Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[CH:6][NH:7]2.C([O-])([O-])=O.[K+].[K+].C([O:20][C:21](=[O:24])[CH2:22]Cl)C>CN(C=O)C>[CH3:1][O:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[CH:5]=[CH:6][N:7]2[CH2:22][C:21]([OH:24])=[O:20]
Reactant: COc1cccc2[nH]ccc12
Reactant: CCOC(=O)CCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COc1cccc2c1ccn2CC(=O)O
Reaction time: 0.17 h

Procedure:
To a solution of 4-methoxyindole (294 mg) in DMF (10 mL) was added K2CO3 (829 mg). After 10 min stirring, ethylchloroacetate (0.426 mL) was added. The reaction mixture was stirred overnight at 120° C., was allowed to cool down and was filtered off. The solid was washed with DCM and the filtrate was concentrated in vacuo. After CC (silica gel, EA/MeOH 9/1) followed by preparative HPLC (I), the resulting material was dissolved in 1M NaOH/THF (20 mL, 1/1). The mixture was stirred at RT overnight, neutralized with 1M HCl (8 mL) and concentrated to dryness. The residue was taken up in DCM and the resulting suspension was filtered off. The filtrate was evaporated in vacuo to afford 340 mg of beige powder. LC-MS (D): tR=0.76 min; [M+H]+: 206.1.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:13]([CH2:14][C:15]3[CH:20]=[CH:19][C:18]([C:21]4[C:22]([C:27]([O:29]C(C)(C)C)=[O:28])=[CH:23][CH:24]=[CH:25][CH:26]=4)=[CH:17][CH:16]=3)[C:12]3[CH:34]=[CH:35][CH:36]=[CH:37][C:11]=3[N:10]=2)=[CH:5][CH:4]=1.FC(F)(F)C(O)=O>>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([C:9]2[N:13]([CH2:14][C:15]3[CH:16]=[CH:17][C:18]([C:21]4[C:22]([C:27]([OH:29])=[O:28])=[CH:23][CH:24]=[CH:25][CH:26]=4)=[CH:19][CH:20]=3)[C:12]3[CH:34]=[CH:35][CH:36]=[CH:37][C:11]=3[N:10]=2)=[CH:7][CH:8]=1
Reactant: COc1ccc(-c2nc3ccccc3n2Cc2ccc(-c3ccccc3C(=O)OC(C)(C)C)cc2)cc1
Solvent: O=C(O)C(F)(F)F
Product: COc1ccc(-c2nc3ccccc3n2Cc2ccc(-c3ccccc3C(=O)O)cc2)cc1

Procedure:
Prepared in analogous manner to Example 9 from tert.butyl 4'-[(2-(4-methoxyphenyl)-benzimidazol-1-yl)-methyl]biphenyl-2-carboxylate and trifluoroacetic acid.
Reaction SMILES: [CH:1]1([C:4]2[C:5]([O:13][CH2:14][CH:15]3[CH2:17][CH2:16]3)=[CH:6][C:7]([C:10]([OH:12])=O)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.[NH2:18][CH2:19][C:20]([CH3:23])([OH:22])[CH3:21]>>[OH:22][C:20]([CH3:23])([CH3:21])[CH2:19][NH:18][C:10]([C:7]1[CH:6]=[C:5]([O:13][CH2:14][CH:15]2[CH2:17][CH2:16]2)[C:4]([CH:1]2[CH2:2][CH2:3]2)=[CH:9][N:8]=1)=[O:12]
Reactant: O=C(O)c1cc(OCC2CC2)c(C2CC2)cn1
Reactant: CC(C)(O)CN
Product: CC(C)(O)CNC(=O)c1cc(OCC2CC2)c(C2CC2)cn1

Procedure:
The title compound was synthesized in analogy to Example 54, using 5-Cyclopropyl-4-cyclopropylmethoxy-pyridine-2-carboxylic acid (Example 42c) and 1-amino-2-methylpropan-2-ol (CAN 2854-16-2) as starting materials and isolated (59 mg, 65%) as colorless oil; MS (ESI, m/z): 305.5 (M+H+).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7]2[CH:8]=[C:9]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:10]=[CH:11][C:12]=2[OH:13])=[CH:3][N:2]=1.[Cl:20][C:21]1[CH:22]=[C:23]([S:28]([N:31](CC2C=CC(OC)=CC=2OC)[C:32]2[S:33][CH:34]=[N:35][N:36]=2)(=[O:30])=[O:29])[CH:24]=[CH:25][C:26]=1F.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[Cl:20][C:21]1[CH:22]=[C:23]([S:28]([NH:31][C:32]2[S:33][CH:34]=[N:35][N:36]=2)(=[O:29])=[O:30])[CH:24]=[CH:25][C:26]=1[O:13][C:12]1[CH:11]=[CH:10][C:9]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:8][C:7]=1[C:4]1[CH:5]=[CH:6][N:1]=[N:2][CH:3]=1
Reactant: Oc1ccc(-c2ccccc2)cc1-c1ccnnc1
Reactant: COc1ccc(CN(c2nncs2)S(=O)(=O)c2ccc(F)c(Cl)c2)c(OC)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: O=S(=O)(Nc1nncs1)c1ccc(Oc2ccc(-c3ccccc3)cc2-c2ccnnc2)c(Cl)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 49.1 %

Procedure:
3-Pyridazin-4-ylbiphenyl-4-ol (Preparation 4, 40 mg, 0.16 mmol) and 3-chloro-N-(2,4-dimethoxybenzyl)-4-fluoro-N-1,3,4-thiadiazol-2-ylbenzenesulfonamide (Preparation 17, 72 mg, 0.16 mmol) were dissolved in dimethylsulfoxide (2 mL). Potassium carbonate (67 mg, 0.5 mmol) was added and the reaction stirred at room temperature for 16 hours. The crude material was partitioned between ethyl acetate (20 mL) and water (20 mL), the organic layer separated, concentrated in vacuo, dissolved in trifluoroacetic acid (1 mL) and the solution stirred for 16 hours at room temperature. The reaction was then concentrated in vacuo and purified by silica gel column chromatography (ISCO™, 12 g silica, 50-100% ethyl acetate in heptane gradient elution). The appropriate fractions were combined and concentrated in vacuo to afford the title compound as a white solid (41 mg, 49%).
Reaction SMILES: Cl.C([O:4][CH:5](OCC)[CH2:6][N:7]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]1=[O:17])C>CC(C)=O>[O:17]=[C:8]1[C:9]2[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:15](=[O:16])[N:7]1[CH2:6][CH:5]=[O:4]
Reactant: CCOC(CN1C(=O)c2ccccc2C1=O)OCC
Agent: Cl
Solvent: CC(C)=O
Product: O=CCN1C(=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 6 h

Procedure:
A 6 N aqueous hydrochloric acid solution (20 ml) was added to a solution of 2-(2,2-diethoxyethyl)-1H-isoindol-1,3(2H)-dione (1.0 g, 3.80 mmol) in acetone (20 ml), the mixture was stirred at room temperature for 6 hours, and the solvent was distilled off under reduced pressure. A saturated sodium hydrogen carbonate aqueous solution was added to the residue, and the mixture was extracted with chloroform. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure to give the desired product as an oil.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[CH3:9][C@@H:10]1[N:15]([S:16]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21](B3OC(C)(C)C(C)(C)O3)[CH:20]=2)(=[O:18])=[O:17])[CH2:14][CH2:13][N:12]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:11]1>>[Cl:1][C:2]1[N:7]=[C:6]([C:23]2[CH:24]=[C:19]([S:16]([N:15]3[CH2:14][CH2:13][N:12]([C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH2:11][C@@H:10]3[CH3:9])(=[O:18])=[O:17])[CH:20]=[CH:21][CH:22]=2)[CH:5]=[CH:4][N:3]=1
Reactant: C[C@H]1CN(C(=O)OC(C)(C)C)CCN1S(=O)(=O)c1cccc(B2OC(C)(C)C(C)(C)O2)c1
Reactant: Clc1ccnc(Cl)n1
Product: C[C@H]1CN(C(=O)OC(C)(C)C)CCN1S(=O)(=O)c1cccc(-c2ccnc(Cl)n2)c1
Yield: 90 %

Procedure:
2,4-dichloropyrimidine and (S)-tert-butyl 3-methyl-4-(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenylsulfonyl)piperazine-1-carboxylate was coupled following procedure A. The yield was 90%. LC-MS showed the product was >95% pure and had the expected M+H+ of 453.
Reaction SMILES: [CH2:1]1[CH:5]2[CH:6]3C=CC([CH:4]2[CH:3]=[CH:2]1)C3.C[SiH:12]([Cl:14])[Cl:13].CCCCCCCCCCCCCCCC>[Ni](Cl)Cl.C(P(CCCC)CCCC)CCC.C1(C)C=CC=CC=1>[CH:5]1([CH2:6][SiH:12]([Cl:14])[Cl:13])[CH2:4][CH2:3][CH:2]=[CH:1]1
Reactant: C[SiH](Cl)Cl
Reactant: C1=CC2C3C=CC(C3)C2C1
Agent: Cl[Ni]Cl
Agent: CCCCP(CCCC)CCCC
Solvent: Cc1ccccc1
Solvent: CCCCCCCCCCCCCCCC
Product: Cl[SiH](Cl)CC1C=CCC1
Reaction time: 1 h
Yield: 285.7 %

Procedure:
As described in Example 2, 3.01 g (0.0228 mol) of dicyclopentadiene, 5.19 g (0.0451 mol) of methyldichlorosilane, 0.032 g (0.000247 mol) of nickel dichloride, 57 μL (0.000230 mol) of tributylphosphine and 4 mL of toluene and 2 mL of hexadecane were placed in a reactor. The reactor was sealed and the reaction was performed at 180° C. for 1 hour. Products were subject to simple vacuum distillation, thereby providing a mixture (11.8 g) of (2-cyclopentenyl)methyldichlorosilane (3.1 g, 38%), other unreacted reactants, toluene, hexadecane, and unidentified compounds.
Reaction SMILES: [F:1][C:2]1([F:32])[C:8]([CH3:10])([CH3:9])[O:7][CH2:6][C:5](=O)[NH:4][C@@:3]1([C:13]1[CH:18]=[C:17]([C:19]2[CH:20]=[N:21][N:22]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[CH:23]=2)[CH:16]=[CH:15][C:14]=1[F:31])[CH3:12].COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:42])=CC=1>O1CCOCC1>[F:1][C:2]1([F:32])[C:8]([CH3:10])([CH3:9])[O:7][CH2:6][C:5](=[S:42])[NH:4][C@@:3]1([C:13]1[CH:18]=[C:17]([C:19]2[CH:20]=[N:21][N:22]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[CH:23]=2)[CH:16]=[CH:15][C:14]=1[F:31])[CH3:12]
Reactant: CC1(C)OCC(=O)N[C@](C)(c2cc(-c3cnn(-c4ccc(F)cc4)c3)ccc2F)C1(F)F
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Solvent: C1COCCO1
Product: CC1(C)OCC(=S)N[C@](C)(c2cc(-c3cnn(-c4ccc(F)cc4)c3)ccc2F)C1(F)F
Yield: 94.5 %

Procedure:
The reaction of (R)-6,6-difluoro-5-{2-fluoro-5-[1-(4-fluoro-phenyl)-1H-pyrazol-4-yl]-phenyl}-5,7,7-trimethyl-[1,4]oxazepan-3-one (189 mg, 422 μmol) with Lawesson's reagent (139 mg, 338 μmol) in 1,4-dioxane (14 ml) yielded the (R)-6,6-difluoro-5-{2-fluoro-5-[1-(4-fluoro-phenyl)-1H-pyrazol-4-yl]-phenyl}-5,7,7-trimethyl-[1,4]oxazepan-3-thione (148 mg, 76% yield) as a white solid. MS (ISP): m/z=464.2.0 [M+H]+.
Reaction SMILES: [CH2:1]([C:6]1[CH:7]=[C:8]([OH:13])[CH:9]=[C:10]([CH:12]=1)[OH:11])[CH2:2][CH2:3][CH2:4][CH3:5].[CH3:14][CH:15]1[S:19][CH:18]([C:20](OC)=[O:21])[C:17](=O)[CH2:16]1>>[OH:13][C:8]1[C:9]2[C:17]3[CH2:16][CH:15]([CH3:14])[S:19][C:18]=3[C:20](=[O:21])[O:11][C:10]=2[CH:12]=[C:6]([CH2:1][CH2:2][CH2:3][CH2:4][CH3:5])[CH:7]=1
Reactant: CCCCCc1cc(O)cc(O)c1
Reactant: COC(=O)C1SC(C)CC1=O
Product: CCCCCc1cc(O)c2c3c(c(=O)oc2c1)SC(C)C3
Yield: 62 %

Procedure:
5-n-Pentyl resorcinol is reacted with methyl 5-methyl-3-oxo-tetrahydrothiophene-2-carboxylate to produce 1,2-dihydro-9-hydroxy-2-methyl-7-n-pentyl-4-oxo-4H-thieno[2,3-c][1] benzopyran, m.p. 188°-190°C, in 62% yield.
Reaction SMILES: C(OC1C=CN(CC(C2C=CC(C[Br:25])=CC=2C)=O)C(=O)C=1)C1C=CC=CC=1.O[CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36](=[O:55])[CH2:37][N:38]2[C:43](=[O:44])[CH:42]=[C:41]([O:45][CH2:46][C:47]3[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][N:48]=3)[CH:40]=[N:39]2)=[C:32]([CH3:56])[CH:31]=1.C(OC1C=CN(CC(C2C=CC(CO)=CC=2C)=O)C(=O)C=1)C1C=CC=CC=1>COC(C)(C)C>[Br:25][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:36](=[O:55])[CH2:37][N:38]2[C:43](=[O:44])[CH:42]=[C:41]([O:45][CH2:46][C:47]3[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][N:48]=3)[CH:40]=[N:39]2)=[C:32]([CH3:56])[CH:31]=1
Reactant: COc1ccc(COc2cnn(CC(=O)c3ccc(CO)cc3C)c(=O)c2)nc1
Reactant: Cc1cc(CBr)ccc1C(=O)Cn1ccc(OCc2ccccc2)cc1=O
Agent: Cc1cc(CO)ccc1C(=O)Cn1ccc(OCc2ccccc2)cc1=O
Solvent: COC(C)(C)C
Product: COc1ccc(COc2cnn(CC(=O)c3ccc(CBr)cc3C)c(=O)c2)nc1
Reaction time: 8 h
Yield: 97 %

Procedure:
2-[2-(4-Bromomethyl-2-methyl-phenyl)-2-oxo-ethyl]-5-(5-methoxy-pyridin-2-ylmethoxy)-2H-pyridazin-3-one is prepared following preparation 1d employing 2-[2-(4-hydroxymethyl-2-methyl-phenyl)-2-oxo-ethyl]-5-(5-methoxy-pyridin-2-ylmethoxy)-2H-pyridazin-3-one (preparation 9c) instead of preparation 1c. The reaction mixture is stirred overnight. Tert-butyl methyl ether is added and the resulting precipitate is filtered off and dried.
Reaction SMILES: [OH:1][CH:2]([CH2:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1)[CH2:3][CH2:4][CH2:5][N:6]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([O:19]CC)=[O:18])[S:7]([CH3:10])(=[O:9])=[O:8].[OH-].[Na+].O>C(O)C>[OH:1][CH:2]([CH2:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=1)[CH2:3][CH2:4][CH2:5][N:6]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][C:17]([OH:19])=[O:18])[S:7]([CH3:10])(=[O:9])=[O:8]
Reactant: CCOC(=O)CCCCCCN(CCCC(O)COc1ccc(F)cc1)S(C)(=O)=O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CS(=O)(=O)N(CCCCCCC(=O)O)CCCC(O)COc1ccc(F)cc1
Reaction time: 20 h

Procedure:
A solution composed of ethyl 7-{N-[4-hydroxy-5-(4-fluorophenoxy)pentyl]methanesulfonamido}heptanoate (4.7 g., 0.11 mole), sodium hydroxide (1.0 g.), water (13 ml.) and ethanol (130 ml.) is kept at room temperature for 20 hours. Most of the solvent is removed in vacuo, water (150 ml.) is added and the solution extracted with ether (100 ml.). The aqueous layer is acidified (hydrochloric acid) and extracted with ethyl acetate (2 × 100 ml.). The organic layer is dried over sodium sulfate then concentrated in vacuo to obtain the subject compound. The yield is 3.7 g. (84%) of heavy oil.
Reaction SMILES: [P:1]12([S:13]P3(SP(SP(S3)([S:9]1)=S)(=S)[S:3]2)=S)=[S:2].Cl[CH2:16][CH2:17][CH2:18][Si:19]([O:26][CH2:27][CH3:28])([O:23][CH2:24][CH3:25])[O:20][CH2:21][CH3:22].[S-2].[Na+].[Na+]>>[CH2:21]([O:20][Si:19]([CH2:18][CH2:17][CH2:16][S:3][P:1](=[S:2])([S:13][CH2:16][CH2:17][CH2:18][Si:19]([O:20][CH2:21][CH3:22])([O:26][CH2:27][CH3:28])[O:23][CH2:24][CH3:25])[S:9][CH2:16][CH2:17][CH2:18][Si:19]([O:23][CH2:24][CH3:25])([O:20][CH2:21][CH3:22])[O:26][CH2:27][CH3:28])([O:26][CH2:27][CH3:28])[O:23][CH2:24][CH3:25])[CH3:22]
Reactant: CCO[Si](CCCCl)(OCC)OCC
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Agent: [Na+]
Agent: [S-2]
Product: CCO[Si](CCCSP(=S)(SCCC[Si](OCC)(OCC)OCC)SCCC[Si](OCC)(OCC)OCC)(OCC)OCC
Temperature: 200 °C
Reaction time: 2.5 h
Yield: 314.1 %

Procedure:
A mixture of 30.8 g (69.2 mmol) P4S10, 200.0 g (830.3 mmol) chloropropyltriethoxysilane and 32.4 g (415.3 mmol) sodium sulfide (Na2S) is initially introduced into a 500 ml three-necked flask in an argon atmosphere and is heated to 200° C. After stirring at 200° C. for 2.5 h, insoluble constituents are filtered off. All the volatile constituents are removed in vacuo. 168.5 g (79% yield) of tetrathiophosphoric acid S,S,S-tris (triethoxysilylpropyl) ester are obtained as a pale yellow clear liquid.
Reaction SMILES: CC1C=CC(S(O[CH2:12][C@@H:13]([C:22]2[CH:23]=[N:24][C:25]([NH:28][C:29](=[O:31])[CH3:30])=[CH:26][CH:27]=2)[O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])(=O)=O)=CC=1.[Br:32][C:33]1[CH:38]=[CH:37][C:36]([CH2:39][CH2:40][NH2:41])=[CH:35][CH:34]=1.CS(C)=O.C(N(CC)C(C)C)(C)C>C(OCC)(=O)C.O>[Br:32][C:33]1[CH:38]=[CH:37][C:36]([CH2:39][CH2:40][NH:41][CH2:12][C@@H:13]([C:22]2[CH:27]=[CH:26][C:25]([NH:28][C:29](=[O:31])[CH3:30])=[N:24][CH:23]=2)[O:14][Si:15]([C:18]([CH3:19])([CH3:20])[CH3:21])([CH3:16])[CH3:17])=[CH:35][CH:34]=1
Reactant: CC(=O)Nc1ccc([C@H](COS(=O)(=O)c2ccc(C)cc2)O[Si](C)(C)C(C)(C)C)cn1
Reactant: NCCc1ccc(Br)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: CS(C)=O
Product: CC(=O)Nc1ccc([C@H](CNCCc2ccc(Br)cc2)O[Si](C)(C)C(C)(C)C)cn1
Temperature: 80 °C
Reaction time: 24 h
Yield: 89.8 %

Procedure:
To a mixture of (2R)-2-[6-(acetylamino)-3-pyridyl]-2-[[tert-butyl(dimethyl)silyl]oxy]ethyl 4-methylbenzenesulfonate (3.50 g), (2-(4-bromophenyl)ethyl]-amine (3.01 g) and dimethyl sulfoxide (1.75 ml) was added N,N-diisopropylethylamine (1.31 ml) and the mixture was stirred at 80° C. for 24 hours. After cooling to room temperature, the mixture was diluted with ethyl acetate (35 ml) and water (35 ml), and the organic layer was separated. The organic layer was washed with water (35 ml×2) and brine (35 ml), and dried over magnesium sulfate. Filtration followed by evaporation gave a yellow paste (5.36 g) which was chromatographed on silica gel (eluent: hexane/ethyl acetate) to give N-[5-[(1R)-2-[[2-(4-bromophenyl)ethyl]-amino]-1-[[tert-butyl(dimethyl)silyl]oxy]ethyl]-2-pyridyl]acetamide (3.33 g) as a colorless paste.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]#[C:9][C:10]2[CH2:14][C:13]3([CH2:18][CH2:17][NH:16][CH2:15]3)[O:12][N:11]=2)[CH:5]=[CH:6][CH:7]=1.[CH3:19][N:20]([CH3:24])[C:21](Cl)=[O:22]>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]#[C:9][C:10]2[CH2:14][C:13]3([CH2:18][CH2:17][N:16]([C:21]([N:20]([CH3:24])[CH3:19])=[O:22])[CH2:15]3)[O:12][N:11]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: Clc1cccc(C#CC2=NOC3(CCNC3)C2)c1
Reactant: CN(C)C(=O)Cl
Solvent: ClCCl
Product: CN(C)C(=O)N1CCC2(CC(C#Cc3cccc(Cl)c3)=NO2)C1
Temperature: 25 °C
Reaction time: 4 h
Yield: 68.8 %

Procedure:
To a solution of Compound 27d (0.12 g, 0.46 mmol) in 10 mL of dichloromethane was added TEA (0.02 mL, 1.38 mmol) followed by N,N-dimethylchloroformamide (0.051 mL, 0.59 mmol). The reaction mixture was stirred at r.t. for 4 h. Afterwards, it was evaporated to dryness and purified by means of automated flash chromatography (SP01®TM-Biotage; gradient Petroleum Ether-EtOAc from 3:7 to 0:1) to give the title compound as a pale yellow solid. Yield: 68.8%.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C@H:7]([C:19]3[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=3)[C@H:8]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:9][O:10]2)=[CH:5][CH:4]=1.[CH3:26][S:27](Cl)(=[O:29])=[O:28].C(OCC)(=O)C.Cl>N1C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([C@H:7]([C:19]3[CH:20]=[CH:21][C:22]([O:25][S:27]([CH3:26])(=[O:29])=[O:28])=[CH:23][CH:24]=3)[C@H:8]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:9][O:10]2)=[CH:5][CH:4]=1
Reactant: COc1ccc2c(c1)OC[C@@H](c1ccccc1)[C@H]2c1ccc(O)cc1
Reactant: CS(=O)(=O)Cl
Agent: Cl
Solvent: c1ccncc1
Solvent: CCOC(C)=O
Product: COc1ccc2c(c1)OC[C@@H](c1ccccc1)[C@H]2c1ccc(OS(C)(=O)=O)cc1
Temperature: 25 °C

Procedure:
(+,-) cis 7-methoxy-4-(4-hydroxy-phenyl)-3-phenyl-chroman (7.5 g, 22.6 mmol) was dissolved in pyridine (35 ml), and methanesulfonylchloride (3.85 ml, 49.6 mmol) was added dropwise in 5 min. The reaction mixture was refluxed for 30 min, cooled to room temperature, and ethyl acetate (100 ml) was added. The reaction mixture was acidified with 6N Hydrochloric acid (100 ml), and the separated aqueous phase extracted with ethyl acetate (25 ml). The combined organic extracts were washed with 1N hydrochloric acid (50 ml), water (2×50 ml), dried with magnesium sulphate and evaporated to give a slightly yellow solid, which was recrystallised from ethanol, and vacuum dried.
Reaction SMILES: O=C1C2C(=CC=CC=2)C(=O)[N:3]1[CH2:12][CH2:13][CH2:14][N:15]([CH:28]([CH3:30])[CH3:29])[S:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[N+:25]([O-:27])=[O:26])(=[O:18])=[O:17].O.NN.C(O)C>C(OCC)C>[NH2:3][CH2:12][CH2:13][CH2:14][N:15]([CH:28]([CH3:30])[CH3:29])[S:16]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[N+:25]([O-:27])=[O:26])(=[O:17])=[O:18]
Reactant: CC(C)N(CCCN1C(=O)c2ccccc2C1=O)S(=O)(=O)c1ccccc1[N+](=O)[O-]
Agent: NN
Solvent: O
Solvent: CCO
Solvent: CCOCC
Product: CC(C)N(CCCN)S(=O)(=O)c1ccccc1[N+](=O)[O-]
Yield: 99.2 %

Procedure:
The compound (8.11 g, 18.80 mmol) obtained in step B and hydrazine monohydrate (5 ml) were added to ethanol (200 ml) and the mixture was heated under reflux for 1 hr. The reaction mixture was cooled, and diluted with diethyl ether. The insoluble material was filtered off, and the solution was concentrated under reduced pressure. The obtained oil was dissolved in dichloromethane, and the solution was extracted with hydrochloric acid. The aqueous layer was alkalified with aqueous sodium hydroxide solution, extracted with dichloromethane, and the organic layer was dried over potassium carbonate. The insoluble material was filtered off, and the solution was concentrated under reduced pressure to give the title compound (5.62 g, yield 99%) as a yellow oil.
Reaction SMILES: [C:1]([NH:9][C:10]1[N:15]=[CH:14][N:13]=[C:12]2[N:16]([C@H:19]3[C@@H:23]4[O:24]C(C)(C)[O:26][C@@H:22]4[C@@H:21](/[CH:29]=[CH:30]/[P:31](=[O:38])([O:35][CH2:36][CH3:37])[O:32][CH2:33][CH3:34])[O:20]3)[N:17]=[CH:18][C:11]=12)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>O>[C:1]([NH:9][C:10]1[N:15]=[CH:14][N:13]=[C:12]2[N:16]([C@@H:19]3[O:20][C@H:21](/[CH:29]=[CH:30]/[P:31](=[O:38])([O:32][CH2:33][CH3:34])[O:35][CH2:36][CH3:37])[C@@H:22]([OH:26])[C@H:23]3[OH:24])[N:17]=[CH:18][C:11]=12)(=[O:8])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOP(=O)(/C=C/[C@H]1O[C@@H](n2ncc3c(NC(=O)c4ccccc4)ncnc32)[C@@H]2OC(C)(C)O[C@@H]21)OCC
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: CCOP(=O)(/C=C/[C@H]1O[C@@H](n2ncc3c(NC(=O)c4ccccc4)ncnc32)[C@H](O)[C@@H]1O)OCC
Temperature: 25 °C
Reaction time: 2 h
Yield: 43.2 %

Procedure:
Compound 22.4 (163 mg, 0.299 mmol) was treated with TFA (1000 μL) and H2O (100 μL) and stirred at room temperature for 2 h. The solvent was removed in vacuo and the residue was subjected to a silica gel column chromatography eluting with 0-20% MeOH—CH2Cl2 to afford compound 25.1 (65 mg, 43% yield) as a white solid: 1H NMR (CDCl3, 300 MHz) 9.51 (br s, 1H), 8.65 (s, 1H), 8.47 (s, 1H), 7.90 (d, J=7.5 Hz, 2H), 7.51 (t, J=7.5 Hz, 1H), 7.43 (t, J=7.5 Hz, 2H), 6.88 (m, 1H), 6.61 (s, 1H), 5.98 (m, 1H), 4.85 (m, 1H), 4.67 (m, 1H), 4.60 (m, 1H), 3.89 (m, 4H), 1.20 (t, 6H); 31P NMR (CDCl3, 121.4 MHz) 16.6; MS (ESI) m/z 504 [M+H]+.
Reaction SMILES: [F:1][C:2]([F:43])([F:42])[C:3]1[CH:4]=[C:5]([CH:35]=[C:36]([C:38]([F:41])([F:40])[F:39])[CH:37]=1)[CH2:6][N:7]1[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:10]([C:18]([C:20]2[N:21]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[N:22]=[N:23][C:24]=2[Si](C)(C)C)=[O:19])[N:9]=[N:8]1.[F-].C([NH3+])(C)(C)C.C(O)(=O)C>C1COCC1>[F:43][C:2]([F:1])([F:42])[C:3]1[CH:4]=[C:5]([CH:35]=[C:36]([C:38]([F:39])([F:41])[F:40])[CH:37]=1)[CH2:6][N:7]1[C:11]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:10]([C:18]([C:20]2[N:21]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[N:22]=[N:23][CH:24]=2)=[O:19])[N:9]=[N:8]1
Reactant: C[Si](C)(C)c1nnn(-c2ccccc2)c1C(=O)c1nnn(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)c1-c1ccccc1
Agent: CC(C)(C)[NH3+]
Agent: [F-]
Solvent: CC(=O)O
Solvent: C1CCOC1
Product: O=C(c1nnn(Cc2cc(C(F)(F)F)cc(C(F)(F)F)c2)c1-c1ccccc1)c1cnnn1-c1ccccc1
Temperature: 65 °C
Reaction time: 72 h

Procedure:
To a solution of [1-(3,5-Bis-trifluoromethyl-benzyl)-5-phenyl-1H-[1,2,3]triazol-4-yl]-(3-phenyl-5-trimethylsilanyl-3H-[1,2,3]triazol-4-yl)-methanone (0.050 g, 0.08 mmol) in THF (2 mL) add t-butyl ammonium flouride (1 M soln. in THF, 1.2 mL, 1.2 mmol) and acetic acid (120 μL, 2.0 mmol) and heat at 65° C. After 72 h., remove from heat, and quench with sat. aq. NH4C1 and H2O. Extract with EtOAc, dry over MgSO4, filter, and purify by flash chromatography (EtOAc/Hexane 0%–50%) to give the title compound. 1H NMR (300 MHz, CDCl3) δ 8.88 (s, 1H), 7.75 (s, 1H), 7.57–7.29 (m, 10H), 7.09 (m, 2H), 5.50 (s, 2H).
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:15]=2)[C:10]([C:23](=[O:29])[C:24]([O:26]CC)=[O:25])=[CH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[K+]>C1COCC1.O>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:15]=2)[C:10]([C:23](=[O:29])[C:24]([OH:26])=[O:25])=[CH:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)C(=O)c1cn(Cc2ccccc2)c2cc(-c3ccccc3)ccc12
Agent: [K+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)C(=O)c1cn(Cc2ccccc2)c2cc(-c3ccccc3)ccc12
Yield: 69.8 %

Procedure:
(1-Benzyl-6-phenyl-1H-indol-3-yl)(oxo)acetic acid was prepared from ethyl (1-benzyl-6-phenyl-1H-indol-3-yl)(oxo)acetate (1.90 g, 4.96 mmol), and potassium hydroxide (0.856 g, 15.3 mmol) in THF (20 mL) and water (20 mL), following the procedure described in Step 4 of Example 5. Crystallization from acetonitrile and drying for 8 hours at 70° C. yielded the title compound as a light yellow solid (1.23 g, 70%), mp: 210-212° C. (dec.). Mass spectrum (+ES, [M+H]+) m/z 356; 1HNMR (500 MHz, DMSO-d6): δ 13.8-14.2 (br s, 1H), 8.7 (s, 1H), 8.25 (d, 1H, J=8.2 Hz), 7.9 (s, 1H), 7.65 (d, 2H, J=8.1 Hz), 7.6 (d, 1H, J=8.4 Hz), 7.45 (t, 2H, J=7.7 Hz), 7.3-7.35 (m, 5H), 7.25-7.3 (m, 1H), and 5.65 ppm (s, 2H). Elemental Analysis for C23H17NO3: Calculated: C, 77.73; H, 4.82; N, 3.94. Found: C, 77.58; H, 4.68; N, 3.90.
Reaction SMILES: C[O:2][C:3](=[O:15])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][CH:7]=1>Cl>[N+:12]([C:9]1[CH:8]=[CH:7][C:6]([O:5][CH2:4][C:3]([OH:15])=[O:2])=[CH:11][CH:10]=1)([O-:14])=[O:13]
Reactant: COC(=O)COc1ccc([N+](=O)[O-])cc1
Agent: Cl
Product: O=C(O)COc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Yield: 92 %

Procedure:
A mixture of methyl(4-nitrophenoxy)acetate 31 (100 g, 474 mmol) and concentrated HCl (1000 ml) was refluxed for 8 hours. The reaction mass was cooled to room temp. Crude 40 was filtered, dried and recrystallised from a mixture of ethyl acetate:hexane (1:5) to give pure 40 (86 g, 92.1%) as a white shining powder. M.p: 186-188.5° C.