Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: S(Cl)([Cl:3])=O.O[CH2:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]=[CH:9][CH:8]=1>ClCCl>[Cl:3][CH2:6][C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[N:10]=[CH:9][CH:8]=1
Reactant: OCc1ccnc2ccccc12
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: ClCc1ccnc2ccccc12
Temperature: 25 °C
Reaction time: 5 h
Yield: 116.7 %

Procedure:
Thionyl chloride (12 mL, 170 mmol) was added dropwise for 15 minutes to a solution of 4-(hydroxymethyl)quinoline (Reference Compound No. 3-1, 13 g 82 mmol) in anhydrous dichloromethane (200 mL) under ice-cooling, and the mixture was stirred for 5 hours at room temperature. The solvent was evaporated under reduced pressure, and the resulting solid was filtered off with ethyl acetate, and washed to give 17 g of mixture containing the title Reference Compound, as a yellow-white solid.
Reaction SMILES: [OH:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH:4]([NH:8]C(=O)OC(C)(C)C)[CH2:3]1.[C:16](O)(C(F)(F)F)=O>C(Cl)Cl>[NH2:8][CH:4]1[CH2:5][CH2:6][CH2:7][C:2]([CH3:16])([OH:1])[CH2:3]1
Reactant: CC(C)(C)OC(=O)NC1CCCC(O)C1
Reactant: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC1(O)CCCC(N)C1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of crude tert-butyl (3-hydroxycyclohexyl)carbamate (4.0 g, crude) in DCM (40 mL) was added TFA (20 mL) under cooling in an ice bath. The resulting reaction mixture was stirred at room temperature for 2 h. The mixture was concentrated to give a crude product (3.0 g, crude), which was used in the next step without further purification. MS (ESI) m/z 130.1 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=2)(=[O:11])=[O:10])=[C:4]([C:22](=[O:30])[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[Cl:29])[CH:3]=1.[BH4-].[Na+]>C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][S:9]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=2)(=[O:10])=[O:11])=[C:4]([CH:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[Cl:29])[OH:30])[CH:3]=1
Reactant: COc1ccc(S(=O)(=O)Nc2ccc(Cl)cc2C(=O)c2ccccc2Cl)cc1OC
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: COc1ccc(S(=O)(=O)Nc2ccc(Cl)cc2C(O)c2ccccc2Cl)cc1OC
Reaction time: 18 h

Procedure:
16 g of N-[4-chloro-2-(2-chlorobenzoyl)phenyl]-3,4-dimethoxybenzenesulfonamide dissolved in 900 ml of ethanol are added portionwise 3.93 g of sodium borohydride, and the mixture is left for 18 hours at room temperature. The reaction medium is concentrated and the residue is taken up in ethyl acetate and washed with water. The organic phase is dried over anhydrous sodium sulfate and concentrated. The residue is solidified with diisopropyl ether; after filtering off and drying the precipitate, 14.66 g of the expected product are obtained.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9](=[O:23])[C:10]([CH3:22])([CH3:21])[O:11][C:12]=2[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C=O)C.[Cl:35][C:36]1[N:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]2=[N:38][C:37]=1[CH2:45]Cl>O>[Cl:35][C:36]1[N:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]2=[N:38][C:37]=1[CH2:45][O:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:9](=[O:23])[C:10]([CH3:21])([CH3:22])[O:11][C:12]=2[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=2)=[CH:6][CH:7]=1
Reactant: COc1ccc(C2=C(c3ccc(O)cc3)C(=O)C(C)(C)O2)cc1
Reactant: ClCc1nc2ccccn2c1Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc(C2=C(c3ccc(OCc4nc5ccccn5c4Cl)cc3)C(=O)C(C)(C)O2)cc1
Temperature: 80 °C
Yield: 82.2 %

Procedure:
4-(4-Hydroxyphenyl)-5-(4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-one (200 mg, 0.64 mmol) was added to a mixture of cesium carbonate (843 mg, 2.5 mmol) and DMF (20 mL) at RT under an atmosphere of nitrogen. The reaction mixture was stirred at RT for 30 min, upon which 3-chloro-2-(chloromethyl)imidazo[1,2-a]pyridine (183 mg, 0.77 mmol) was added. The mixture was heated at 80° C. for 4 h (the reaction was monitored by TLC) upon which, the mixture was diluted with water and extracted with EtOAc. The combined organics were dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography using 18% ethyl acetate in n-hexane and silica gel (230-400 mesh) to afford 4-(4-((3-chloroimidazo[1,2-a]pyridin-2-yl)methoxy)phenyl)-5-(4-methoxyphenyl)-2,2-dimethylfuran-3(2H)-one (250 mg, 81%,) as an off-white solid. 1H NMR: 500 MHz, DMSO-d6: δ 8.4 (d, 1H), 7.7 (d, 1H), 7.55 (Ar, 3H), 7.7-6.9 (Ar, 10H), 5.2 (s, 2H) 3.8 (s, 3H), 1.4 (s, 6H). MS: [M+H]+: m/z=470.7. HPLC: (97.2%, Condition-A).
Reaction SMILES: [H-].[Na+].[CH3:3][C:4]([O:13][OH:14])([CH2:6][CH2:7][C:8]([CH3:12])([O:10][OH:11])[CH3:9])[CH3:5].[C:15]([N:19]=[N:20][C:21]1(Cl)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)([CH3:18])([CH3:17])[CH3:16]>O1CCOCC1>[CH3:5][C:4]([O:13][O:14][C:21]1([N:20]=[N:19][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)([CH2:6][CH2:7][C:8]([CH3:12])([O:10][O:11][C:21]1([N:20]=[N:19][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)[CH3:9])[CH3:3]
Reactant: CC(C)(CCC(C)(C)OO)OO
Reactant: CC(C)(C)N=NC1(Cl)CCCCC1
Agent: [H-]
Agent: [Na+]
Solvent: C1COCCO1
Product: CC(C)(C)N=NC1(OOC(C)(C)CCC(C)(C)OOC2(N=NC(C)(C)C)CCCCC2)CCCCC1
Temperature: 30 °C
Reaction time: 4 h
Yield: 80 %

Procedure:
To a cooled slurry of 2.47 grams (.0586 moles) of 57% sodium hydride in 80 ml. of dioxane in a 250 ml. 4 neck round bottom flask equipped with a magnetic stirrer, thermometer, addition fummel and gas outlet, was slowly added 3.88 grams (0.0196 moles) of 90% 2,5-dimethyl-2,5-dihydroperoxy-hexane containing 8% water. After the addition was complete the reaction was stirred for 4 hours at 30° C, cooled to 15° C in a cold water bath and 7.96 grams (.0392 moles) of 1-t-butylazo-1-chlorocyclohexane was added dropwise holding the temperature at 15° to 20° C. After the addition was complete the reaction was stirred for 30 minutes at 15° to 20° C and poured into 200 ml. of ice cold water. The product was extracted with 50 ml. of cold pentane, the pentane solution washed with ice cold water, saturated NaHCO3 solution, dried over anhydrous sodium sulfate, filtered and the pentane evaporated under reduced pressure while holding the temperature of the solution below 10° C. The product was a light yellow liquid weighing 8.0 grams (80% yield). The infrared spectrum of the crude azo-peroxide was in agreement with the stucture of the desired product.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[OH:12])[CH:3]=1.[H-].[Na+].[CH3:15]I.O>CN(C)C=O>[NH2:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[O:12][CH3:15])[CH:3]=1
Reactant: Nc1ccc2c(O)cccc2c1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1cccc2cc(N)ccc12
Temperature: 5 °C
Reaction time: 0.25 h
Yield: 77.2 %

Procedure:
A solution of commercially available 2-amino-5-hydroxynaphthalene (5.16 g, 31.48 mmol) in dimethylformamide (125 ml) was cooled with ice in an inert nitrogen atmosphere. Subsequently, NaH (1.39 g dispersion in a mineral oil at 60%, 34.6 mmoles) was added keeping the temperature below 10° C. and was shaken during 15 min. at ≈5° C. Subsequently methyl iodide (4.47 g, 31.48 mmol) solved in dimethylformamide (5 ml) was added and was left stirring at room temperature during 20 hrs. Water was added and it was evaporated to dryness in a rotavapor. To the remaining residue, water and ethylic ether were added. The aqueous phase was newly extracted with ether and the collection of organic phases was dried over Na2SO4, filtered, and evaporated to dryness. To the resulting crude slurry, a mixture of isopropylic alcohol/petroleum ether 1/1 was added, stirred during a few minutes and the insoluble precipitate was filtered. 4.21 g (77%) of 2-amino-5-methoxynaphthalene were obtained, with a purity determined by HPLC of 99%.
Reaction SMILES: I[CH:2]([CH3:4])[CH3:3].[OH:5][C:6]1[CH:15]=[C:14]([I:16])[CH:13]=[CH:12][C:7]=1[C:8]([O:10][CH3:11])=[O:9].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[I:16][C:14]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([O:5][CH:2]([CH3:4])[CH3:3])[CH:15]=1
Reactant: CC(C)I
Reactant: COC(=O)c1ccc(I)cc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)c1ccc(I)cc1OC(C)C
Yield: 98.3 %

Procedure:
2-Iodopropane (6.42 g) was added at room temperature to a mixture of methyl 2-hydroxy-4-iodobenzoate (7.00 g), potassium carbonate (6.96 g), and DMF (100 mL), and the resultant mixture was stirred at 70 C for 2 days in a nitrogen atmosphere. Water was added to the reaction mixture at room temperature, followed by extraction with ethyl acetate. The obtained organic layer was washed with water and saturated saline in this order and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (7.92 g)
Reaction SMILES: C([NH:4][C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:14])=[CH:11][CH:12]=2)[NH:7][C:6]=1[C:15](=[O:25])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([OH:24])=[O:23])[CH:17]=1)(=O)C.Cl.[CH3:27]O>>[NH2:4][C:5]1[C:13]2[C:8](=[CH:9][C:10]([Cl:14])=[CH:11][CH:12]=2)[NH:7][C:6]=1[C:15](=[O:25])[C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([C:22]([O:24][CH3:27])=[O:23])[CH:17]=1
Reactant: CC(=O)Nc1c(C(=O)c2cccc(C(=O)O)c2)[nH]c2cc(Cl)ccc12
Reactant: CO
Agent: Cl
Product: COC(=O)c1cccc(C(=O)c2[nH]c3cc(Cl)ccc3c2N)c1
Temperature: 60 °C

Procedure:
A mixture of 3-acetylamino-6-chloro-2-(3-carboxybenzoyl)indole (Example 132, 0.9 g, 2.5 mmol) and 10% HCl—MeOH (30 ml) was heated at 60° C. for 8 h. The mixture was cooled and concentrated, and the residue partitioned between water (100 ml) and ethyl acetate (100 ml). The organic layer was separated and washed with brine (50 ml), and dried (MgSO4) and solvent removed by evaporation. The residual solid was purified by flash column chromatography eluting with hexane/ethyl acetate (2/1) to afford 0.5 g of a title compound as a yellow solid. m.p.: 187-189° C. (ethyl acetate/hexane) 1H-NMR (DMSO-d6) δ: 9.14 (1H, br s), 8.47 (1H, dd, J=1.8, 1.1 Hz), 8.20 (1H, ddd, J=7.7, 1.8, 1.1 Hz), 8.03 (1H, ddd, J=7.7, 1.8, 1.1 Hz), 7.69-7.58 (2H, m), 7.28 (1H, d, J=1.8 Hz), 6.97 (1H, dd, J=1.4, 8.4 Hz), 6.04 (2H, br s), 3.95 (3H, s)
Reaction SMILES: [C:1]([OH:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8]/[CH:9]=[CH:10]\[CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].CC(C)C.NC(N)=O>ClCCCl>[C:1]1(=[O:20])[O:19][CH: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])[CH2:3][CH2:2]1
Reactant: CCCCCCCC/C=C\CCCCCCCC(=O)O
Agent: CC(C)C
Agent: NC(N)=O
Solvent: ClCCCl
Product: CCCCCCCCCCCCCCC1CCC(=O)O1
Yield: 8 %

Procedure:
One hundred grams of 98% oleic acid were heated in an autoclave at 220° C. for 3 hours in the presence of 10 grams of clay (bentonite), 70 grams of isobutane and 200 grams of 1,2-dichloroethane. Maximum pressure reached was 700 p.s.i. The autoclave was cooled, the isobutane released, catalyst removed by filtration, and the 1,2-dichloroethane removed at a reduced pressure of about 0.05 mm. The crude product mixture was distilled to give 69 grams of distillate and 31 grams of polymerized acids. The monomeric distillate was fractionated by urea adduction to give 53 grams of branched chain fatty acids, 8 grams of straight chain fatty acids and 8 grams of γ-stearolactone. GLC of the straight chain fraction showed it to be mostly saturated. The branched chain acids were C18 by GLC.
Reaction SMILES: [CH3:1][N:2]1[C:6]([CH:7]2[O:14][C:11]3([CH2:13][CH2:12]3)[CH2:10][CH:9]([CH3:15])[O:8]2)=[C:5]([N+:16]([O-:18])=[O:17])[CH:4]=[N:3]1.C(=O)([O-])[O-].[Na+].[Na+].C([O-])(O)=O.[Na+]>C(Cl)Cl.[Ti](Cl)(Cl)(Cl)Cl>[CH3:15][CH:9]1[CH2:10][C:11](=[O:14])[CH2:13][CH2:12][CH:7]([C:6]2[N:2]([CH3:1])[N:3]=[CH:4][C:5]=2[N+:16]([O-:18])=[O:17])[O:8]1
Reactant: CC1CC2(CC2)OC(c2c([N+](=O)[O-])cnn2C)O1
Agent: Cl[Ti](Cl)(Cl)Cl
Agent: O=C([O-])O
Agent: O=C([O-])[O-]
Solvent: ClCCl
Product: CC1CC(=O)CCC(c2c([N+](=O)[O-])cnn2C)O1
Temperature: 0 °C
Reaction time: 1 h
Yield: 74.9 %

Procedure:
To a solution of 1-methyl-5-(5-methyl-6,8-dioxaspiro[2.5]octan-7-yl)-4-nitro-pyrazole (1.0 g, 3.95 mmol) in DCM (20 mL) at −78° C. was added titanium tetrachloride (6.6 mL, 59.3 mmol) dropwise. Halfway through the addition, the reaction mixture became harder to stir so more DCM (10 mL) was added. The brown slurry was warmed to 0° C. and stirred for 1 hr. Solid sodium carbonate (5 g) was cautiously added followed by saturated aqueous NaHCO3 (100 mL) and DCM (100 mL). The organic layer was washed with saturated aqueous NaHCO3, (100 mL) and brine (100 mL), separated, dried over Na2SO4 and concentrated under reduced pressure. Purification via silica gel column chromatography (0-100% EtOAc/isohexane) gave 2-methyl-7-(2-methyl-4-nitro-pyrazol-3-yl)oxepan-4-one as a colourless solid (749 mg, 75%). 1H NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 5.69 (dd, J=11.0, 2.4 Hz, 1H), 4.21-4.14 (m, 1H), 4.01 (s, 3H), 3.07-2.97 (m, 1H), 2.79-2.63 (m, 3H), 2.19-2.07 (m, 1H), 2.07-1.91 (m, 1H), 1.30 (d, J=6.2 Hz, 3H).
Reaction SMILES: C(OC([N:11]1[CH2:15][C@@H:14]([OH:16])[C@H:13]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:12]1)=O)C1C=CC=CC=1.[H][H]>CO.O1CCCC1.[OH-].[Pd+2].[OH-]>[OH:16][C@@H:14]1[CH2:15][NH:11][CH2:12][C@H:13]1[NH:17][C:18](=[O:19])[O:20][C:21]([CH3:23])([CH3:22])[CH3:24]
Reactant: [H][H]
Reactant: CC(C)(C)OC(=O)N[C@@H]1CN(C(=O)OCc2ccccc2)C[C@H]1O
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N[C@@H]1CNC[C@H]1O
Yield: 85.3 %

Procedure:
To a solution of trans-3-tert-butoxycarbonylamino-4-hydroxy-pyrrolidine-1-carboxylic acid benzyl ester (3.9 g) in methanol (31 mL) and tetrahydrofuran (7 mL) was added palladium hydroxide (20 wt % Pd on carbon, 500 mg) and the mixture was stirred at room temperature under 40-45 psi of hydrogen atmosphere overnight. The resulting mixture was filtered and the filtrate was concentrated in vacuo. The residue was triturated in the mixture of ethyl acetate and diisopropylether and filtered to remove the insoluable materials. The filtrate was concentrated in vacuo to afford 2.0 g of trans-tert-butyl [4-hydroxypyrrolidin-3-yl]carbamate (yield was 94%) as a powder. MS obsd. (ESI+) [(M+H)+] 203.
Reaction SMILES: [Cl:1][C:2]1[CH:12]=[CH:11][C:10]([N:13]2[C:18](=[O:19])[C:17]3[CH2:20][CH2:21][CH2:22][C:16]=3[NH:15][C:14]2=[O:23])=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5].Br[CH2:25][C:26]#[CH:27]>>[Cl:1][C:2]1[CH:12]=[CH:11][C:10]([N:13]2[C:18](=[O:19])[C:17]3[CH2:20][CH2:21][CH2:22][C:16]=3[N:15]([CH2:27][C:26]#[CH:25])[C:14]2=[O:23])=[CH:9][C:3]=1[C:4]([O:6][CH2:7][CH3:8])=[O:5]
Reactant: CCOC(=O)c1cc(-n2c(=O)[nH]c3c(c2=O)CCC3)ccc1Cl
Reactant: C#CCBr
Product: C#CCn1c2c(c(=O)n(-c3ccc(Cl)c(C(=O)OCC)c3)c1=O)CCC2

Procedure:
using ethyl 2-chloro-5-(1,2,4,5,6,7-hexahydro-2,4-dioxo-3H-cyclopenta[d]pyrimidin-3-yl)-benzoate and 3-bromo-1-propyne there is obtained ethyl 2-chloro-5-{1,2,4,5,6,7-hexahydro-1-(2-propynyl)-2,4-dioxo-3H-cyclopenta[d]pyrimidin-3-yl}-benzoate, m.p. 121°-123° C.,
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:18])=[C:6]([CH:17]=1)[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][OH:16])=[CH:10][CH:9]=1.[CH2:19](Br)[CH:20]=[CH2:21].[OH-].[K+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O>[CH2:21]([O:16][CH2:15][CH2:14][C:11]1[CH:12]=[CH:13][C:8]([CH2:7][C:6]2[CH:17]=[C:2]([Br:1])[CH:3]=[CH:4][C:5]=2[Cl:18])=[CH:9][CH:10]=1)[CH:20]=[CH2:19]
Reactant: OCCc1ccc(Cc2cc(Br)ccc2Cl)cc1
Reactant: C=CCBr
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [I-]
Agent: [K+]
Solvent: O
Product: C=CCOCCc1ccc(Cc2cc(Br)ccc2Cl)cc1
Temperature: 25 °C
Reaction time: 6 h
Yield: 89 %

Procedure:
A mixture of 2-(4-(5-bromo-2-chlorobenzyl)phenyl)ethanol (intermediate BH) (245 mg, 0.75 mmol), allyl bromide (2.6 mL, 3.01 mmol), potassium hydroxide (84 mg, 1.5 mmol) and tetra-n-butylammonium iodide (13.9 mg, 0.037 mmol) was stirred at room temperature for 6 h. Water (1 mL) was added and extracted with chloroform (3×1 mL), washed with brine (1 mL) and dried (Na2SO4), filtered and evaporated. Preparative TLC using 10:1 hexane:EtOAc gave intermediate BI (246 mg, yield 89%), 1H NMR (300 MHz, CDCl3): δ 7.26-7.08 (m, 7H), 5.90 (m, 1H), 5.22 (m, 2H), 4.02 (s, 2H), 3.99 (m, 2H), 3.64 (t, J=6.9, 7.2 Hz, 2H), 2.89 (t, J=6.9, 7.2 Hz, 2H).
Reaction SMILES: CS(Cl)(=O)=O.[CH3:6][O:7][C:8]1[CH:24]=[CH:23][C:11]2[CH2:12][CH2:13][C:14]3[CH:15]=[CH:16][N:17]([CH2:19][C@H:20](O)[CH3:21])[C:18]=3[C:10]=2[CH:9]=1.C(N(CC)CC)C.[N-:32]=[N+:33]=[N-:34].[Na+]>ClCCl.C(OCC)C.CN(C)C=O.O>[N:32]([C@@H:20]([CH3:21])[CH2:19][N:17]1[C:18]2[C:10]3[CH:9]=[C:8]([O:7][CH3:6])[CH:24]=[CH:23][C:11]=3[CH2:12][CH2:13][C:14]=2[CH:15]=[CH:16]1)=[N+:33]=[N-:34]
Reactant: COc1ccc2c(c1)-c1c(ccn1C[C@@H](C)O)CC2
Reactant: [N-]=[N+]=[N-]
Agent: CS(=O)(=O)Cl
Agent: [Na+]
Solvent: CCOCC
Solvent: O
Solvent: ClCCl
Product: COc1ccc2c(c1)-c1c(ccn1C[C@H](C)N=[N+]=[N-])CC2
Yield: 72.1 %

Procedure:
1.4 ml of methanesulfonyl chloride were added dropwise while stirring to a solution, cooled to 0° C., of 2.25 g of (R)-1-(4,5-dihydro-8-methoxy-1H-benz[g]indol-1-yl)-propan-2-ol and 5 ml of triethyl-amine in 60 ml of dichloromethane and the mixture was stirred at this temperature for an additional 1.5 hours. The reaction mixture was subsequently diluted with 300 ml of diethyl ether, washed twice with 100 ml of saturated sodium hydrogen carbonate solution and the combined aqueous phases were extracted once with 100 ml of diethyl ether. The combined organic phases were washed with 100 ml of saturated sodium chloride solution, dried over magnesium sulfate and evaporated in a vacuum. The brown oil obtained was dissolved in 50 ml of anhydrous dimethyl formamide, treated with 1.17 g of sodium azide and the reaction mixture was heated to 60° for 15 hours while stirring. After cooling, the solution was poured into 140 ml of water and extracted twice with 140 ml of diethyl ether each time. The combined organic phases were washed once with 100 ml of water and once with 100 ml of saturated sodium chloride solution, dried over magnesium sulfate and the solution was concentrated in a vacuum. The brown oil obtained was purified by column chromatography on silica gel (toluene). 1.78 g (71%) of (S)-1-(2-azido-propyl)-4,5-dihydro-8-methoxy-1H-benz[g]indole were obtained as a colorless oil.
Reaction SMILES: Cl.[C:2]1([C@@H:8]2[CH2:10][C@H:9]2[NH2:11])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[S:12]1[CH2:18][C:16](=[O:17])[NH:15][C:13]1=S.C(N(C(C)C)CC)(C)C>C(#N)C>[C:2]1([C@@H:8]2[CH2:10][C@H:9]2[NH:11][C:13]2[S:12][CH2:18][C:16](=[O:17])[N:15]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: N[C@@H]1C[C@H]1c1ccccc1
Reactant: O=C1CSC(=S)N1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: O=C1CSC(N[C@@H]2C[C@H]2c2ccccc2)=N1
Temperature: 0 °C
Reaction time: 48 h
Yield: 40.8 %

Procedure:
To a suspension of (1R,2S)-2-phenyl-cyclopropylamine hydrochloride (0.8 μg, 5 mmol) and rhodanine (2-thioxo-thiazolin-4-one) (0.68 g, 5 mmol) in acetonitrile (20 mL) was added DIEA (diisopropylethylamine) (2.61 mL, 15 mmol) at room temperature. Then, this solution was cooled to 0° C. and mercuric chloride (1.35 g, 5 mmol) was added in two portions within a period of 10 min. After addition, the suspension was allowed to warm to room temperature and stirred for 2 days. The resulting black solids were filtered through a plug of celite and washed with ethyl acetate (500 mL). The filtrates were removed under the vacuum and the crude residue was diluted with water (100 mL) and ethyl acetate (100 mL). The two layers were separated and the aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic extracts were washed with brine solution and dried over anhydrous magnesium sulfate. Filtration of the drying agent and removal of the solvent under the vacuum gave the crude residue which was purified by using a Biotage silica gel column chromatography to obtain 0.474 g (42% yield) of 2-((1R,2S)-2-phenyl-cyclopropylamino)-thiazol-4-one as a white amorphous solid: EI-HRMS m/e calcd for C12H12N2OS (M+) 232.0670, found 232.0665.
Reaction SMILES: N(OC(C)(C)C)=O.CN(C)C=O.N[C:14]1[S:15][C:16]([CH2:19][C:20]2[CH:21]=[C:22]3[C:27](=[CH:28][CH:29]=2)[CH2:26][CH:25]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH2:24][CH2:23]3)=[CH:17][N:18]=1>C(OCC)(=O)C>[S:15]1[C:16]([CH2:19][C:20]2[CH:21]=[C:22]3[C:27](=[CH:28][CH:29]=2)[CH2:26][CH:25]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH2:24][CH2:23]3)=[CH:17][N:18]=[CH:14]1
Reactant: CCOC(=O)C1CCc2cc(Cc3cnc(N)s3)ccc2C1
Agent: CC(C)(C)ON=O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CCOC(=O)C1CCc2cc(Cc3cncs3)ccc2C1
Temperature: 50 °C
Reaction time: 1 h
Yield: 75.6 %

Procedure:
A mixture of 0.49 g of tertiary butyl nitrite and 5 ml of dimethylformamide was heated at 50° C. and then 1.0 g of ethyl 6-(2-amino-5-thiazolylmethyl)-1,2,3,4-tetrahydro-2-naphthalenecarboxylate was added portionwise thereto. The resulting mixture was stirred at 60° C. for 1 hour. After cooling, ethyl acetate was added to the reaction mixture and the mixture was washed with water and dried and then concentrated in vacuo. The residue was purified by silica gel column chromatography using a mixture of methanol and chloroform (1:50 by volume) for elution to give 720 mg of ethyl 6-(5-thiazolylmethyl)-1,2,3,4-tetrahydro-2-naphthalenecarboxylate as an oil.
Reaction SMILES: [O:1]=[C:2]1[C:10]2([C:22]3[C:13](=[CH:14][C:15]4[O:20][CH2:19][CH2:18][O:17][C:16]=4[CH:21]=3)[O:12][CH2:11]2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]1[CH2:23][C:24]1[CH:25]=[CH:26][C:27]([NH:30]C(=O)OCCCC)=[N:28][CH:29]=1.FC(F)(F)C(O)=O>ClCCl>[NH2:30][C:27]1[N:28]=[CH:29][C:24]([CH2:23][N:3]2[C:4]3[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=3)[C:10]3([C:22]4[C:13](=[CH:14][C:15]5[O:20][CH2:19][CH2:18][O:17][C:16]=5[CH:21]=4)[O:12][CH2:11]3)[C:2]2=[O:1])=[CH:25][CH:26]=1
Reactant: CCCCOC(=O)Nc1ccc(CN2C(=O)C3(COc4cc5c(cc43)OCCO5)c3ccccc32)cn1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Nc1ccc(CN2C(=O)C3(COc4cc5c(cc43)OCCO5)c3ccccc32)cn1
Temperature: 25 °C
Reaction time: 3 h
Yield: 94 %

Procedure:
To a cooled (0° C.) suspension of tent-butyl {5-[(2′-oxo-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-1′(2′H)-yl)methyl]pyridin-2-yl}carbamate (0.27 g, 0.53 mmol) in anhydrous dichloromethane (12 mL) was added trifluoroacetic acid (4 mL). The mixture was stirred at ambient temperature for 3 h and concentrated in vacuo. The residue was dissolved in dichloromethane (100 mL), washed with saturated aqueous sodium bicarbonate (35 mL) and brine (35 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to afford 1-′[(6-aminopyridin-3-yl)methyl]-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1′H)-one (0.20 g, 93%) as a colorless solid: mp 117-119° C.; 1H NMR (300 MHz, DMSO-d6) 8.00-7.96 (m, 1H), 7.37-7.24 (m, 2H), 7.19-7.07 (m, 2H), 7.07-6.98 (m, 1H), 6.52 (s, 1H), 6.43-6.38 (m, 1H), 6.01-5.96 (m, 3H), 4.82-4.62 (m, 4H), 4.21-4.07 (m, 4H); 13C NMR (75 MHz, DMSO-d6) δ 176.6, 159.2, 154.6, 147.0, 144.1, 141.9, 137.7, 136.7, 131.7, 128.7, 123.5, 122.9, 121.2, 119.3, 110.7, 109.4, 108.0, 98.7, 79.2, 64.1, 63.5, 57.1; MS (ES+) m/z 401.9 (M+1).
Reaction SMILES: Br[C:2]1[N:7]=[CH:6][C:5]([CH:8]([NH:10][C:11](=[O:13])[CH3:12])[CH3:9])=[CH:4][CH:3]=1.[CH2:14]([O:16][C:17]1[CH:27]=[CH:26][C:20]([O:21][CH:22]2[CH2:25][NH:24][CH2:23]2)=[CH:19][CH:18]=1)[CH3:15]>>[CH2:14]([O:16][C:17]1[CH:27]=[CH:26][C:20]([O:21][CH:22]2[CH2:25][N:24]([C:2]3[N:7]=[CH:6][C:5]([CH:8]([NH:10][C:11](=[O:13])[CH3:12])[CH3:9])=[CH:4][CH:3]=3)[CH2:23]2)=[CH:19][CH:18]=1)[CH3:15]
Reactant: CCOc1ccc(OC2CNC2)cc1
Reactant: CC(=O)NC(C)c1ccc(Br)nc1
Product: CCOc1ccc(OC2CN(c3ccc(C(C)NC(C)=O)cn3)C2)cc1

Procedure:
Example 8.6 is prepared analogously to 8.1. (N-[1-(6-Bromo-pyridin-3-yl)-ethyl]-acetamide (I.4) and 3-(4-ethoxy-phenoxy)-azetidine are used as starting materials.