Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([N:7]([C:21]2[CH:26]=[CH:25][C:24](B3OC(C)(C)C(C)(C)O3)=[CH:23][CH:22]=2)[C:8]2[C:13]3[S:14][C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=4[C:12]=3[CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[K+].[K+].[C:42]1([CH3:48])[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>O.CCO.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>[CH:46]1[C:47]2[NH:7][C:1]3[C:48](=[CH:5][CH:4]=[CH:3][CH:2]=3)[C:42]=2[CH:43]=[C:44]([C:24]2[CH:23]=[CH:22][C:21]([N:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[C:8]3[C:13]4[S:14][C:15]5[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=5[C:12]=4[CH:11]=[CH:10][CH:9]=3)=[CH:26][CH:25]=2)[CH:45]=1
Reactant: Cc1ccccc1
Reactant: CC1(C)OB(c2ccc(N(c3ccccc3)c3cccc4c3sc3ccccc34)cc2)OC1(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCO
Product: c1ccc(N(c2ccc(-c3ccc4[nH]c5ccccc5c4c3)cc2)c2cccc3c2sc2ccccc23)cc1
Yield: 91 %

Procedure:
To a solution of N-phenyl-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)dibenzo[b,d]thiophen-4-amine (5.9 g, 12.4 mmol), 3-bromocabazole (3.5 g, 14.2 mmol), K2CO3 (16.6 g, 120.0 mmol) in toluene (150 mL), water (50 mL) and EtOH (50 mL) was bubbled for 30 min. Pd(PPh3)4 (0.4 g, 0.4 mmol) was added. The mixture was bubbled for 15 min. The resultant mixture was refluxed for 12 h. After cooling, the reaction mixture was extracted by CH2Cl2 and dried by MgSO4. The solvent was removed in vacuo and the residue was purified by flash chromatography using 25-50% CH2Cl2/hexane to afford N-(4-(9H-carbazol-3-yl)phenyl)-N-phenyldibenzo[b,d]thiophen-4-amine (5.8 g, 91% yield) as a white solid.
Reaction SMILES: [NH2:1][C:2]([CH3:12])=[CH:3][C:4](=[O:11])[CH2:5][S:6]([NH:9][CH3:10])(=[O:8])=[O:7].[CH2:13](Br)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[NH2:1][C:2]([CH3:12])=[CH:3][C:4](=[O:11])[CH2:5][S:6]([N:9]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH3:10])(=[O:7])=[O:8]
Reactant: BrCc1ccccc1
Reactant: CNS(=O)(=O)CC(=O)C=C(C)N
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(N)=CC(=O)CS(=O)(=O)N(C)Cc1ccccc1
Temperature: 25 °C
Reaction time: 9 h

Procedure:
In accordance with the procedure described in Example 7, a solution of 3.8 g of 4-amino-N-methyl-2-oxo-3-pentenesulfonamide and 3.6 ml of benzyl bromide in 50 ml of dimethylformamide was treated with 6 g of potassium carbonate and the mixture was stirred intensively at room temperature for 9 hours. The product was firstly chromatographed on 300 g of silica gel with ethyl acetate as the elution agent and then recrystallized from isopropanol. There were obtained 3.4 g of 4-amino-N-benzyl-N-methyl-2-oxo-3-pentenesulfonamide in the form of colorless crystals, m.p. 115°-118°.
Reaction SMILES: [C:1]([NH:5][NH:6][C:7]([C:12]#[N:13])([CH:9]1[CH2:11][CH2:10]1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].C(Cl)Cl.BrBr>O>[C:1]([N:5]=[N:6][C:7]([C:12]#[N:13])([CH:9]1[CH2:10][CH2:11]1)[CH3:8])([CH3:2])([CH3:3])[CH3:4]
Reactant: CC(C)(C)NNC(C)(C#N)C1CC1
Agent: BrBr
Solvent: O
Solvent: ClCCl
Product: CC(C)(C)N=NC(C)(C#N)C1CC1
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 81.9 %

Procedure:
To a mixture of 10.0g (.055 m.) of crude 1-t-butylhydrazo-1-cyano-1-cyclopropylethane, 100 ml methylene chloride, and 50 ml water, cooled to 0°C in an ice bath, was added 8.75 g (.055 m.) of bromine dropwise over 15 minutes holding the temperature at 0° to 5°C. After the bromine addition, the reaction was stirred 10 minutes, the methylene chloride layer separated, washed twice with saturated sodium bicarbonate solution, dried over anhydrous sodium sulfate, filtered and the methylene chloride evaporated off. The yield was 8.9g (90%) of a brown liquid. The liquid was chromatographed over an alumina column, eluting it with pentane, to give 8.1g of a light tan liquid which solidifies in the freezer. The infrared spectrum was consistent with the structure of the proposed compound. The product is a thermally sensitive free radical and gas generating compound. The compound has a 10 hour half-life in trichlorobenzene at 62°C.
Reaction SMILES: C(O[C@H:5]1[O:22][C@H:21]([CH2:23][O:24][C:25](=[O:27])[CH3:26])[C@@H:16]([O:17][C:18](=[O:20])[CH3:19])[C@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:6]1[O:7][C:8](=[O:10])[CH3:9])(=O)C.C[Si]([N:32]=[N+:33]=[N-:34])(C)C.[Sn](Cl)(Cl)(Cl)Cl>C(Cl)Cl>[C:8]([O:7][C@@H:6]1[C@@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:16]([O:17][C:18](=[O:20])[CH3:19])[C@@H:21]([CH2:23][O:24][C:25](=[O:27])[CH3:26])[O:22][C@@H:5]1[N:32]=[N+:33]=[N-:34])(=[O:10])[CH3:9]
Reactant: C[Si](C)(C)N=[N+]=[N-]
Reactant: CC(=O)OC[C@H]1O[C@H](OC(C)=O)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: Cl[Sn](Cl)(Cl)Cl
Solvent: ClCCl
Product: CC(=O)OC[C@H]1O[C@H](N=[N+]=[N-])[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 25 °C
Reaction time: 18 h
Yield: 82 %

Procedure:
1,2,3,4,6-Penta-O-acetyl-α-D-glucopyranose (5.00 g, 12.8 mmol) was dissolved in 10-15 mL dry CH2Cl2 under an inert atmosphere. Trimethylsilyl azide (4.24 mL, 32.1 mmol) and tin (IV) chloride (0.75 mL, 6.41 mmol) were added, and the reaction was stirred for 18 hours at room temperature. The reaction mixture was diluted with CH2Cl2 (30 mL) and washed twice with saturated NaHCO3 (20 mL) and with brine (20 mL). The organic phase was dried, filtered and concentrated to leave 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl azide as a white solid (3.92 g, 82%). 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl azide (0.30 g, 80 mmol) was then dissolved in dry THF (115 mL), and Pd/C was added (˜5%) to this solution. The mixture was stirred under H2 overnight. TLC revealed the reduction was completed (Rfazide=0.80, Rfamine=0.10). In a separate flask, compound 23 (0.17 g, 0.30 mmol) and 0.5 M HBTU in DMF (1.20 mL, 0.60 mmol) were combined, followed by the addition of DMF (˜2 mL) and DIEA (104 μL, 0.60 mmol). This solution was then added to the reaction flask, and the reaction mixture was stirred under N2 overnight. The resulting suspension was filtered through celite which was washed well with ethyl acetate (˜100 mL), and the filtrate was washed with 5 M HCl (50 mL), saturated NaHCO3 (2×50 mL), and brine (1×50 mL). The organic solution was dried over magnesium sulfate, filtered, and concentrated. The residue was purified using a silica gel column chromatography with 10% MeOH/DCM to yield V (0.16 g, 59.33). 1H NMR δ (CDCl3) 0.78 (3H, t, J=7 Hz), 1.16-1.23 (32H, brm), 1.35 (2H, m) 1.52 (2H, m) 1.57 (6H, brs), 1.86 (6H, brs), 1.91-2.00 (15H, m), 2.14 (2H, m), 2.99 (2H, t, J=7 Hz), 3.75 (2H, m), 3.95-4.07 (3H, m), 4.15-4.29 (4H, m), 4.43-4.38 (1H, m) 4.80 (1H, dd, J=5, 11 Hz), 4.84-4.89 (2H, m), 4.95-5.02 (3H, m), 5.12-5.24 (3H, m), 5.35 (1H, d, J=3 Hz), 5.47 (11H, t, J=9.8 Hz), 6.28 (1H, dd, J=7.6, 19 Hz), 6.60 (11H, d, J=9.3 Hz), 7.18 (1H, d, J=9.1 Hz), 7.34 (1H, d, J=9.1 Hz). LC-MS (ESI) m/z calcd for C47H78N4O12 [M+H]+ 891.56, found [M+H]+ 891.69.
Reaction SMILES: [O:1]1[CH2:3][C@H:2]1[CH2:4][O:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:11]2[C:7]=1[CH:8]=[CH:9][NH:10]2.[F:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[CH:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1.[C:28]([OH:33])(=[O:32])[C:29]([OH:31])=[O:30].CO>C(OCC)(=O)C>[C:28]([OH:33])(=[O:32])[C:29]([OH:31])=[O:30].[NH:10]1[C:11]2[C:7](=[C:6]([O:5][CH2:4][C@@H:2]([OH:1])[CH2:3][N:25]3[CH2:26][CH2:27][CH:22]([C:17]4[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=4[F:15])[CH2:23][CH2:24]3)[CH:14]=[CH:13][CH:12]=2)[CH:8]=[CH:9]1
Reactant: Fc1ccccc1C1CCNCC1
Reactant: c1cc(OC[C@@H]2CO2)c2cc[nH]c2c1
Agent: O=C(O)C(=O)O
Solvent: CO
Solvent: CCOC(C)=O
Product: O[C@H](COc1cccc2[nH]ccc12)CN1CCC(c2ccccc2F)CC1

Procedure:
The title compound was prepared in similar fashion from (S)-(+)-4-(oxiranylmethoxy)-1H-indole and 4-(2-fluorophenyl)piperidine. The resulting free base was dissolved in ethyl acetate, and precipitated with one equivalent of oxalic acid in ethyl acetate in 40% overall yield. FDMS m/e=368 (M+ of free base). α[D]589 =-12.31 (c=0.61, methanol).
Reaction SMILES: Br[C:2]1[Se:3][CH:4]=[CH:5][CH:6]=1.[F:7][C:8]1[C:13]([F:14])=[C:12](B(O)O)[CH:11]=[CH:10][C:9]=1[C:18]1[CH:23]=[CH:22][C:21]([CH2:24][CH3:25])=[CH:20][CH:19]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.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>[CH2:24]([C:21]1[CH:22]=[CH:23][C:18]([C:9]2[CH:10]=[CH:11][C:12]([C:2]3[Se:3][CH:4]=[CH:5][CH:6]=3)=[C:13]([F:14])[C:8]=2[F:7])=[CH:19][CH:20]=1)[CH3:25]
Reactant: CCc1ccc(-c2ccc(B(O)O)c(F)c2F)cc1
Reactant: Brc1ccc[se]1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: CCc1ccc(-c2ccc(-c3ccc[se]3)c(F)c2F)cc1

Procedure:
A mixture of 56.0 g (0.27 mol) of 2-bromoselenophene, 70.0 g (0.27 mol) of 2,3-difluoro-4′-ethylbiphenyl-4-ylboronic acid, 22.0 g (19.0 mmol) of tetrakis(triphenylphosphine)palladium(0) and 800 ml of 2 N sodium carbonate soln. in 2.5 l of toluene/ethanol (1:1) is heated at 90° C. for 17 h. After cooling, the organic phase is separated off, and the aqueous phase is extracted with toluene. The combined organic phases are washed with water, and the solution is dried using sodium sulfate. The solution is concentrated to dryness, and the residue is purified by column chromatography (SiO2, toluene). The further purification is carried out by recrystallisation from ethanol and n-heptane. 2-(4′-Ethyl-2,3-difluorobiphenyl-4-yl)-selenophene is obtained as a yellowish solid.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O.[C:32]([O:36][C:37](=[O:50])[NH:38][C:39]1[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[C:42]([OH:49])=[CH:41][CH:40]=1)([CH3:35])([CH3:34])[CH3:33].[O:51]1[CH2:56][CH2:55][CH:54](O)[CH2:53][CH2:52]1>C1COCC1>[C:32]([O:36][C:37](=[O:50])[NH:38][C:39]1[C:48]2[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=2)[C:42]([O:49][CH:54]2[CH2:55][CH2:56][O:51][CH2:52][CH2:53]2)=[CH:41][CH:40]=1)([CH3:35])([CH3:33])[CH3:34]
Reactant: OC1CCOCC1
Reactant: CC(C)(C)OC(=O)Nc1ccc(O)c2ccccc12
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)Nc1ccc(OC2CCOCC2)c2ccccc12
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 55 %

Procedure:
Triphenylphosphine (2.8 g, 10.8 mmol) was dissolved in THF (5 mL) and cooled to 0° C. To this colorless solution diethylazodicarboxylate (1.9 grams, 10.8 mmol) was added dropwise to afford an orange solution. After 15 min at 0° C., a copious precipitate had formed. 4-Hydroxy-naphthalen-1-yl-carbamic acid tert-butyl ester (934 mg, 3.6 mmol) and tetrahydro-4H-pyran-4-ol (552 mg, 5.4 mmol) were then added in one portion as a solution in 2 mL of THF. The purple suspension was stirred at 0° C. for one h then at room temperature for 48 h. The solvent was then evaporated and chromatographed on silica gel (40% EtOAc-hexanes) to provide 680 mg (55%) of [4-(tetrahydro-pyran-4-yloxy)-naphthalen-1-yl]-carbamic acid tert-butyl ester as a purple solid.
Reaction SMILES: [C:1]([NH:3][C:4](=[O:25])[CH:5]([O:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=2)=[CH:10][CH:9]=1)[CH3:6])#[N:2].[C:26](=O)([O-])[O-].[K+].[K+].CI>CC(CC)=O>[C:1]([N:3]([CH3:26])[C:4](=[O:25])[CH:5]([O:7][C:8]1[CH:9]=[CH:10][C:11]([O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=2)=[CH:12][CH:13]=1)[CH3:6])#[N:2]
Reactant: O=C([O-])[O-]
Reactant: CC(Oc1ccc(Oc2ccc(C(F)(F)F)cc2)cc1)C(=O)NC#N
Agent: [K+]
Solvent: CCC(C)=O
Solvent: CI
Product: CC(Oc1ccc(Oc2ccc(C(F)(F)F)cc2)cc1)C(=O)N(C)C#N
Reaction time: 2 h
Yield: 59.8 %

Procedure:
17.5 g (0.05 mole) of 2-[4-(4-trifluoromethylphenoxy)phenoxy]propionic acid N-cyanamide are dissolved in 60 ml of methylethyl ketone and with 7.6 g (0.055 mole) of potassium carbonate heated for 30 minutes to reflux. Then 3.6 ml (0.057 mole) of methyl iodide are added at 30° C. to the colourless suspension and the mixture is stirred for two hours at the same temperature. The reaction mixture is then filtered and the filtrate is concentrated by evaporation. The oily residue is chromatographed through silica gel eluted with petroleum ether/ethyl acetate (3:1) and the main fraction is concentrated by evaporation, affording 10.9 g (59.9% of theory) of 2-[4-(4-trifluoromethylphenoxy)phenoxy]propionic acid N-cyano-N-methylamide as a clear, colourless oil with a refractive index of nD23 =1.5228.
Reaction SMILES: [CH2:1]([CH:8]1[C:14](=[O:15])[N:13]2[CH:9]1[CH2:10][CH:11]=[C:12]2[C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:26]([SH:28])[CH3:27].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[CH2:1]([CH:8]1[C:14](=[O:15])[N:13]2[CH:9]1[CH2:10][CH:11]([S:28][CH2:26][CH3:27])[CH:12]2[C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(OCc1ccccc1)C1=CCC2C(Cc3ccccc3)C(=O)N12
Reactant: CCS
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCSC1CC2C(Cc3ccccc3)C(=O)N2C1C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
Benzyl 6-benzyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (138) (0.420 g) was dissolved in dry dimethylformamide (5 ml) and treated with ethanethiol (0.12 ml) and potassium carbonate (0.087 g). It was stirred at ambient temperature for 1 hour and the solvent was then distilled off under high vacuum. The residue was partitioned between ethyl acetate and brine, and the ethyl acetate solution was dried over sodium sulphate and concentrated. The residue was carefully chromatographed on a column of silica gel 60 (<230 mesh) eluting with ethyl acetate/60°-80° petroleum ether 3:7 to give three diastereoisomers of benzyl 6-benzyl-3-ethylthio-7-oxo-1-azabicyclo[3.2.0]heptane-2-carboxylate as gums. The first compound in increasing order of polarity was the 2α, 3α-isomer (139) (0.054 g); νmax (CHCl3) 2950, 1765 and 1745 sh; τ(CDCl3) 2.6-2.9 (10H, m, phenyls), 4.86(2H, s, OCH2), 5.59(1H, d J 5 Hz, C2-H), 6.1-6.5(2H, m, C3-H and C5-H), 6.6-7.2(3H, m, C6-H, C8-H2), 7.50(2H, q J7 Hz, SCH2), 7.55 (1H, dt J14 and 7 Hz, C4-H), 8.41(1H, dt J14 and 7 Hz, C4-H) and 8.84(3H, t J7 Hz, CH3); (M+ at m/e 395.1554. C23H25NO3S requires 395.1553). Next was the 2α, 3β-isomer (98 ) (0.260 g); νmax (CHCl3) 2960, 1765 and 1750 sh cm-1 ; τ(CDCl3) 2.6-2.9 (10H m, phenyls), 4.87 (2H, s, OCH2), 5.26(1H, d, J7 Hz, C2-H), 6.10(1H, td, J51/2& 21/2 Hz, C5-H), 6.52(1H, td J9 and 7 Hz, C3-H), 6.7-7.2(3H, m, C6-H, C8-H2), 7.47(2H, q, J7 Hz, SCH2), 7.89 (2H, dd J9 and 51/2 Hz, C4-H2) and 8.85(3H, t J7 Hz, CH3); (M+ at m/e 395.1553. C23H25NO3S requires 395.1553). Lastly was obtained the 2β, 3α-isomer (140) (0.112 g); νmax (CHCl3) 2960, 1770 and 1745 cm-1 ; τ(CDCl3) 2.6-2.9(10H, m, phenyls), 4.82(2H, s, OCH2), 5.94(1H, d J8 Hz, C2-H), 6.2-7.2(5H, m, C3-H, C5-H, C6-H and C8-H2), 7.51(2H, d J7 Hz, SCH2), 7.83(1H, dt J12 and 6 Hz, C4-H), 8.10(1H, td J12 and 9 Hz, C4-H) and 8.86(3H, t J7 Hz, CH3); (M+ at m/e 394.1560. C23H25NO3S requires 395.1553).
Reaction SMILES: [OH:1][CH:2]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:16]=[C:15]([C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:18]=3[C:28]([F:31])([F:30])[F:29])[O:14][N:13]=2)=[CH:8][CH:7]=1)[C:3]([OH:5])=O.CN1CCOCC1.[N:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1[CH2:45][NH2:46].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CN(C=O)C>[OH:1][CH:2]([C:6]1[CH:7]=[CH:8][C:9]([C:12]2[N:16]=[C:15]([C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)[C:18]=3[C:28]([F:31])([F:30])[F:29])[O:14][N:13]=2)=[CH:10][CH:11]=1)[C:3]([NH:46][CH2:45][C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][N:39]=1)=[O:5]
Reactant: NCc1ccccn1
Reactant: O=C(O)C(O)c1ccc(-c2noc(-c3onc(-c4ccccc4)c3C(F)(F)F)n2)cc1
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN1CCOCC1
Solvent: CN(C)C=O
Product: O=C(NCc1ccccn1)C(O)c1ccc(-c2noc(-c3onc(-c4ccccc4)c3C(F)(F)F)n2)cc1
Reaction time: 8 h
Yield: 41.3 %

Procedure:
(R/S)-2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-V, 20 mg, 0.046 mmol) was dissolved in DMF (1 mL) prior to the addition of 4-methylmorpholine (0.031 mL, 0.278 mmol), pyridin-2-ylmethanamine (9.03 mg, 0.083 mmol), and BOP (36.9 mg, 0.083 mmol). This was stirred overnight and was then purified via preparative LCMS with the following conditions: Column: Waters XBridge C18, 19×250 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: 5:95 methanol:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 methanol:water with 10-mM ammonium acetate; Gradient: 50-100% B over 25 minutes, then a 5-minute hold at 100% B; Flow rate=20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to give (R/S)-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)-N-(pyridin-2-ylmethyl)acetamide (9.9 mg, 0.019 mmol, 40.5% yield): LCMS=522.0 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.47 (1H, dd, J=5.40, 1.88 Hz), 8.11-8.23 (2 H, m), 7.62-7.77 (5 H, m), 7.48-7.61 (3 H, m), 7.21-7.32 (2 H, m), 5.20 (1 H, s), 4.44-4.62 (2 H, m); Analytical LCMS: column: Mac-mod Halo C18, 4.6×50 mm, 2.7-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 0.05% TFA; Mobile Phase B: 90:10 acetonitrile:water with 0.05% TFA; Temperature: 45° C.; Gradient: 0-100% B over 4 minutes, flow rate=4 mL/min, product retention=2.1 min.
Reaction SMILES: I[C:2]1[CH:3]=[C:4]([CH3:9])[CH:5]=[C:6]([CH3:8])[CH:7]=1.[C:10]1([SH:16])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C([O-])([O-])=O.[K+].[K+].C(O)CO>[Cu]I.CC(O)C>[C:10]1([S:16][C:2]2[CH:3]=[C:4]([CH3:9])[CH:5]=[C:6]([CH3:8])[CH:7]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: Cc1cc(C)cc(I)c1
Reactant: Sc1ccccc1
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)O
Solvent: OCCO
Product: Cc1cc(C)cc(Sc2ccccc2)c1
Yield: 91.4 %

Procedure:
The general procedure in example 39 was followed. 5-Iodo-m-Xylene (144 μL, 1.0 mmol), thiophenol (103 μL, 1.0 mmol), CuI (10 mg, 0.05 mmol), K2CO3 (276 mg, 2.0 mmol), ethylene glycol (111 μL, 2.0 mmol) and 2-Propanol (1.0 mL) were used to obtain the 3,5-dimethylphenyl phenyl sulfide (196 mg, 92% yield) as colorless liquid. Column chromatography solvent (hexane). Rf=0.5 (hexane). 1H NMR (CDCl3, 300 MHz) δ 7.19-7.29 (m, 5 H), 6.97 (s, 2 H), 6.87 (s, 1 H). MS (EI) m/z (relative intensity) 214 (100), 137 (30).
Reaction SMILES: [NH2:1][C:2]1([C:23]([NH2:25])=[O:24])[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][CH2:10][CH2:11][C:12]([C:14]2[CH:19]=[C:18]([Cl:20])[CH:17]=[CH:16][C:15]=2[O:21][CH3:22])=[O:13])[CH2:4][CH2:3]1.[C:26](N1C=CN=C1)(N1C=CN=C1)=[S:27].CN(C=O)C>O>[Cl:20][C:18]1[CH:17]=[CH:16][C:15]([O:21][CH3:22])=[C:14]([C:12](=[O:13])[CH2:11][CH2:10][CH2:9][CH2:8][N:5]2[CH2:4][CH2:3][C:2]3([NH:1][C:26](=[S:27])[NH:25][C:23]3=[O:24])[CH2:7][CH2:6]2)[CH:19]=1
Reactant: COc1ccc(Cl)cc1C(=O)CCCCN1CCC(N)(C(N)=O)CC1
Reactant: S=C(n1ccnc1)n1ccnc1
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc(Cl)cc1C(=O)CCCCN1CCC2(CC1)NC(=S)NC2=O
Yield: 29 %

Procedure:
A mixture of 4-amino-1-[5-(5-chloro-2-methoxyphenyl)-5-oxopentyl]-piperidine-4-carboxamide (0.36 g, 1 mmol), prepared as in Example 21, 1,1'-thiocarbonyldiimidazole (0.23 g, 1.3 mmol), and DMF (3 mL) was heated 5 hours at 50°-60° C. and then diluted with water. The mixture was extracted with ethyl acetate and the extract was dried (MgSO4) and concentrated. The residue was purified by column chromatography eluting with methylene chloride/methanol+ammonium hydroxide (95:5) to give 8-[5-(5-chloro-2-methoxyphenyl)-5-oxopentyl]-2-thioxo-1,3,8-triazaspiro[4.5]decane-4-one (0.12 g, 0.29 mmol), m.p. 152°-154° C. (dec).
Reaction SMILES: CC1N=CC=CC=1C(N)=O.[C:11]([C:15]1[N:20]=[C:19]([Cl:21])[C:18]([CH:22]([NH2:24])[CH3:23])=[CH:17][CH:16]=1)([CH3:14])([CH3:13])[CH3:12].[C:25]([C:27]1[C:32]2[N:33]([CH2:36][C:37](O)=[O:38])[CH:34]=[N:35][C:31]=2[CH:30]=[CH:29][CH:28]=1)#[N:26].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>>[C:11]([C:15]1[N:20]=[C:19]([Cl:21])[C:18]([CH:22]([NH:24][C:37](=[O:38])[CH2:36][N:33]2[C:32]3[C:27]([C:25]#[N:26])=[CH:28][CH:29]=[CH:30][C:31]=3[N:35]=[CH:34]2)[CH3:23])=[CH:17][CH:16]=1)([CH3:14])([CH3:12])[CH3:13]
Reactant: CC(N)c1ccc(C(C)(C)C)nc1Cl
Reactant: N#Cc1cccc2ncn(CC(=O)O)c12
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cc1ncccc1C(N)=O
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Product: CC(NC(=O)Cn1cnc2cccc(C#N)c21)c1ccc(C(C)(C)C)nc1Cl

Procedure:
The title compound was synthesized according to the procedure described for the synthesis of 2-methylnicotinamide, starting from [1-(6-tert-butyl-2-chloropyridin-3-yl)ethyl]amine (intermediate 26) (100 mg, 0.47 mmol), 7-cyanobenzimidazole-1-acetic acid (0.42 mmol), HATU (191 mg, 0.5 mmol) and DIPEA (182 μL, 1.41 mmol). The product was recovered by filtration following precipitation induced by the addition of water. Yield 111 mg, 67%. 1H NMR (400 MHz, DMSO-D6) δ ppm 1.27 (s, 9 H), 1.38 (d, J=7.03 Hz, 3 H), 5.05-5.13 (m, 1 H), 5.21-5.32 (m, 2 H), 7.34 (dd, J=8.01, 7.62 Hz, 1 H), 7.43 (d, J=8.01 Hz, 1 H), 7.71 (dd, J=7.62, 0.98 Hz, 1 H), 7.86 (d, J=8.01 Hz, 1 H), 8.01 (dd, J=8.01, 0.98 Hz, 1 H), 8.34 (s, 1 H), 9.06 (d, J=7.23 Hz, 1 H). MS [MH+] calc. 396.1591 found 396.3.
Reaction SMILES: [C:1]([N:4]1[C:12]2[CH:11]=[C:10]3[O:13][CH2:14][O:15][C:9]3=[CH:8][C:7]=2[CH:6]([CH2:16][CH2:17]Br)[CH2:5]1)(=[O:3])[CH3:2].[C:19]1([C:25]2[CH2:26][CH2:27][NH:28][CH2:29][CH:30]=2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>>[C:1]([N:4]1[C:12]2[CH:11]=[C:10]3[O:13][CH2:14][O:15][C:9]3=[CH:8][C:7]=2[CH:6]([CH2:16][CH2:17][N:28]2[CH2:27][CH:26]=[C:25]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:30][CH2:29]2)[CH2:5]1)(=[O:3])[CH3:2]
Reactant: C1=C(c2ccccc2)CCNC1
Reactant: CC(=O)N1CC(CCBr)c2cc3c(cc21)OCO3
Product: CC(=O)N1CC(CCN2CC=C(c3ccccc3)CC2)c2cc3c(cc21)OCO3

Procedure:
In the manner described in Example 1, treatment of 5-acetyl-7-(2-bromoethyl)-6,7-dihydro-5H-1,3-dioxolo[4,5-f]-indole with 1,2,3,6-tetrahydro-4-phenylpyridine gives white crystals, m.p. 90°-91°C., after recrystallization from dilute acetone.
Reaction SMILES: [CH2:1]([OH:4])[CH2:2][CH3:3].CC(C)([O-])C.[K+].Cl[C:12]1[C:17]([C:18]#[N:19])=[C:16]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:15]([C:26]#[N:27])=[C:14]([S:28][CH2:29][C:30]2[N:31]=[C:32]([C:35]3[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=3)[S:33][CH:34]=2)[N:13]=1>CN(C=O)C>[Cl:41][C:38]1[CH:37]=[CH:36][C:35]([C:32]2[S:33][CH:34]=[C:30]([CH2:29][S:28][C:14]3[C:15]([C:26]#[N:27])=[C:16]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:17]([C:18]#[N:19])=[C:12]([O:4][CH2:1][CH2:2][CH3:3])[N:13]=3)[N:31]=2)=[CH:40][CH:39]=1
Reactant: N#Cc1c(Cl)nc(SCc2csc(-c3ccc(Cl)cc3)n2)c(C#N)c1-c1ccccc1
Reactant: CCCO
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCOc1nc(SCc2csc(-c3ccc(Cl)cc3)n2)c(C#N)c(-c2ccccc2)c1C#N
Reaction time: 0.25 h

Procedure:
37 μl (0.501 mmol) of 1-propanol are initially charged in 2 ml of DMF, 20 mg (0.184 mmol) of potassium tert-butoxide are added and the mixture is stirred for 15 minutes, after which 100 mg (0.167 mmol) of 2-chloro-6-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulphanyl)-4-phenylpyridine-3,5-dicarbonitrile, dissolved in 2 ml of DMF, are added. The reaction mixture is stirred at room temperature for one hour and then purified by preparative HPLC (acetonitrile/water: 10:90→95:5, with 0.1% TFA added). This gives 13 mg (15% of theory) of the target compound.