Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: COC1C=C(OC)C=CC=1C[N:6]([C:21]1[S:25][N:24]=[CH:23][N:22]=1)[S:7]([C:10]1[C:19]([F:20])=[CH:18][C:13]2[NH:14][C:15](=[O:17])[O:16][C:12]=2[CH:11]=1)(=[O:9])=[O:8].N(/C(OC(C)(C)C)=O)=N\C(OC(C)(C)C)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[CH2:68][C:69]1[CH:70]=[CH:71][CH:72]=[C:73]2[C:78]=1[CH:77]=[N:76][C:75]([NH:79]C(=O)OC(C)(C)C)=[CH:74]2>C1COCC1>[NH2:79][C:75]1[N:76]=[CH:77][C:78]2[C:73]([CH:74]=1)=[CH:72][CH:71]=[CH:70][C:69]=2[CH2:68][N:14]1[C:13]2[CH:18]=[C:19]([F:20])[C:10]([S:7]([NH:6][C:21]3[S:25][N:24]=[CH:23][N:22]=3)(=[O:8])=[O:9])=[CH:11][C:12]=2[O:16][C:15]1=[O:17]
Reactant: COc1ccc(CN(c2ncns2)S(=O)(=O)c2cc3oc(=O)[nH]c3cc2F)c(OC)c1
Reactant: CC(C)(C)OC(=O)Nc1cc2cccc(CO)c2cn1
Agent: CC(C)(C)OC(=O)/N=N/C(=O)OC(C)(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Nc1cc2cccc(Cn3c(=O)oc4cc(S(=O)(=O)Nc5ncns5)c(F)cc43)c2cn1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
N-(2,4-dimethoxybenzyl)-5-fluoro-2-oxo-N-(1,2,4-thiadiazol-5-yl)-2,3-dihydrobenzo[d]oxazole-6-sulfonamide (11-3, 50 mg, 0.107 mmol), (E)-di-tert-butyl diazene-1,2-dicarboxylate (49.4 mg, 0.214 mmol) and triphenylphosphine (56.2 mg, 0.214 mmol) were added to a 5 mL RB flask. Then THF was added and r×n mixture was stirred at 0° C. for 10 min before addition of tert-butyl (8-(hydroxymethyl)isoquinolin-3-yl)carbamate (29.4 mg, 0.107 mmol) in THF. After stirring at 0° C. for 2 h, the reaction was filtered and concentrated in vacuo. Residue was dissolved in 1 mL of DCM and treated with 0.25 mL of TFA. After stirring at RT for 30 minutes, the solvent and TFA were removed in vacuo. Purified by reverse phase chromatography (10-95% MeCN in water w/0.1% TFA, C18 column) to yield 27-5. 1H NMR δ (ppm)(DMSO-d6): 9.08 (1H, s), 7.65 (1H, d, J=5.39 Hz), 7.47 (1H, d, J=8.47 Hz), 7.34-7.26 (2H, m), 6.92 (1H, d, J=7.03 Hz), 6.65 (1H, s), 5.50 (2H, s). HRMS [M+H]C19H13FN6O4S2 calc'd 473.0496. Found 473.0499.
Reaction SMILES: [CH3:1][N:2]([CH3:30])[CH2:3][CH2:4][N:5]1[C:11](=[O:12])[C@H:10]([OH:13])[C@H:9]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)[S:8][C:7]2[C:22]([C:26]([O:28][CH3:29])=[O:27])=[CH:23][CH:24]=[CH:25][C:6]1=2.N1C=CC=CC=1.[C:37](Cl)(=[O:39])[CH3:38]>C(Cl)Cl>[C:37]([O:13][C@@H:10]1[C@H:9]([C:14]2[CH:15]=[CH:16][C:17]([O:20][CH3:21])=[CH:18][CH:19]=2)[S:8][C:7]2[C:22]([C:26]([O:28][CH3:29])=[O:27])=[CH:23][CH:24]=[CH:25][C:6]=2[N:5]([CH2:4][CH2:3][N:2]([CH3:1])[CH3:30])[C:11]1=[O:12])(=[O:39])[CH3:38]
Reactant: CC(=O)Cl
Reactant: COC(=O)c1cccc2c1S[C@@H](c1ccc(OC)cc1)[C@@H](O)C(=O)N2CCN(C)C
Solvent: c1ccncc1
Solvent: ClCCl
Product: COC(=O)c1cccc2c1S[C@@H](c1ccc(OC)cc1)[C@@H](OC(C)=O)C(=O)N2CCN(C)C
Temperature: 22 °C
Reaction time: 3 h

Procedure:
To a solution of 19 mg (0.045 mmol) of (+/−)-(2S,3S)-methyl 5-(2-(dimethylamino)ethyl)-3-hydroxy-2-(4-methoxyphenyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]thiazepine-9-carboxylate in 0.5 mL of DCM was added 22 μL (0.27 mmol) of pyridine and 4 μL (0.06 mmol) of acetyl chloride. The reaction was stirred at 22° C. for 3 hours. The reaction mixture was diluted with DCM, washed sequentially with 1 M Na2CO3 and water, dried (Na2SO4), and evaporated. The residue was purified by flash chromatography on silica gel, eluting with DCM then gradually increasing to 3% methanol/DCM to give 1a. MS found M+H=473. The hydrochloride salt of 1a was recrystallized from ethyl acetate; mp 169-172° C.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH:28]=2)=[CH:8][C:9]=1[N:10]([C@H:20]1[CH2:25][CH2:24][C@H:23](O)[CH2:22][CH2:21]1)[C:11]([C@H:13]1[CH2:18][CH2:17][C@H:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12])=[O:4].C(I)(F)F.[H-].[Na+]>CN(C=O)C.C1C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[S:6][C:7]([C:27]2[CH2:32][CH2:31][CH2:30][CH2:29][CH:28]=2)=[CH:8][C:9]=1[N:10]([CH:20]1[CH2:25][CH2:24][CH:23]=[CH:22][CH2:21]1)[C:11]([C@H:13]1[CH2:18][CH2:17][C@H:16]([CH3:19])[CH2:15][CH2:14]1)=[O:12])=[O:4]
Reactant: COC(=O)c1sc(C2=CCCCC2)cc1N(C(=O)[C@H]1CC[C@H](C)CC1)[C@H]1CC[C@H](O)CC1
Agent: FC(F)I
Agent: [H-]
Agent: [Na+]
Solvent: c1ccccc1
Solvent: CN(C)C=O
Product: COC(=O)c1sc(C2=CCCCC2)cc1N(C(=O)[C@H]1CC[C@H](C)CC1)C1CC=CCC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 5-cyclohex-1-enyl-3-[(trans-4-hydroxy-cyclohexyl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester 390 mg, 0.85 mmol) in dry DMF (3 mL) at 0° C. was added 0.34 mL of 10M solution of CHF2I in benzene, followed by NaH (60% suspension in oil, 68 mg, 1.70 mmol), and the mixture was stirred for 2 h allowing to warm up to room temperature. Then it has been transferred into a sealed tube and heated in a microwave oven for 20 min at 120° C. The mixture was treated as described in example 4, and purified by column chromatography on silica gel eluting with 0→50% ethyl acetate in hexane to give 5-cyclohex-1-enyl-3-[cyclohex-3-enyl-(trans-4-methyl-cyclohexanecarbonyl)-amino]-thiophene-2-carboxylic acid methyl ester (132 mg, 35%).
Reaction SMILES: [CH:1]1([NH:7][C@H:8]2[CH2:13][CH2:12][C@H:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH2:10][CH2:9]2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:20][C:21]1[CH:29]=[CH:28][C:24]([C:25](Cl)=[O:26])=[CH:23][CH:22]=1>>[Cl:20][C:21]1[CH:29]=[CH:28][C:24]([C:25]([N:7]([C@H:8]2[CH2:9][CH2:10][C@H:11]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:12][CH2:13]2)[CH:1]2[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]2)=[O:26])=[CH:23][CH:22]=1
Reactant: O=C(Cl)c1ccc(Cl)cc1
Reactant: c1ccc([C@H]2CC[C@H](NC3CCCCC3)CC2)cc1
Product: O=C(c1ccc(Cl)cc1)N(C1CCCCC1)[C@H]1CC[C@H](c2ccccc2)CC1

Procedure:
from trans-N-cyclohexyl-4-phenylcyclohexylamine and 4-chlorobenzoylchloride. Melting point: 164°-166° C.
Reaction SMILES: [OH:1][C:2]1[CH:6]=[CH:5][S:4][C:3]=1[C:7]([O:9][CH3:10])=[O:8].[Br:11]Br.OS([O-])=O.[Na+]>C(O)(=O)C>[Br:11][C:6]1[C:2]([OH:1])=[C:3]([C:7]([O:9][CH3:10])=[O:8])[S:4][CH:5]=1
Reactant: COC(=O)c1sccc1O
Reactant: BrBr
Agent: O=S([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Product: COC(=O)c1scc(Br)c1O
Reaction time: 16 h

Procedure:
To a solution of 31 g (0.2 mole) of methyl 3-hydroxy-2-thiophenecarboxylate in 400 milliliters (mL) of glacial acetic acid was added 31.3 g (0.2 mole) of Br2 over 45 minutes (min). After 16 hours (hr), another 31.3 g of Br2 was added over 6 hr and the reaction was stirred another 18 hr. The reaction mixture was poured into aqueous NaHSO3 and extracted with ether. The organic phase was separated, washed with water (2×300 mL), dried over MgSO4, filtered and concentrated to a viscous oil. This oil (47 g) was dissolved in 200 mL of methanol and after 48 hr at 15° C., 36 g (77%) of light pink crystals were collected by filtration. mp 79-80° C. 1H NMR (300 MHz, CDCl3): δ 9.8 (br, 1H); 7.4 (s, 1H); 3.9 (s, 3H). Anal. Calc'd for C6H5BrO3S: C, 30.04; H, 2.23; S, 13.52. Found: C, 30.04; H, 1.92; S, 14.01.
Reaction SMILES: [F:1][C:2]([F:25])([F:24])[C:3]1[CH:4]=[N:5][C:6]2[CH2:7][CH2:8][N:9]([C:13]([C:15]34[CH2:22][CH2:21][CH2:20][CH:19]3[CH2:18][C:17](=O)[CH2:16]4)=[O:14])[CH2:10][C:11]=2[CH:12]=1.[C:26]1([CH:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[Na].C(O)(=O)C.C(=O)(O)[O-].[Na+]>ClCCCl>[C:26]1([CH:32]2[CH2:33][CH2:34][N:35]([CH:17]3[CH2:16][C:15]4([C:13]([N:9]5[CH2:8][CH2:7][C:6]6[N:5]=[CH:4][C:3]([C:2]([F:25])([F:24])[F:1])=[CH:12][C:11]=6[CH2:10]5)=[O:14])[CH:19]([CH2:20][CH2:21][CH2:22]4)[CH2:18]3)[CH2:36][CH2:37]2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: c1ccc(C2CCNCC2)cc1
Reactant: O=C1CC2CCCC2(C(=O)N2CCc3ncc(C(F)(F)F)cc3C2)C1
Agent: O=C([O-])O
Agent: [Na+]
Agent: [Na]
Solvent: ClCCCl
Solvent: CC(=O)O
Product: O=C(N1CCc2ncc(C(F)(F)F)cc2C1)C12CCCC1CC(N1CCC(c3ccccc3)CC1)C2
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 3a-(3-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-6-carbonyl)hexahydropentalen-2(1H)-one (0.175 g, 0.497 mmol) in DCE (4.3 mL) was added 4-phenylpiperidine (0.080 g, 0.50 mmol). The reaction mixture was stirred at ambient temperature for about 2 h then sodium triacetoxyborohydide (0.158 g, 0.745 mmol) and acetic acid (0.043 mL, 0.74 mmol) were added. The reaction mixture was then stirred at ambient temperature for about 18 h. Saturated aqueous sodium bicarbonate was added to the reaction mixture and the product was extracted into DCM (3×10 mL). The solvent was removed under reduced pressure and the crude material was purified by RP-HPLC to provide [2-(4-phenyl-piperidin-1-yl)-hexahydro-pentalen-3a-yl]-(3-trifluoromethyl-7,8-dihydro-5H-[1,6]naphthyridin-6-yl)-methanone as a mixture of four diastereomers (0.075 g). RP-HPLC (Table A, Method c) Rt 2.05 min; m/z: (M+H)+ 498. In addition, the diastereomers were separated using a two-step chiral HPLC method (Step 1: Diastereomer separation: Isocratic using 85% heptane, 7.5% methanol, 7.5% ethanol with 0.2% diethylamine on a Daicel OD-H column (20×250 mm) at 35 deg C. and 12 mL/min flow rate (UV wavelength monitored=265 nm). Step 2: Enantiomer separation: 10-70% gradient over 19 min of isopropanol in heptane with 0.2% diethylamine on a Daicel AD-H column (20×250 mm) at 35 deg C. and 16 ml/min flow rate (UV wavelength monitored=265 nm)) to provide the four enantiomers—the absolute configuration of each compound was not determined. Isomer 1: RP-HPLC (Table A, Method d) Rt 12.66 min. Isomer 2: RP-HPLC (Table A, Method d) Rt 13.57 min. Isomer 3: RP-HPLC (Table A, Method d) Rt 8.46 min. Isomer 4: RP-HPLC (Table A, Method d) Rt 11.76 min.
Reaction SMILES: [F:1][C:2]1[CH:34]=[CH:33][CH:32]=[CH:31][C:3]=1[CH2:4][NH:5][C:6]1[C:7]([NH2:30])=[N:8][C:9]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[CH:19][CH:20]=3)[N:15]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[F:29])[N:14]=2)=[N:10][C:11]=1[NH2:12].C1N=CN([C:40](N2C=NC=C2)=[O:41])C=1.C(N(CC)CC)C>CN(C)C=O>[NH2:30][C:7]1[N:8]=[C:9]([C:13]2[C:21]3[C:16](=[N:17][CH:18]=[CH:19][CH:20]=3)[N:15]([CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=3[F:29])[N:14]=2)[N:10]=[C:11]2[C:6]=1[N:5]([CH2:4][C:3]1[CH:31]=[CH:32][CH:33]=[CH:34][C:2]=1[F:1])[C:40](=[O:41])[NH:12]2
Reactant: Nc1nc(-c2nn(Cc3ccccc3F)c3ncccc23)nc(N)c1NCc1ccccc1F
Reactant: O=C(n1ccnc1)n1ccnc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Nc1nc(-c2nn(Cc3ccccc3F)c3ncccc23)nc2[nH]c(=O)n(Cc3ccccc3F)c12
Temperature: 100 °C
Reaction time: 8 h

Procedure:
268 mg (0.48 mmol) of the compound from example 66A were initially charged in dimethylformamide (2.6 ml), then 389 mg (2.40 mmol) of N,N-carbonyldiimidazole and 0.80 ml (5.75 mmol) of triethylamine were added and the mixture was stirred at 100° C. overnight. Subsequently, 380 mg (2.34 mmol) of N,N-carbonyldiimidazole were added and the mixture was stirred again at 100° C. overnight. The reaction mixture was purified directly by means of preparative HPLC (eluent: acetonitrile/water with 0.1% formic acid gradient). This gave 130 mg (56% of theory) of the title compound.
Reaction SMILES: [C:1]([O:5][C:6](=[O:31])[NH:7][CH:8]([C:10](=[O:30])[NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([Cl:18])[C:13]=1[C:19](=O)[NH:20][C:21]1[CH:26]=[C:25]([F:27])[CH:24]=[C:23]([F:28])[CH:22]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.II>C(Cl)Cl>[C:1]([O:5][C:6](=[O:31])[NH:7][CH:8]([C:10]1[O:30][C:19](=[N:20][C:21]2[CH:26]=[C:25]([F:27])[CH:24]=[C:23]([F:28])[CH:22]=2)[C:13]2[C:14]([Cl:18])=[CH:15][CH:16]=[CH:17][C:12]=2[N:11]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(NC(=O)OC(C)(C)C)C(=O)Nc1cccc(Cl)c1C(=O)Nc1cc(F)cc(F)c1
Agent: II
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(NC(=O)OC(C)(C)C)c1nc2cccc(Cl)c2c(=Nc2cc(F)cc(F)c2)o1
Temperature: 2.5 °C
Reaction time: 0.5 h
Yield: 52 %

Procedure:
A 100-mL, three-neck, round bottomed flask equipped with a magnetic stirrer and thermometer was purged with nitrogen and charged with compound 168 (3.30 mmol), anhydrous methylene chloride (25 mL), N,N-diisopropylethylamine (4.60 g, 35.7 mmol) and triphenylphosphine (3.98 g, 15.2 mmol). The reaction mixture was then cooled to 0-5° C. in an ice/water bath. Iodine (3.61 g, 14.2 mmol) was then added portion-wise to the reaction mixture over 1 h. Once the addition was complete, the cooling bath was removed, and the mixture was stirred at room temperature for an additional 30 min. The reaction was then quenched with 10% aqueous potassium carbonate (25 mL), the organic layer separated, dried over sodium sulfate, filtered and concentrated under reduced pressure. Column chromatography of the resulting solid (silica gel, EtOAc/hexanes) gave a 52% yield of compound 169 as a white solid. m.p. 117-118° C.; 1H NMR (DMSO-d6) δ (ppm) 7.72-7.60 (m, 2H), 7.42 (dd, 1H, J=7.6 Hz, 1.3 Hz), 7.31 (d, 1H, J=7.0 Hz), 6.95 (t, 1H, J=9.3 Hz), 6.82 (m, 2H), 4.27 (m, 1H), 1.33 (s, 9H), 1.28 (d, 3H, J=7.2 Hz); m/z=436 (M+H). The reaction described above and compound 169 are shown below.
Reaction SMILES: [CH2:1]([C:5]1[N:6]=[C:7]([CH3:34])[N:8]([C:27]2[N:32]=[CH:31][C:30]([OH:33])=[CH:29][N:28]=2)[C:9](=[O:26])[C:10]=1[CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]2[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=2)=[CH:14][CH:13]=1)[CH2:2][CH2:3][CH3:4].C(=O)([O-])[O-].[K+].[K+].I[CH2:42][CH3:43]>C(#N)C>[CH2:1]([C:5]1[N:6]=[C:7]([CH3:34])[N:8]([C:27]2[N:32]=[CH:31][C:30]([O:33][CH2:42][CH3:43])=[CH:29][N:28]=2)[C:9](=[O:26])[C:10]=1[CH2:11][C:12]1[CH:13]=[CH:14][C:15]([C:18]2[C:19]([C:24]#[N:25])=[CH:20][CH:21]=[CH:22][CH:23]=2)=[CH:16][CH:17]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc(C)n(-c2ncc(O)cn2)c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Reactant: CCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCCCc1nc(C)n(-c2ncc(OCC)cn2)c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Temperature: 60 °C
Reaction time: 5 h

Procedure:
Process 1: To the acetonitrile (1 mL) solution of 4′-{[4-butyl-1-(5-hydroxypyrimidin-2-yl)-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl]methyl}biphenyl-2-carbonitrile (68 mg, 0.15 mmol), potassium carbonate (41 mg, 0.30 mmol) and iodoethane (70 mg, 0.448 mmol) were added and stirred at 60° C. for 5 hrs. After that, the reaction mixture was filtered and washed with ethyl acetate. The filtrate was distilled off to obtain 4′-{[4-butyl-1-(5-ethoxypyrimidin-2-yl)-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl]methyl}biphenyl-2-carbonitrile.
Reaction SMILES: Cl[S:2]([CH2:5][C@H:6]([CH3:17])[C:7]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8])(=[O:4])=[O:3].[C:18]([N:25]1[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]1)([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19].CCN(CC)CC>C(Cl)Cl>[C:21]([O:20][C:18]([N:25]1[CH2:30][CH2:29][N:28]([S:2]([CH2:5][C@H:6]([CH3:17])[C:7]([O:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:8])(=[O:4])=[O:3])[CH2:27][CH2:26]1)=[O:19])([CH3:24])([CH3:22])[CH3:23]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: C[C@@H](CS(=O)(=O)Cl)C(=O)OCc1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C[C@@H](CS(=O)(=O)N1CCN(C(=O)OC(C)(C)C)CC1)C(=O)OCc1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 89.8 %

Procedure:
A 100 mL round bottom flask equipped with magnetic stirring bar and N2 inlet was charged with 5.2 g benzyl 3-chlorosulfonyl-2(R)-methylpropionate in 50 mL CH2Cl2. The flask was cooled to 0° C. and charged with 3.5 g N-Boc-piperazine and 2.9 mL (1.1 eq.) NEt3. The reaction was stirred 30 minutes at 0° C., concentrated in vacuo and partitionned between ethyl acetate/water. The combined organics were washed with 5% aqueous. citric acid, saturated aqueous sodium bicarbonate, brine, and concentrated in vacuo to yield a yellow liquid. Purification via flash chromatography on silica gel (30% ethyl acetate/hexane) yielded 7.2 g (90%) product as a clear oil.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([N:10]2[CH:14]=[N:13][CH:12]=[N:11]2)=[C:6]([CH:9]=1)[C:7]#[N:8].[ClH:15]>C(O)C>[ClH:15].[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:10]2[CH:14]=[N:13][CH:12]=[N:11]2)=[C:6]([CH2:7][NH2:8])[CH:9]=1
Reactant: N#Cc1cc(F)ccc1-n1cncn1
Agent: Cl
Solvent: CCO
Product: NCc1cc(F)ccc1-n1cncn1
Reaction time: 6 h
Yield: 98 %

Procedure:
A solution of 5-fluoro-2-(1H-1,2,4-triazol-1-yl)benzonitrile (2.94 g, 15.59 mmol) in ethanol (100 mL) and 1N HCl (50 mL) was degassed by bubbling N2. Then, 10% Pd/C was added, the flask evacuated and vented to H2 three times and left on a Parr shaker under a H2 atmosphere (40 psi). After 6 h, the reaction mixture was filtered, concentrated and the aqueous solution lyophilized to afford the title compound (4.07 g, 98%) as a white powder. LCMS (M+H) calcd for C9H10FN4: 193.09; found: 193.15.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.I[C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=1>>[CH3:18][O:17][C:14]1[CH:15]=[CH:16][C:11]([N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH:3]=[CH:2]2)=[CH:12][CH:13]=1
Reactant: c1ccc2[nH]ccc2c1
Reactant: COc1ccc(I)cc1
Product: COc1ccc(-n2ccc3ccccc32)cc1

Procedure:
Prepared by Procedure C and Scheme O using 1H-indole and 1-iodo-4-methoxybenzene: ESMS m/e: 224.0 (M+H)+.
Reaction SMILES: [C:1]([O:5][CH3:6])(=[O:4])[CH2:2][SH:3].ClC[C:9]1[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=1[C:11]([NH2:13])=[O:12].[CH3:18]COC(C)=O.C(Cl)Cl.[K+].[Br-]>C1(C)C=CC=CC=1>[CH3:6][O:5][C:1](=[O:4])[CH2:2][S:3][CH2:18][NH:13][C:11](=[O:12])[C:10]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:9]=1
Reactant: NC(=O)c1ccccc1CCl
Reactant: CCOC(C)=O
Reactant: COC(=O)CS
Agent: [Br-]
Agent: [K+]
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: COC(=O)CSCNC(=O)c1ccccc1

Procedure:
Methyl thioglycolate (2 g, 18.84 mmol) and chloromethylbenzamide (3.2 g, 18.84 mmol) was dissolved in 60 ml of dry toluene, and the clear solution was stirred for 18 hours at 25° C. under nitrogen at which time a TLC (10% EtOAc/CH2Cl2) showed that the reaction was complete. Solid materials were removed by filtration and the toluene was evaporated to give a pale yellow oil. Purification on silica gel (10% EtOAc/CH2Cl2) yielded a colorless oil that solidified on standing: mp 65°-68° C.; IR (KBr) 3280, 1730, 1620 cm-1 ; NMR (CDCl3) δ7.98-7.25 (m, 5, aryl), 4.77 (d, 2, --SCH2NH--), 3.77 (s, 3, --OCH3), 3.43 (s, 2, --SCH2C=O).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11](=[O:14])[NH:12][N:13]=2)=[CH:4][CH:3]=1.[CH:15]([NH:17][NH:18][CH:19]=O)=O>>[N:17]1[N:18]=[CH:19][N:1]([C:2]2[CH:7]=[CH:6][C:5]([C:8]3[CH2:9][CH2:10][C:11](=[O:14])[NH:12][N:13]=3)=[CH:4][CH:3]=2)[CH:15]=1
Reactant: O=CNNC=O
Reactant: Nc1ccc(-c2ccc(=O)[nH]n2)cc1
Product: O=C1CCC(c2ccc(-n3cnnc3)cc2)=NN1
Temperature: 220 °C

Procedure:
A mixture of 6-(4-aminophenyl)-3(2H)-pyridazinone (3.78 g, 0.02 mol) and diformylhydrazine (1.76, 0.02 mol) are heated together at 220° C. for six hours. The solid mass is chromatographed and finally crystallized from acetonitrile/methanol to yield the product 4,5-dihydro-6-[4-(4H-1,2,4-triazol-4-yl)phenyl]-3(2H)-pyridazinone, mp 292.5°-293° C. (dec).
Reaction SMILES: ClCCl.C(O)(=O)C.[CH2:8]([O:15][C@H:16]1[C@H:25]([O:26][C:27](=[O:29])[CH3:28])[C@@H:24]([CH2:30][O:31]C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[O:23][CH:18]([O:19][C:20](=[O:22])[CH3:21])[C@@H:17]1[O:51][C:52](=[O:54])[CH3:53])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>O>[CH2:8]([O:15][C@H:16]1[C@H:25]([O:26][C:27](=[O:29])[CH3:28])[C@@H:24]([CH2:30][OH:31])[O:23][CH:18]([O:19][C:20](=[O:22])[CH3:21])[C@@H:17]1[O:51][C:52](=[O:54])[CH3:53])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: CC(=O)OC1O[C@H](COC(c2ccccc2)(c2ccccc2)c2ccccc2)[C@@H](OC(C)=O)[C@H](OCc2ccccc2)[C@H]1OC(C)=O
Solvent: O
Solvent: ClCCl
Solvent: CC(=O)O
Product: CC(=O)OC1O[C@H](CO)[C@@H](OC(C)=O)[C@H](OCc2ccccc2)[C@H]1OC(C)=O

Procedure:
A solution of crude 17 in the minimum amount of dichloromethane was stirred at room temperature with aqueous 80% acetic acid (100 mL) until TLC demonstrated the disappearance of 17. Water was then added with stirring; the solid was removed and the filtrate was concentrated. The crude 3-O-benzyl-1,2,4-tri-O-acetyl-D-glucopyranose (18) was thus obtained; 1H NMR data: 60:40 mixture of anomers 6.32 (d, 1 H, alpha-H), 5.64 (d, 1 H, beta-H). A solution of the crude residue 18 in acetone was cooled to -5° C. and a solution of chromium trioxide in 3.5M sulfuric acid was added dropwise with stirring. The mixture was allowed to attain room temperature, and, after 5 hours at room temperature, was poured into ice-cold water and extracted with chloroform. The extract was washed with water and concentrated, and a solution of the crude methyl ester of 3-O-benzyl-1,2,4-tri-O-acetyl-D-glucopyranosuronic acid (19) in ether was esterified with ethereal diazomethane. The product was eluted from a column of silica gel with chloroform-ethyl acetate (20:10) to give 19 (54%). 1H NMR date: mixture of anomers alpha:beta=60:40; 7.23-7.36 (m, 5 H, arom.), 6.38 (d, 1 H, alpha-H), 5.69 (d, 1 H, beta-H), 3.72 (s, 3 H, alpha-COOMe), 3.71 (s, 3 H, beta-COOMe), 1.96-2.16 (9 H, Ac).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9](=[O:11])[CH3:10])=[CH:4][CH:3]=1.[Br:12]N1C(=O)CCC1=O.N(C(C)(C)C#N)=NC(C)(C)C#N>C(Cl)(Cl)(Cl)Cl>[Br:12][CH:8]([C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=1)[C:9](=[O:11])[CH3:10]
Reactant: CC(=O)Cc1ccc(Br)cc1
Reactant: O=C1CCC(=O)N1Br
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Product: CC(=O)C(Br)c1ccc(Br)cc1
Temperature: 80 °C
Yield: 27.4 %

Procedure:
A solution of 1-(4-bromophenyl)propan-2-one (1.173 mmol) in carbon tetrachloride (2.5 mL) was degassed with a stream of nitrogen for five minutes, at which point the solution was treated with N-bromosuccinimide (1.291 mmol) and azobisisobutyronitrile (0.059 mmol). The reaction vessel was purged with nitrogen and sealed, and the mixture was heated overnight at 80° C. with stirring. The resulting orange solution was concentrated to dryness in vacuo. Purification of the crude material by silica gel chromatography (0-35% ethyl acetate/hexanes) afforded the title compound (94 mg, 19%). 1H NMR (400 MHz, DMSO-d6) d ppm 2.27 (s, 3 H) 6.12 (s, 1 H) 7.39 (m, J=8.59 Hz, 2 H) 7.62 (d, J=8.59 Hz, 2 H).
Reaction SMILES: C(P(CC[CH2:12][CH3:13])CCCC)CCC.ClCCCl.[Cl:18][SiH:19]([Cl:21])[Cl:20]>>[Cl:18][Si:19]([Cl:21])([Cl:20])[CH2:12][CH2:13][Si:19]([Cl:21])([Cl:20])[Cl:18]
Reactant: Cl[SiH](Cl)Cl
Reactant: CCCCP(CCCC)CCCC
Solvent: ClCCCl
Product: Cl[Si](Cl)(Cl)CC[Si](Cl)(Cl)Cl
Yield: 336.8 %

Procedure:
In the same apparatus and procedure as Example 1 above, 0.30 g (1.5 mmol) of tri-n-butylphosphine, 0.74 g (7.5 mmol) of 1,2-dichloroethane, and 10.2 g (75.0 mmol) of trichlorosilane were reacted at 150° C. for 12 hrs. The resulting mixture was distilled to give 1.5 g of 1,2-bis(trichlorosilyl)ethane (bp; 201° C., yield; 67%) and 0.1 g of 2-(chloroethyl)trichlorosilane (bp; 152-3° C., yield; 5%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][CH:10]2[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]2)=[CH:5][CH:4]=1.[CH3:23][O:24][C:25]1[CH:26]=[C:27]([C:35]2[CH:36]=[C:37]([CH:41]=[CH:42][CH:43]=2)[C:38](O)=[O:39])[CH:28]=[C:29]([O:33][CH3:34])[C:30]=1[O:31][CH3:32]>>[C:19]([O:18][C:16]([N:13]1[CH2:14][CH2:15][CH:10]([N:9]([C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)[C:38](=[O:39])[C:37]2[CH:41]=[CH:42][CH:43]=[C:35]([C:27]3[CH:26]=[C:25]([O:24][CH3:23])[C:30]([O:31][CH3:32])=[C:29]([O:33][CH3:34])[CH:28]=3)[CH:36]=2)[CH2:11][CH2:12]1)=[O:17])([CH3:22])([CH3:21])[CH3:20]
Reactant: COc1ccc(NC2CCN(C(=O)OC(C)(C)C)CC2)cc1
Reactant: COc1cc(-c2cccc(C(=O)O)c2)cc(OC)c1OC
Product: COc1ccc(N(C(=O)c2cccc(-c3cc(OC)c(OC)c(OC)c3)c2)C2CCN(C(=O)OC(C)(C)C)CC2)cc1

Procedure:
4-(p-Anisidino)-1-(tert-butoxycarbonyl)piperidine (613 mg) and 3-(3,4,5-trimethoxyphenyl)benzoic acid (577 mg) were condensed in the same manner as described in Example 1 to give the title compound.