Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]=[C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[NH:12][C:11]2=[O:19])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:27][CH2:28][CH2:29][CH2:30][Cl:31]>CN(C=O)C>[Cl:31][CH2:30][CH2:29][CH2:28][CH2:27][O:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][CH:9]=[C:10]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[NH:12][C:11]2=[O:19])=[CH:4][CH:3]=1
Reactant: ClCCCCBr
Reactant: O=C1Nc2ccccc2C1=CNc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C1Nc2ccccc2C1=CNc1ccc(OCCCCCl)cc1
Temperature: 40 °C
Yield: 47 %

Procedure:
A solution of 3-[(4-hydroxy-phenylamino)-methylene]-1,3-dihydro-indol-2-one (0.945 g, 3.75 mmol) in 20 mL DMF is treated with potassium carbonate (777 mg, 1.5 equiv.) and 1-bromo-4-chlorobutane (1.1 equiv.). The reaction mixture is heated to 40° C. for 3 h. The reaction mixture is partitioned between EtOAc and water. The organic layer is collected and washed sequentially with H2O (1×), saturated aqueous NaHCO3 solution (1×), and brine (1×). The organic phase is dried and concentrated to give a solid. The solid is triturated with MeOH and collected by filtration to give the named compound as yellow solid (600 mg, 47%).
Reaction SMILES: [Cr](Cl)([O-])(=O)=[O:2].[NH+]1C=CC=CC=1.[F:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]([CH2:37][OH:38])=[CH:20][C:21]2[CH:26]=[CH:25]C(C3C=C(C=CC=3)C(OC)=O)=[CH:23][CH:22]=2)=[CH:15][CH:14]=1.[CH2:39]([O:41][CH2:42][CH3:43])C>ClCCl>[F:12][C:13]1[CH:14]=[CH:15][C:16]([C:19]([CH:37]=[O:38])=[CH:20][C:21]2[CH:26]=[CH:25][C:43]([C:42]([O:41][CH3:39])=[O:2])=[CH:23][CH:22]=2)=[CH:17][CH:18]=1
Reactant: CCOCC
Reactant: COC(=O)c1cccc(-c2ccc(C=C(CO)c3ccc(F)cc3)cc2)c1
Reactant: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Product: COC(=O)c1ccc(C=C(C=O)c2ccc(F)cc2)cc1
Yield: 53 %

Procedure:
Pyridinium chlorochromate (PCC) (1.12 g, 5.2 mmol) was dissolved in dichloromethane (20 mL). The solution of methyl 3-(4-(2-(4-fluorophenyl)-3-hydroxyprop-1-en-1-yl)phenyl)benzoate (1.14 g, 4 mmol) in dichloromethane (4 mL) was added dropwise under constant stirring and the reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with diethyl ether (100 mL) and filtered through celite; the filtrate was washed with saturated aqueous NaHCO3 solution (2×100 mL) and water (100 mL). The organic layer was dried over anhydrous Na2SO4 and concentrated to afford the pure title compound as a white solid (0.58 g, 53% yield)
Reaction SMILES: C(OC1C=CC(CNC2(CCC(C)(C)C)C3C(=CC=CC=3)C(O)=C(C3NC4C=CC(NS(C)(=O)=O)=CC=4S(=O)(=O)N=3)C2=O)=CC=1)C1C=CC=CC=1.C([O:59][C:60]1[CH:102]=[CH:101][CH:100]=[CH:99][C:61]=1[CH2:62][NH:63][C:64]1([CH2:93][CH2:94][C:95]([CH3:98])([CH3:97])[CH3:96])[C:73]2[C:68](=[CH:69][CH:70]=[CH:71][CH:72]=2)[C:67]([OH:74])=[C:66]([C:75]2[NH:80][C:79]3[CH:81]=[CH:82][C:83]([NH:85][S:86]([CH3:89])(=[O:88])=[O:87])=[CH:84][C:78]=3[S:77](=[O:91])(=[O:90])[N:76]=2)[C:65]1=[O:92])C1C=CC=CC=1>>[CH3:96][C:95]([CH3:98])([CH3:97])[CH2:94][CH2:93][C:64]1([NH:63][CH2:62][C:61]2[CH:99]=[CH:100][CH:101]=[CH:102][C:60]=2[OH:59])[C:73]2[C:68](=[CH:69][CH:70]=[CH:71][CH:72]=2)[C:67]([OH:74])=[C:66]([C:75]2[NH:80][C:79]3[CH:81]=[CH:82][C:83]([NH:85][S:86]([CH3:89])(=[O:88])=[O:87])=[CH:84][C:78]=3[S:77](=[O:91])(=[O:90])[N:76]=2)[C:65]1=[O:92]
Reactant: CC(C)(C)CCC1(NCc2ccccc2OCc2ccccc2)C(=O)C(C2=NS(=O)(=O)c3cc(NS(C)(=O)=O)ccc3N2)=C(O)c2ccccc21
Agent: CC(C)(C)CCC1(NCc2ccc(OCc3ccccc3)cc2)C(=O)C(C2=NS(=O)(=O)c3cc(NS(C)(=O)=O)ccc3N2)=C(O)c2ccccc21
Product: CC(C)(C)CCC1(NCc2ccccc2O)C(=O)C(C2=NS(=O)(=O)c3cc(NS(C)(=O)=O)ccc3N2)=C(O)c2ccccc21

Procedure:
The procedure of Example 91 was followed, except substituting the product from Example 81 with the product from Example 88. The title compound was prepared as a light yellow solid (8 mg, 57%). 1H NMR (300 MHz, DMSO-d6) δ ppm 0.41-0.59 (m, 1H), 0.66 (s, 9H), 0.91-1.08 (m, 1H), 1.74-2.26 (m, 2H), 3.01 (s, 3H), 6.75 (d, J=5.15 Hz, 2H), 7.13 (d, J=5.88 Hz, 2H), 7.32-7.39 (m, 1H), 7.40-7.55 (m, 3H), 7.55-7.68 (m, 1H), 7.75-7.90 (m, 1H), 8.14 (d, J=6.99 Hz, 1H), 9.94 (s, 1H); MS m/z 639.3 (M+H)+.
Reaction SMILES: [F:1][C:2]([F:20])([F:19])[C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=3)[CH2:12][CH2:11][NH:10]2)=[CH:5][CH:4]=1.CCN(C(C)C)C(C)C.[N:30]([C:33]1[CH:34]=[N:35][CH:36]=[CH:37][CH:38]=1)=[C:31]=[O:32]>C(Cl)Cl>[N:35]1[CH:36]=[CH:37][CH:38]=[C:33]([NH:30][C:31]([N:10]2[CH2:11][CH2:12][C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH:9]2[C:6]2[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:19])[F:20])=[CH:8][CH:7]=2)=[O:32])[CH:34]=1
Reactant: FC(F)(F)c1ccc(C2NCCc3ccccc32)cc1
Reactant: O=C=Nc1cccnc1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C(Nc1cccnc1)N1CCc2ccccc2C1c1ccc(C(F)(F)F)cc1

Procedure:
A solution of 1-(4-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydroisoquinoline (97 mg, 0.350 mmol, example 9 (step 3), DIEA (61 μL, 0.35 mmol), and 3-iso-cyanatopyridine (42 mg, 0.35 mmol) in DCM (1 mL) was stirred at RT for 16 h. A white precipitate was observed. The reaction mixture was then filtered and the solid was dried in vacuo to give the title compound as a white solid. MS (ESI, positive ion) m/z: 398 (M+H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:15])[CH2:9][NH:10][S:11]([CH3:14])(=[O:13])=[O:12])=[CH:4][CH:3]=1.[CH:16]([C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[CH:22][CH:23]=1)=[O:17].C(=O)([O-])[O-].[K+].[K+].O>C1(C)C=CC=CC=1>[CH:16]([C:18]1[CH:23]=[C:22]([C:2]2[CH:7]=[CH:6][C:5]([CH:8]([CH3:15])[CH2:9][NH:10][S:11]([CH3:14])(=[O:13])=[O:12])=[CH:4][CH:3]=2)[CH:21]=[CH:20][CH:19]=1)=[O:17]
Reactant: CC(CNS(C)(=O)=O)c1ccc(Br)cc1
Reactant: O=Cc1cccc(B(O)O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: O
Product: CC(CNS(C)(=O)=O)c1ccc(-c2cccc(C=O)c2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 43.2 %

Procedure:
To a degassed solution of 1.5 g (5.1 mmol) of material from Example 1, 1.2 g (8.1 mmol) of 3-formylbenzeneboronic acid and 1.1 g (8.1 mmol) of potassium carbonate in 30 mL of toluene was added 0.3 g (0.3 mmol) of tetrakis-(triphenyl-phosphine)palladium(0). The mixture was heated to 100° C. for 16 hours whereupon 5 mL of water was added and heating continued for 1 hour. The mixture was then cooled to ambient temperature and 10 mL of water was added. The organic portion was separated and the aqueous portion was extracted twice with ethyl acetate. The combined organics were dried (MgSO4), filtered and concentrated in vacuo. Chromatography on 50 g silica gel (40% ethyl acetate/hexane) afforded 0.7 g (41%) of the title compound.
Reaction SMILES: O[CH2:2][CH2:3][C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[CH:6][CH:5]=1.[C:12]1(=[O:22])[NH:16][C:15](=[O:17])[C:14]2=[CH:18][CH:19]=[CH:20][CH:21]=[C:13]12.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>CN(C)C=O>[O:17]=[C:15]1[C:14]2[C:13](=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:12](=[O:22])[N:16]1[CH2:2][CH2:3][C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[CH:6][CH:5]=1
Reactant: N#Cc1ccc(CCO)cc1
Reactant: O=C1NC(=O)c2ccccc21
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Product: N#Cc1ccc(CCN2C(=O)c3ccccc3C2=O)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 92.9 %

Procedure:
Under argon, a solution of 4-(2-hydroxy-ethyl)-benzonitrile [Helv. Chim. Acta 64 (1981) 1688-1703] (4.49 g, 30.5 mmol), phthalimide (4.94 g, 33.55 mmol), triphenylphosphine (8.8 g, 33.55 mmol) and dimethyl formamide (100 mL) was stirred at 0° C. for 20 minutes, then diethyl azodicarboxylate (7.59 mL, 48.8 mmol) was added dropwise at 0° C. The so obtained reaction mixture was stirred at room temperature overnight, then poured into ice-water (740 mL). The precipitated product was filtered off, washed with water and dried. The crude product was recrystallized from 2-propanol to yield 7.83 g (93%) of the title compound as a yellow solid.
Reaction SMILES: [N:1]1[N:2]=[C:3]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([O:20][CH2:21][C:22]4(O)[CH2:25][N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:23]4)[CH:14]=[CH:15][CH:16]=3)[N:11]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.COCCN(S(F)(F)[F:44])CCOC.C([O-])(O)=O.[Na+]>C(Cl)Cl>[N:1]1[N:2]=[C:3]([C:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([O:20][CH2:21][C:22]4([F:44])[CH2:25][N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:23]4)[CH:14]=[CH:15][CH:16]=3)[N:11]=2)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12
Reactant: CC(C)(C)OC(=O)N1CC(O)(COc2cccc3ccc(-c4nnc5ccccn45)nc23)C1
Reactant: COCCN(CCOC)S(F)(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CC(F)(COc2cccc3ccc(-c4nnc5ccccn45)nc23)C1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 22.2 %

Procedure:
(NOTE: the reaction was run in a 10 mL plastic bottle) To a 0° C. cloudy solution of tert-butyl 3-((2-([1,2,4]triazolo[4,3-a]pyridin-3-yl)quinolin-8-yloxy)methyl)-3-hydroxyazetidine-1-carboxylate (0.070 g, 0.156 mmol) in 2 mL DCM was added Deoxo-Fluor (0.0346 mL, 0.188 mmol). The reaction mixture was warmed to ambient temperature, and after 30 minutes, it was cooled back to 0° C., and another 2 equiv. of DeoxoFluor was added, and the reaction mixture continued to stir at 0° C. After a total of 3.5 hours, saturated NaHCO3 was carefully added dropwise until the excess Deoxofluor was quenched. The mixture was extracted with DCM, and the combined extracts were dried (Na2SO4), filtered, and concentrated. The residue was purified by preparative TLC (2 mm plate, 9:1 DCM:MeOH) to give the desired product (0.0156 g, 22.2% yield) as a white foam.
Reaction SMILES: [CH2:1]([NH:8][C:9]1[CH:14]=[C:13]([C:15]2[N:20]=[C:19]([N:21]3[CH2:26][CH:25]4[CH2:27][CH:22]3[CH2:23][NH:24]4)[N:18]3[CH:28]=[CH:29][N:30]=[C:17]3[CH:16]=2)[CH:12]=[CH:11][N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(Cl)Cl.C(O[BH-](O[C:45](=O)[CH3:46])OC(=O)C)(=O)C.[Na+].[C:49](=O)(O)[O-].[Na+]>ClCCl.CC(C)=O>[CH2:1]([NH:8][C:9]1[CH:14]=[C:13]([C:15]2[N:20]=[C:19]([N:21]3[CH2:26][C@@H:25]4[CH2:27][C@H:22]3[CH2:23][N:24]4[CH:45]([CH3:46])[CH3:49])[N:18]3[CH:28]=[CH:29][N:30]=[C:17]3[CH:16]=2)[CH:12]=[CH:11][N:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Reactant: c1ccc(CNc2cc(-c3cc4nccn4c(N4CC5CC4CN5)n3)ccn2)cc1
Reactant: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)=O
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Product: CC(C)N1C[C@@H]2C[C@H]1CN2c1nc(-c2ccnc(NCc3ccccc3)c2)cc2nccn12
Reaction time: 0.5 h

Procedure:
The title compound was analogously synthesized by the method described in Example 55 with the addition of one step. To a solution of benzyl-(4-[5-(2,5-diaza-bicyclo[2.2.1]hept-2-yl)imidazo[1,2-c]pyrimidin-7-yl]pyridin-2-yl)amine (0.400 g) was added chloroform (4 mL) followed by acetone (5 mL), and sodium triacetoxy borohydride (0.600 mg) at 70° C. After 30 min, work up between dichloromethane and sodium bicarbonate followed by flash column purification afforded the title compound as an off white solid. MS (ES+): 440 (M+H)+; (ES−): 438(M−H)−.
Reaction SMILES: C(N(CC)CC)C.Cl[C:9]1[N:14]=[C:13]([CH:15]=[CH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:12]=[C:11]([CH3:23])[CH:10]=1.[H][H]>[Pd].CC([O-])=O.CC([O-])=O.[Pb+2].C(O)C>[CH3:23][C:11]1[CH:10]=[CH:9][N:14]=[C:13]([CH:15]=[CH:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:12]=1
Reactant: Cc1cc(Cl)nc(C=Cc2ccccc2)n1
Reactant: [H][H]
Agent: [Pd]
Agent: CC(=O)[O-]
Agent: [Pb+2]
Solvent: CCO
Solvent: CCN(CC)CC
Product: Cc1ccnc(C=Cc2ccccc2)n1

Procedure:
9.02 ml of triethylamine and 1.365 g of Lindlar catalyst are added to 13.65 g (59.17 mmol) of 6-chloro-4-methyl-2-(2-phenylethenyl)pyrimidine in 220 ml of absolute ethanol and hydrogenation is carried out at room temperature under normal pressure. When 1 equivalent of hydrogen has been absorbed, hydrogenation is terminated (after about 7.5 hours), and the reaction mixture is filtered with suction over Hyflo Super Cel® and concentrated in a rotary evaporator. Chromatography twice on silica gel with chloroform and then n-hexane/ethyl acetate 5-20% as eluants yields the pure title compound; m.p. 65°-67°.
Reaction SMILES: C(O[C:5]1[CH2:12][S:11][CH:10]2[N:7]([C:8](=[O:14])[CH:9]2[NH2:13])[C:6]=1[C:15]([OH:17])=[O:16])(=O)C.C([O:25][C:26]([CH:28](C(Cl)=O)[CH2:29][C@@:30]([CH:35]=[CH2:36])([C:32](Cl)=[O:33])[NH2:31])=[O:27])C1C=CC=CC=1.[C:40]([O:43][CH2:44]C)(=[O:42])[CH3:41]>>[NH2:31][C:30]([CH:35]=[CH2:36])([CH2:29][CH2:28][C:26]([OH:25])=[O:27])[C:32]([NH:13][CH:9]1[C:8](=[O:14])[N:7]2[CH:10]1[S:11][CH2:12][C:5]([CH2:44][O:43][C:40](=[O:42])[CH3:41])=[C:6]2[C:15]([OH:17])=[O:16])=[O:33]
Reactant: C=C[C@](N)(CC(C(=O)Cl)C(=O)OCc1ccccc1)C(=O)Cl
Reactant: CC(=O)OC1=C(C(=O)O)N2C(=O)C(N)C2SC1
Reactant: CCOC(C)=O
Product: C=CC(N)(CCC(=O)O)C(=O)NC1C(=O)N2C(C(=O)O)=C(COC(C)=O)CSC12

Procedure:
A mixture of 1 gram of 3-acetyloxy-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid and 1 g of 4-benzyloxycarbonyl-2-vinylglutamic acid chloride wherein the free amino group is protected with tert-butoxycarbonyl in 50 ml of ethyl acetate is refluxed for 2 hours after which the solvent is removed leaving a residue which is treated with mild acid and chromatographed on silica gel using benzene-acetone as the eluant to give 7-[[2-amino-4-carboxy-2-vinylbutyryl]amino]-3-acetyloxymethyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid.
Reaction SMILES: [F:1][C:2]([F:21])([F:20])[C:3]1[C:8]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[C:7]([OH:14])[C:6]([CH3:15])=[C:5]([C:16]([F:19])([F:18])[F:17])[N:4]=1.Br[CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25].C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[F:21][C:2]([F:20])([F:1])[C:3]1[C:8]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[C:7]([O:14][CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])[C:6]([CH3:15])=[C:5]([C:16]([F:19])([F:18])[F:17])[N:4]=1
Reactant: CCOC(=O)c1c(C(F)(F)F)nc(C(F)(F)F)c(C)c1O
Reactant: CCOC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)COc1c(C)c(C(F)(F)F)nc(C(F)(F)F)c1C(=O)OCC
Yield: 69.1 %

Procedure:
A mixture of 5.0 g (0.016 mol) of product of Example 35, 3.95 g (0.024 mol) of ethyl bromoacetate, 2.18 g (0.016 mol) of K2CO3 and 75 ml of acetone was held at reflux for 18 hours and filtered. The filtrate was concentrated. The residue was stirred with toluene and filtered. The toluene filtrate was concentrated to give 4.46 g (70.2%) of product as a solid; mp 42°-44° C.
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[CH2:5]1[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[CH2:7][CH:6]1[CH2:14][C:15]([O:17][CH3:18])=[O:16].[C:19](Cl)(=[O:21])[CH3:20]>C(Cl)Cl>[C:19]([C:10]1[CH:9]=[C:8]2[C:13](=[CH:12][CH:11]=1)[CH2:5][CH:6]([CH2:14][C:15]([O:17][CH3:18])=[O:16])[CH2:7]2)(=[O:21])[CH3:20]
Reactant: CC(=O)Cl
Reactant: COC(=O)CC1Cc2ccccc2C1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: COC(=O)CC1Cc2ccc(C(C)=O)cc2C1
Temperature: 0 °C
Reaction time: 0.67 h
Yield: 91 %

Procedure:
Added to 160 ml of methylene chloride were 52.9 g (0.388 mol) of anhydrous aluminum chloride. While chilling with ice water, a solution of 25.03 g (0.132 mol) of methyl (indan-2-yl)acetate in 40 ml of methylene chloride was added dropwise to the solution, followed by the addition of 13.1 ml (0.185 mol) of acetyl chloride. After stirring the mixture at the same temperature for 40 minutes, the reaction mixture was poured into ice water to take out an organic layer separated. After the organic layer was washed with water and dried, the solvent was distilled off under reduced pressure. The resultant residue was purified by column chromatography on silica gel (ethyl acetate-hexane=1:2), thereby obtaining 27.8 g of an oily substance. Yield: 91%.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]=[CH:11][CH:12]=[C:13]3[C:17]=2[C:16](=O)[C:15]([CH3:25])(C2CCCCC2)[CH2:14]3)[CH:5]=[C:6]([CH3:8])[CH:7]=1.[BH4-].[Na+].CO.S(=O)(=O)(O)O>C1(C)C=CC=CC=1.O>[CH3:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:10]=[CH:11][CH:12]=[C:13]3[C:17]=2[CH2:16][C:15]([CH2:25][CH:2]2[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]2)=[CH:14]3)[CH:5]=[C:6]([CH3:8])[CH:7]=1
Reactant: Cc1cc(C)cc(-c2cccc3c2C(=O)C(C)(C2CCCCC2)C3)c1
Agent: O=S(=O)(O)O
Agent: [BH4-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CO
Solvent: O
Product: Cc1cc(C)cc(-c2cccc3c2CC(CC2CCCCC2)=C3)c1
Temperature: 50 °C
Reaction time: 3 h
Yield: 183.5 %

Procedure:
25.3 g (76.1 mmole) 7-(3′,5′-Dimethylphenyl)-2-cyclohexyl-methyl-indan-1-one were dissolved in 90 ml toluene in a 500 ml—roundbottom flask equipped with a reflux condenser. 3.17 g (1.1 eq.) sodium borohydride were added. Then 13.3 ml (4.35 eq.) methanol were added at 50° C. and the mixture was stirred for 3 h at 50° C. 2M sulphuric acid was added until the gas evolution ceased. After addition of 100 ml water the layers were separated and the organic layer was washed two times with 2M sulphuric acid and once with a saturated sodium chloride solution. The solvent was evaporated and the crude indanol was dissolved in approx. 90 ml of toluene. After addition of 0.3 g p-toluene sulfonic acid the mixture was heated to reflux using a Dean-Stark-trap until TLC showed complete conversion (90 min). The solution was washed twice with a saturated NaHCO3-solution, once with water and once with a saturated sodium chloride solution. Drying over magnesium sulphate and evaporation of the solvent afforded 22.1 g (92%) of the desired indene as a slightly offwhite oil. 1H-NMR (400 MHz, CDCl3): δ=7.35 (d, 1H, aromatic), 7.24 (m, 1H, aromatic), 7.15 (m, 3H, aromatic), 7.01 (s, 1H, aromatic), 6.68 (s, 1H, C═CH), 3.37 (s, 2H, benzylic), 2.39 (s, 6H, PhCH3), 2.36 (d, 2H, CH2Cy), 1.74-0.91 (m, 11H, aliphatic) ppm.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:25]([SH:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.CN(C=O)C>O>[CH2:12]([O:11][C:3]1[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=1[S:32][CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: O=[N+]([O-])c1ccc(Br)c(OCc2ccccc2)c1
Reactant: SCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1ccc(SCc2ccccc2)c(OCc2ccccc2)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 100 %

Procedure:
A mixture of 35.5 g (115.2 mmol) 2-bromo-5-nitro-O-benzylphenol, 26.3 g (190 mmol) potassium carbonate, 15 mL (127 mmol) benzyl mercaptan, and 200 mL DMF were stirred at room temperature 18 h. TLC analysis indicated a complete reaction, so the thick reaction mixture was transferred to a 2 L Erlenmeyer containing 1 L water and the resulting mixture was stirred in a ice/water bath 30 min. The precipitate was filtered, washed with three 300 mL portions of water, dried at 40° C. 18 h under vacuum to give 2-benzyloxy-4-nitro-S-benzylthiophenol 40.5 g (115.2 mmol, 100%) as a yellow solid.
Reaction SMILES: Cl[C:2](OC(Cl)(Cl)Cl)=[O:3].[NH2:9][C:10]1[CH:15]=[CH:14][C:13]([N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][C:17]2=[O:22])=[CH:12][CH:11]=1>C1COCC1>[N:9]([C:10]1[CH:15]=[CH:14][C:13]([N:16]2[CH2:21][CH2:20][CH2:19][CH2:18][C:17]2=[O:22])=[CH:12][CH:11]=1)=[C:2]=[O:3]
Reactant: O=C(Cl)OC(Cl)(Cl)Cl
Reactant: Nc1ccc(N2CCCCC2=O)cc1
Solvent: C1CCOC1
Product: O=C=Nc1ccc(N2CCCCC2=O)cc1

Procedure:
1.2 0.032 ml of trichloromethyl chloroformate is added under a nitrogen atmosphere to a solution of 50 mg of 1-(4-aminophenyl)piperidin-2-one (prepared from 1-(4-nitrophenyl)piperidin-2-one by hydrogenation using Raney nickel as catalyst) in 5 ml of THF, and the mixture is subsequently refluxed for 1.5 hours, giving 1-(4-isocyanatophenyl)piperidin-2-one (“AB”).
Reaction SMILES: [C:1]([C:4]1[C:5](=[O:31])[N:6]([CH3:30])[C:7]2[C:12]([C:13]=1[NH2:14])=[CH:11][C:10]([C:15]1[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=1)=[C:9]([C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=1[Cl:29])[N:8]=2)(=[O:3])[CH3:2].[H-].[Na+].[CH3:34][N:35]([CH3:39])[C:36](Cl)=[O:37]>C1COCC1>[C:1]([C:4]1[C:5](=[O:31])[N:6]([CH3:30])[C:7]2[C:12]([C:13]=1[NH:14][C:36](=[O:37])[N:35]([CH3:39])[CH3:34])=[CH:11][C:10]([C:15]1[CH:16]=[CH:17][C:18]([Cl:21])=[CH:19][CH:20]=1)=[C:9]([C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][C:23]=1[Cl:29])[N:8]=2)(=[O:3])[CH3:2]
Reactant: CN(C)C(=O)Cl
Reactant: CC(=O)c1c(N)c2cc(-c3ccc(Cl)cc3)c(-c3ccc(Cl)cc3Cl)nc2n(C)c1=O
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(=O)c1c(NC(=O)N(C)C)c2cc(-c3ccc(Cl)cc3)c(-c3ccc(Cl)cc3Cl)nc2n(C)c1=O
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
A solution of the product from Example 2 (70 mg) in THF (1 mL), under nitrogen, was cooled to 0° C. and treated with sodium hydride (60% in mineral oil) (7 mg). The suspension was stirred for 10 min were upon dimethylcarbamyl chloride (15 uL) was added. The reaction was allowed to warm to room temperature and was stirred overnight. The reaction mixture was quenched with water and extracted twice with ethyl acetate. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. Purification on a preparative silica TLC plate eluted with 50% EtOAc in hexane afforded the title compound. HPLC/MS: 543.0 (M+1), 545.0 (M+3); Rt=4.27 min.
Reaction SMILES: Br[CH2:2][C:3]1[C:4]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[C:5]([S:9]([NH:12][C:13]([CH3:16])([CH3:15])[CH3:14])(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1.[C:22]([O-:25])(=[O:24])[CH3:23].[K+].C(OCC)(=O)C.CCCCCC>CS(C)=O>[C:22]([O:25][CH2:2][C:3]1[C:4]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[C:5]([S:9]([NH:12][C:13]([CH3:16])([CH3:15])[CH3:14])(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1)(=[O:24])[CH3:23]
Reactant: CC(=O)[O-]
Reactant: CCOC(=O)c1c(CBr)cccc1S(=O)(=O)NC(C)(C)C
Agent: [K+]
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: CCOC(=O)c1c(COC(C)=O)cccc1S(=O)(=O)NC(C)(C)C
Yield: 54.6 %

Procedure:
A solution of 5.0 g of 3-bromomethyl-2-carboethoxy-N-(1,1-dimethylethyl)benzenesulfonamide and 1.5 g of potassium acetate in 50 mL of dimethylsulfoxide was stirred at room temperature for 6 hours. The resulting reaction mixture was poured onto ice and extracted with ethyl acetate. The organic phase was washed with a solution of saturated sodium chloride and then dried over magnesium sulfate. Removal of the drying agent by filtration and concentration provided a white solid. Chromatography on silica gel with 1:1 ethyl acetate/hexane provided 2.58 g of a white solid, m.p. 81°-82° C.