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 91.2 %

Procedure:
To a mixture of methyl 5-cyano-3-methyl-1-benzofuran-2-carboxylate (4.20 g) synthesized above, tetrahydrofuran (80 mL), water (20 mL) and methanol (20 mL) was added lithium hydroxide monohydrate (1.64 g), and the mixture was stirred overnight at room temperature, and concentrated under reduced pressure. 1N Hydrochloric acid was added to the residue, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was washed with diisopropyl ether to give the title object compound (3.58 g, 91%) as a pale-brown solid.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:25])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]([C:18]([O:20]C(C)(C)C)=[O:19])[C:11]([O:13]C(C)(C)C)=[O:12])[CH3:2].C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:25])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]([C:11]([OH:13])=[O:12])[C:18]([OH:20])=[O:19])[CH3:2]
Reactant: CCOC(=O)CCCCCC(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCOC(=O)CCCCCC(C(=O)O)C(=O)O
Reaction time: 8 h
Yield: 95.3 %

Procedure:
To a solution of triester 61 (500 mg, 1.395 mmol) in CH2Cl2 (20 mL) was added TFA (2.0 mL) and the reaction mixture stirred overnight. Volatile components were evaporated under vacuum, and the residue repeatedly dissolved in CH2Cl2 and evaporated to remove all traces of TFA. A solid 62 (327 mg, 1.33 mmol) was obtained and used directly in the next step without further purification. 1H-NMR(400 MHz, DMSO-d6) δ 12.62 (br s, 2H), 4.03 (q, 2H), 3.16 (t, 1H), 2.25 (t, 2H), 1.67 (m, 2H), 1.49 (m, 2H), 1.25 (m, 4H), 1.16 (t, 3H).
Reaction SMILES: [CH2:1]([O:8][N:9]1[CH2:13][CH2:12][NH:11][C:10]1=[N:14][C:15]1[C:20]([Cl:21])=[CH:19][CH:18]=[CH:17][C:16]=1[Cl:22])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:23](=O)([O-])[O-].[Na+].[Na+].CI.Cl>CO.CC(C)=O.O1CCOCC1.CCOCC>[ClH:21].[CH2:1]([O:8][N:9]1[CH2:13][CH2:12][N:11]=[C:10]1[N:14]([CH3:23])[C:15]1[C:16]([Cl:22])=[CH:17][CH:18]=[CH:19][C:20]=1[Cl:21])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Clc1cccc(Cl)c1N=C1NCCN1OCc1ccccc1
Reactant: O=C([O-])[O-]
Agent: Cl
Agent: [Na+]
Solvent: CI
Solvent: CCOCC
Solvent: C1COCCO1
Product: CN(C1=NCCN1OCc1ccccc1)c1c(Cl)cccc1Cl
Reaction time: 4 h

Procedure:
A solution of 16.8 g of 1-(benzyloxy)-2-[(2,6-dichlorophenyl)imino]imidazolidine in 150 ml of dry methanol is treated with 5.83 g of sodium carbonate and 7.81 g of methyl iodide. The mixture is heated to reflux while stirring for 4 hours and then evaporated in vacuo. The residue is partitioned between water and methylene chloride. The organic phase is dried and evaporated. The residual oil is chromatographed on silica gel while eluting with a mixture of chloroform and ethanol (9:1). There is obtained an oil which is dissolved in acetone and treated with hydrogen chloride in dioxane and then with ether until turbidity occurs. The 1-(benzyloxy)-2-(2,6-dichloro-N-methylanilino)-2-imidazoline hydrochloride obtained melts at 185°-186°.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[CH:9](O)[CH2:8][CH2:7][CH2:6]2.P(Cl)(Cl)(Cl)=O.[C:21]([O-])(=[O:23])C.[Na+].O>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH3:14])[CH:9]=[C:8]([CH:21]=[O:23])[CH2:7][CH2:6]2
Reactant: CC(=O)[O-]
Reactant: COc1cc2c(cc1OC)C(O)CCC2
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O=P(Cl)(Cl)Cl
Solvent: O
Product: COc1cc2c(cc1OC)CCC(C=O)=C2
Temperature: 90 °C
Reaction time: 0.17 h
Yield: 46 %

Procedure:
A solution of 6,7-dimethoxy-1,2,3,4-tetrahydronaphthalen-1-ol (208 mg, 1 mmol) in dry DMF (5 mL) was cooled in an ice bath and phosphoryl chloride (0.2 mL, 2.3 mmol) was added dropwise. The reaction mixture was heated at 90° C. for 3 hours, then cooled and treated with a cold saturated aqueous solution of sodium acetate (2 mL) and stirred at room temperature for 10 min. Water was added and the mixture was extracted with DCM. The combined organic phase was washed with brine and dried over sodium sulfate. The solvent was then removed under reduced pressure to afford 6,7-dimethoxy-3,4-dihydronaphthalene-2-carbaldehyde as white solid (160 mg, 46%). LC-MS (ES-API); rt 8.23 min; m/z calculated for C13H14O3 [M+H]+ 219.1, found 219.0.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[CH2:9]([N:13]1[CH:17]=[CH:16][N:15]=[N:14]1)[CH2:10][C:11]#[CH:12].C(N(CC)CC)C.ClCCl>CN(C=O)C.[Cu](I)I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:8][C:5]1[N:4]=[CH:3][C:2]([C:12]#[C:11][CH2:10][CH2:9][N:13]2[CH:17]=[CH:16][N:15]=[N:14]2)=[CH:7][N:6]=1
Reactant: Clc1ncc(Br)cn1
Reactant: C#CCCn1ccnn1
Agent: I[Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Clc1ncc(C#CCCn2ccnn2)cn1
Reaction time: 4 h

Procedure:
5-Bromo-2-chloro-pyrimidine (0.500 g, 2.53 mmol), 1-but-3-ynyl-1H-[1,2,3]triazole (0.368 g, 3.03 mmol) and triethyl amine (NEt3) (5.0 ml) are dissolved in DMF (10 ml) and copper iodide (CuI) (0.052 g, 0.27 mmol) is added under stirring. After passing a stream of argon through the mixture for 10 min tetrakis(triphenylphosphine)palladium(0) (0.149 g, 0.13 mmol) is added and stirring is continued for 4 h at 80° C. Dichloromethane (125 ml) is added, the mixture is washed with 0.5N hydrochloric acid (HCl) and brine, dried over Na2SO4 and concentrated in vacuo. The crude product is purified by flash column chromatography (ethyl acetate/hexanes 4:1) yielding 2-chloro-5-(4-[1,2,3]triazol-1-yl-but-1-ynyl)-pyrimidine as a colorless solid. Yield 373 mg (63%).
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([O:10][Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:13])[CH3:12])=[CH:9][C:4]=2[CH:3]=[CH:2]1.[N+](=[CH:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])=[N-]>ClCCl.[O-]S(C(F)(F)F)(=O)=O.[Cu+]>[CH2:24]([O:23][C:21]([C@H:20]1[C@H:3]2[C@@H:2]1[O:1][C:5]1[CH:6]=[CH:7][C:8]([O:10][Si:11]([C:14]([CH3:17])([CH3:16])[CH3:15])([CH3:12])[CH3:13])=[CH:9][C:4]=12)=[O:22])[CH3:25]
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc2occc2c1
Reactant: CCOC(=O)C=[N+]=[N-]
Agent: [Cu+]
Agent: O=S(=O)([O-])C(F)(F)F
Solvent: ClCCl
Product: CCOC(=O)[C@@H]1[C@H]2Oc3ccc(O[Si](C)(C)C(C)(C)C)cc3[C@H]21
Yield: 108 %

Procedure:
Copper (I) triflate (2:1 complex with toluene, 250 mg, 2.4%) and (S,S)-(±)-2,2-isopropylidenebis(4-tert-butyl)-2-oxazoline (205 mg, 3.4%) were stirred in dichloromethane (15 mL) at ambient temperature under N2 atmosphere for 1 hour. A solution of (benzofuran-5-yloxy)(tert-butyl)dimethylsilane (5.0 g, 20.2 mmol) in dichloromethane (85 mL) was added, followed by a slow addition of ethyl diazoethanoate (40 mL, 380 mmol) during a period of 10 hours using a syringe pump. The mixture was concentrated and purified by column chromatography to afford crude compound (7.3 g) which was used for the next step without any further purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[C:9](B2OC(C)(C)C(C)(C)O2)[CH:8]=[CH:7][C:4]=1[C:5]#[N:6].Br[C:21]1[CH:22]=[N:23][CH:24]=[C:25]([Cl:30])[C:26]=1[CH:27]([OH:29])[CH3:28].C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:30][C:25]1[C:26]([CH:27]([OH:29])[CH3:28])=[C:21]([C:9]2[CH:8]=[CH:7][C:4]([C:5]#[N:6])=[C:3]([O:2][CH3:1])[CH:10]=2)[CH:22]=[N:23][CH:24]=1
Reactant: CC(O)c1c(Cl)cncc1Br
Reactant: COc1cc(B2OC(C)(C)C(C)(C)O2)ccc1C#N
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: COc1cc(-c2cncc(Cl)c2C(C)O)ccc1C#N
Temperature: 100 °C
Yield: 50.4 %

Procedure:
To the solution of 2-Methoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzonitrile (570 mg, 2.20 mmol), 1-(3-Bromo-5-chloro-pyridin-4-yl)-ethanol (520 mg, 2.20 mmol) and PdCl2(dppf). CH2Cl2 adduct (65 mg, 0.08 mmol) in DMF (10 mL) was added Na2CO3 solution (2M in eater, 2.75 ml, 5.50 mmol) under Nitrogen atmosphere. The mixture was stirred and heated at 100° C. for 6 hrs. After letting cool to room temperature, solvent was removed in vacuo. The residue was dissolved in DCM and saturated NH4Cl solution. After extraction with DCM and separation, the combined extracts were concentrated and purified by ISCO 40 g (10% MeOH/DCM, v/v, 0-25%) to give 4-[5-Chloro-4-(1-hydroxy-ethyl)-pyridin-3-yl]-2-methoxy-benzonitrile (320 mg, 50%) as colorless solid; ESI-MS m/z: 289 [M+1]+, Retention time: 1.30 min; 1H-NMR (MeOD, 400 MHz) δ 1.55 (d, J=6.8 Hz, 3H), 4.01 (s, 3H), 5.13 (q, J=6.8 Hz, 1H), 7.07 (dd, J=8.0, 2.0 Hz, 1H), 7.19 (d, J=2.0 Hz, 1H), 7.73 (d, J=8.0 Hz, 1H), 8.31 (s, 1H), 8.61 (s, 1H).
Reaction SMILES: [C:1]([C:4]1[C:12]2[C:7](=[CH:8][C:9]([C:13]([NH2:15])=[O:14])=[CH:10][CH:11]=2)[N:6]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[Cl:23])[C:5]=1[CH2:24][CH2:25][CH3:26])(=O)[CH3:2].Cl.[NH2:28][OH:29].C([O-])(=O)C.[Na+]>C(O)C>[Cl:23][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[CH2:16][N:6]1[C:7]2[C:12](=[CH:11][CH:10]=[C:9]([C:13]([NH2:15])=[O:14])[CH:8]=2)[C:4]([C:1](=[N:28][OH:29])[CH3:2])=[C:5]1[CH2:24][CH2:25][CH3:26]
Reactant: CCCc1c(C(C)=O)c2ccc(C(N)=O)cc2n1Cc1ccccc1Cl
Reactant: NO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: CCCc1c(C(C)=NO)c2ccc(C(N)=O)cc2n1Cc1ccccc1Cl
Temperature: 100 °C
Yield: 86.1 %

Procedure:
To a suspension of 3-acetyl-l-(2-chlorobenzyl)-2-propylindole-6-carboxamide (36.5 mg) in ethanol (5 ml) was added hydroxylamine hydrochloride (70 mg) and sodium acetate (200 mg), and the mixture was heated in a sealed tube at 100° C. The reaction was evaporated in vacuo, then the residue was diluted with ethyl acetate and washed with water and brine. The organic phase was dried over sodium sulfate and evaporated in vacuo. The residue was triturated with diisopropyl ether to give l-(2-chlorobenzyl)-3-(1-hydroxyiminoethyl)-2-propylindole-6-carboxamide (32.7 mg).
Reaction SMILES: [N+]([O-])(O)=O.[N+:5]([O:8][CH2:9][CH2:10][NH2:11])([O-:7])=[O:6].[O:12]=[C:13]1[NH:17][CH:16]([C:18](O)=[O:19])[CH:15]([C:21]2[S:22][CH:23]=[CH:24][CH:25]=2)[S:14]1>>[N+:5]([O:8][CH2:9][CH2:10][NH:11][C:18]([CH:16]1[CH:15]([C:21]2[S:22][CH:23]=[CH:24][CH:25]=2)[S:14][C:13](=[O:12])[NH:17]1)=[O:19])([O-:7])=[O:6]
Reactant: NCCO[N+](=O)[O-]
Reactant: O=C1NC(C(=O)O)C(c2cccs2)S1
Solvent: O=[N+]([O-])O
Product: O=C1NC(C(=O)NCCO[N+](=O)[O-])C(c2cccs2)S1

Procedure:
A procedure similar to that described in Example 1 was repeated, but using 350 mg of N-(2-nitrooxyethyl)amine nitrate and 400 mg of 2-oxo-5-(2-thienyl)thiazolidine-4-carboxylic acid, to obtain 260 mg of the title compound as colorless crystals, melting at 120°-122° C. (after recrystallization from ethanol).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:38])[C:5]([CH3:37])([O:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][C:17]2[N:18]=[C:19]([C:23]3[CH:28]=[CH:27][C:26]([C:29]#[C:30]C4C=CC=CC=4)=[CH:25][CH:24]=3)[O:20][C:21]=2[CH3:22])=[CH:10][CH:9]=1)[CH3:6])[CH3:2]>CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:38])[C:5]([O:7][C:8]1[CH:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][C:17]2[N:18]=[C:19]([C:23]3[CH:28]=[CH:27][C:26]([C:29]#[CH:30])=[CH:25][CH:24]=3)[O:20][C:21]=2[CH3:22])=[CH:12][CH:13]=1)([CH3:6])[CH3:37])[CH3:2]
Reactant: CCOC(=O)C(C)(C)Oc1ccc(OCCc2nc(-c3ccc(C#Cc4ccccc4)cc3)oc2C)cc1
Solvent: CCOC(C)=O
Product: C#Cc1ccc(-c2nc(CCOc3ccc(OC(C)(C)C(=O)OCC)cc3)c(C)o2)cc1

Procedure:
2-Methyl-2-(4-{2-[5-methyl-2-(4-phenylethynylphenyl)-oxazol-4-yl]ethoxy}-phenoxy)propionic acid ethyl ester Rf=0.38 in 1:4 EtOAc:hexanes; 1H NMR (400 MHz, CDCl3) δ 7.93 (d, 2H), 7.56 (d, 2H) 7.48, (m, 2H), 7.33-7.32 (m, 3H) 6.81-6.74 (m, 4H), 4.21-4.15 (m, 4H), 2.93 (t, 2H), 2.34 (s, 3H), 1.53 (s, 6H), 1.24 (t, 3H); MS (EI) 532.2 (M+Na)+, 510.2 (M+H)+.
Reaction SMILES: [CH2:1]([O:8][CH2:9][C:10]1[CH2:14][CH2:13][C:12](=[O:15])[CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl>CCOCC>[CH2:1]([O:8][CH2:9][C@@H:10]1[CH2:14][CH2:13][C:12](=[O:15])[CH2:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C1C=C(COCc2ccccc2)CC1
Agent: Cl
Solvent: CCOCC
Product: O=C1CC[C@@H](COCc2ccccc2)C1
Yield: 75.9 %

Procedure:
Prepared according to the general procedure from 3-(benzyloxymethyl)cyclopent-2-enone (202 mg, 1 mmol) for 24 h at 0° C. After the reaction mixture was passed though a short pad of silica gel, the resulting solution was poured into 5 mL of a 10% HCl solution and diluted with 5 mL of Et2O. The organic layer was washed with 5 mL of a 10% HCl solution (4×) and with 5 mL of water (1×). The resulting solution was dried over MgSO4 and concentrated in vacuo to provide the title compound as a colorless oil (155 mg, 76% yield, 91% ee) after purification by flash chromatography on silica gel (15% Et2O/pentane). The enantiomeric ratio was determined by GLC using a Hydrodex-B-TBDAc (50 m×0.25 mm) column (150° C. isotherm, 1 mL/min.); (S) isomer tr=151.2 min. and (R) isomer tr=153.2 min. IR (film) 3030, 2860, 1740, 1404, 1100 cm−1; 1H NMR (300 MHz, CDCl3) δ 7.42-7.28 (m, 5H), 4.55 (s, 2H), 3.51 (d, 2H, J=6.3 Hz), 2.61-2.49 (m, 1H), 2.44-2.25 (m, 2H), 2.23-2.01 (m, 3H), 1.84-1.71 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 219.2, 138.1, 128.3, 127.4, 126.8, 73.2, 73.0, 41.9, 37.8, 36.7, 26.0; HRMS (EI+) exact mass calculated for [M]+ (C13H16O2) requires m/z 204.1150, found m/z 204.1144; [α]D22=+31.2° (c=1.0, CHCl3).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[NH:7][C:6]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:5]=3[C:4]=2[CH:3]=1.[C:16](#[N:19])[CH:17]=[CH2:18].O>C1C=CC=CC=1.C1(C)C=CC=CC=1.CO.ClCCl>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:18][CH2:17][C:16]#[N:19])[C:6]3[CH2:11][CH2:12][N:13]([CH3:15])[CH2:14][C:5]=3[C:4]=2[CH:3]=1
Reactant: CN1CCc2[nH]c3ccc(Cl)cc3c2C1
Reactant: C=CC#N
Solvent: Cc1ccccc1
Solvent: O
Solvent: ClCCl
Product: CN1CCc2c(c3cc(Cl)ccc3n2CCC#N)C1
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
8-chloro-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (1.00 g, 4.5 mmol) was stirred in benzene (15 mL) and toluene (20 mL). To this solution acrylonitrile (0.5 mL, 7.5 mmol) was added. The resulting reaction mixture was stirred at 0° C. for 10 minutes. Ice cold solution of 1 ml of Triton-B® was added to it. The reaction mixture was again stirred at room temperature for 4 h. The reaction was monitored by TLC in 10% Methanol-dichloromethane. Water was added to the reaction mixture and extracted organic layer was given water wash (3 times). The organic layer was then concentrated and purified by silica gel (100-200 mesh) chromatography using 0-10% methanol:dichloromethane as eluent. The obtained 3-(8-chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)propanenitrile was converted into its oxalate salt. 1H NMR (DMSO) 7.65 (d, 1H), 7.55 (s, 1H), 7.20 (d, 1H), 4.50 (t, 2H), 4.30 (m, 2H), 3.40 (m, 2H), 3.20 (m, 2H), 3.0 (t, 2H), 2.90 (s, 3H).
Reaction SMILES: [CH:1]([O:4][P:5]([CH2:7][CH3:8])[OH:6])([CH3:3])[CH3:2].[C:9](#[N:12])[CH:10]=[CH2:11].C(O)(C)C.[Na]>>[C:9]([CH2:10][CH2:11][P:5]([CH2:7][CH3:8])(=[O:6])[O:4][CH:1]([CH3:3])[CH3:2])#[N:12]
Reactant: C=CC#N
Reactant: CCP(O)OC(C)C
Agent: [Na]
Solvent: CC(C)O
Product: CCP(=O)(CCC#N)OC(C)C
Reaction time: 1 h

Procedure:
To 34 g of ethylphosphonous acid-isopropylester and 16.45 ml of acrylonitrile is added with stirring 40 ml of isopropanol containing 0.25 mol of sodium isopropylate. The reaction is exothermic. After 1 hour stirring at 20° the mixture is fractionated. There is obtained isopropyl 2-cyanoethyl(ethyl)phosphinate as a colorless oil, b.p. 102°-104°/10 Pa.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([N:9]1[CH2:13][CH:12]([OH:14])[CH2:11][CH:10]1[CH:15]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[O:16][CH:17]([C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1)[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)=[O:8].N1C=CC=CC=1.C1(=O)N(N[C:52]([O:54][CH2:55][CH:56]([O:77][CH2:78][CH2:79][CH2:80][CH2:81][CH2:82][CH2:83][CH2:84][CH2:85][CH2:86][CH2:87][CH2:88][CH2:89][CH2:90][CH2:91][CH2:92][CH2:93][CH2:94][CH3:95])[CH2:57][O:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH3:76])=[O:53])C(=O)CC1.CO.C(Cl)(Cl)Cl>ClCCl>[CH2:78]([O:77][CH:56]([CH2:57][O:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH3:76])[CH2:55][O:54][C:52](=[O:53])[NH:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([N:9]1[CH2:13][CH:12]([OH:14])[CH2:11][CH:10]1[CH:15]([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[O:16][CH:17]([C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][CH:27]=1)[C:18]1[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=1)=[O:8])[CH2:79][CH2:80][CH2:81][CH2:82][CH2:83][CH2:84][CH2:85][CH2:86][CH2:87][CH2:88][CH2:89][CH2:90][CH2:91][CH2:92][CH2:93][CH2:94][CH3:95]
Reactant: COc1ccc(C(OC(c2ccccc2)C2CC(O)CN2C(=O)CCCCCN)c2ccc(OC)cc2)cc1
Reactant: CCCCCCCCCCCCCCCCCCOCC(COC(=O)NN1C(=O)CCC1=O)OCCCCCCCCCCCCCCCCCC
Solvent: ClCCl
Solvent: c1ccncc1
Solvent: ClC(Cl)Cl
Product: CCCCCCCCCCCCCCCCCCOCC(COC(=O)NCCCCCC(=O)N1CC(O)CC1C(OC(c1ccc(OC)cc1)c1ccc(OC)cc1)c1ccccc1)OCCCCCCCCCCCCCCCCCC
Temperature: 0 °C
Reaction time: 3 h
Yield: 89 %

Procedure:
Amine 5 (10.5 g, 19.7 mmol) was dissolved in anhydrous dichloromethane (50 mL) and cooled to 0° C. To the solution were added pyridine (10 mL) and compound 11 (12.5 g, 17.3 mmol) successively. The reaction temperature was brought to ambient temperature and stirred further for 3 h. The completion of the reaction was ascertained by TLC (10% MeOH/CHCl3). The reaction mixture was diluted with dichloromethane and washed with saturated NaHCO3, water followed by brine. The organic layer was dried over sodium sulfate, filtered and concentrated under vacuum to afford the crude product. Compound 12 (17.8 g, 89%) was obtained as a white solid after column chromatography over silica gel.