Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][CH2:2][CH2:3][S:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[CH:7][CH:6]=1.C(N(CC)CC)C.[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([S:30](Cl)(=[O:32])=[O:31])=[CH:26][CH:25]=1>C(Cl)Cl>[Cl:23][C:24]1[CH:29]=[CH:28][C:27]([S:30]([NH:1][CH2:2][CH2:3][S:4][C:5]2[CH:10]=[CH:9][C:8]([CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[CH:7][CH:6]=2)(=[O:32])=[O:31])=[CH:26][CH:25]=1
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1
Reactant: NCCSc1ccc(CCC(=O)O)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(O)CCc1ccc(SCCNS(=O)(=O)c2ccc(Cl)cc2)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a mixture of 3-[4-(2-aminoethylthio)phenyl]propionic acid (0.8 g), triethylamine (1.6 ml) and methylene chloride (50 ml) was added 4-chlorophenylsulfonyl chloride (0.79 g), and the mixture was stirred at room temperature for 16 hours. The reaction mixture was washed successively with 3% hydrochloric acid and a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. Evaporation of the solvent under reduced pressure gave a residue, which was then crystallized from ethyl acetate - n-hexane to give 3-{4-[2-(4-chlorophenylsulfonylamino)ethylthio]phenyl}propionic acid (Compound No. 52) (1.07 g).
Reaction SMILES: [CH2:1]([C:8]1[CH:13]=[C:12]([I:14])[CH:11]=[CH:10][C:9]=1[OH:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:16][O:17][CH2:18]Cl.O1CCCC1.[H-].[Na+]>O>[CH2:1]([C:8]1[CH:13]=[C:12]([I:14])[CH:11]=[CH:10][C:9]=1[O:15][CH2:16][O:17][CH3:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COCCl
Reactant: Oc1ccc(I)cc1Cc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: COCOc1ccc(I)cc1Cc1ccccc1

Procedure:
10.1 g of 2-benzyl-1-hydroxy-4-iodobenzene and 3 ml of chloromethyl methyl ether were added to 100 ml of tetrahydrofuran and while stirring on an ice bath, 1.45 g of 60% (oily) sodium hydride was added dropwise to the mixture. After stirring for 2 hours, water was added to the reaction mixture, which then was extracted with ethyl acetate, washed with saturated brine and thereafter dried over anhydrous magnesium sulfate. The solvent was removed, and the residue was purified by silica gel column chromatography with 10% ethyl acetate/hexane, to give 8.7 g of the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4]([CH3:33])=[C:5]([C:24]([O:31][CH3:32])=[C:25]([O:29][CH3:30])[C:26]=1[O:27][CH3:28])[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:11]([CH:15]=1)[C:12]([OH:14])=[O:13].[CH3:34][Si](C=[N+]=[N-])(C)C.C(O)(=O)C>CO>[CH3:1][O:2][C:3]1[C:4]([CH3:33])=[C:5]([C:24]([O:31][CH3:32])=[C:25]([O:29][CH3:30])[C:26]=1[O:27][CH3:28])[CH2:6][C:7]1[CH:8]=[CH:9][C:10]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:11]([CH:15]=1)[C:12]([O:14][CH3:34])=[O:13]
Reactant: C[Si](C)(C)C=[N+]=[N-]
Reactant: COc1c(C)c(Cc2ccc(OCc3ccccc3)c(C(=O)O)c2)c(OC)c(OC)c1OC
Solvent: CO
Solvent: CC(=O)O
Product: COC(=O)c1cc(Cc2c(C)c(OC)c(OC)c(OC)c2OC)ccc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 95.4 %

Procedure:
5-(3,4,5,6-Tetramethoxy-2-methylbenzyl)-2-benzyloxybenzoic acid (1.22 g, 2.6548 mmol) was dissolved in methanol (100 ml), trimethylsilyl diazomethane (36.3 g, 10% solution in hexane, 31.8421 mmol) was added thereto under cooling with ice and the mixture was stirred at room temperature for 2 hours. To the reaction solution was added acetic acid (0.5 ml) and the mixture was allowed to stand at room temperature for 16 hours so as to decompose an excessive reagent. The residue obtained by concentration of the reaction solution was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to give the title compound (1.18 g, 2.5321 mmol, 95%).
Reaction SMILES: [C:1]([NH:8][C@H:9]([C@H:17]1[O:21][C:20](=[O:22])[CH2:19][CH2:18]1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:34][C:35]1[CH:36]=[C:37]([CH:40]=[CH:41][CH:42]=1)[C:38]#[N:39].CCCCCC.C(OCC)(=O)C>C1COCC1.CCCCCC>[C:1]([NH:8][C@H:9]([C@H:17]1[O:21][C:20](=[O:22])[C@H:19]([CH2:34][C:35]2[CH:42]=[CH:41][CH:40]=[C:37]([C:38]#[N:39])[CH:36]=2)[CH2:18]1)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)([O:3][C:4]([CH3:6])([CH3:7])[CH3:5])=[O:2]
Reactant: N#Cc1cccc(CBr)c1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)[C@@H]1CCC(=O)O1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CCCCCC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)[C@@H]1C[C@@H](Cc2cccc(C#N)c2)C(=O)O1

Procedure:
Analogously to Example 21 D) 1)c), 2.0 g (6.55 mmol) of 5(S)-[1(S)-(Boc-amino)-2-phenylethyl]-dihydrofuran-2-(3H)-one [Example 21 D) 1)b)] dissolved in 40 ml of THF are deprotonated at -75° C. with 13.1 ml of lithium bis(trimethylsilyl)amide 1M in THF and alkylated (60 min -60° C.) with 1.4 g (7.2 mmol) of 3-bromomethylbenzonitrile (Fluka; Buchs/Switzerland). Column chromatography (SiO2, hexane/ethyl acetate 2:1) and stirring in hexane yields the pure title compound: TLC Rf (D)=0.41; tRet (I)=16.1 min.
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[F:5][C:6]1[CH:30]=[CH:29][C:9]([CH2:10][CH2:11][N:12]2[CH2:17][CH2:16][CH:15]([N:18]3[C:26]4[C:21](=[CH:22][CH:23]=[C:24]([CH2:27][NH2:28])[CH:25]=4)[CH2:20][CH2:19]3)[CH2:14][CH2:13]2)=[CH:8][CH:7]=1.C(N(CC)CC)C.[OH-].[Na+]>C(#N)C.O>[F:5][C:6]1[CH:30]=[CH:29][C:9]([CH2:10][CH2:11][N:12]2[CH2:13][CH2:14][CH:15]([N:18]3[C:26]4[C:21](=[CH:22][CH:23]=[C:24]([CH2:27][NH:28][C:1](=[O:3])[CH3:2])[CH:25]=4)[CH2:20][CH2:19]3)[CH2:16][CH2:17]2)=[CH:8][CH:7]=1
Reactant: CC(=O)Cl
Reactant: NCc1ccc2c(c1)N(C1CCN(CCc3ccc(F)cc3)CC1)CC2
Agent: [Na+]
Agent: [OH-]
Solvent: CC#N
Solvent: CCN(CC)CC
Solvent: O
Product: CC(=O)NCc1ccc2c(c1)N(C1CCN(CCc3ccc(F)cc3)CC1)CC2
Yield: 54 %

Procedure:
Under ice cooling, acetyl chloride (6.6 ml) was added dropwise into a solution of 1-[1-(4-fluorophenethyl)piperidin-4-yl]-6-aminomethylindoline (30 g) obtained above and triethylamine (9.4 g) in acetonitrile (500 ml) and the resultant mixture was stirred at room temperature for 1 hr. After adding a 5 N aqueous solution (40 ml) of sodium hydroxide and water (500 ml) to the reaction solution, the resulting crystalline precipitates were collected by filtration, washed successively with water and ethyl acetate and then dried at 50° C. overnight to give the crude title compound (22.8 g). This crude product was recrystallized successively from ethyl acetate and ethanol to give the title compound (17.9 g) as white needles (yield: 54%).
Reaction SMILES: [CH3:1]I.[Cl:3][C:4]1[CH:18]=[CH:17][C:7]2[C@@H:8]3[C@@H:13]([CH2:14][CH2:15][C:6]=2[CH:5]=1)[NH:12][C:11](=[O:16])[CH2:10][CH2:9]3.[OH-].[Na+]>C1COCC1>[Cl:3][C:4]1[CH:18]=[CH:17][C:7]2[C@@H:8]3[C@@H:13]([CH2:14][CH2:15][C:6]=2[CH:5]=1)[N:12]([CH3:1])[C:11](=[O:16])[CH2:10][CH2:9]3
Reactant: CI
Reactant: O=C1CC[C@@H]2c3ccc(Cl)cc3CC[C@H]2N1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CN1C(=O)CC[C@@H]2c3ccc(Cl)cc3CC[C@H]21
Yield: 142.9 %

Procedure:
To a 1-liter flask equipped with a condenser and a stirrer were added 470 mL of THF, 18.7 g of methyl iodide and 47 g of (4aR)-(10bR)-8-chloro-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one, and stirring was begun at ambient temperature. To the mixture was added 100 ml of 50% aqueous sodium hydroxide in one portion, and gentle heating was begun. The temperature was raised as high as 41° and was then gradually lowered to 29° at the end of 16 hours of stirring. HPLC liquid chromatography, eluting with 1:1 acetonitrile:aqueous buffer (5% ammonium acetate) and monitoring at 220 nanometers, then showed that all the starting material had been consumed and the aqueous layer was removed. The organic layer was concentrated to an oil under vacuum, and the residue was dissolved in ethyl acetate. The solution was washed with brine, and the organic layer was washed with 200 mL of water twice, and was dried over magnesium sulfate and evaporated under vacuum while heptane was added portionwise as the ethyl acetate was removed. A total of 500 mL of heptane was added, and the product began to crystallize when about half of it had been added. The slurry was concentrated to about 300 ml, and filtered, and the solids were washed with heptane and dried in vacuum at 40°-50° to obtain 47.03 g of product, m.p. 97°-99°, of 98.7% purity.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[CH:6]1([C:12]2[CH:17]=[CH:16][C:15]([C:18]3[O:22][N:21]=[C:20]([C:23]4[CH:28]=[CH:27][C:26]([CH2:29][OH:30])=[CH:25][CH:24]=4)[N:19]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1.C(N(CC)CC)C.O>ClCCl>[CH:6]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[O:22][N:21]=[C:20]([C:23]4[CH:28]=[CH:27][C:26]([CH2:29][O:30][S:2]([CH3:1])(=[O:4])=[O:3])=[CH:25][CH:24]=4)[N:19]=3)=[CH:16][CH:17]=2)[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11]1
Reactant: CS(=O)(=O)Cl
Reactant: OCc1ccc(-c2noc(-c3ccc(C4CCCCC4)cc3)n2)cc1
Solvent: O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)OCc1ccc(-c2noc(-c3ccc(C4CCCCC4)cc3)n2)cc1
Temperature: 5 °C
Reaction time: 0.5 h

Procedure:
Methanesulfonyl chloride (0.157 mL, 0.0020 mol) is added to a stirred solution of {4-[5-(4-cyclohexyl phenyl)-[1,2,4]oxadiazole-3-yl]-phenyl}-methanol (0.45 g, 0.0013 mol) and triethylamine (0.376 mL, 0.0027 mol) in dichloromethane (10 mL) at 5° C. Reaction mixture is stirred at 5° C. for 30 minutes, then treated with demineralized water (10 mL). Dichloromethane layer is separated and aqueous layer is extracted with dichloromethane (2×15 mL). Combined organic layer is dried over sodium sulphate and concentrated under reduced pressure to yield methanesulfonic acid 4-[5-(4-cyclohexyl-phenyl)[1,2,4]oxadiazol-3-yl]-benzyl ester.
Reaction SMILES: [CH3:1][C:2]1[O:3][C:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH:5][C:6]=1[CH:7]=O.[CH3:15][CH:16]([CH3:32])[C:17]([NH:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH:26]2[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)[CH:21]=1)=[O:18]>>[CH3:15][CH:16]([CH3:32])[C:17]([NH:19][C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([CH:26]2[CH2:31][CH2:30][N:29]([CH2:7][C:6]3[CH:5]=[C:4]([C:9]4[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=4)[O:3][C:2]=3[CH3:1])[CH2:28][CH2:27]2)[CH:21]=1)=[O:18]
Reactant: CC(C)C(=O)Nc1cccc(C2CCNCC2)c1
Reactant: Cc1oc(-c2ccccc2)cc1C=O
Product: Cc1oc(-c2ccccc2)cc1CN1CCC(c2cccc(NC(=O)C(C)C)c2)CC1

Procedure:
Prepared by Procedure F and Scheme R using 2-methyl-5-phenyl-3-furaldehyde and 2-methyl-N-[3-(4-piperidinyl)phenyl]propanamide: ESMS m/e: 417.2 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[C:3]=1O.[CH3:10]I.[C:12]([O-:15])([O-])=O.[K+].[K+]>CC(C)=O>[CH3:10][O:5][C:4]1[CH:6]=[CH:7][CH:8]=[C:2]([CH3:1])[C:3]=1[O:15][CH3:12]
Reactant: O=C([O-])[O-]
Reactant: Cc1cccc(O)c1O
Reactant: CI
Agent: [K+]
Solvent: CC(C)=O
Product: COc1cccc(C)c1OC
Temperature: 25 °C
Reaction time: 1 h

Procedure:
In a round bottom flask, 3-methyl catechol (5.0 g, 40.3 mmol), MeI (22.3 g, 157.1 mmol), and K2CO3 (18.9 g, 136.9 mmol) were dissolved in acetone (20.0 ml). The reaction mixture was stirred at room temperature for 1 h, then at 60° C. for overnight. The reaction mixture was concentrated and chromatographed on silica gel using EtOAc/Hexane (5:95). A pale yellow liquid was isolated in 100% (6.13 g). The characterization of the compound matched previous report: Xing, L.; Wang, X.; Cheng, X.; Zhu, R.; Liu, B.; Hu, Y. Tetrahedron Letters 2007, 63, (38), 9382-9386.
Reaction SMILES: CS(Cl)(=O)=O.[Cl:6][C:7]1[CH:11]=[C:10]([C:12]([OH:14])=O)[N:9]([C:15]2[C:20]([Cl:21])=[CH:19][CH:18]=[CH:17][N:16]=2)[N:8]=1.[CH2:22]([N:24](CC)CC)C.[Na+].[NH2:30][C:31]1[C:32]([C:38]([O-:40])=O)=[N:33][CH:34]=[N:35][C:36]=1[CH3:37]>C(#N)C.O>[Cl:6][C:7]1[CH:11]=[C:10]([C:12]([NH:30][C:31]2[C:32]([C:38]([NH:24][CH3:22])=[O:40])=[N:33][CH:34]=[N:35][C:36]=2[CH3:37])=[O:14])[N:9]([C:15]2[C:20]([Cl:21])=[CH:19][CH:18]=[CH:17][N:16]=2)[N:8]=1
Reactant: O=C(O)c1cc(Cl)nn1-c1ncccc1Cl
Reactant: CCN(CC)CC
Reactant: Cc1ncnc(C(=O)[O-])c1N
Agent: CS(=O)(=O)Cl
Agent: [Na+]
Solvent: O
Solvent: CC#N
Product: CNC(=O)c1ncnc(C)c1NC(=O)c1cc(Cl)nn1-c1ncccc1Cl
Reaction time: 0.33 h
Yield: 22.2 %

Procedure:
To a solution of 0.26 mL (3.3 mmol) of methanesulfonyl chloride in 18 mL of acetonitrile at 0° C. was added 0.77 g (3.0 mmol) of 3-chloro-1-(3-chloro-2-pyridinyl)-1H-pyrazol-5-carboxylic acid from Step J. 0.42 mL (3.0 mmol) of triethylamine in 9 mL of acetonitrile was added dropwise. After 20 minutes at 0° C., 0.525 g (3.0 mmol) of material from Step F was added. After 15 minutes 0.42 mL (3.0 mmol) of triethylamine was added dropwise. After 2 hours 0.26 mL (3.3 mmol) of methanesulfonyl chloride was added. After stirring overnight. The reaction mixture was poured into water. Filtration afforded 0.27 g of the title compound.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[O:12][CH:13]=[CH:14][CH:15]=2)=[O:10])=[CH:4][C:3]=1[N+:16]([O-:18])=[O:17].C([O-])([O-])=O.[K+].[K+].[SH:25][C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=1>CN(C=O)C.O>[OH:32][C:29]1[CH:30]=[CH:31][C:26]([S:25][C:2]2[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]3[O:12][CH:13]=[CH:14][CH:15]=3)=[O:10])=[CH:4][C:3]=2[N+:16]([O-:18])=[O:17])=[CH:27][CH:28]=1
Reactant: O=C(Nc1ccc(F)c([N+](=O)[O-])c1)c1ccco1
Reactant: Oc1ccc(S)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C(Nc1ccc(Sc2ccc(O)cc2)c([N+](=O)[O-])c1)c1ccco1
Temperature: 80 °C
Yield: 97.1 %

Procedure:
The product of Example 255a (1.00 g, 2.89 mmol) was dissolved in DMF to which K2CO3 (801 mg, 5.79 mmol), and 4-mercapto-phenol (366 mg, 2.89 mmol) were added. The reaction mixture was then heated to 80° C. for 2 hrs. At this point the reaction mixture was cooled to room temperature and diluted with water which was then extracted with ethyl acetate to isolate the desired compound (1.00 g, 99%).
Reaction SMILES: [NH2:1][CH:2]1[CH2:11][CH2:10][C:9]2[C:8]([O:12][CH2:13][C:14]([OH:16])=[O:15])=[CH:7][CH:6]=[CH:5][C:4]=2[CH2:3]1.[C:17]1([S:23](Cl)(=[O:25])=[O:24])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[OH-].[Na+].Cl>>[C:17]1([S:23]([NH:1][CH:2]2[CH2:11][CH2:10][C:9]3[C:8]([O:12][CH2:13][C:14]([OH:16])=[O:15])=[CH:7][CH:6]=[CH:5][C:4]=3[CH2:3]2)(=[O:25])=[O:24])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: NC1CCc2c(cccc2OCC(=O)O)C1
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: O=C(O)COc1cccc2c1CCC(NS(=O)(=O)c1ccccc1)C2

Procedure:
10 mmol of 6-amino-5,6,7,8-tetrahydro-naphth-1-yl-oxyacetic acid and 20 mmol of benzenesulphonyl chloride are warmed at 80° C. in 40 ml of 10% strength NaOH for 2 hours. The mixture is then acidified with concentrated HCl and the milky suspension is extracted by shaking twice with ethyl acetate. The combined ethyl acetate phases are rapidly extracted by shaking with 10% strength NaOH (product precipitates out of the ethyl acetate), the NaOH phase is acidified with concentrated HCl and extracted by shaking twice with ethyl acetate and the extract is dried over Na2SO4 and evaporated. The residue is boiled up in ethyl acetate and the mixture is filtered. The product crystallizes out after 2-3 hours in a refrigerator.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[C:9]2[C:4]=1[C:5](=[O:27])[NH:6][C:7]([C:15]1[CH:20]=[CH:19][C:18]([N:21]3[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]3)=[CH:17][CH:16]=1)=[N:8]2.C(=O)([O-])[O-].[K+].[K+].Br[CH2:35][CH2:36][OH:37]>CN(C=O)C.O>[OH:37][CH2:36][CH2:35][N:24]1[CH2:23][CH2:22][N:21]([C:18]2[CH:19]=[CH:20][C:15]([C:7]3[NH:6][C:5](=[O:27])[C:4]4[C:9](=[CH:10][C:11]([O:13][CH3:14])=[CH:12][C:3]=4[O:2][CH3:1])[N:8]=3)=[CH:16][CH:17]=2)[CH2:26][CH2:25]1
Reactant: COc1cc(OC)c2c(=O)[nH]c(-c3ccc(N4CCNCC4)cc3)nc2c1
Reactant: OCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1cc(OC)c2c(=O)[nH]c(-c3ccc(N4CCN(CCO)CC4)cc3)nc2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 9 %

Procedure:
To a solution of 5,7-dimethoxy-2-(4-(piperazin-1-yl)phenyl)quinazolin-4(3H)-one (1) (0.68 mmol) in DMF (8 mL) was added potassium carbonate (0.68 mmol) and 2-bromoethanol (0.68 mmol). The resulting solution was stirred at room temperature overnight. Then, the mixture was diluted with water, extracted with EtOAc, washed with brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to afford 2. The material was purified by flash chromatography on silica gel, eluting with 50% to 100% of 92:7:1 CHCl3/MeOH/concentrated NH4OH in CH2Cl2. The product was further purified by reverse-phase chromatography, eluting with 10% to 90% CH3CN in H2O, to afford the title compound (0.025 g, 9%). 1H NMR (300 MHz, DMSO-d6): δ 11.45 (s, 1H), 8.08 (d, J=8.9 Hz, 2H), 7.00 (d, J=9.1 Hz, 2H), 6.68 (s, 1H), 6.46 (s, 1H), 4.30-4.55 (m, 1H), 3.88 (s, 3H), 3.83 (s, 3H), 3.43-3.67 (m, 2H), 3.10-3.43 (m, 7H), 2.77-3.04 (m, 1H), 2.31-2.64 (m, 2H). ESI MS m/z 411 [M+H]+.
Reaction SMILES: [F:1][C:2]([F:17])([F:16])[C:3]1[CH:8]=[CH:7][C:6]([CH2:9][S:10]([CH2:13][C:14]#[N:15])(=[O:12])=[O:11])=[CH:5][CH:4]=1.[F:18][C:19]([S:22][CH2:23][CH2:24]OS(C(F)(F)F)(=O)=O)([F:21])[F:20]>>[F:17][C:2]([F:1])([F:16])[C:3]1[CH:4]=[CH:5][C:6]([CH2:9][S:10]([CH:13]([CH2:24][CH2:23][S:22][C:19]([F:21])([F:20])[F:18])[C:14]#[N:15])(=[O:12])=[O:11])=[CH:7][CH:8]=1
Reactant: N#CCS(=O)(=O)Cc1ccc(C(F)(F)F)cc1
Reactant: O=S(=O)(OCCSC(F)(F)F)C(F)(F)F
Product: N#CC(CCSC(F)(F)F)S(=O)(=O)Cc1ccc(C(F)(F)F)cc1

Procedure:
Compound II-11 was prepared from (4-trifluoromethyl-phenylmethanesulfonyl)-acetonitrile and trifluoro-methanesulfonic acid 2-trifluoromethylsulfanyl-ethyl ester as described for compound II-1.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7]([O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[OH:16])[CH3:8].Cl[CH2:18][C:19]#[N:20].N>C(O)C.O.CC(C)=O>[CH2:7]([O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[O:16][CH2:18][C:19]#[N:20])[CH3:8]
Reactant: N#CCCl
Reactant: CCOc1ccccc1O
Agent: N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC(C)=O
Solvent: CCO
Product: CCOc1ccccc1OCC#N
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 84.8 %

Procedure:
Potassium carbonate (550 g, 3.98 mol) was added to acetone (1800 ml) and resulting suspension was stirred for 30 min. 2-Ethoxyphenol (460 g, 3.329 mol) was gradually added under stirring. The mixture was heated to reflux. Chloroacetonitrile (275 g, 3.642 mol) was added and the mixture was stirred under reflux for 24 hours. The reaction mixture was cooled down to room temperature. Solid was filtered off, washed with acetone (750 ml) and combined filtrates were evaporated to give oil. The oil was dissolved in ethanol (180 ml), the solution was heated to reflux and mixture of water (530 ml) and aqueous ammonia (45 ml) was added. The mixture was cooled to 5-10° C. under stirring. Crude crystalline product was filtered, washed with mixture of ethanol (250 ml) and water (400 ml). The crude product was recrystallized from ethanol /water mixture to give pure product (500 g).
Reaction SMILES: [C:1]([O:5][CH3:6])(=[O:4])[CH2:2][SH:3].[H-].[Na+].[O:9]=[C:10]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[S:13][C:12]([C:20]2[N:25]=[C:24]([CH2:26]S([O-])(=O)=O)[CH:23]=[CH:22][CH:21]=2)=[N:11]1.C(OCC)(=O)C>CN(C=O)C.O>[O:9]=[C:10]1[C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[S:13][C:12]([C:20]2[N:25]=[C:24]([CH2:26][S:3][CH2:2][C:1]([O:5][CH3:6])=[O:4])[CH:23]=[CH:22][CH:21]=2)=[N:11]1
Reactant: COC(=O)CS
Reactant: O=c1nc(-c2cccc(CS(=O)(=O)[O-])n2)sc2ccccc12
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Solvent: CCOC(C)=O
Product: COC(=O)CSCc1cccc(-c2nc(=O)c3ccccc3s2)n1
Temperature: 25 °C
Reaction time: 18 h
Yield: 51.1 %

Procedure:
Methyl thioglycolate (0.35 g, 3.30 mmol) and sodium hydride (60% in oil, 0.15 g, 3.60 mmol) were dissolved in DMF (30 ml), and 6-(4-oxo-4H-1,3-benzothiazin-2-yl)-2-pyridylmethanesulfonate (1.05 g, 3.00 mmol) was added thereto. The reaction mixture was stirred at room temperature for 18 hrs and combined with ethyl acetate and water. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was recrystallized from ethanol to give the titled compound (0.55 g, 51%) as pale yellow crystals.
Reaction SMILES: FC(F)(F)C(O)=O.[Cl:8][C:9]1[C:13]2[C:14]([NH:18]C(C)(CC(C)(C)C)C)=[N:15][CH:16]=[CH:17][C:12]=2[N:11]([C:27]([O:29][CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[O:28])[CH:10]=1>ClCCl>[NH2:18][C:14]1[C:13]2[C:9]([Cl:8])=[CH:10][N:11]([C:27]([O:29][CH2:30][C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)=[O:28])[C:12]=2[CH:17]=[CH:16][N:15]=1
Reactant: CC(C)(C)CC(C)(C)Nc1nccc2c1c(Cl)cn2C(=O)OCc1ccccc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Nc1nccc2c1c(Cl)cn2C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 79.8 %

Procedure:
Trifluoroacetic acid (1.5 mL) was added drop wise to an ice-cooled suspension of benzyl 3-chloro-4-[(2,4,4-trimethylpentan-2-yl)amino]-1H-pyrrolo[3,2-c]pyridine-1-carboxylate (610 mg) in dichloromethane (10 mL). The reaction mixture was stirred at room temperature for about 4 hours. Upon completion, the reaction mixture was concentrated under vacuum and the residue was stirred in excess aqueous ammonia solution. The precipitated solid was filtered under suction, washed with water and dried to afford benzyl 4-amino-3-chloro-1H-pyrrolo[3,2-c]pyridine-1-carboxylate (354.8 mg, 95%) as an off-white solid.
Reaction SMILES: I[C:2]1[C:3](=[O:17])[NH:4][C:5](=[O:16])[N:6]([CH:15]=1)[C@@H:7]1[O:14][C@H:11]([CH2:12][OH:13])[C@@H:9]([OH:10])[CH2:8]1.C[Sn](C)(C)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=1>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.O1CCOCC1>[N:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[C:2]1[C:3](=[O:17])[NH:4][C:5](=[O:16])[N:6]([CH:15]=1)[C@@H:7]1[O:14][C@H:11]([CH2:12][OH:13])[C@@H:9]([OH:10])[CH2:8]1
Reactant: O=c1[nH]c(=O)n([C@H]2C[C@H](O)[C@@H](CO)O2)cc1I
Reactant: C[Sn](C)(C)c1ccccn1
Agent: Cl[Pd]Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1COCCO1
Product: O=c1[nH]c(=O)n([C@H]2C[C@H](O)[C@@H](CO)O2)cc1-c1ccccn1
Temperature: 60 °C
Reaction time: 1 h
Yield: 82.9 %

Procedure:
In a 25 mL pear shaped flask was placed 5-iodo-2'-deoxyuridine (0.354 g, 1.0 mmol), 2-trimethylstannylpyridine (0.84 g, 3.5 mmol), Bis (triphenylphosphine)-palladium (II) chloride (0.070 g, 0.1 mmol), and anhydrous 1,4-dioxane (15 mL). The reaction was heated at 60° C. for 15 hrs then at 90° C. for 1 h. The solvent was evaporated and the residue purified by silica gel chromatography (10% CH3OH in CH2Cl2 (1% NH3)) to yield 0.253 g (83%) of the title compound as a white solid m.p. 201°-203° C.
Reaction SMILES: [CH3:1][Si:2]([CH3:23])([CH3:22])[C:3]1[CH:4]=[C:5]([C:13]2[CH2:14][C:15]3[C:20]([CH:21]=2)=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:6]=[C:7]([Si:9]([CH3:12])([CH3:11])[CH3:10])[CH:8]=1.[CH2:24]([Li])[CH2:25][CH2:26][CH3:27].[Cl-:29].[Cl-].[Cl-].[Cl-].[Hf+4:33]>C(OCC)C>[Cl-:29].[Cl-:29].[CH3:12][Si:9]([CH3:10])([CH3:11])[C:7]1[CH:6]=[C:5]([C:13]2[CH:14]([Hf+2:33][CH:24]3[C:15]4[C:27](=[CH:20][CH:21]=[CH:13][CH:14]=4)[CH:26]=[C:25]3[C:5]3[CH:6]=[C:7]([Si:9]([CH3:10])([CH3:12])[CH3:11])[CH:8]=[C:3]([Si:2]([CH3:23])([CH3:1])[CH3:22])[CH:4]=3)[C:15]3[C:20]([CH:21]=2)=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:4]=[C:3]([Si:2]([CH3:23])([CH3:22])[CH3:1])[CH:8]=1
Reactant: C[Si](C)(C)c1cc(C2=Cc3ccccc3C2)cc([Si](C)(C)C)c1
Reactant: [Li]CCCC
Reactant: [Hf+4]
Agent: [Cl-]
Solvent: CCOCC
Product: C[Si](C)(C)c1cc(C2=Cc3ccccc3C2[Hf+2]C2C(c3cc([Si](C)(C)C)cc([Si](C)(C)C)c3)=Cc3ccccc32)cc([Si](C)(C)C)c1
Temperature: -10 °C
Reaction time: 2 h
Yield: 56 %

Procedure:
2-(3,5-Bis(trimethylsilyl)phenyl)indene (22.3 g, 0.066 mol) and anhydrous diethyl ether (250 mL) were placed in a 1 L three-necked flask under argon. n-Butyllithium (41 mL of a 1.6 M solution in hexanes, 0.066 mol) was added over a thirty minute period at 0° C. The solution was stirred for an additional two hours. Hafnium tetrachloride (10.5 g, 0.033 mol) was added incrementally over a one-hour period. The mixture was then stirred overnight. The ethereal solution was chilled to −10° C. and the solids were collected by filtration. The solids were taken up in 300 mL of dichloromethane and the residual solids were removed by filtration through celite. The celite was washed with an additional 100 mL of dichloromethane and the solvents were evaporated to give 17.3 g of bis(2-(3,5-bis(trimethylsilyl)phenyl)indenyl)hafnium dichloride product (56% yield).