Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([S:7]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[N+:17]([O-])=O)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Sn].O>CO.Cl>[C:1]1([S:7]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[NH2:17])(=[O:8])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=[N+]([O-])c1ccccc1CS(=O)(=O)c1ccccc1
Agent: Cl
Agent: [Sn]
Solvent: CO
Solvent: O
Product: Nc1ccccc1CS(=O)(=O)c1ccccc1
Temperature: 45 °C
Reaction time: 5 h

Procedure:
A stirred mixture of 2-(phenylsulfonylmethyl)-1-nitrobenzene (5.55 g, 20.0 mmol) and granular tin (10.4 g, 88 mmol) in methanol and concentrated HCl (60 mL) is stirred under nitrogen at 45° C. for 5 h, cooled to ambient temperature over an 18 h period, poured onto NaHCO3 (80 g) with stirring, treated with water and extracted with ethyl acetate. The combined extracts are washed with brine (2×100 mL), dried over MgSO4, and concentrated in vacuo to afford the title product as an off-white solid, 4.41 g (89%) mp 175-176° C., identified by HNMR and mass spectral analyses.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=2)=[CH:7][C:6]([CH2:18][N:19]2[CH:24]=[CH:23][C:22]([C:25]#[N:26])=[CH:21][C:20]2=[O:27])=[CH:5][CH:4]=1.Cl.[OH-:29].[Na+]>>[CH3:1][O:2][C:3]1[C:8]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([N+:15]([O-:17])=[O:16])[CH:10]=2)=[CH:7][C:6]([CH2:18][N:19]2[CH:24]=[CH:23][C:22]([C:25]([NH2:26])=[O:29])=[CH:21][C:20]2=[O:27])=[CH:5][CH:4]=1
Reactant: [OH-]
Reactant: COc1ccc(Cn2ccc(C#N)cc2=O)cc1-c1cccc([N+](=O)[O-])c1
Agent: Cl
Agent: [Na+]
Product: COc1ccc(Cn2ccc(C(N)=O)cc2=O)cc1-c1cccc([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 22 %

Procedure:
Into a 20 mL vial with a stir bar was added P-196 (132 mg, 0.37 mmol) and concentrated HCl (2 mL). The reaction was stirred at rt for 18 hours, basified with 4N aqueous NaOH, and the product was extracted with ethyl acetate (3×5 mL). The combined organics were concentrated to half their original volume and 5 mL of hexane was added. The resulting solids were filtered, washed with hexane, and triturated with ether to afford 29.8 mg (22%) of P-207 as a tan solid. 1H NMR (400 MHz, DMSO-d6) 8.28 (s, 1H), 8.20 (dd, J=1.4, 8.3 Hz, 1H), 8.05 (br. s., 1H), 7.93 (t, J=7.4 Hz, 2H), 7.72 (t, J=8.0 Hz, 1H), 7.61 (br s, 1H), 7.48 (d, J=2.0 Hz, 1H), 7.42 (dd, J=2.1, 8.5 Hz, 1H), 7.15 (d, J=8.5 Hz, 1H), 6.84 (d, J=1.5 Hz, 1H), 6.54 (dd, J=1.8, 7.0 Hz, 1H), 5.10 (s, 2H), 3.79 (s, 3H) ppm. MS: 380.1 (APCI+).
Reaction SMILES: [CH:1]12[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH:2]1[C:11]#[N:12])[CH2:8]2.C([N-]C(C)C)(C)C.[Li+].Cl[C:22]([O:24][CH3:25])=[O:23]>O1CCCC1>[C:11]([C:2]1([C:22]([O:24][CH3:25])=[O:23])[CH:3]2[CH2:9][CH:7]3[CH2:6][CH:5]([CH2:10][CH:1]1[CH2:8]3)[CH2:4]2)#[N:12]
Reactant: COC(=O)Cl
Reactant: N#CC1C2CC3CC(C2)CC1C3
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COC(=O)C1(C#N)C2CC3CC(C2)CC1C3
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 59.9 %

Procedure:
To a solution of adamantane-2-carbonitrile (1.17 g, 7.23 mmol) in anhydrous tetrahydrofuran (75 mL) was added lithium diisopropylamide (2.0 M solution in tetrahydrofuran, ethylbenzene and heptanes, 5.4 mL, 11.00 mmol)-78° C. The reaction mixture was stirred under a nitrogen atmosphere for 30 minutes, and then methyl chloroformate (0.83 mL, 11.00 mmol) was added. After 1.5 hour, the reaction was warmed to ambient temperature and quenched by addition of 1 M hydrochloric acid (150 mL). The mixture was diluted with ethyl acetate (200 mL), washed with 1 M hydrochloric acid (150 mL), brine (150 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to dryness. The residue was purified by column chromatography with a gradient of 0-10% ethyl acetate in hexanes to afford the title compound as a colorless oil (0.95 g, 60%): 1H NMR (300 MHz, CDCl3) δ 3.80 (s, 3H), 2.51 (br s, 2H), 2.23-2.18 (m, 2H), 1.93-1.91 (m, 1H), 1.85-1.71 (m, 9H); MS (ES−) m/z 220.2 (M+1).
Reaction SMILES: CC([O:6][CH2:7]/[CH:8]=[CH:9]/[C:10]#[C:11][CH2:12][C:13]#[C:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])OCC.S(=O)(=O)(O)O>CC(C)=O>[CH2:7]([OH:6])/[CH:8]=[CH:9]/[C:10]#[C:11][CH2:12][C:13]#[C:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]
Reactant: CCCCCC#CCC#C/C=C/COC(C)OCC
Agent: O=S(=O)(O)O
Solvent: CC(C)=O
Product: CCCCCC#CCC#C/C=C/CO
Reaction time: 3 h
Yield: 91.7 %

Procedure:
A solution of (E)-4-methyl-3,5-dioxa-7-octadecen-9,12-diyne(3.76 g) in acetone (60 mL) was treated with aqueous sulfuric acid (0.2 N, 6 mL) and left at room temperature for 3 hours. Half of the acetone was removed in vacuo and the residual solution was poured into water, extracted with ether and the combined extracts were dried (MgSO4), concentrated and purified by liquid chromatography (4:1 parts by volume hexane-ethyl acetate) to yield pure material (E)-2-tridecen-4,7-diyn-1-ol (2.5 g).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[O:10][CH2:11][CH:12]([C:14]2[CH:19]=[CH:18][C:17](Br)=[CH:16][CH:15]=2)[N:13]=1.[CH2:21]([O:24][C:25]1[CH:30]=[CH:29][C:28]([Sn](C)(C)C)=[CH:27][N:26]=1)[CH2:22][CH3:23].[Cl-].[Li+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[O:10][CH2:11][CH:12]([C:14]2[CH:19]=[CH:18][C:17]([C:28]3[CH:29]=[CH:30][C:25]([O:24][CH2:21][CH2:22][CH3:23])=[N:26][CH:27]=3)=[CH:16][CH:15]=2)[N:13]=1
Reactant: Fc1cccc(F)c1C1=NC(c2ccc(Br)cc2)CO1
Reactant: CCCOc1ccc([Sn](C)(C)C)cn1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cl-]
Agent: [Li+]
Solvent: C1COCCO1
Product: CCCOc1ccc(-c2ccc(C3COC(c4c(F)cccc4F)=N3)cc2)cn1

Procedure:
2-(2,6-Difluorophenyl)4-(4-bromophenyl)oxazoline (VP4) (2.0 g, 2.9 mmol) was mixed with 2-n-propyloxy-5-trimethylstannylpyridine (4.6 g, 50%, 7.7 mmol), Pd(PPh3)4 (0.35 g, 0.3 mmol) and lithium chloride (50 mg) in dioxane and refluxed under nitrogen (7 hours). After chromatography and recrystallization in heptane/ethyl acetate 95:5, 2-(2,6-difluorophenyl)4-[4-(2-n-propyloxypyridin-5-yl)phenyl]oxazoline was obtained, 1.21 g, colorless crystals;
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[C:10]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=1)=O.C(N(CC)CC)C.ClC(OC)=O>O1CCCC1>[CH3:9][O:8][C:6]1[CH:5]=[CH:4][C:3]([CH2:10][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH3:19])[CH:13]=2)=[C:2]([OH:1])[CH:7]=1
Reactant: COc1cccc(C(=O)c2ccc(OC)cc2O)c1
Agent: COC(=O)Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COc1cccc(Cc2ccc(OC)cc2O)c1
Reaction time: 0.8 h
Yield: 97.6 %

Procedure:
The title compound was synthesized by referring to Tetrahedron Lett., 1995, 36 (30), 5335. To a solution of (2-hydroxy-4-methoxyphenyl)(3-methoxyphenyl)methanone (5.2 g) in tetrahydrofuran (100 ml) were sequentially added triethylamine (3.0 g) and methyl chloroformate (2.2 g) on an ice bath, the solution was stirred for 48 minutes, and then the reaction mixture was filtered. To a solution of sodium borohydride (3.0 g) in water (50 ml) was added dropwise the above-mentioned filtrate on an ice bath, and the solution was stirred for 1 hour and 10 minutes. The reaction solution was concentrated in vacuo, extracted with ethyl acetate, then sequentially washed with water and brine, dried over anhydrous magnesium sulfate, and then the solvent was evaporated in vacuo. The residue was purified by silica gel column chromatography (hexane-ethyl acetate system) to provide the title compound (4.8 g).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]#[C:15][C:16]2[CH:21]=[C:20]([Br:22])[CH:19]=[CH:18][C:17]=2[OH:23])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C)C=O>[Cu](I)I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(N(CC)CC)C>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([C:14]2[O:23][C:17]3[CH:18]=[CH:19][C:20]([Br:22])=[CH:21][C:16]=3[CH:15]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCC(C#Cc2cc(Br)ccc2O)CC1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: I[Cu]I
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCC(c2cc3cc(Br)ccc3o2)CC1
Temperature: 55 °C

Procedure:
A mixture of 4-(5-bromo-2-hydroxy-phenylethynyl)-piperidine-1-carboxylic acid tert-butyl ester (70 mg), copper iodide (9 mg), N,N-dimethylformamide (1 mL), triethylamine (100 μL), and Pd(PPh3)2Cl2 (7 mg) is heated under an argon atmosphere to 55° C. for 0.5 h. The reaction mixture is diluted with ice water after cooling to room temperature and extracted with ethyl acetate. The combined extracts are dried over MgSO4 and concentrated in vacuo. The residue is chromatographed on silica gel (cyclohexane/ethyl acetate 80:20→50:50) to give the title compound. LC (method 2): tR=1.49 min; Mass spectrum (ESI+): m/z=380, 382 [M+H]+.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]1[CH2:16][CH2:15][N:14]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:13][CH2:12][NH:11]1)([O-])=O.[C:23](N1C=CN=C1)(N1C=CN=C1)=[S:24]>COCCOC.C(Cl)(Cl)Cl>[C:17]1([N:14]2[CH2:15][CH2:16][N:10]3[C:5]4[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=4[NH:1][C:23](=[S:24])[N:11]3[CH2:12][CH2:13]2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: O=[N+]([O-])c1ccccc1N1CCN(c2ccccc2)CCN1
Reactant: S=C(n1ccnc1)n1ccnc1
Solvent: COCCOC
Solvent: ClC(Cl)Cl
Product: S=C1Nc2ccccc2N2CCN(c3ccccc3)CCN12

Procedure:
Hexahydro-1-(2-nitrophenyl)-5-phenyl-1H-1,2,5-triazepine (22.4 g) was hydrogenated in 1,2-dimethoxyethane (800 ml) as in Example 11 and the volume reduced to 250 ml. 1,1'-Thiocarbonyldiimidazole (27 g) was added and the mixture, protected from moisture, was heated under reflux on a steam bath overnight. The solution was evaporated to dryness. The residue was dissolved in toluene and applied to a column (63×8.0 cm) of dry column grade neutral alumina prepacked in toluene. Elution with toluene (several liters) removed a faster moving yellow component from the column. The eluting solvent was changed to toluene-chloroform (4:1, 2 l) and then to chloroform. Monitoring of fractions was by t.l.c. on Alox-25 uv254 plates (Brinkmann) with chloroform as developer and on silica gel GF (Analtech) plates with chloroform as developer. A slightly faster moving minor purple component was eluted in the earlier fractions containing the major component. In later fractions a slower moving yellow component contaminated the major component. The first fractions (having none of the slower yellow minor component) were evaporated to smaller volume. Coevaporation with toluene caused crystallization. Addition of heptane completed the process; wt. 12.46 g (crop 1), mp=206°-208°. The later yellow fractions similarly gave 5.33 g (crop 2), mp=203°-208° of crude titled product. Recrystallization of crop 2 (from chloroform-toluene-heptane) gave material which was combined with crop 1. This material was dissolved in chloroform and the solution was decolorized. Evaporation to smaller volume followed by coevaporation with toluene and addition of heptane gave 17.6 g (76%) of crude titled product, mp=205°-209°. Recrystallization from the same solvent system gave titled product, mp=205°-208°.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:40])[C@H:4]([NH:20][C:21]([C:23]1[CH:24]=[C:25]([C:30]2[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=2)[CH:26]=[CH:27][C:28]=1[NH2:29])=[O:22])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[C:14]([Cl:19])[CH:13]=2)=[CH:8][CH:7]=1.[C:41](Cl)(=[O:45])[CH:42]([CH3:44])[CH3:43]>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:40])[C@H:4]([NH:20][C:21]([C:23]1[CH:24]=[C:25]([C:30]2[CH:31]=[CH:32][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:34][CH:35]=2)[CH:26]=[CH:27][C:28]=1[NH:29][C:41](=[O:45])[CH:42]([CH3:44])[CH3:43])=[O:22])[CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[C:14]([Cl:19])[CH:13]=2)=[CH:8][CH:7]=1
Reactant: COC(=O)[C@@H](Cc1ccc(-c2ccc(F)c(Cl)c2)cc1)NC(=O)c1cc(-c2ccc(C(F)(F)F)cc2)ccc1N
Reactant: CC(C)C(=O)Cl
Solvent: ClCCl
Product: COC(=O)[C@@H](Cc1ccc(-c2ccc(F)c(Cl)c2)cc1)NC(=O)c1cc(-c2ccc(C(F)(F)F)cc2)ccc1NC(=O)C(C)C
Yield: 84.7 %

Procedure:
To 20 mg (0.035 mmol) of 2(R)-[(4-amino-4′-trifluoromethyl-biphenyl-3-carbonyl)-amino]-3-(3′-chloro-4′-fluoro-biphenyl-4-yl)-propionic acid methyl ester in 1 mL of DCM was added 12 mg (0.11 mmol) of isobutyryl chloride following general procedure M to give the title compound (19 mg).
Reaction SMILES: [C:1]1([CH:8]=[CH:7][CH:6]=[C:4]([OH:5])[CH:3]=1)[OH:2].Br[C:10]1[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=1.Cl.CN(C)CC(O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(N(C)C)=O.C(OCC)(=O)C.[Cu]I>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([O:2][C:1]2[CH:3]=[C:4]([OH:5])[CH:6]=[CH:7][CH:8]=2)=[CH:11][CH:12]=1
Reactant: Clc1ccc(Br)cc1
Reactant: Oc1cccc(O)c1
Agent: [Cu]I
Agent: CN(C)CC(=O)O
Agent: Cl
Solvent: CC(=O)N(C)C
Solvent: CCOC(C)=O
Product: Oc1cccc(Oc2ccc(Cl)cc2)c1
Temperature: 90 °C
Yield: 60.3 %

Procedure:
A suspension of resorcinol (12.58 g, 114.2 mmol), 4-bromochlorobenzene (10.94 g, 57.14 mmol), dimethylglycine HCl (2.39 g, 17.1 mmol), and cesium carbonate (37.2 g, 114 mmol) in DMA (80 mL) was treated with CuI (1.09 g, 5.71 mmol) and heated at 90° C. for 16 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (500 mL) and extracted with 1 N NaOH (400 mL), and brine (200 mL). The organic layer was dried (MgSO4) and concentrated. The residue was purified (FCC) to give the title compound as a yellow oil (7.6 g, 60%). MS (ESI+): calcd. for C12H9ClNO2, 220.03. m/z found, 221.1 (M+H)+. 1H NMR (d6-DMSO): 9.63 (s, 1H), 7.43 (d, J=8.9 Hz, 2H), 7.17 (t, J=8.1 Hz, 1H), 7.03 (d, J=8.9 Hz, 2H), 6.58-6.54 (m, 1H), 6.46-6.41 (m, 1H), 6.38 (t, J=2.3 Hz, 1H).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1([C:11]2[O:12][C:13]3[CH:20]=[CH:19][C:18]([CH2:21]Br)=[CH:17][C:14]=3[C:15]=2[Br:16])[CH2:10][CH2:9][CH2:8][CH2:7]1)=[O:5])[CH3:2].[CH2:23]([C:25]1[NH:26][C:27]2[C:28]([N:35]=1)=[N:29][C:30]([CH3:34])=[CH:31][C:32]=2[CH3:33])[CH3:24]>>[CH2:1]([O:3][C:4]([C:6]1([C:11]2[O:12][C:13]3[CH:20]=[CH:19][C:18]([CH2:21][N:35]4[C:28]5=[N:29][C:30]([CH3:34])=[CH:31][C:32]([CH3:33])=[C:27]5[N:26]=[C:25]4[CH2:23][CH3:24])=[CH:17][C:14]=3[C:15]=2[Br:16])[CH2:10][CH2:9][CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: CCc1nc2nc(C)cc(C)c2[nH]1
Reactant: CCOC(=O)C1(c2oc3ccc(CBr)cc3c2Br)CCCC1
Product: CCOC(=O)C1(c2oc3ccc(Cn4c(CC)nc5c(C)cc(C)nc54)cc3c2Br)CCCC1

Procedure:
The product of Step 6, above (60), was alkylated as described in Example 12, Step 3 using 2-ethyl-5,7-dimethylimidazo[4,5-b]pyridine (7) to obtain the title compound (61).
Reaction SMILES: [Br:1]N1C(C)(C)C(=O)N(Br)C1=O.[CH3:12][C:13]1[C:21]([N+:22]([O-:24])=[O:23])=[CH:20][CH:19]=[CH:18][C:14]=1[C:15]([OH:17])=[O:16]>OS(O)(=O)=O>[Br:1][C:19]1[CH:20]=[C:21]([N+:22]([O-:24])=[O:23])[C:13]([CH3:12])=[C:14]([CH:18]=1)[C:15]([OH:17])=[O:16]
Reactant: Cc1c(C(=O)O)cccc1[N+](=O)[O-]
Reactant: CC1(C)C(=O)N(Br)C(=O)N1Br
Agent: O=S(=O)(O)O
Product: Cc1c(C(=O)O)cc(Br)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 5 h
Yield: 176.7 %

Procedure:
1,3-Dibromo-5,5-dimethyl-2,4-imidazolidinedione (13.0 g, 45.7 mmol) was added to a mixture of 2-methyl-3-nitrobenzoic acid (15 g, 82.8 mmol) in conc. H2SO4 (60 mL), and the reaction mixture stirred at room temperature for 5 h. After completion of reaction, the mixture was slowly poured onto ice cold water (400 mL). The precipitated was filtered and dried under vacuum to obtain desired 5-bromo-2-methyl-3-nitrobenzoic acid (21 g, 98.2%).
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH:9]([OH:13])[CH2:10][CH:11]=[CH2:12])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:14]([Si:17]([CH:24]([CH3:26])[CH3:25])([CH:21]([CH3:23])[CH3:22])[CH:18]([CH3:20])[CH3:19])C=C.CCCCCC.CCOCC>C(Cl)Cl.CC1C=C(C)C(N2C(=[Ru](Cl)(Cl)=CC3C=CC=CC=3OC(C)C)N(C3C(C)=CC(C)=CC=3C)CC2)=C(C)C=1>[C:1]1([CH2:7][CH2:8][CH:9]([OH:13])[CH2:10][CH:11]=[CH:12][CH2:14][Si:17]([CH:18]([CH3:20])[CH3:19])([CH:24]([CH3:26])[CH3:25])[CH:21]([CH3:23])[CH3:22])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C=CCC(O)CCc1ccccc1
Reactant: C=CC[Si](C(C)C)(C(C)C)C(C)C
Agent: Cc1cc(C)c(N2CCN(c3c(C)cc(C)cc3C)C2=[Ru](Cl)(Cl)=Cc2ccccc2OC(C)C)c(C)c1
Solvent: CCCCCC
Solvent: CCOCC
Solvent: ClCCl
Product: CC(C)[Si](CC=CCC(O)CCc1ccccc1)(C(C)C)C(C)C
Yield: 61.3 %

Procedure:
To a round-bottomed flask containing 1-phenyl-hex-5-en-3-ol (43 mg, 0.24 mmol, 1 eq)) in DCM (2 mL) was added allyltriisopropylsilane (0.173 mL, 0.72 mmol, 3 eq). Hoveyda-Grubbs' Catalyst (4 mg, 0.006 mmol, 0.025 eq) was subsequently added as a solid and the reaction was left to stir under an atmosphere of argon. After 6 days the reaction was concentrated under reduced pressure to a dark brown oil. Column chromatography (hexane:ether, 100:0, 90:10, 85:15) gave 1-phenyl-7-(triisopropylsilyl)hept-5-en-3-ol as a colourless oil (51 mg, 61% yield). For major isomer E: 1H NMR (400 MHz, CDCl3) δ 1.05 (s, 21H, Si(i−Pr)3), 1.60-1.62 (d, 2H, CH2 Si(i−Pr)3, J=8 Hz), 1.72-1.85 (m, 2H, CH2CH2CHOH), 2.06-2.14 (m, 1H, CHOHCH2CH), 2.22-2.34 (m, 1H, CHOHCH2CH), 2.64-2.74 (m, 1H, PhCH2), 2.78-2.87 (m, 1H, PhCH2), 3.58-3.64 (m, 1H, CHOH), 5.24-5.34 (m, 1H, CH2CHCH), 5.58-5.66 (dt, 1H, CH2CHCH, J=16, 8 Hz), 7.17-7.23 (m, 4H, Ph), 7.27-7.31 (m, 1H, Ph); 13C NMR (100 MHz, CDCl3) δ 11.0 (Si(i−Pr)3), 15.6 (CH2 Si(i−Pr)3), 18.7 (Si(i−Pr)3), 32.1 (PhCH2), 38.4 (PhCH2CH2), 41.1 (CHOHCH2), 70.4 (CHOH), 123.9 (CH2CHCH), 125.7 (Ph), 128.3 (Ph), 128.4 (Ph), 131.9 (CH2CHCH), 142.2 (Ph). For minor isomer Z: 1H NMR (400 MHz, CDCl3) δ 1.05 (s, 21H, Si(i−Pr)3), 1.60-1.62 (d, 2H, CH2 Si(i−Pr)3, J=8 Hz), 1.72-1.85 (m, 2H, CH2CH2CHOH), 2.06-2.14 (m, 1H, CHOHCH2CH), 2.22-2.34 (m, 1H, CHOHCH2CH), 2.64-2.74 (m, 1H, PhCH2), 2.78-2.87 (m, 1H, PhCH2), 3.65-3.71 (m, 1H, CHOH), 5.24-5.34 (m, 1H, CH2CHCH), 5.68-5.75 (dt, 1H, CH2CHCH, J=12, 8 Hz), 7.17-7.23 (m, 4H, Ph), 7.27-7.31 (m, 1H, Ph); 13C NMR (100 MHz, CDCl3) δ 11.0 (Si(i−Pr)3), 15.6 (CH2 Si(i−Pr)3), 18.7 (Si(i−Pr)3), 32.1 (PhCH2), 35.3 (CHOHCH2), 38.4 (PhCH2CH2), 70.9 (CHOH), 122.3 (CH2CHCH), 125.7 (Ph), 128.3 (Ph), 128.4 (Ph), 130.3 (CH2CHCH), 142.2 (Ph); IR (v, cm−1) 3362 (OH), 3026 (Ar—H), 1604 (C═C), 1496 (Ar), 1462 (Ar), 699 (Si—C); HRMS required for C22H38OSi: 346.2692, found 346.2683.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([C:14]([NH:16][NH:17][C:18]([C@H:20]2[CH2:26][CH2:25][C@@H:24]3[CH2:27][N:21]2[C:22](=[O:35])[N:23]3[O:28][CH2:29][C:30]([O:32]CC)=[O:31])=[O:19])=[O:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-].[Li+].S([O-])(O)(=O)=O.[K+].C(OCC)(=O)C>O1CCCC1.O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([C:14]([NH:16][NH:17][C:18]([C@H:20]2[CH2:26][CH2:25][C@@H:24]3[CH2:27][N:21]2[C:22](=[O:35])[N:23]3[O:28][CH2:29][C:30]([OH:32])=[O:31])=[O:19])=[O:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)CON1C(=O)N2C[C@H]1CC[C@@H]2C(=O)NNC(=O)[C@@H]1CCCN(C(=O)OC(C)(C)C)C1
Agent: O=S(=O)([O-])O
Agent: [K+]
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)OC(=O)N1CCC[C@@H](C(=O)NNC(=O)[C@H]2CC[C@@H]3CN2C(=O)N3OCC(=O)O)C1
Reaction time: 3 h
Yield: 28.4 %

Procedure:
To a clear solution of trans-3-{N′-(6-ethoxycarbonylmethoxy-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)-hydrazinocarbonyl}-(R)-piperidin-1-carboxylic acid tert-butyl ester (600 mg, 1.20 mmol) in tetrahydrofuran (32 ml) and water (12 ml) was added lithium hydroxide (43.2 mg, 1.8 mmol) at 0° C. The reaction mixture was stirred for 3 hours and was neutralized to pH 6 by addition of aqueous 1 N potassium hydrogen sulfate. It was exacted with ethyl acetate (3×25 ml). Layers were separated and aqueous layer was acidified with 1 N potassium hydrogen sulfate to pH 1 and extracted with ethyl acetate (3×25 ml). The Organic layer was dried over sodium sulfate and evaporated to dryness under vacuum to provide 160 mg of tilted intermediate as a solid in 27% yield.
Reaction SMILES: C(N(CC)C(C)C)C.[CH3:9][C:10]1[C:15]([C:16]([OH:18])=O)=[CH:14][N:13]=[C:12]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)[N:11]=1.[N:25]1([NH2:34])[C:33]2[C:28](=[N:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[N:25]1([NH:34][C:16]([C:15]2[C:10]([CH3:9])=[N:11][C:12]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=3)=[N:13][CH:14]=2)=[O:18])[C:33]2[C:28](=[N:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26]1
Reactant: Cc1nc(-c2ccccn2)ncc1C(=O)O
Reactant: Nn1ccc2ncccc21
Agent: CCN(CC)C(C)C
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Product: Cc1nc(-c2ccccn2)ncc1C(=O)Nn1ccc2ncccc21
Temperature: 80 °C
Reaction time: 8 h
Yield: 62.6 %

Procedure:
Diethyl-iso-propylamine (1.88 mmol) is added a solution of 4-methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid (0.75 mmol), pyrrolo[3,2-b]pyridine-1-ylamine (0.75 mmol) and TBTU (0.9 mmol) in anhydrous DMF (7 mL) at rt, and the reaction mixture is stirred at 80° C. for 8 h. The reaction mixture is concentrated in vacuo. The residue is purified by silica gel chromatography eluting with 0-10% MeOH in DCM to afford 4-methyl-2-pyridin-2-yl-pyrimidine-5-carboxylic acid pyrrol[3,2-b]pyridine-1-ylamide (155 mg, 63%) as a solid. MS: 331 (M+H); 1H NMR (300 MHz, CD3OD): δ 2.89 (s, 3H), 7.01 (d, H), 7.64-7.77 (m, 2H), 8.15 (m, H), 8.25 (m, H), 8.59-8.76 (m, 3H), 8.82 (d, H), 9.31 (s, 2H). IC50=13 nM.
Reaction SMILES: [CH:1]1([CH2:6][C:7]([OH:9])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.N[C@H](C([C:16]1([NH2:41])[C:22](=[O:23])[N:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C:20]2[CH:30]=[CH:31][CH:32]=[CH:33][C:19]=2[N:18]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C:17]1=[O:40])=O)C>>[CH:1]1([CH2:6][C:7]([NH:41][C@H:16]([C:22]([NH:41][CH:16]2[C:22](=[O:23])[N:21]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:39]3[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=3[N:18]([C:19]3[CH:20]=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:17]2=[O:40])=[O:23])[CH3:17])=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: O=C(O)CC1CCCC1
Reactant: C[C@H](N)C(=O)C1(N)C(=O)N(c2ccccc2)c2ccccc2N(c2ccccc2)C1=O
Agent: Cl
Product: C[C@H](NC(=O)CC1CCCC1)C(=O)NC1C(=O)N(c2ccccc2)c2ccccc2N(c2ccccc2)C1=O

Procedure:
Following General Procedure I above using cyclopentylacetic acid (Aldrich) and 3-(L-alaninyl)-amino-2,4-dioxo-1,5-bis-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine hydrochloride (Example 8-W), the title compound was prepared as an amorphous white solid. Purification was by flash chromatography eluting with CH2Cl2/EtOAc (1:1). Rf=0.44 (CH2Cl2/EtOAc, 1:1).
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([C:22]#[N:23])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.P([O-])(OCC)(SCC)=[S:25].C([O-])(O)=O.[Na+]>ClCCl.O.C(OCC)(=O)C>[N:1]1([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3([C:22](=[S:25])[NH2:23])[CH2:17][CH2:18][O:19][CH2:20][CH2:21]3)=[CH:12][CH:11]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: N#CC1(c2ccc(OCCCN3CCCC3)cc2)CCOCC1
Reactant: CCOP([O-])(=S)SCC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: ClCCl
Product: NC(=S)C1(c2ccc(OCCCN3CCCC3)cc2)CCOCC1
Temperature: 55 °C
Reaction time: 2 h
Yield: 27.3 %

Procedure:
4-[4-(3-Pyrrolidin-1-yl-propoxy)-phenyl]-tetrahydro-pyran-4-carbonitrile (2 g, 6.4 mmol), diethyl dithiophosphate (15 mL, 8.9 mmol), and water (1.5 mL) were combined and stirred at ambient temperature for 5 hours, 55° C. for 2 hours then 70° C. for 2 hours. The reaction mixture was diluted with dichloromethane (100 mL) and basified to pH 8 with a saturated solution of NaHCO3 in water, and solid NaHCO3. The layers were separated, and further dichloromethane (100 mL) was used to extract the product. The combined organics were dried using Na2SO4, filtered and concentrated in vacuo to leave a yellow oil. The compound was purified with column chromatography on 50 g of silica, eluting with dichloromethane:methanol:ammonia (96:4:0.4) to dichloromethane:methanol:ammonia (90:10:1) to give a clear oil. The clear oil was dissolved in ethyl acetate (150 mL) and washed with 10% Na2CO3 solution. The organic layer was dried using Na2SO4, filtered and concentrated in vacuo to give the title compound as a white solid (0.61 g, 28%).