Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[S:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12](OC)=[S:13].[NH2:16][CH2:17][CH2:18][NH:19][C:20](=[O:22])[CH3:21]>O>[C:20]([NH:19][CH2:18][CH2:17][NH:16][C:12](=[S:13])[CH2:11][CH2:10][CH2:9][CH2:8][S:7][CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6][O:1]1)(=[O:22])[CH3:21]
Reactant: COC(=S)CCCCSC1CCCCO1
Reactant: CC(=O)NCCN
Solvent: O
Product: CC(=O)NCCNC(=S)CCCCSC1CCCCO1
Temperature: 75 °C

Procedure:
Methyl [3-(tetrahydropyran-2-ylthio)propyl]thioacetate (1 g, 3.7 mmol) was added dropwise to N-(2-aminoethyl)-acetamide (1.25 g, 12.25 mmol) and the mixture heated at 75° C. for 2.5 h. Volatile components were then removed under reduced pressure (45° C. at 0.02 mmHg) to give an oil which was taken up into water. This aqueous solution was then extracted with dichloromethane (adding potassium chloride to the aqueous layer to prevent emulsion formation if necessary). The dichloromethane extracts were then dried (MgSO4), filtered, and the solvent removed under reduced pressure to give the crude N-(2-acetylaminoethyl)-3-(tetrahydropyran-2-ylthio)propylthioacetamide. A pure sample of this material (0.25 g, 22%) was obtained by reverse phase h.p.l.c. using aqueous methanol as the eluant.
Reaction SMILES: C[Al](C)C.[I:5][C:6]1[N:15]([S:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)(=[O:18])=[O:17])[C:9]2=[N:10][CH:11]=[C:12]([NH2:14])[CH:13]=[C:8]2[CH:7]=1.[F:25][C:26]1[C:35]([N:36]([S:43]([CH2:46][CH2:47][CH3:48])(=[O:45])=[O:44])[S:37]([CH2:40][CH2:41][CH3:42])(=[O:39])=[O:38])=[CH:34][CH:33]=[C:32]([F:49])[C:27]=1[C:28](OC)=[O:29]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[F:25][C:26]1[C:35]([N:36]([S:37]([CH2:40][CH2:41][CH3:42])(=[O:39])=[O:38])[S:43]([CH2:46][CH2:47][CH3:48])(=[O:44])=[O:45])=[CH:34][CH:33]=[C:32]([F:49])[C:27]=1[C:28]([NH:14][C:12]1[CH:13]=[C:8]2[CH:7]=[C:6]([I:5])[N:15]([S:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)(=[O:17])=[O:18])[C:9]2=[N:10][CH:11]=1)=[O:29]
Reactant: Nc1cnc2c(c1)cc(I)n2S(=O)(=O)c1ccccc1
Reactant: CCCS(=O)(=O)N(c1ccc(F)c(C(=O)OC)c1F)S(=O)(=O)CCC
Agent: C[Al](C)C
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: CCCS(=O)(=O)N(c1ccc(F)c(C(=O)Nc2cnc3c(c2)cc(I)n3S(=O)(=O)c2ccccc2)c1F)S(=O)(=O)CCC
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 86.8 %

Procedure:
Trimethylaluminum (0.51 mL, 1.01 mmol, 2.0M solution in toluene) was added dropwise via a syringe to a cold (0° C.) suspension of 2-iodo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-amine (0.135 g, 0.338 mmol) in toluene (10 mL). The cold bath was removed and the mixture was stirred at room temperature for 20 minutes. Methyl 2,6-difluoro-3-(N-(propylsulfonyl)propylsulfonamido)benzoate (0.149 g, 0.372 mmol) was added, and the reaction mixture was heated to 90° C. under N2 for 2 hours. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (50 mL) 30% Aqueous potassium sodium tartrate solution (50 mL) was carefully added, and the resulting emulsion was stirred at room temperature for 30 minutes. The aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic layers were dried, filtered and concentrated. The crude product was purified by column chromatography, eluting with hexanes/ethyl acetate (4:1), hexanes/ethyl acetate (2:1) to give 2,6-difluoro-N-(2-iodo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-3-(N-(propylsulfonyl)propylsulfonamido)benzamide (0.225 g, 87%) as a foam.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]2[CH2:25][C:9]3([CH2:24][C:11]4([CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]4)[CH2:10]3)[O:8][C:5]2=[CH:6][N:7]=1.[CH3:26][S:27]([N:30]1[CH2:35][CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[CH2:32][CH2:31]1)(=[O:29])=[O:28].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1>[CH3:26][S:27]([N:30]1[CH2:31][CH:32]=[C:33]([C:2]2[CH:3]=[C:4]3[CH2:25][C:9]4([CH2:24][C:11]5([CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[CH2:13][CH2:12]5)[CH2:10]4)[O:8][C:5]3=[CH:6][N:7]=2)[CH2:34][CH2:35]1)(=[O:29])=[O:28]
Reactant: CC1(C)OB(C2=CCN(S(C)(=O)=O)CC2)OC1(C)C
Reactant: CC(C)(C)OC(=O)N1CCC2(CC1)CC1(Cc3cc(Cl)ncc3O1)C2
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)N1CCC2(CC1)CC1(Cc3cc(C4=CCN(S(C)(=O)=O)CC4)ncc3O1)C2
Temperature: 150 °C
Reaction time: 1.5 h

Procedure:
A mixture of 5-chloro-1″-tert-butoxycarbonyl-dispiro[2,3-dihydrofuro[2,3-c]pyridine-2,1′-cyclobutane-3′,4″-piperidine] (0.10 g), 1-methanesulfonyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,2,3,6-tetrahydro-pyridine (0.10 g), 2 M aqueous Na2CO3 solution (0.37 mL), and 1,4-dioxane (2 mL) is sparged with argon for 10 min. Tetrakis(triphenylphosphine)palladium(0) (20 mg) is added and the mixture is stirred in a microwave oven at 150° C. for 1.5 h. After cooling to room temperature, water and methanol are added and the resulting mixture is filtered. The filtrate is concentrated and the residue is chromatographed on reversed phase (HPLC, methanol/water) to give the title compound. LC (method 2): tR=1.63 min; Mass spectrum (ESI+): m/z=490 [M+H]+.
Reaction SMILES: [C:1]([OH:5])(=[O:4])[CH2:2][CH3:3].C1CCC(N=C=N[CH:15]2[CH2:20][CH2:19]CCC2)CC1.[C:21](=O)=O.C(O)[C@H](O)[C@H]1OC(=O)C(O)=C1O>CN(C=O)C>[C:1]([O:5][C:20]([CH3:19])([CH3:15])[CH3:21])(=[O:4])[CH2:2][CH3:3]
Reactant: CCC(=O)O
Reactant: O=C=O
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Agent: O=C1O[C@H]([C@@H](O)CO)C(O)=C1O
Solvent: CN(C)C=O
Product: CCC(=O)OC(C)(C)C

Procedure:
972-Cascade:methane[4]:(3-oxo-6-oxa-2-azaheptylidyne):(3-oxo-2-azapentylidyne)4 :tert-butyl propanoate (28) was prepared (45%), as a spongy white solid, from 324-acid 27 (5.40 g, 146 μmol), amine 2 (20.00 g, 48.1 mmol), DCC (9.91 g, 48.1 mmol), 1-HBT (6.50 g, 48.1 mmol), and DMF (250 mL) via Procedure A: 10.87 g; mp 138°-142 ° C.; 1H NMR δ1.39 (s, CH3, 8748H), 1.93-2.17 (m, CH2, 5808H); 13C NMR δ28.0 (CH3), 29.5 (CH2CH2, 57.4 (4°CNH), 80.4 (CMe3), 170.4 (CO2), 172.6 (CONH); IR 3310 (NH), 1730 (ester C=O), 1645 (amide C=O), 1155 ester C--O) cm-1. Anal. Calcd for C8745H15064N484O 2432 :C, 63.31; H, 9.15; N, 4.09. Found: C, 63.47; H, 9.31; N, 4.04.
Reaction SMILES: [CH:1]1([C:4](=O)[CH2:5][C:6]([CH:8]2[CH2:10][CH2:9]2)=O)[CH2:3][CH2:2]1.O.[NH2:13][NH2:14].O.CCOC(C)=O>C(O)C>[CH:1]1([C:4]2[CH:5]=[C:6]([CH:8]3[CH2:10][CH2:9]3)[NH:14][N:13]=2)[CH2:3][CH2:2]1
Reactant: O=C(CC(=O)C1CC1)C1CC1
Reactant: NN
Solvent: O
Solvent: CCOC(C)=O
Solvent: CCO
Product: c1c(C2CC2)n[nH]c1C1CC1
Temperature: 25 °C

Procedure:
Intermediate 1 (5.3 g, 35 mmol) and hydrazine hydrate (1.8 mL, 38.3 mmol) in ethanol (20 mL) were refluxed overnight. Work-up (H2O/AcOEt) after cooling the mixture to ambient temperature gave the title compound as a brown solid. M. P.: 161-164° C. 1H-NMR (δ ppm, CDCl3, 400 MHz): 15.2 (bs, 1H), 5.65 (s, 1H), 2.16-2.09 (m, 2H), 1.18-1.14 (m, 4H), 0.98-0.94 (m, 4H). MS (m/z): 149.04 [M+H]+.
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][C:11]2([N:17]3[N:18]=[C:19]([C:24]4[CH:29]=[CH:28][C:27]([O:30][C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=5)=[CH:26][CH:25]=4)[C:20]([C:21]([NH2:23])=[O:22])=[C:16]3[NH:15][CH2:14]2)[CH2:10][CH2:9]1)C1C=CC=CC=1>CO.CC(O)=O.[OH-].[OH-].[Pd+2]>[O:30]([C:27]1[CH:26]=[CH:25][C:24]([C:19]2[C:20]([C:21]([NH2:23])=[O:22])=[C:16]3[NH:15][CH2:14][C:11]4([CH2:10][CH2:9][NH:8][CH2:13][CH2:12]4)[N:17]3[N:18]=2)=[CH:29][CH:28]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1
Reactant: NC(=O)c1c(-c2ccc(Oc3ccccc3)cc2)nn2c1NCC21CCN(Cc2ccccc2)CC1
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Solvent: CC(=O)O
Product: NC(=O)c1c(-c2ccc(Oc3ccccc3)cc2)nn2c1NCC21CCNCC1
Reaction time: 16 h
Yield: 51.4 %

Procedure:
A mixture of 1′-benzyl-6-(4-phenoxyphenyl)-1,2-dihydrospiro[imidazo[1,2-b]pyrazole-3,4′-piperidine]-7-carboxamide (50 mg, 0.10 mmol), 10% w/w Pd(OH)2/C (5 mg) in MeOH (10 mL) and HOAc (1 drop) was stirred for 16 hr under H2. The mixture was filtrated and the filtrate was concentrated to give the crude product (20 mg 51.4%) as a yellow solid. MS (ESI, m/e) [M+1]+ 390.0.
Reaction SMILES: FC1C=C(C=CC=1)[O:5][CH:6](OC1C=CC=C(F)C=1)[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)[N:8]=1.C(O)(=O)C>O>[F:20][C:16]1[CH:15]=[C:14]([CH:19]=[CH:18][CH:17]=1)[O:13][C:9]1[N:8]=[C:7]([CH:6]=[O:5])[CH:12]=[CH:11][CH:10]=1
Reactant: Fc1cccc(Oc2cccc(C(Oc3cccc(F)c3)Oc3cccc(F)c3)n2)c1
Solvent: CC(=O)O
Solvent: O
Product: O=Cc1cccc(Oc2cccc(F)c2)n1
Temperature: 150 °C
Reaction time: 8 h

Procedure:
A solution of 2.5 g (0.0059 m) of 2-[bis-(3-fluorophenoxy)methyl]-6-(3-fluorophenoxy)pyridine and 20 ml of 80 percent acetic acid was heated, with stirring, at 150° C. overnight. The reaction mixture was cooled, diluted with water and extracted with methylene chloride. The extract was washed with water and concentrated under reduced pressure. The desired 6-(3-fluorophenoxy)picolinaldehyde which melted at 42°-43° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]2[N:9]=[C:10]([NH2:12])[S:11][C:7]=2[C:6]([CH:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:5][CH:4]=1.Cl[C:20](OC1C=CC=CC=1)=[O:21].[O:29]1[C:33]2([CH2:38][CH2:37][NH:36][CH2:35][CH2:34]2)[O:32][CH2:31][CH2:30]1>>[CH3:1][O:2][C:3]1[C:8]2[N:9]=[C:10]([NH:12][C:20]([N:36]3[CH2:37][CH2:38][C:33]4([O:32][CH2:31][CH2:30][O:29]4)[CH2:34][CH2:35]3)=[O:21])[S:11][C:7]=2[C:6]([CH:13]2[CH2:18][CH2:17][O:16][CH2:15][CH2:14]2)=[CH:5][CH:4]=1
Reactant: O=C(Cl)Oc1ccccc1
Reactant: COc1ccc(C2CCOCC2)c2sc(N)nc12
Reactant: C1CC2(CCN1)OCCO2
Product: COc1ccc(C2CCOCC2)c2sc(NC(=O)N3CCC4(CC3)OCCO4)nc12

Procedure:
Using 4-methoxy-7-(tetrahydro-pyran-4-yl)-benzothiazol-2-ylamine, phenyl chloroformate and 1,4-dioxa-8-aza-spiro[4.5]decane, the title compound was prepared as white crystals (53% yield). MS: m/e=434(M+H+), mp 208-209° C.
Reaction SMILES: O.C[C:3]1[CH:11]=[CH:10][C:6]2[NH:7][N:8]=[N:9][C:5]=2[CH:4]=1.[OH-].[Na+].[N+]([O-])([O-])=O.[Ag+:18].[CH2:19](O)C>>[Ag:18].[CH3:19][C:10]1[C:6]2[N:7]=[N:8][NH:9][C:5]=2[CH:4]=[CH:3][CH:11]=1
Reactant: CCO
Reactant: [Ag+]
Reactant: Cc1ccc2[nH]nnc2c1
Agent: O=[N+]([O-])[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: Cc1cccc2[nH]nnc12
Product: [Ag]

Procedure:
In a mixed solvent of water (200 ml) and ethanol (200 ml), 60 g of 5-methylbenzotriazole and 17.6 g of sodium hydroxide were added. To the stirred solution, 100 ml of an aqueous solution of 4N silver nitrate. The resulting mixture was subjected to filtration and the solid residue was thoroughly washed first with water, then with methanol, so as to obtain a high-purity solid methylbenzotriazole silver salt emulsion that was free of any excess unreacted matter.
Reaction SMILES: [NH2:1][C:2]1[CH:14]=[CH:13][C:5]([CH2:6][C@H:7]2[CH2:11][O:10][C:9](=[O:12])[NH:8]2)=[CH:4][CH:3]=1.[CH2:15]([O:17][C:18]([C:20]1[C:21](=[O:43])[C:22]2[CH:27]=[N:26][C:25](S(C)(=O)=O)=[N:24][C:23]=2[N:32]([C:34]2[CH:35]=[C:36]3[C:40](=[CH:41][CH:42]=2)[CH2:39][CH2:38][CH2:37]3)[CH:33]=1)=[O:19])[CH3:16]>>[CH2:15]([O:17][C:18]([C:20]1[C:21](=[O:43])[C:22]2[CH:27]=[N:26][C:25]([NH:1][C:2]3[CH:14]=[CH:13][C:5]([CH2:6][C@H:7]4[CH2:11][O:10][C:9](=[O:12])[NH:8]4)=[CH:4][CH:3]=3)=[N:24][C:23]=2[N:32]([C:34]2[CH:35]=[C:36]3[C:40](=[CH:41][CH:42]=2)[CH2:39][CH2:38][CH2:37]3)[CH:33]=1)=[O:19])[CH3:16]
Reactant: Nc1ccc(C[C@H]2COC(=O)N2)cc1
Reactant: CCOC(=O)c1cn(-c2ccc3c(c2)CCC3)c2nc(S(C)(=O)=O)ncc2c1=O
Product: CCOC(=O)c1cn(-c2ccc3c(c2)CCC3)c2nc(Nc3ccc(C[C@H]4COC(=O)N4)cc3)ncc2c1=O

Procedure:
Using the procedure outlined in Example 1(g) the title compound was prepared from (4S)-4-(4-amino-benzyl)-1,3-oxazolidin-2-one (46 mg, 0.24 mmol) and 8-indan-5-yl-2-methanesulfonyl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (from Example 1(e) above, 100 mg, 0.24 mmol). The title compound was obtained as a white solid (56 mg, 44%). 1H NMR (400 MHz, CDCl3) δ (ppm): 9.00 (br, 1H), 8.42 (s, 1H), 7.50 (br, 1H), 7.33 (d, J=7.9 Hz, 1H), 7.28 (br, 2H), 7.18 (s, 1H), 7.08 (d, J=7.8 Hz, 1H), 6.81 (br, 2H), 5.88 (s, 1H), 4.41 (t, J=8.2 Hz, 1H), 4.31 (q, J=7.0 Hz, 2H), 4.05 (m, 1H), 3.98 (m, 1H), 2.99 (t, J=7.4 Hz, 2H), 2.92 (t, J=7.4 Hz, 2H), 2.79-2.66 (m, 2H), 2.15 (m, 2H), 1.31 (t, J=7.1 Hz, 3H).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH:4]([CH2:7][OH:8])[CH2:3][CH2:2]1.C(Cl)Cl.[C:12]1([CH3:22])[CH:17]=[CH:16][C:15]([S:18](Cl)(=[O:20])=[O:19])=[CH:14][CH:13]=1>N1C=CC=CC=1>[CH3:22][C:12]1[CH:17]=[CH:16][C:15]([S:18]([O:8][CH2:7][CH:4]2[CH2:5][CH2:6][O:1][CH2:2][CH2:3]2)(=[O:20])=[O:19])=[CH:14][CH:13]=1
Reactant: OCC1CCOCC1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OCC2CCOCC2)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of tetrahydro-2H-pyran-4-ylmethanol (Combi-Blocks, 2.0 g, 17.2 mmol) in 10 mL of of CH2Cl2 and 10 mL of of pyridine was added p-toluenesulfonyl chloride (3.5 g, 18.1 mmol) in portions over 15 minutes. The mixture stirred at ambient temperature for 16 hours and was quenched with 10 mL of saturated, aqueous NaHCO3. The layers were separated and the aqueous layer was extracted with three 10 mL portions of CH2Cl2. The combined organic extracts were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford the title compound. 1H NMR (300 MHz, dimethylsulfoxide-d6) δ ppm 1.05-1.25 (m, 2H), 1.40-1.53 (m, 2H), 1.73-1.94 (m, 1H), 2.43 (s, 3H), 3.14-3.28 (m, 2H), 3.71-3.84 (m, 2H), 3.88 (d, J=6.4 Hz, 2H), 7.48 (d, J=8.5 Hz, 2H), 7.79 (d, J=8.5 Hz, 2H); MS (DCI/NH3) m/z 288 (M+NH4)+.
Reaction SMILES: CCOC(/N=N/C(OCC)=O)=O.[OH:13][C:14]1[CH:15]=[C:16]([C:24]([O:26][CH3:27])=[O:25])[CH:17]=[C:18]([CH:23]=1)[C:19]([O:21][CH3:22])=[O:20].[CH2:28](O)[CH2:29][O:30][CH2:31][CH2:32][O:33][CH2:34][CH2:35][O:36][CH2:37][CH2:38][O:39][CH2:40][CH2:41][O:42][CH2:43][CH2:44][OH:45].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[OH:45][CH2:44][CH2:43][O:42][CH2:41][CH2:40][O:39][CH2:38][CH2:37][O:36][CH2:35][CH2:34][O:33][CH2:32][CH2:31][O:30][CH2:29][CH2:28][O:13][C:14]1[CH:23]=[C:18]([C:19]([O:21][CH3:22])=[O:20])[CH:17]=[C:16]([CH:15]=1)[C:24]([O:26][CH3:27])=[O:25]
Reactant: COC(=O)c1cc(O)cc(C(=O)OC)c1
Reactant: OCCOCCOCCOCCOCCOCCO
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: COC(=O)c1cc(OCCOCCOCCOCCOCCOCCO)cc(C(=O)OC)c1
Temperature: 0 °C
Yield: 31.2 %

Procedure:
Diethylazodicarboxylate (22.7 g, 130 mmol) was added over 3 min to a stirred solution of dimethyl 5-hydroxyisophthalate (21 g, 100 mmol), hexaethylene glycol (32 g, 113 mmol) and triphenylphosphine (34 g, 130 mmol) in 250 mL of anhydrous THF. After 2 h the reaction was concentrated and the residue suspended in 200 mL of ethyl ether. After being cooled at 0° C. for 30 min the precipitated triphenylphosphine oxide was removed by filtration and filtrate concentrated. The resultant mixture was chromatographed on silica eluting, first, with ethyl acetate to separate Ph3PO and symmetrical bis-substituted hexaethylene glycol by-product and, second, with 5% MeOH in ethyl acetate to elute desired mono-substituted hexaethylene glycol derivative. Evaporation of the solvent and drying under high vacuum afforded 14.8 g (31%) of the title compound as viscous oil. 1H NMR (DMSO-d6) δ 8.08 (s, 1H), 7.70 (s, 2H), 4.58 (t, J=5.5 Hz, 1H), 4.25 (m, 2H), 3.90 (s, 6H), 3.76 (m, 2H), 3.60 (m, 2H), 3.51 (m, 16H), 3.40 (m, 2H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:17])=[C:6]([CH:8]=[N:9][C:10]([O:12][Si](C)(C)C)=[CH2:11])[CH:7]=1.C(OC([N:25]1[C:33]2[C:28](=[CH:29][CH:30]=[C:31]([Cl:34])[CH:32]=2)[C:27](=[CH:35][C:36]2[CH:41]=[C:40]([Cl:42])[CH:39]=[CH:38][C:37]=2[O:43][C:44]2([C:48]([O:50][CH3:51])=[O:49])[CH2:47][CH2:46][CH2:45]2)[C:26]1=[O:52])=O)(C)(C)C.C(O)(C(F)(F)F)=O>C1(C)C=CC=CC=1>[Cl:34][C:31]1[CH:32]=[C:33]2[NH:25][C:26](=[O:52])[C:27]3([CH:35]([C:36]4[CH:41]=[C:40]([Cl:42])[CH:39]=[CH:38][C:37]=4[O:43][C:44]4([C:48]([O:50][CH3:51])=[O:49])[CH2:45][CH2:46][CH2:47]4)[CH2:12][C:10](=[O:11])[NH:9][CH:8]3[C:6]3[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=3[CH3:17])[C:28]2=[CH:29][CH:30]=1
Reactant: COC(=O)C1(Oc2ccc(Cl)cc2C=C2C(=O)N(C(=O)OC(C)(C)C)c3cc(Cl)ccc32)CCC1
Reactant: C=C(N=Cc1cc(F)ccc1C)O[Si](C)(C)C
Solvent: Cc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)C1(Oc2ccc(Cl)cc2C2CC(=O)NC(c3cc(F)ccc3C)C23C(=O)Nc2cc(Cl)ccc23)CCC1
Temperature: 80 °C
Reaction time: 0.33 h

Procedure:
To a toluene solution of 1-(5-fluoro-2-methylphenyl)-3-trimethylsilyoxy-2-aza-1,3-butadiene in toluene (2 M, 5 mL, 10 mmol) was added E/Z 6-chloro-3-[5-chloro-2-(1-methoxycarbonyl-cyclobutoxy)-benzylidene]-2-oxo-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester (1.5 g, 2.9 mmol). The reaction mixture was heated at 80° C. overnight under argon protection, then TFA (5 mL) was added, and the resulting mixture was stirred at room temperature for 20 min, evaporated in vacuo. The residue was partitioned between ethyl acetate and NaOH aq. (1 M). The organic layer was washed with water, dried over anhydrous Na2SO4, concentrated and purified by column chromatography to give the title compound as a white solid (340 mg).
Reaction SMILES: [CH:1]1[C:6]([C:7]2[C:16](=[O:17])[C:15]3[CH:14]=[CH:13][C:12]([O:18][C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O)=[CH:11][C:10]=3[O:9][CH:8]=2)=[CH:5][CH:4]=[C:3]([OH:30])[CH:2]=1.[CH:31]1[C:36]([C:37]2[C:46](=[O:47])[C:45]3[C:44]([OH:48])=[CH:43][C:42]([O:49][C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O)=[CH:41][C:40]=3[O:39][CH:38]=2)=[CH:35][CH:34]=[C:33]([OH:61])[CH:32]=1.CO.Cl>O>[CH:5]1[C:6]([C:7]2[C:16](=[O:17])[C:15]3[CH:14]=[CH:13][C:12]([OH:18])=[CH:11][C:10]=3[O:9][CH:8]=2)=[CH:1][CH:2]=[C:3]([OH:30])[CH:4]=1.[CH:35]1[C:36]([C:37]2[C:46](=[O:47])[C:45]3[C:44]([OH:48])=[CH:43][C:42]([OH:49])=[CH:41][C:40]=3[O:39][CH:38]=2)=[CH:31][CH:32]=[C:33]([OH:61])[CH:34]=1
Reactant: O=c1c(-c2ccc(O)cc2)coc2cc(O[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)ccc12
Reactant: O=c1c(-c2ccc(O)cc2)coc2cc(O[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)cc(O)c12
Agent: Cl
Solvent: O
Solvent: CO
Product: O=c1c(-c2ccc(O)cc2)coc2cc(O)cc(O)c12
Product: O=c1c(-c2ccc(O)cc2)coc2cc(O)ccc12
Reaction time: 8 h

Procedure:
To each of 1 g samples of daidzin and genistin obtained in Example 7 were added 45 ml of methanol and 10 ml of 12N HCl, and the glycoside was decomposed under reflux for 6 hours. After cooling, the reaction mixture was diluted with water, and the solid product was collected by filtration, washed with water, dissolved in 90 ml of a 80% ethanol solution, filtered through a filter paper to give a supernatant. The supernatant was left standing at room temperature to deposit a crystalline product. The mixture was left standing overnight, and the crystals were collected and dried to give daidzein and genistein in the yields of 410 mg and 440 mg, respectively.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH3:9].[Li][CH2:11][CH2:12][CH2:13][CH3:14].[O:15]1[C@H](CC)C1>C1COCC1>[CH2:13]([C:12]1[CH:11]=[CH:4][CH:5]=[CH:6][C:7]=1[C@H:2]([OH:15])[CH2:3][CH2:8][CH3:9])[CH3:14]
Reactant: CCc1ccccc1Br
Reactant: CC[C@@H]1CO1
Reactant: [Li]CCCC
Solvent: C1CCOC1
Product: CCC[C@@H](O)c1ccccc1CC
Temperature: -78 °C

Procedure:
The 1-bromo-2-ethylbenzene (2.0 g) was dissolved in dry THF and the mixture was cooled to −78° C. 1.6 M n-BuLi (20.26 ml) was slowly added to the reaction mixture and then the mixture was stirred at −78° C. After 1 h (R)-(+)-1,2-epoxybutane (1.1 g) was added in 10 ml of THF. The reaction mixture was allowed to warm to ambient temperature and then stirred over night. The reaction was quenched with ice-water and product extracted in heptanes, and finally purified by using the separation method E yielding the title compound (1.1 g).
Reaction SMILES: [NH3:1].[N+:2]([NH:5][C:6](=[O:10])[O:7][CH2:8][CH3:9])([O-:4])=[O:3].C(Cl)Cl>CO>[N+:2]([NH:5][C:6](=[O:10])[O:7][CH2:8][CH3:9])([O-:4])=[O:3].[NH4+:1]
Reactant: N
Agent: CCOC(=O)N[N+](=O)[O-]
Solvent: CO
Solvent: ClCCl
Product: [NH4+]

Procedure:
Anhydrous NH3 (g) was bubbled into a stirred solution of ethyl N-nitrocarbamate (503.0 g, 3.75 mol, mp 63°-66° C.), CH2Cl2 (1625 mL) and dry CH3OH (825 mL), precooled to 9° C. under N2, until the exothermic reaction subsided (the NH3 addition rate was controlled so as not to exceed a reaction temperature of 23° C.). After the NH3 addition was complete, the mixture was filtered and the collected solid was dried under high vacuum (overnight) to give ammonium ethyl N-nitrocarbamate as colorless crystals (563.0 g, 99%). mp 175°-176° C. IR (KBr) 3230 (s), 3000 (m), 1725 (s) and 1685 (s), 1445 and 1395 (s), 1310 (m), 1220 (s), 1100 (S), 1030 (m) cm-1. 1H NMR (90 MHz, d6 -DMSO) δ 7.30 (bs, 4H, exch D2O), 3.90 (q, 2H, J=4.5 Hz), 1.10 (t, 3H, J=4.5 Hz).
Reaction SMILES: [OH:1][C:2]1[C:3]([C:12]([OH:14])=O)=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.N1(C(N2C=CN=C2)=O)C=CN=C1.[N:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[CH2:33][NH2:34]>C1COCC1>[OH:1][C:2]1[C:3]([C:12]([NH:34][CH2:33][C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][N:27]=2)=[O:14])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2
Reactant: O=C(O)c1ccc2cccnc2c1O
Reactant: NCc1ccccn1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: O=C(NCc1ccccn1)c1ccc2cccnc2c1O
Temperature: 60 °C
Yield: 61.3 %

Procedure:
A mixture of 8-hydroxyquinoline-7-carboxylic acid (100 mg, 0.53 mmol) and di(1H-imidazol-1-yl)methanone (86 mg, 0.53 mmol) in THF (5 mL) was heated to 60° C. for 3 h, under nitrogen. The reaction mixture was allowed to cool to RT and pyridin-2-ylmethanamine (46 mg, 0.424 mmol) was added. The resulting mixture was heated to 40° C. for 2 h and then stirred at RT. The reaction mixture was quenched with H2O and an aqueous saturated solution of sodium hydrogen carbonate, and twice extracted with DCM. The separated organics were dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by SPE-SI cartridge (2 g, DCM to DCM:MeOH 99:1) affording the title compound (73 mg, 0.26 mmol) as a off-white solid.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:11](=[C:12]([NH:17][C:18]([C:20]3[N:24]4[CH:25]=C(C=C)[CH:27]=[CH:28][C:23]4=[N:22][CH:21]=3)=[O:19])[CH:13]=[CH:14][CH:15]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[N+]1([O-])CC[O:35]CC1.[CH3:39][C:40]([CH3:42])=[O:41].O>C(O)(C)(C)C.C(OCC)(=O)C.[Os](=O)(=O)(=O)=O>[CH2:1]([N:8]1[C:16]2[C:11](=[C:12]([NH:17][C:18]([C:20]3[N:24]4[CH:25]=[C:39]([CH:40]([OH:41])[CH2:42][OH:35])[CH:27]=[CH:28][C:23]4=[N:22][CH:21]=3)=[O:19])[CH:13]=[CH:14][CH:15]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C=Cc1ccc2ncc(C(=O)Nc3cccc4c3cnn4Cc3ccccc3)n2c1
Reactant: C[N+]1([O-])CCOCC1
Reactant: CC(C)=O
Agent: O=[Os](=O)(=O)=O
Solvent: CC(C)(C)O
Solvent: O
Solvent: CCOC(C)=O
Product: O=C(Nc1cccc2c1cnn2Cc1ccccc1)c1cnc2ccc(C(O)CO)cn12
Temperature: 25 °C
Reaction time: 24 h

Procedure:
A mixture of N-(1-benzyl-1H-indazol-4-yl)-6-vinylimidazo[1,2-a]pyridine-3-carboxamide (63 mg; 0.16 mmol), osmium tetroxide (0.008 mmol; 2.5% solution in t-butanol) and N-methylmorpholine N-oxide (21 mg; 0.18 mmol) in acetone/water (3:2; 1 mL) was stirred at ambient temperature for 24 hours. Additional osmium tetroxide was added (250 μL of a 2.5% solution in t-butanol) and the mixture was stirred for an additional 24 hours. The mixture was diluted with ethyl acetate and solids were isolated by filtration. The material was purified by reverse phase chromatography (acetonitrile/water) to give the desired product as a solid (3.6 mg). MS (APCI), m/z=428.2 (M+H).