Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O[C@@H]1[C@H](OC(=O)C)[C@@H](COC(=O)C)O[C@H]1N1C2N=CN=C(O)C=2N=C1)(=[O:3])C.C(C1NC=CN=1)CC.[CH:37]1[CH:42]=[CH:41][C:40]([P:43]([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[C:44]2[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=2)=[CH:39][CH:38]=1.II.C(N(C(C)C)C(C)C)C>C1(C)C=CC=CC=1>[P:43]([C:40]1[CH:39]=[CH:38][CH:37]=[CH:42][CH:41]=1)([C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:3]
Reactant: CC(=O)OC[C@H]1O[C@@H](n2cnc3c(O)ncnc32)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Agent: CCCc1ncc[nH]1
Agent: II
Solvent: CCN(C(C)C)C(C)C
Solvent: Cc1ccccc1
Product: O=P(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 95 °C
Reaction time: 4 h

Procedure:
A suspension of 2′,3′,5′-tri-O-acetylinosine (1.58 g, 4.0 mmol), 2-propylimidazole (1.60 g, 14.4 mmol), Ph3P (2.58 g, 9.6 mmol), I2 (2.14 g, 8.32 mmol), and EtN(i-Pr)2 (3.6 mL, 2.67 g, 20.2 mmol) in dried toluene (40 mL) was stirred at 95° C. for 4 h. Volatiles were evaporated in vacuo, and the residue was extracted with boiling EtOAc. The combined extracts were evaporated to dryness, and the residue was chromatographed (CH2Cl2/MeOH, 1:40) to give a solid contaminated with Ph3PO. This material was dissolved in AcOH (160 mL), and AcCl (2.2 mL, 2.43 g, 31 mmol) was added. The solution was stirred at 65° C. overnight, and volatiles were evaporated in vacuo. The residue was dissolved in CH2Cl2 and extracted with 0.1 N NaOH/H2O. The aqueous layer was washed (CH2Cl2), and precipitation with CO2 followed by filtration and thorough washing (H2O) gave a solid (0.66 g, 72%). This material was dissolved in MeOH and decolorized with charcoal. Recrystallization (MeOH) gave 6-(2-propylimidazol-1-yl)purine as a colorless solid: mp 242.5-243.5° C.; UV (MeOH) max 278 nm (∈ 13 700), min 235 nm (∈ 5000); 1H NMR (300 MHz, DMSO-d6) δ 13.90 (br s, 1H), 8.86 (s, 1H), 8.69 (s, 1H), 8.36 (s, 1H), 7.07 (d, J=1.5 Hz, 1H), 3.18 (t, J=7.3 Hz, 2H), 1.72 (sext, J=7.3 Hz, 2H), 0.93 (t, J=7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 155.5, 152.0, 149.8, 146.9, 145.8, 128.5, 123.6, 121.4, 32.2, 21.5, 14.5; HRMS m/z 228.1109 (M+[C11H12N6]=228.1123). Anal. Calcd for C11H12N6: C, 57.88; H, 5.30; N, 36.82. Found: C, 58.09; H, 5.19; N, 37.00.
Reaction SMILES: O.[NH2:2][NH2:3].[Br:4][C:5]1[CH:10]=[CH:9][C:8](F)=[CH:7][N:6]=1>O>[Br:4][C:5]1[CH:10]=[CH:9][C:8]([NH:2][NH2:3])=[CH:7][N:6]=1
Reactant: NN
Reactant: Fc1ccc(Br)nc1
Solvent: O
Product: NNc1ccc(Br)nc1
Temperature: 110 °C
Reaction time: 0.08 h
Yield: 32.8 %

Procedure:
To hydrazine monohydrate (5.51 mL, 114 mmol) was added 2-bromo-5-fluoropyridine (1.00 g, 5.68 mmol). The mixture was heated under microwave irradiation in a sealed, thick-walled glass tube for 1 h at 110° C. The thick, white suspension was poured into 60 mL water and stirred vigorously for 5 min. The precipitate was collected by filtration, rinsed with water, and then dried under reduced pressure to provide the title compound (0.35 g) as a white solid. LCMS m/z=188.2 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 4.13 (s, 2H), 7.09 (dd, J=8.7, 3.2 Hz, 1H), 7.11 (bs, 1H), 7.26 (d, J=8.6 Hz, 1H), 7.87 (d, J=2.9 Hz, 1H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9](=[CH2:15])[C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8].Cl.[CH2:17]([O:19][C:20](=[O:24])[CH2:21][CH2:22][NH2:23])[CH3:18].O>C(N(CC)CC)C>[CH2:17]([O:19][C:20](=[O:24])[CH2:21][CH2:22][NH:23][CH2:15][CH:9]([C:4]1[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=1)[C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH3:18]
Reactant: C=C(C(=O)OCC)c1ccc(Cl)c(Cl)c1
Reactant: CCOC(=O)CCN
Agent: Cl
Solvent: O
Solvent: CCN(CC)CC
Product: CCOC(=O)CCNCC(C(=O)OCC)c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 14 h
Yield: 52.4 %

Procedure:
To a solution of the compound (38.1 g) obtained in step 1 in triethylamine (20.4 mL) was added β-alanine ethyl ester monohydrochloride (22.5 g), and the mixture was stirred at room temperature for 14 hr. The reaction mixture was poured into water, and the resultant product was extracted with diethyl ether. The organic layer was washed with brine and dried, and the solvent was evaporated under reduced pressure to give N-[2-(3,4-dichlorophenyl)-3-ethoxy-3-oxopropyl]-β-alanine ethyl ester (27.8 g, 78%) as a colorless oil.
Reaction SMILES: C(N(C(C)C)C(C)C)C.[Cl:10][C:11]1[CH:31]=[CH:30][CH:29]=[CH:28][C:12]=1[C:13]([NH:15][C@H:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([C:25](O)=[O:26])[CH:23]=2)[CH2:18][CH2:17]1)=[O:14].O.ON1C2C=CC=CC=2N=N1.[CH2:43]1[C:48]2([CH2:53][CH2:52][N:51]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:50][CH2:49]2)[CH2:47][CH2:46][CH2:45][NH:44]1>C(Cl)Cl>[Cl:10][C:11]1[CH:31]=[CH:30][CH:29]=[CH:28][C:12]=1[C:13]([NH:15][C@H:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([C:25]([N:44]3[CH2:45][CH2:46][CH2:47][C:48]4([CH2:49][CH2:50][N:51]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:52][CH2:53]4)[CH2:43]3)=[O:26])[CH:23]=2)[CH2:18][CH2:17]1)=[O:14]
Reactant: O=C(O)c1ccc2c(c1)[C@H](NC(=O)c1ccccc1Cl)CC2
Reactant: CC(C)(C)OC(=O)N1CCC2(CCCNC2)CC1
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CCC2(CCCN(C(=O)c3ccc4c(c3)[C@H](NC(=O)c3ccccc3Cl)CC4)C2)CC1
Temperature: 0 °C
Reaction time: 60 h
Yield: 70 %

Procedure:
N-Ethyl-diisopropylamine (4 eq.) was added to a solution of (3R)-3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid (E-03) (0.952 mmol, 1 eq.) in methylene chloride (18 ml). The reaction mixture was cooled to 0° C. and N-ethyl-N′-3-(dimethylamino)-propyl-carbodiimide hydrochloride (1.2 eq.) and 1-hydroxybenzotriazole hydrate (0.2 eq.) were then added. The mixture was stirred at this temperature for 15 min, before tert-butyl 2,9-diazaspiro[5.5]undecane-9-carboxylate (1.1 eq.) was added. The reaction mixture was stirred at room temperature for 2.5 d. Then, the reaction mixture was washed in each case 1× with 10% NH4Cl solution, sat. NaHCO3 solution and sat. NaCl solution. The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (silica; ethyl acetate/hexane/ammonia (25 aq.) 70:10:0.8). Yield: 70%
Reaction SMILES: [CH:1]1([C:4]2[CH:9]=[CH:8][N:7]=[C:6]([C:10]#[N:11])[CH:5]=2)[CH2:3][CH2:2]1.[O-:12][CH2:13][CH3:14].[Na+]>C(O)C>[CH:1]1([C:4]2[CH:9]=[CH:8][N:7]=[C:6]([C:10](=[NH:11])[O:12][CH2:13][CH3:14])[CH:5]=2)[CH2:3][CH2:2]1
Reactant: N#Cc1cc(C2CC2)ccn1
Reactant: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: CCOC(=N)c1cc(C2CC2)ccn1
Temperature: 25 °C
Reaction time: 3 h
Yield: 87.6 %

Procedure:
To a solution of 4-cyclopropylpicolinonitrile (0.04 g, 0.27 mmol) in ethanol was added sodium ethoxide (0.022 g, 0.33 mmol) and the reaction mixture was stirred at room temperature for 3 h. The reaction mixture was concentrated under vacuum, quenched with water, extracted with ethyl acetate, dried over sodium sulfate, filtered and concentrated under reduced pressure to afford ethyl 4-cyclopropylpicolinimidate (0.045 g). The material was used without further purification. MS (ES+APCI) (M+H) 190.9; LCMS retention time 1.700 min (Method G).
Reaction SMILES: [CH3:1][C@:2]12[O:7][C@H:6]1[CH2:5][N:4]([C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9])[CH2:3]2.[OH-].[NH4+:19]>O1CCOCC1>[NH2:19][C@@H:6]1[CH2:5][N:4]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:3][C@:2]1([OH:7])[CH3:1]
Reactant: [NH4+]
Reactant: C[C@@]12CN(C(=O)OCc3ccccc3)C[C@@H]1O2
Agent: [OH-]
Solvent: C1COCCO1
Product: C[C@@]1(O)CN(C(=O)OCc2ccccc2)C[C@H]1N
Temperature: 100 °C

Procedure:
A mixture of (1R,5S)-benzyl 1-methyl-6-oxa-3-azabicyclo[3.1.0]hexane-3-carboxylate (4.50 g, 19.29 mmol) and concentrated ammonium hydroxide (16 mL, 411 mmol) in dioxane (8 mL) in a sealed vessel was heated to 100° C. for 15 h. The resulting mixture was concentrated to afford (3R,4R)-benzyl 4-amino-3-hydroxy-3-methylpyrrolidine-1-carboxylate along with its regioisomer (4.8 g, 85:15 ratio), which was used in the next step without purification. MS (ES+) m/z: 218.2 (M+H).
Reaction SMILES: Br[C:2]1[CH:8]=[C:7]([CH3:9])[C:6]([Cl:10])=[CH:5][C:3]=1[NH2:4].[Cu][C:12]#[N:13].N>CN1CCCC1=O>[C:12]([C:2]1[CH:8]=[C:7]([CH3:9])[C:6]([Cl:10])=[CH:5][C:3]=1[NH2:4])#[N:13]
Reactant: N#C[Cu]
Reactant: Cc1cc(Br)c(N)cc1Cl
Agent: N
Solvent: CN1CCCC1=O
Product: Cc1cc(C#N)c(N)cc1Cl
Temperature: 25 °C
Reaction time: 2 h
Yield: 66.4 %

Procedure:
To a solution of 2-bromo-5-chloro-4-methylaniline (13.0 g 58.96 mmol) in N-methylpyrrolidinone (100 ml) was added copper(I) cyanide (10.56 g, 118 mmol). The reaction mixture was placed in an oil bath preheated to 163° C. and stirred at this temperature for 2 h. The reaction mixture was allowed to cool to room temperature and then poured in ice-water (300 ml) and aqueous ammonia (90 ml). The brown precipitate was collected by filtration, washed with water (150 ml), dissolved in dichloromethane and the insoluble material was removed by filtration. The filtrate was washed with brine (100 ml), dried (MgSO4) and concentrated in vacuo. Purification, on gradient elution with dichloromethane in petroleum ether 60-80° C. (65 to 95%), afforded a white solid (6.52 g), mp 180° C.; 1H-NMR (DMSO-d6) 2.14 (s, 3H, 4-CH3), 6.11 (s, 2H, NH2), 6.86 (s, 1H, 6-H), 7.39 (s, 1H, 3-H); MS (FAB, m/z) 166,168 [(M+H)+; 90%, 40% respectively; Cl isotopic pattern]; FAB-HRMS: measured 166.0307; calculated for C8H8ClN2 (M+H)+ 166.0298.
Reaction SMILES: [OH-].[Na+].Cl[C:4]([O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:5].[C:14]([C:16]1([CH2:29]OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]1)#[N:15]>O1CCOCC1>[CH2:29]1[C:16]2([CH2:21][CH2:20][N:19]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH2:18][CH2:17]2)[CH2:14][N:15]1[C:4]([O:6][CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:5]
Reactant: Cc1ccc(S(=O)(=O)OCC2(C#N)CCN(C(=O)OC(C)(C)C)CC2)cc1
Reactant: O=C(Cl)OCc1ccccc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)N1CCC2(CC1)CN(C(=O)OCc1ccccc1)C2
Reaction time: 16 h
Yield: 85.5 %

Procedure:
Under ice-cooling, 1M sodium hydroxide aqueous solution (6.0 ml) and benzyl chloroformate (1.03 g) were sequentially added to a dioxane (50 ml) suspension of tert-butyl 4-cyano-4-({[(4-methylphenyl)sulfonyl]oxy}methyl)piperidine-1-carboxylate (2.15 g), and stirring was performed at room temperature for 16 hours. The reaction liquid was concentrated under reduced pressure, and extracted with EtOAc. The organic layer was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (EtOAc/hexane) to obtain 2-benzyl 7-tert-butyl 2,7-diazaspiro[3.5]nonane-2,7-dicarboxylate (1.68 g).
Reaction SMILES: [F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([CH:33]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:35]=1)[C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[CH2:19][CH2:18][N:17]([C:20](=[O:25])[C:21](F)(F)F)[CH2:16][CH2:15]2)[CH:10]([C:26]2[CH:31]=[CH:30][C:29]([CH3:32])=[CH:28][CH:27]=2)[CH2:9]1)=[O:7].[CH:42]1(C(Cl)=O)C[CH2:43]1>C(Cl)(Cl)Cl>[F:39][C:36]([F:37])([F:38])[C:34]1[CH:33]=[C:5]([C:6]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[CH2:19][CH2:18][N:17]([C:20]([CH:21]4[CH2:43][CH2:42]4)=[O:25])[CH2:16][CH2:15]3)[CH:10]([C:26]3[CH:27]=[CH:28][C:29]([CH3:32])=[CH:30][CH:31]=3)[CH2:9]2)=[O:7])[CH:4]=[C:3]([C:2]([F:1])([F:40])[F:41])[CH:35]=1
Reactant: O=C(Cl)C1CC1
Reactant: Cc1ccc(C2CN(C(=O)c3cc(C(F)(F)F)cc(C(F)(F)F)c3)CCC2N2CCN(C(=O)C(F)(F)F)CC2)cc1
Solvent: ClC(Cl)Cl
Product: Cc1ccc(C2CN(C(=O)c3cc(C(F)(F)F)cc(C(F)(F)F)c3)CCC2N2CCN(C(=O)C3CC3)CC2)cc1

Procedure:
The title compound, MS: m/e=568.3 (M+H+), [α]58920=−6.48 (c=0.4012, chloroform), was prepared in accordance with the general method of example 102 (part1) and example 38 from (−)-(1-{4-[1-(3,5-bis-trifluoromethyl-benzoyl)-3-p-tolyl-piperidin-4-yl]-piperazin-1-yl}-2,2,2-trifluoro-ethanone and cyclopropyl carbonyl chloride.
Reaction SMILES: [CH2:1]([O:10][C:11]([C:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]([CH2:22][CH2:23][CH2:24][C:25]([O:27]CC2C=CC=CC=2)=[O:26])[CH:14]=1)=[O:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]>CO.O1CCOCC1.[C].[Pd]>[CH2:1]([O:10][C:11]([C:13]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[N:15]([CH2:22][CH2:23][CH2:24][C:25]([OH:27])=[O:26])[CH:14]=1)=[O:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH3:9]
Reactant: CCCCCCCCCOC(=O)c1cn(CCCC(=O)OCc2ccccc2)c2ccccc12
Agent: [Pd]
Solvent: CO
Solvent: C1COCCO1
Product: CCCCCCCCCOC(=O)c1cn(CCCC(=O)O)c2ccccc12
Yield: 82978.3 %

Procedure:
A mixture of benzyl 4-(3-nonyloxycarbonyl-1-indolyl)butyrate (368 mg) obtained in Ex. 62 and 10% palladium carbon (0.10 g) in methanol and 1,4-dioxane was stirred at room temperature for 2 hours under a hydrogen atmosphere at 3 atm. Removal of the catalyst and evaporation of the solvent afforded 4-(3-nonyloxycarbonyl-1-indolyl)butyric acid (246 g) as a solid.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][CH2:5][NH:6][C:7](=[S:10])SC.O.[NH2:12][NH2:13]>C(O)C>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][NH:6][C:7](=[S:10])[NH:12][NH2:13]
Reactant: COCCCNC(=S)SC
Reactant: NN
Solvent: O
Solvent: CCO
Product: COCCCNC(=S)NN
Temperature: 70 °C
Reaction time: 4.5 h
Yield: 98.5 %

Procedure:
A solution of methyl N-(3-methoxypropyl)dithiocarbamate (100.2 g) in ethanol (300 ml) was added dropwise at 3° C. over 30 minutes to a solution of hydrazine hydrate (28 g) in ethanol (200 ml). The mixture was stirred for 4.5 hours at 70° C. The reaction mixture was concentrated and to the residue were added water and diethyl ether. The diethyl ether extract was dried over magnesium sulfate and evaporated in vacuo to give pinkish oil of 4-(3-methoxypropyl)thiosemicarbazide (89.9 g).
Reaction SMILES: [C:1]([C:5]1[N:10]=[CH:9][C:8]([C:11]2[N:12]([C:32](Cl)=[O:33])[C@@:13]([C:25]3[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=3)([CH3:24])[C@@:14]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)([CH3:16])[N:15]=2)=[C:7]([O:35][CH2:36][CH3:37])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH:38]1[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]1.[CH:44]1([C:47](O)=[O:48])[CH2:46][CH2:45]1>>[C:1]([C:5]1[N:10]=[CH:9][C:8]([C:11]2[N:12]([C:32]([N:38]3[CH2:43][CH2:42][N:41]([C:47]([CH:44]4[CH2:46][CH2:45]4)=[O:48])[CH2:40][CH2:39]3)=[O:33])[C@@:13]([C:25]3[CH:26]=[CH:27][C:28]([Cl:31])=[CH:29][CH:30]=3)([CH3:24])[C@@:14]([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=3)([CH3:16])[N:15]=2)=[C:7]([O:35][CH2:36][CH3:37])[CH:6]=1)([CH3:2])([CH3:4])[CH3:3]
Reactant: O=C(O)C1CC1
Reactant: C1CNCCN1
Reactant: CCOc1cc(C(C)(C)C)ncc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)Cl
Product: CCOc1cc(C(C)(C)C)ncc1C1=N[C@@](C)(c2ccc(Cl)cc2)[C@@](C)(c2ccc(Cl)cc2)N1C(=O)N1CCN(C(=O)C2CC2)CC1

Procedure:
In a manner analogous to the method described in examples 8, (4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl chloride (example 51) was coupled with piperazine-cyclopropanecarboxylic acid (Aldrich) to give the title compound. HR-MS (ES, m/z) calculated for C37H44Cl2N5O3 [(M+H)+] 676.2816, observed 676.2814.
Reaction SMILES: [C:1]([O:5][C:6](=[O:39])[C@@H:7]([NH:13][C:14]([NH:16][C@@H:17]([CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30](=[O:38])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([I:37])[CH:32]=1)[C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])=[O:15])[CH2:8][CH2:9][C:10]([OH:12])=O)([CH3:4])([CH3:3])[CH3:2].NCC[C:43]1[CH:48]=[CH:47][C:46]([S:49]([NH2:52])(=[O:51])=[O:50])=[CH:45][CH:44]=1.C[N:54](C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[C:1]([O:5][C:6](=[O:39])[C@@H:7]([NH:13][C:14](=[O:15])[NH:16][C@@H:17]([CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30](=[O:38])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([I:37])[CH:32]=1)[C:18]([O:20][C:21]([CH3:22])([CH3:24])[CH3:23])=[O:19])[CH2:8][CH2:9][C:10](=[O:12])[NH:54][C:43]1[CH:48]=[CH:47][C:46]([S:49](=[O:51])(=[O:50])[NH2:52])=[CH:45][CH:44]=1)([CH3:3])([CH3:4])[CH3:2]
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Reactant: CC(C)(C)OC(=O)[C@H](CCCCNC(=O)c1cccc(I)c1)NC(=O)N[C@@H](CCC(=O)O)C(=O)OC(C)(C)C
Reactant: NCCc1ccc(S(N)(=O)=O)cc1
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)[C@H](CCCCNC(=O)c1cccc(I)c1)NC(=O)N[C@@H](CCC(=O)Nc1ccc(S(N)(=O)=O)cc1)C(=O)OC(C)(C)C

Procedure:
A solution of (S)-5-tert-butoxy-4-(3-((S)-1-tert-butoxy-6-(3-iodobenzamido)-1-oxohexan-2-yl)ureido)-5-oxopentanoic acid (212 mg, 0.32 mmol), 4-(2-aminoethyl)benzenesulfonamide (80 mg, 0.40 mmol), HATU (152 mg, 0.40 mmol), and DIPEA (0.50 mL) in DMF (5 mL) was stirred at 50° C. overnight. The solvents were evaporated under reduced pressure to give a residue, which was purified utilizing a Biotage SP4 with a gradient of 10-100% EtOAc in hexane to give (S)-tert-butyl 2-(3-((S)-1-tert-butoxy-1,5-dioxo-5-(4-sulfamoylphenylamino)pentan-2-yl)ureido)-6-(3-iodobenzamido)hexanoate. A solution of the above product was dissolved in TFA (2.0 mL)/DCM (2.0 mL) and stirred at room temperature for 3 h. The solvents were removed under reduced pressure to give a residue, which was purified by Amberchrom™ to give ((S)-2-(3-((S)-1-carboxy-4-oxo-4-(4-sulfamoylphenethylamino)butyl)ureido)-6-(3-iodobenzamido)hexanoic acid (40 mg, 17% over 2 steps) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.54 (t, J=5.4 Hz, 1H), 8.17 (s, 1H), 7.97 (t, J=5.4 Hz, 1H), 7.86 (d, J=8.0 Hz, 1H), 7.83 (d, J=8.0 Hz, 1H), 7.72 (d, J=8.4 Hz, 2H), 7.37 (d, J=8.0 Hz, 2H), 7.28-7.23 (m, 3H), 6.32 (t, J=7.0 Hz, 2H), 4.07-3.99 (m, 2 H), 3.27-2.80 (m, 2H), 2.75 (t, J=7.2 Hz, 2H), 2.10-1.29 (m, 10H); ESMS m/z: 732.2 (M+H)+. Synthesis of Exemplary Formula IV Compounds
Reaction SMILES: [Cl:1][C:2]1[C:7](B2OC(C)(C)C(C)(C)O2)=[CH:6][N:5]=[C:4]2[N:17](COCC[Si](C)(C)C)[CH:18]=[C:19]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[O:26][CH3:27])[C:3]=12.Br[C:37]1[CH:38]=[C:39]([CH:43]([OH:49])[C:44]([N:46]([CH3:48])[CH3:47])=[O:45])[CH:40]=[N:41][CH:42]=1.C([O-])([O-])=O.[Na+].[Na+]>C(#N)C>[Cl:1][C:2]1[C:7]([C:37]2[CH:38]=[C:39]([CH:43]([OH:49])[C:44]([N:46]([CH3:47])[CH3:48])=[O:45])[CH:40]=[N:41][CH:42]=2)=[CH:6][N:5]=[C:4]2[NH:17][CH:18]=[C:19]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[O:26][CH3:27])[C:3]=12
Reactant: COc1ccccc1-c1cn(COCC[Si](C)(C)C)c2ncc(B3OC(C)(C)C(C)(C)O3)c(Cl)c12
Reactant: CN(C)C(=O)C(O)c1cncc(Br)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CC#N
Product: COc1ccccc1-c1c[nH]c2ncc(-c3cncc(C(O)C(=O)N(C)C)c3)c(Cl)c12
Temperature: 23 °C
Reaction time: 0.25 h
Yield: 20 %

Procedure:
Into a 5 mL Personal Chemistry microwave reaction vial were added 4-Chloro-3-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridine (38 mg, 0.075 mmol), 2-(5-Bromo-pyridin-3-yl)-2-hydroxy-N,N-dimethyl-acetamide (29 mg, 0.12 mmol; preparation described below), 1,1′-bis(diphenylphosphino)ferrocenepalladium(II)-dichloride dichloromethane adduct (3 mg, 0.004 mmol), acetonitrile (1 mL) and saturated aqueous Na2CO3 (75 μL). The vial was purged with nitrogen, sealed, and irradiated in a Personal Chemistry Optimizer at 120° C. for 30 min. Sodium sulfate was added to the reaction mixture and the slurry was filtered over Celite and concentrated. The crude product was dissolved in 1 mL TFA and stirred at 23° C. for 15 min. The solvent was evaporated and the resulting oil was dissolved in 1 mL DMSO and 50 μL ethylenediamine and purified by mass triggered reverse phase HPLC to afford the title compound (9.5 mg, 0.015 mmol, 25% yield). 1H NMR (500 MHz, DMSO-d6) δ 12.24 (s, 1H), 8.58 (m, 2H), 8.20 (s, 1H), 7.83 (t, J=2 Hz, 1H), 7.33 (td, J=8 Hz, J2=1.5 Hz, 1H), 7.27 (dd, J=7 Hz, J2=1.5 Hz, 1H), 7.05 (d, J=8 Hz, 1H), 6.95 (td, J=8 Hz, J2=1 Hz, 1H), 5.81 (d, J=6.5 Hz, 1H), 5.56 (d, J=6.5 Hz, 1H), 3.68 (s, 3H), 2.95 (s, 3H), 2.84 (s, 3H). MS: m/z 437.0 (M+H+).
Reaction SMILES: [F:1][C:2]1[C:7]([CH:8]2[CH2:13][CH2:12]S[CH2:10][CH2:9]2)=[CH:6][CH:5]=[CH:4][N:3]=1.C[N+]1([O-])CCOCC1.[S:22]([O-:25])(O)=[O:23].[Na+]>CC(C)=O.O.[Os](=O)(=O)(=O)=O>[O:23]=[S:22]1(=[O:25])[CH2:10][CH2:9][CH:8]([C:7]2[C:2]([F:1])=[N:3][CH:4]=[CH:5][CH:6]=2)[CH2:13][CH2:12]1
Reactant: Fc1ncccc1C1CCSCC1
Reactant: O=S([O-])O
Agent: O=[Os](=O)(=O)=O
Agent: C[N+]1([O-])CCOCC1
Agent: [Na+]
Solvent: O
Solvent: CC(C)=O
Product: O=S1(=O)CCC(c2cccnc2F)CC1
Reaction time: 8 h

Procedure:
To a stirred mixture of 2-fluoro-3-(tetrahydro-2H-thiopyran-4-yl)pyridine (1.2 g, 6.08 mmol), 4-methylmorpholine 4-oxide (1.781 g, 15.21 mmol) in acetone/water (7:3, 30 mL) was added osmium(VIII) oxide (0.631 mL, 0.304 mmol). Stirring was continued at RT overnight. A saturated solution of sodium hydrogensulfite (10 mL) was added and stirred in 15 min., extracted with EtOAc (3×), dried over MgSO4, concentrated to give the tan solid. MS (M+1): 230.2.
Reaction SMILES: [F:1][C:2]([F:6])([F:5])[CH2:3]I.[CH2:7]([O:9][C:10](=[O:20])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([OH:18])=[C:14]([Br:19])[CH:13]=1)[CH3:8].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(Cl)Cl.O>[CH2:7]([O:9][C:10](=[O:20])[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:3][C:2]([F:6])([F:5])[F:1])=[C:14]([Br:19])[CH:13]=1)[CH3:8]
Reactant: FC(F)(F)CI
Reactant: CCOC(=O)Cc1ccc(O)c(Br)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Solvent: ClCCl
Product: CCOC(=O)Cc1ccc(OCC(F)(F)F)c(Br)c1
Temperature: 150 °C
Reaction time: 0.5 h

Procedure:
1,1,1-Trifluoro-2-iodoethane (0.15 mL, 1.5 mmol, 1 eq.) was added to a solution of (3-bromo-4-hydroxy-phenyl)-acetic acid ethyl ester (456 mg, 1.5 mmol, 1 eq.) and potassium carbonate (622 mg, 4.5 mmol, 3 eq.) in DMF (1.5 mL). The resulting mixture was stirred at 150° C. under microwave irradiation for 30 min. The reaction mixture was diluted with DCM and water. The layers were separated and the aq. phase was extracted with DCM (2×). The comb. org. layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by flashmaster (column: 50 g, flow: 30 mL/min, 30 fractions of 30 mL, Heptane 100% to Heptane+AcOEt 20%) to yield the title compound as a colorless oil.
Reaction SMILES: [CH2:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[O:11]=O>O>[CH2:7]1[CH:8]([OH:11])[CH2:9][C:10]2[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=2)[CH2:6]1.[C:9]1(=[O:11])[C:10]2[C:5](=[CH:4][CH:3]=[CH:2][CH:1]=2)[CH2:6][CH2:7][CH2:8]1
Reactant: O=O
Reactant: c1ccc2c(c1)CCCC2
Solvent: O
Product: O=C1CCCc2ccccc21
Product: OC1CCc2ccccc2C1

Procedure:
The thus-obtained metal complex (1.5 mM) was dispersed as a catalyst in water. Tetralin (15 mM) was dispersed therein as a reaction substrate, and the mixture was shaked in an atmosphere of oxygen at 1 atmospheric pressure to produce tetralol and tetralone. After 24 hours, concentration of tetralin was decreased to 30 % or less based on the initial concentration.
Reaction SMILES: [C:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH2:20]Br)=[CH:14][C:15]=2[N+:17]([O-:19])=[O:18])[C:10]([Br:22])=[C:9]1[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CCN(CC)CC.[O:36]=[S:37]1(=[O:43])[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1.[NH4+].[Cl-]>C(Cl)Cl>[C:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([CH2:20][N:40]3[CH2:41][CH2:42][S:37](=[O:43])(=[O:36])[CH2:38][CH2:39]3)=[CH:14][C:15]=2[N+:17]([O-:19])=[O:18])[C:10]([Br:22])=[C:9]1[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]
Reactant: O=S1(=O)CCNCC1
Reactant: CC(C)(C)OC(=O)n1c(-c2ccccc2)c(Br)c2cc(CBr)cc([N+](=O)[O-])c21
Agent: [Cl-]
Agent: [NH4+]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)n1c(-c2ccccc2)c(Br)c2cc(CN3CCS(=O)(=O)CC3)cc([N+](=O)[O-])c21
Temperature: 25 °C
Reaction time: 12 h
Yield: 73.1 %

Procedure:
1-BOC-3-bromo-5-bromomethyl-7-nitro-2-phenyl-indole (1.0 g, 2 mmol) obtained in Step 2 was dissolved in DCM (10 mL), and thereto Et3N (560 uL, 4 mmol) and 1,1-dioxo-thio-morpholine (300 mg, 3 mmol) were added. The mixture was stirred for 12 hours at room temperature. At the end of the reaction, added saturated aqueous NH4Cl solution, extracted with DCM. After drying the extract, the solvent was removed under reduced pressure and the residue was purified by column chromatography to give 1-BOC-3-bromo-5-(1,1-dioxo-thiomorpholine-4-yl)methyl-7-nitro-2-phenyl-1H-indole (825 mg, 78%).