Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:60]/[O:61][C:62]([C:75]2[CH:80]=[CH:79][CH:78]=[CH:77][CH:76]=2)([C:69]2[CH:74]=[CH:73][CH:72]=[CH:71][CH:70]=2)[C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)/[C:27]([NH:29][C@@H:30]2[C:58](=[O:59])[N:32]3[C:33]([C:42]([O:44][CH:45]([C:52]4[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=4)[C:46]4[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=4)=[O:43])=[C:34](OS(C)(=O)=O)[CH2:35][S:36][C@H:31]23)=[O:28])[N:25]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[SH:81][C:82]1[CH:87]=[CH:86][N:85]=[CH:84][CH:83]=1.C(N(CC)C(C)C)(C)C.Cl>CN(C=O)C>[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:60]/[O:61][C:62]([C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][CH:64]=2)([C:75]2[CH:76]=[CH:77][CH:78]=[CH:79][CH:80]=2)[C:69]2[CH:70]=[CH:71][CH:72]=[CH:73][CH:74]=2)/[C:27]([NH:29][C@@H:30]2[C:58](=[O:59])[N:32]3[C:33]([C:42]([O:44][CH:45]([C:46]4[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=4)[C:52]4[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=4)=[O:43])=[C:34]([S:81][C:82]4[CH:87]=[CH:86][N:85]=[CH:84][CH:83]=4)[CH2:35][S:36][C@H:31]23)=[O:28])[N:25]=1)([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)([C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: CS(=O)(=O)OC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)[C@@H](NC(=O)/C(=N\OC(c3ccccc3)(c3ccccc3)c3ccccc3)c3csc(NC(c4ccccc4)(c4ccccc4)c4ccccc4)n3)[C@H]2SC1
Reactant: Sc1ccncc1
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(OC(c1ccccc1)c1ccccc1)C1=C(Sc2ccncc2)CS[C@@H]2[C@H](NC(=O)/C(=N\OC(c3ccccc3)(c3ccccc3)c3ccccc3)c3csc(NC(c4ccccc4)(c4ccccc4)c4ccccc4)n3)C(=O)N12
Temperature: 5 °C
Reaction time: 1 h
Yield: 13.5 %

Procedure:
To a solution of diphenylmethyl 7β-[2-(2-tritylaminothiazol-4-yl)-2-(Z)-(trityloxyimino)acetamido]-3-methanesulfonyloxy-3-cephem-4-carboxylate (10.01 g, 8.98 m mol) in DMF (200 ml) was added 4-mercaptopyridine (2.00 g, 18.0 m mol) at −15° C., followed by dropwise addition of N,N-diisopropylethylamine (1.16 g, 8.98 m mol). The mixture was stirred at −15° C. for 4.5 hours and at 5° C. for 1 hour. The mixture was poured into a mixture of ice water (1.2 l) and 6N HCl (3 ml) and the precipitates were collected by filtration and washed with water. The powder was dissolved in THF, and ethyl acetate and water were added. The separated organic layer was washed with brine, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel to give diphenylmethyl 7β-[2-(2-tritylaminothiazol-4-yl)-2-(Z)-(trityloxyimino)acetamido]-3-(4-pyridylthio)-3-cephem-4-carboxylate (1.37 g).
Reaction SMILES: C([O:3][C:4]([C:6]1([S:20]([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH2:30][C:31]#[C:32][CH3:33])=[CH:25][CH:24]=2)(=[O:22])=[O:21])[CH2:11][CH2:10][N:9]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([Br:19])=[CH:15][CH:14]=2)[CH2:8][CH2:7]1)=[O:5])C.CO.[OH-].[Na+]>C1COCC1>[Br:19][C:16]1[CH:15]=[CH:14][C:13]([CH2:12][N:9]2[CH2:10][CH2:11][C:6]([S:20]([C:23]3[CH:24]=[CH:25][C:26]([O:29][CH2:30][C:31]#[C:32][CH3:33])=[CH:27][CH:28]=3)(=[O:22])=[O:21])([C:4]([OH:5])=[O:3])[CH2:7][CH2:8]2)=[CH:18][CH:17]=1
Reactant: CC#CCOc1ccc(S(=O)(=O)C2(C(=O)OCC)CCN(Cc3ccc(Br)cc3)CC2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: CC#CCOc1ccc(S(=O)(=O)C2(C(=O)O)CCN(Cc3ccc(Br)cc3)CC2)cc1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
1-(4-Bromo-benzyl)-4-(4-but-2-ynyloxy-benzenesulfonyl)-piperdine-4-carboxylic acid was prepared starting from 1-(4-bromo-benzyl)-4-(4-but-2-ynyloxy-benzenesulfonyl)-piperdine-4-carboxylic acid ethyl ester (1.36 g, 2.54 mmol) dissolved in THF:methanol (100:50 ml) and 10 N NaOH (15 ml). The reaction mixture was stirred at room temperature for 24 hrs. The reaction mixture was then concentrated and residue was cooled and neutralized with concentrated HCl. The separated solid was extracted with chloroform:methanol (3:1) (300 ml) and washed with water. The chloroform layer was dried and concentrated. The product was crystallized from methanol. Yield 800 mg (62%); off white solid; mp 197° C.; MS: 507.9 (M+H)+.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][C:5]([S:8][CH3:9])=[N:6][CH:7]=1.[C:10]1([C:16]#[CH:17])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(N(CC)CC)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1.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.[Cu]I>[CH3:9][S:8][C:5]1[N:4]=[CH:3][C:2]([C:17]#[C:16][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[CH:7][N:6]=1
Reactant: CSc1ncc(Br)cn1
Reactant: C#Cc1ccccc1
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CSc1ncc(C#Cc2ccccc2)cn1
Temperature: 65 °C
Reaction time: 3 h

Procedure:
Bis-(triphenylphosphine)-palladium(II)dichloride (120 mg, 0.16 mmol) were dissolved in 50 ml THF and 5-bromo-2-methylsulfanyl-pyrimidine (840 mg, 4.1 mmol) and phenylacetylene (410 μl, 4.1 mmol) were added at room temperature. Triethylamine (1.36 ml, 12.3 mmol), triphenylphosphine (28 mg, 0.12 mmol) and copper(I)iodide (19 mg, 0.08 mmol) were added and the mixture was stirred for 3 hours at 65° C. The reaction mixture was cooled and extracted once with saturated NaHCO3 solution and three times with ethyl acetate. The organic layers were combined, dried with sodium sulfate, filtered and evaporated to dryness. The crude product was purified by flash chromatography on silicagel (heptane:ethyl acetate 100:0→50:50). The desired compound was obtained as a light yellow solid (400 mg, 44%), MS: m/e=227.3 (M+H+).
Reaction SMILES: Cl[C:2]1[N:7]2[N:8]=[CH:9][C:10]([C:11]3[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=3[CH3:19])=[C:6]2[N:5]=[C:4]([CH3:20])[CH:3]=1.[CH2:21]([NH:24][CH2:25][CH3:26])[CH2:22][CH3:23].[CH3:27]N1CCCC1=O>>[CH3:27][C:9]1[C:10]([C:11]2[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=2[CH3:19])=[C:6]2[N:5]=[C:4]([CH3:20])[CH:3]=[C:2]([N:24]([CH2:25][CH3:26])[CH2:21][CH2:22][CH3:23])[N:7]2[N:8]=1
Reactant: CN1CCCC1=O
Reactant: Cc1cc(C)c(-c2cnn3c(Cl)cc(C)nc23)c(C)c1
Reactant: CCCNCC
Product: CCCN(CC)c1cc(C)nc2c(-c3c(C)cc(C)cc3C)c(C)nn12
Temperature: 135 °C

Procedure:
A mixture of 7-chloro-5-methyl-3-(2,4,6-trimethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (200 mg, 0.66 mmol) and N-propylethylamine (2 ml) in 1 ml of N-methylpyrrolidinone was heated at 135° C. oil bath for 4 hours. The mixture was quenched with water and extracted with ethyl acetate. The organic layer was dried and concentrated and purified through silica gel column chromatography using hexane to 10% ethyl acetate in hexane as eluent to give 150 mg of the title compound as a clear green oil. 1H NMR (CDCl3) ä 6.95(s, 2H), 5.80(s, 1H), 3.85(q, 2H), 3.67(dd, 2H), 2.41(s, 3H), 2.32(s, 3H), 2.21(s, 3H), 2.03(s, 6H), 1.76(m, 2H), 1.29(t, 3H), 0.98(t, 3H) ppm.
Reaction SMILES: C[C:2]1[C:7]2[N:8]=C(NC3C=CC=CC=3C)[O:10][C:6]=2[CH:5]=[C:4]([CH2:19][C:20](NC2C=CC(C(C)CC(O)=O)=NC=2)=[O:21])[CH:3]=1.[C:35]1([CH3:44])[C:36]([N:41]=[C:42]=S)=[CH:37][CH:38]=[CH:39][CH:40]=1.C1(N=C=NC2CCCCC2)CCCCC1.C([OH:62])C>>[C:35]1([CH3:44])[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[NH:41][C:42]1[O:10][C:6]2[CH:5]=[C:4]([CH2:19][C:20]([OH:21])=[O:62])[CH:3]=[CH:2][C:7]=2[N:8]=1
Reactant: Cc1ccccc1N=C=S
Reactant: CCO
Reactant: Cc1ccccc1Nc1nc2c(C)cc(CC(=O)Nc3ccc(C(C)CC(=O)O)nc3)cc2o1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Product: Cc1ccccc1Nc1nc2ccc(CC(=O)O)cc2o1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A mixture of ethyl 4-amino-3-hydroxy-phenylacetate (3.3 g, Reference Example 3) and o-tolylisothiocyanate (2.5 mL) in ethanol (150 mL) was stirred at room temperature for about 2 hours. After standing at room temperature overnight the mixture was evaporated and the residue was subjected to flash chromatography on silica eluting with a mixture of pentane and ethyl acetate (7:3, v/v) to give a yellow foam. A solution of this material in ethanol (150 mL) was treated with dicyclohexylcarbodiimide (3.0 g) and the mixture was heated at reflux temperature for 2 hours. The mixture was evaporated and the residue subjected to short column chromatography on silica eluting with a mixture of 5-10% tert-butyl methyl ether in dichloromethane to remove dicyclohexylurea. The resulting light yellow oil was dissolved in ethanol (100 mL) and the solution was treated with sodium hydroxide solution (15 mL, 1M) then heated at reflux temperature for 2 hours. The reaction mixture was evaporated and the residue was dissolved in water. The solution was washed with ethyl acetate and the aqueous layer was acidified to pH 1 by addition of concentrated hydrochloric acid. The resulting white precipitate was collected by filtration, then washed thoroughly with water, and then dried to give the title compound (1.8 g) as a white solid.
Reaction SMILES: [C:1]([NH2:5])(=[O:4])[CH:2]=[CH2:3].Br[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.[OH-].[K+].C1C2NC3C(=CC=CC=3)SC=2C=CC=1>C1C=CC=CC=1.CN(C)C=O>[O:15]([CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][NH:5][C:1](=[O:4])[CH:2]=[CH2:3])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: C=CC(N)=O
Reactant: BrCCCCCCCCOc1ccccc1
Agent: [K+]
Agent: [OH-]
Agent: c1ccc2c(c1)Nc1ccccc1S2
Solvent: c1ccccc1
Solvent: CN(C)C=O
Product: C=CC(=O)NCCCCCCCCOc1ccccc1
Yield: 79.2 %

Procedure:
Added to 20 ml of N,N-dimethylformamide were 0.62 g of acrylic amide and 2.0 g of (8-bromooctyloxy)benzene. With stirring, 0.49 g of flaky potassium hydroxide which had been ground in a mortar was added. Phenothiazine was added in an amount of 0.5% based on the acrylic amde. After they were reacted at 0°-5° C. for 6 hours, insoluble filtered off from the liquid reaction mixture. The solvent and unreacted raw materials were distilled off from the filtrate. The residue was extracted with benzene-water, thereby obtaining the intended product in the benzene layer. Benzene was then driven off from the benzene layer to obtain 1.53 g of N-(8-phenoxyoctyl)acrylic amide (yield: 79%). It was purified further with column chromatography in which silica gel and benzene were used as an adsorbent and developer respectively. Its melting point was measured and its elementary analysis was also conducted. The following results were obtained. Melting point: 45°-47° C. Elementary analysis data: C, 74.21% (Calculated: 74.14%); H, 9.09% (9.15 %); N, 5.12% (5.09%).
Reaction SMILES: [CH2:1]([O:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[C:11]([O:25]C)[N:12]2[CH2:15][CH2:16][CH2:17][CH2:18][CH:19]2[CH2:24][CH2:23][CH2:22][NH:21][CH2:20]2)=[C:8]([NH2:27])[N:7]=1)[CH2:2][CH2:3][CH3:4].Br[CH2:29][CH2:30][OH:31]>>[NH2:27][C:8]1[N:7]=[C:6]([O:5][CH2:1][CH2:2][CH2:3][CH3:4])[N:14]=[C:13]2[C:9]=1[NH:10][C:11](=[O:25])[N:12]2[CH2:15][CH2:16][CH2:17][CH2:18][CH:19]1[CH2:24][CH2:23][CH2:22][N:21]([CH2:29][CH2:30][OH:31])[CH2:20]1
Reactant: OCCBr
Reactant: CCCCOc1nc(N)c2nc(OC)n(CCCCC3CCCNC3)c2n1
Product: CCCCOc1nc(N)c2[nH]c(=O)n(CCCCC3CCCN(CCO)C3)c2n1

Procedure:
Prepared similarly to Example 1 from 2-(butyloxy)-8-(methyloxy)-9-[4-(3-piperidinyl)butyl]-9H-purin-6-amine (for example, as prepared for Intermediate 26) and 2-bromoethanol (commercially available, for example, from Aldrich).
Reaction SMILES: [F:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][CH2:12][OH:13])[CH2:6][CH2:5]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F:33][C:34]1[C:42]([O:43][C:44]2[C:53]3[C:48](=[CH:49][C:50](O)=[C:51]([O:54][CH3:55])[CH:52]=3)[N:47]=[CH:46][N:45]=2)=[CH:41][CH:40]=[C:39]2[C:35]=1[CH:36]=[C:37]([CH3:57])[NH:38]2>ClCCl>[F:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([CH2:10][CH2:11][CH2:12][O:13][C:50]2[CH:49]=[C:48]3[C:53]([C:44]([O:43][C:42]4[C:34]([F:33])=[C:35]5[C:39](=[CH:40][CH:41]=4)[NH:38][C:37]([CH3:57])=[CH:36]5)=[N:45][CH:46]=[N:47]3)=[CH:52][C:51]=2[O:54][CH3:55])[CH2:6][CH2:5]1
Reactant: COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1O
Reactant: OCCCN1CCN(CCF)CC1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OCCCN1CCN(CCF)CC1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 83.2 %

Procedure:
Diisopropyl azadicarboxylate (230 μl, 1.17 mmol) was added dropwise to a solution of 3-[4-(2-fluoroethyl)piperazin-1-yl]propan-1-ol (203 mg, 1.07 mmol), triphenylphosphine (357 mg, 1.36 mmol) and 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-7-hydroxy-6-methoxyquinazoline (330 mg, 0.97 mmol), (prepared as described for the starting material in Example 7), in dichloromethane (8.5 ml). The reaction mixture was stirred at ambient temperature for 1.5 hours and then loaded directly onto a silica column, eluting with a mixture of methanol in methylene chloride (11/89) to give 7-{3-[4-(2-fluoroethyl)piperazin-1-yl]propoxy}-4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxyquinazoline (413 mg, 83%) as a white solid.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6](SC)[N:5]=[C:4]([N:10]2[C@H:15]([C:16]([F:19])([F:18])[F:17])[CH2:14][CH2:13][C@H:12]([C:20]([NH:22][CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[O:21])[CH2:11]2)[CH:3]=1.O[O:31][S:32]([O-:34])=O.[K+].[CH3:36]O>O>[Cl:1][C:2]1[N:7]=[C:6]([S:32]([CH3:36])(=[O:34])=[O:31])[N:5]=[C:4]([N:10]2[CH:15]([C:16]([F:18])([F:19])[F:17])[CH2:14][CH2:13][CH:12]([C:20]([NH:22][CH2:23][C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)=[O:21])[CH2:11]2)[CH:3]=1
Reactant: CO
Reactant: O=S([O-])OO
Reactant: CSc1nc(Cl)cc(N2C[C@@H](C(=O)NCc3ccccc3)CC[C@H]2C(F)(F)F)n1
Agent: [K+]
Solvent: O
Product: CS(=O)(=O)c1nc(Cl)cc(N2CC(C(=O)NCc3ccccc3)CCC2C(F)(F)F)n1
Temperature: 25 °C

Procedure:
A suspension of cis-1-[6-chloro-2-(methylthio)-4-pyrimidinyl]-N-(phenylmethyl)-6-(trifluoromethyl)-3-piperidinecarboxamide (550 mg, 1.236 mmol) in CH3OH (5 mL) and water (1.5 mL) was cooled in an ice bath and treated slowly with a premixed solution of oxone (2280 mg, 3.71 mmol) in water (0.5 mL). The reaction was stirred at room temperature over the weekend. Water (10 mL) was added and the resulting mixture was filtered. The solid was dried in vacuum oven at 35° C. overnight to afford the crude title compound (834 mg) as an off-white solid. LC-MS (ES) m/z=477 [M+H]+.
Reaction SMILES: [H-].[Na+].[CH2:3]([O:5][C:6]1[CH:11]=[CH:10][C:9]([CH:12]([C:15]([F:18])([F:17])[F:16])[CH2:13][OH:14])=[CH:8][CH:7]=1)[CH3:4].[Cl:19][C:20]1[CH:34]=[CH:33][C:23]([O:24][C:25]2[CH:26]=[C:27]([CH:30]=[CH:31][CH:32]=2)[CH2:28]Br)=[CH:22][CH:21]=1>C1COCC1>[Cl:19][C:20]1[CH:34]=[CH:33][C:23]([O:24][C:25]2[CH:26]=[C:27]([CH:30]=[CH:31][CH:32]=2)[CH2:28][O:14][CH2:13][CH:12]([C:9]2[CH:8]=[CH:7][C:6]([O:5][CH2:3][CH3:4])=[CH:11][CH:10]=2)[C:15]([F:16])([F:17])[F:18])=[CH:22][CH:21]=1
Reactant: Clc1ccc(Oc2cccc(CBr)c2)cc1
Reactant: CCOc1ccc(C(CO)C(F)(F)F)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCOc1ccc(C(COCc2cccc(Oc3ccc(Cl)cc3)c2)C(F)(F)F)cc1
Temperature: 25 °C

Procedure:
Under a nitrogen atmosphere, 171 mg of sodium hydride (60% oil dispersion) was added to 20 ml of dry THF. A solution of 1.0 g of 2-(4-ethoxyphenyl)-3,3,3-trifluoropropanol and 1.25 g of 3-(4-chlorophenoxy)-benzyl bromide in 30 ml of dry THF was then added with ice-cooling, and the reaction solution was stirred with ice-cooling for 1 hour and at room temperature for 12 hours. Thereafter, the reaction mixture was poured into dilute HCl-ice water and extracted twice with diethyl ether. The ether layers were combined, washed with saturated sodium chloride solution and dried over anhydrous magnesium sulfate. The solvent was removed under a reduced pressure, and the residue was subjected to column chromatography on silica gel [eluted with n-hexane/ethyl acetate (50:1) mixture] to obtain 1.22 of the desired compound.
Reaction SMILES: [OH:1][C:2]1[C:3]([CH:12]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([O:23][CH3:24])[C:19]=3[O:21][CH3:22])[N:14]([CH2:25][C:26]3[O:27][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:29][CH:30]=3)[C:13]2=[O:35])=[CH:4][C:5]2[O:10][CH2:9][CH2:8][O:7][C:6]=2[CH:11]=1.[C:36]1(C(C2C=CC=CC=2)N2C3C(=CC=CC=3)C(C3C=C(C)C(OC)=CC=3O)C2=O)C=CC=CC=1>>[CH3:22][O:21][C:19]1[C:18]([O:23][CH3:24])=[CH:17][CH:16]=[C:15]2[C:20]=1[C:12]1([C:3]3[C:2](=[CH:11][C:6]4[O:7][CH2:8][CH2:9][O:10][C:5]=4[CH:4]=3)[O:1][CH2:36]1)[C:13](=[O:35])[N:14]2[CH2:25][C:26]1[O:27][C:28]([C:31]([F:32])([F:33])[F:34])=[CH:29][CH:30]=1
Reactant: COc1ccc2c(c1OC)C(c1cc3c(cc1O)OCCO3)C(=O)N2Cc1ccc(C(F)(F)F)o1
Reactant: COc1cc(O)c(C2C(=O)N(C(c3ccccc3)c3ccccc3)c3ccccc32)cc1C
Product: COc1ccc2c(c1OC)C1(COc3cc4c(cc31)OCCO4)C(=O)N2Cc1ccc(C(F)(F)F)o1

Procedure:
Following the procedure as described in EXAMPLE 2 and making non-critical variations using 3-(7-hydroxy-2,3-dihydro-1,4-benzodioxin-6-yl)-4,5-dimethoxy-1-{[5-(trifluoromethyl)furan-2-yl]methyl}-1,3-dihydro-2H-indol-2-one to replace 1-(diphenylmethyl)-3-(2-hydroxy-4-methoxy-5-methylphenyl)-1,3-dihydro-2H-indol-2-one, 4′,5′-dimethoxy-1′-{[5-(trifluoromethyl)furan-2-yl]methyl}-2,3-dihydrospiro[furo[2,3-g][1,4]benzodioxine-8,3′-indol]-2′(1H)-one was obtained (77%): mp 62-65° C.; 1H NMR (300 MHz, CDCl3) δ6.80 (d, J=8.4 Hz, 1H), 6.74-6.69 (m, 1H), 6.62 (d, J=8.4 Hz, 1H), 6.45 (s, 1H), 6.38-6.32 (m, 1H), 6.20 (s, 1H), 4.90 (ABq, 2H), 4.85-4.81 (m, 2H), 4.18-4.05 (m, 4H), 3.78 (s, 3H), 3.40 (s, 3H); 13C NMR (75 MHz, CDCl3) δ177.0, 155.6, 152.3, 152.2, 149.9, 146.6, 144.6, 137.9, 135.1, 125.0, 120.3, 112.7, 111.1, 109.2, 103.7, 99.1, 78.2, 64.5, 63.9, 60.4, 57.7, 56.3, 37.1; MS (ES+) m/z 503.9 (M+1).
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][C@H:11]([CH2:13][N:14]3[CH:18]=[C:17]([CH3:19])[N:16]=[N:15]3)[O:10][C:9]2=[O:20])=[CH:4][CH:3]=1.C[Sn](C)(C)[C:23]1[S:27][C:26]([C:28]2[CH2:32][CH:31]([CH2:33][OH:34])[O:30][N:29]=2)=[CH:25][CH:24]=1.O1C=CC=C1P(C1OC=CC=1)C1OC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd]>[OH:34][CH2:33][CH:31]1[O:30][N:29]=[C:28]([C:26]2[S:27][C:23]([C:2]3[CH:7]=[CH:6][C:5]([N:8]4[CH2:12][C@H:11]([CH2:13][N:14]5[CH:18]=[C:17]([CH3:19])[N:16]=[N:15]5)[O:10][C:9]4=[O:20])=[CH:4][CH:3]=3)=[CH:24][CH:25]=2)[CH2:32]1
Reactant: Cc1cn(C[C@H]2CN(c3ccc(I)cc3)C(=O)O2)nn1
Reactant: C[Sn](C)(C)c1ccc(C2=NOC(CO)C2)s1
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: c1coc(P(c2ccco2)c2ccco2)c1
Solvent: ClC(Cl)Cl
Product: Cc1cn(C[C@H]2CN(c3ccc(-c4ccc(C5=NOC(CO)C5)s4)cc3)C(=O)O2)nn1
Temperature: 90 °C
Yield: 35.4 %

Procedure:
(5R)-3-(4-Iodophenyl)-5-[(4-methyl-1H-1,2,3-triazol-1-yl)methyl]-1,3-oxazolidin-2-one (222 mg, 0.58 mM), {3-[5-(trimethylstannyl)thien-2-yl]4,5-dihydroisoxazol-5-yl}methanol (200 mg, 0.58 mM), tris(dibenzylideneacetone)dipalladium (0)-chloroform adduct (60 mg, 0.058 mM) and tri-2-furylphosphine (27 mg, 0.116 mM) were placed in a flask. The solids were degassed and placed under nitrogen. Anhydrous dioxane (5 ml) was added and the suspension was heated at 90° C. for 16 hours. The reaction mixture was cooled and the solvent was evaporated. The residue was chromatographed on silica gel eluting with 5% methanol in dichloromethane to give the title compound (90 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]=[CH:9][C:10]1[N:11]=[CH:12][N:13](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:14]=1.C(Cl)(Cl)Cl.C(O)(=O)C.Cl>C(O)C.[Pd]>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][CH2:9][C:10]1[N:11]=[CH:12][NH:13][CH:14]=1
Reactant: Clc1ccccc1C=Cc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Agent: [Pd]
Agent: Cl
Solvent: CC(=O)O
Solvent: CCO
Solvent: ClC(Cl)Cl
Product: Clc1ccccc1CCc1c[nH]cn1
Temperature: 25 °C
Yield: 28.9 %

Procedure:
To a stirred mixture of 4-[2-(2-chloro-phenyl)-vinyl]-1-trityl-1H-imidazole (329 mg) at r.t. in ethanol (7 ml) and chloroform (3 ml) under an argon atmosphere were added acetic acid (0.2 ml) and 10% Pd/C (30 mg). The mixture was hydrogenated (ambient pressure) over night. The catalyst was filtered off and washed with ethanol. The mixture was concentrated to leave a light brown gum. This material was taken up in ethanol (3 ml) and 2 N HCl (3 ml) and heated to reflux for 3 h. Then, the mixture was cooled to r.t., concentrated. The residual solid was taken up in 1 N NaOH (10 ml) and extracted with CH2Cl2/MeOH 4:1. The combined organics were dried over MgSO4, filtered and concentrated. The crude product was purified by column chromatography (silica gel; gradient: CH2Cl2→CH2Cl2/MeOH 9:1) to give 4-[2-(2-chloro-phenyl)-ethyl]-1H-imidazole (44 mg) as light brown gum. MS (ISP): 207.1 ([M+H]+)
Reaction SMILES: [N:1]([CH:4]1[CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5]1)=[C:2]=[O:3].[OH:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18]C(=O)C1C=CC=CC=1>>[OH:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:2]([NH:1][CH:4]1[CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5]1)=[O:3]
Reactant: O=C=NC1Cc2ccccc2C1
Reactant: O=C(NCCCCO)c1ccccc1
Product: O=C(NCCCCO)NC1Cc2ccccc2C1
Yield: 61 %

Procedure:
1-(4-Hydroxybutyl)-3-indan-2-ylurea (60B) is prepared from 60A as described for 1D.
Reaction SMILES: [OH:1][C:2]1[CH:15]=[CH:14][C:5]([CH:6]=[CH:7][C:8]([CH2:10]C(=O)C)=[O:9])=[CH:4][C:3]=1[N+:16]([O-:18])=[O:17].Cl.[C:20]([NH2:28])(=[NH:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[CH2:29](N(CC)CC)[CH3:30].C(OCC)(=O)C>C(O)CCC>[C:8]([C:7]1[CH:6]([C:5]2[CH:14]=[CH:15][C:2]([OH:1])=[C:3]([N+:16]([O-:18])=[O:17])[CH:4]=2)[NH:28][C:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[N:27][C:29]=1[CH3:30])(=[O:9])[CH3:10]
Reactant: N=C(N)c1ccccc1
Reactant: CC(=O)CC(=O)C=Cc1ccc(O)c([N+](=O)[O-])c1
Reactant: CCN(CC)CC
Agent: Cl
Solvent: CCCCO
Solvent: CCOC(C)=O
Product: CC(=O)C1=C(C)N=C(c2ccccc2)NC1c1ccc(O)c([N+](=O)[O-])c1
Reaction time: 1 h

Procedure:
A mixture of 2-(4-hydroxy-3-nitrobenzylidene)acetylacetone (40 g), benzamidine hydrochloride (30.2 g) and triethylamine (31.2 ml) in n-butanol (400 ml) was refluxed for 2 hours. The reaction mixture, added ethyl acetate (100 ml), was washed with water (200 ml) and 5% hydrochloric acid (200 ml) successively. The solvent was evaporated and the residue was stirred with ethyl acetate (200 ml) for 1 hour. The crystals were collected by filtration, added a mixture of chloroform (200 ml) and water (200 ml) and adjusted to pH 8.5 by saturated potassium carbonate. The organic layer was evaporated in vacuo to give crude 5-acetyl-1,6-dihydro-6-(4-hydroxy-3-nitrophenyl)-4-methyl-2-phenylpyrmidine (45.5 g).
Reaction SMILES: Cl.[C:2]1([C@@H:8]2[CH2:10][C@H:9]2[NH2:11])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[CH:18][N:19]2[C@@H:22]2[O:26][C@H:25]([CH2:27][OH:28])[C@@H:24]([N:29]=[N+:30]=[N-:31])[CH2:23]2)=[C:15](Cl)[N:14]=1>O>[NH2:12][C:13]1[N:21]=[C:20]2[C:16]([N:17]=[CH:18][N:19]2[C@@H:22]2[O:26][C@H:25]([CH2:27][OH:28])[C@@H:24]([N:29]=[N+:30]=[N-:31])[CH2:23]2)=[C:15]([NH:11][C@@H:9]2[CH2:10][C@H:8]2[C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[N:14]=1
Reactant: [N-]=[N+]=N[C@H]1C[C@H](n2cnc3c(Cl)nc(N)nc32)O[C@@H]1CO
Reactant: N[C@@H]1C[C@H]1c1ccccc1
Agent: Cl
Solvent: O
Product: [N-]=[N+]=N[C@H]1C[C@H](n2cnc3c(N[C@@H]4C[C@H]4c4ccccc4)nc(N)nc32)O[C@@H]1CO
Temperature: 50 °C

Procedure:
Trans-2-phenylcyclopropylamine hydrochloride (Aldrich, lot #01903MK, 2.5 g, 14.7 mmol) was dissolved in 5 mL H2O and the pH adjusted to pH 12. The aqueous solution was extracted with 10 mL EtOAc. The EtOAc was evaporated to dryness and dissolved in 25 mL EtOH. 2-Amino-9-(3-azido-2,3-dideoxy-β-D-erythro-pentofuranosyl)-6-chloro-9H-purine (Example 3d) (0.4 g, 1.29 mmol) was added to the ethanolic solution then placed in a sealed tube and heated at 50° C. for 18 hours. The solvents were removed in vacuo to yield a dark oil. The oil was chromatographed on basic alumina eluted with 1% MeOH in CHCl3. The impure product fractions were combined, evaporated, and rechromatographed on silica gel eluted with 5% MeOH in CHCl3. The collected impure product was again applied to basic alumina eluted with 1% MeOH in CHCl3 to give, after combination and evaporation of appropriate fractions, 0.0802 g (0.2 mMol, 15.5%); mp=65°-70°C.