Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1([SH:8])[CH:6]=[CH:5][CH:4]=[C:3]([SH:7])[CH:2]=1.[CH3:9]C1CCCO1.COS(OC)(=O)=O.[OH-].[Na+]>C(OC)(C)(C)C>[CH3:9][S:7][C:3]1[CH:2]=[C:1]([SH:8])[CH:6]=[CH:5][CH:4]=1
Reactant: Sc1cccc(S)c1
Reactant: CC1CCCO1
Agent: [Na+]
Agent: [OH-]
Solvent: COC(C)(C)C
Solvent: COS(=O)(=O)OC
Product: CSc1cccc(S)c1
Temperature: 50 °C
Yield: 78 %

Procedure:
A solution of benzene-1,3-dithiol (50 g, 0.351 mmol) in 2-methyltetrahydrofuran (375 mL, 0.351 mmol) was treated with dimethylsulfate (33.3 mL, 0.351 mol) followed by 2-methyltetrahydrofuran (25 mL, used as line wash). The resulting solution was cooled to between 0° C. and 5° C. and sodium hydroxide (2M aqueous solution, 210.6 mL) was added drop wise maintaining the temperature of the reaction mixture below 15° C. followed by 2-methyltetrahydrofuran (25 mL, used as line wash) and heated under nitrogen to 50° C. for 4 hours. After cooling to ambient temperature the resulting solution was treated with tert-butylmethylether (500 mL) and the phases were separated. The organic phase was extracted with sodium hydroxide (2 M aqueous solution, 250 mL) and the combined aqueous phases were cooled to 10° C. and hydrochloric acid (6M aqueous solution, 500 mL) was added whilst maintaining the temperature of the mixture below 25° C. The resulting solution was extracted with tert-butylmethylether (2-fold 250 mL) and the combined organic phases were washed with water (500 mL) and concentrated in vacuo to give the title compound as a yellow oil, 78% yield, 42.9 g.
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:23]([OH:25])=[O:24])[CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[NH:16][CH:15]=1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO.[CH2:28]1CCC(N=C=NC2CCCCC2)CC1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:28][O:24][C:23](=[O:25])[C@H:12]([CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[NH:16][CH:15]=1)[NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10]
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Reactant: O=C(N[C@@H](Cc1c[nH]c2ccccc12)C(=O)O)OCc1ccccc1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CO
Product: COC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirred suspension of (S)—N-benzyloxycarbonyl-L-tryptophan 1a (2.45 g, 7.2 mmol) in 10 ml anhydrous CH2Cl2, was added DMAP (0.1 g, 0.82 mmol) and methanol (0.28 g, 11.8 mmol). At 0° C., DCC in CH2Cl2 solution was slowly added to the mixture and then it was allowed to warm to room temperature and stirred overnight. After twice filtration and evaporation, the residue was purified by flash column chromatography (n-hexane/EA, 4:1 to 2:1) and afforded the desired product (S)-2a as a colourless oil (2.5 g, 98%).
Reaction SMILES: [OH:1][C:2]1[C:3]2[CH:27]=[CH:26][S:25][C:4]=2[N:5]([CH:22]([CH3:24])[CH3:23])[C:6](=[O:21])[C:7]=1[C:8]([NH:10][CH2:11][CH2:12][CH2:13][N:14]1[CH2:19][CH2:18][CH:17](C)[CH2:16][CH2:15]1)=[O:9].[CH2:28]([Li])CCC.CI>C1COCC1>[CH:22]([N:5]1[C:6](=[O:21])[C:7]([C:8]([NH:10][CH2:11][CH2:12][CH2:13][N:14]2[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]2)=[O:9])=[C:2]([O:1][CH3:28])[C:3]2[CH:27]=[CH:26][S:25][C:4]1=2)([CH3:24])[CH3:23]
Reactant: CC1CCN(CCCNC(=O)c2c(O)c3ccsc3n(C(C)C)c2=O)CC1
Reactant: [Li]CCCC
Solvent: C1CCOC1
Solvent: CI
Product: COc1c(C(=O)NCCCN2CCCCC2)c(=O)n(C(C)C)c2sccc12
Temperature: 0 °C
Reaction time: 4 h
Yield: 98.3 %

Procedure:
To a solution of 6,7-dihydro-4-hydroxy-7-isopropyl-N-(3-(4-methylpiperidin-1-yl)propyl)-6-oxothieno[2,3-b]pyridine-5-carboxamide (0.075 g, 0.20 mmol) in THF (2.5 mL) at −78° C. was added n-butyllithium (0.087 mL, 2.5 M in hexanes, 0.22 mmol). The reaction mixture was warmed to 0° C. for 30 min and re-cooled to −78° C.; then methyl iodide (0.037 mL, 0.40 mmol) was added. The mixture was warmed to room temperature, stirred for 4 h and concentrated. The residue was dissolved in dichloromethane; the resulting solution was washed with water, dried over anhydrous sodium sulfate and concentrated to afford the title compound as an off-white solid (0.077 g, 99%). 1H NMR (400 MHz, CD3OD): δ 7.35 (d, 1 H), 7.20 (d, 1 H), 3.55 (t, 2 H), 3.49-3.45 (m, 2 H), 3.40 (t, 4 H), 3.09 (s, 3 H), 2.17-2.09 (m, 2 H), 1.91 (m, 4 H), 1.76-1.62 (m, 2 H), 1.64 (d, 6 H); MS: m/e 392 (M+H+).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([NH2:10])=O)[CH:3]=1.C(OC(C(F)(F)F)=O)(C(F)(F)F)=O.CC(OO)=O.C([O-])([O-])=O.[K+].[K+]>CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]#[N:10])[CH:3]=1
Reactant: NC(=O)c1cc(Cl)ccn1
Agent: CC(=O)OO
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Solvent: CCOC(C)=O
Product: N#Cc1cc(Cl)ccn1
Reaction time: 0.5 h
Yield: 87.6 %

Procedure:
4-Chloro-2-pyridinecarboxamide (93.9 g, 0.6 moles) and TEA (125 mL, 0.9 moles) in EtOAc (500 mL) was cooled to 0.2° C. via an external chiller unit. TFAA (92 mL, 0.66 moles) was added via addition funnel over 40 min. The internal temperature rose to 10° C. during the addition. The temperature at the completion of the addition was 0.0° C. After addition, the chiller was turned off. After an additional 30 min, HPLC analysis showed 4.3% (LCAP) of the starting material. An additional 8.3 mL (0.06 moles) of TFAA was added. After stirring the reaction mixture for an additional 20 min, HPLC analysis indicated complete conversion. 10% Aqueous K2CO3 (w/v, 500 mL) was added. The internal temperature rose from 13.7 to 22.0° C. The mixture was transferred to a separatory funnel after stirring for 20 min. The layers were separated and the aqueous layer extracted with EtOAc (150 mL). The combined organic layers were washed with 10% aqueous citric acid (w/v, 300 mL), dried (Na2SO4), filtered, and concentrated. The crude product was dried in a vacuum oven at 50° C. for 16 h to afford 72.85 g (87%) of the title compound: 1H NMR (400 MHz, CDCl3) δ 8.6 (m, 1H), 7.7 (m, 1H), 7.5 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 151.8, 145.3, 134.9, 128.7, 127.4, 116.1; HPLC>99% (LCAP).
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]#[N:13])=[CH:9][CH:10]=2)[C:5](Cl)=[N:4][N:3]=1.Cl.[CH2:16]([C:18]1[CH:19]=[C:20]([CH:23]=[CH:24][C:25]=1[O:26][CH3:27])[CH2:21][NH2:22])[CH3:17].C1CCN2C(=NCCC2)CC1>CN1CCCC1=O>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]#[N:13])=[CH:9][CH:10]=2)[C:5]([NH:22][CH2:21][C:20]2[CH:23]=[CH:24][C:25]([O:26][CH3:27])=[C:18]([CH2:16][CH3:17])[CH:19]=2)=[N:4][N:3]=1
Reactant: CCc1cc(CN)ccc1OC
Reactant: N#Cc1ccc2c(Cl)nnc(Cl)c2c1
Agent: Cl
Solvent: CN1CCCC1=O
Solvent: C1CCC2=NCCCN2CC1
Product: CCc1cc(CNc2nnc(Cl)c3ccc(C#N)cc23)ccc1OC

Procedure:
1,4-Dichlorophthalazine-6-carbonitrile and 3-ethyl-4-methoxybenzylamine hydrochloride were stirred at room temperature in 1-methyl-2-pyrrolidinone in the presence of DBU, whereby 1-chloro-4-[(3-ethyl-4-methoxybenzyl)amino]-6-phthalazine carbonitrile was obtained as a less polar compound.
Reaction SMILES: C([Li])CCC.[CH2:6]([O:8][CH:9]([O:12][CH2:13][CH3:14])[C:10]#[CH:11])[CH3:7].[CH3:15][O:16][C:17]1[CH:18]=[C:19]([CH:22]=[C:23]([O:27][CH3:28])[C:24]=1[O:25][CH3:26])[CH:20]=[O:21].[Cl-].[NH4+]>O1CCCC1.CCOCC>[CH2:6]([O:8][CH:9]([O:12][CH2:13][CH3:14])[C:10]#[C:11][C:20]([C:19]1[CH:22]=[C:23]([O:27][CH3:28])[C:24]([O:25][CH3:26])=[C:17]([O:16][CH3:15])[CH:18]=1)=[O:21])[CH3:7]
Reactant: C#CC(OCC)OCC
Reactant: COc1cc(C=O)cc(OC)c1OC
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCOCC
Product: CCOC(C#CC(=O)c1cc(OC)c(OC)c(OC)c1)OCC
Reaction time: 0.5 h

Procedure:
43.6 ml of n-butyllithium solution (1.6M in hexane) are added at -78° to a solution of 10 ml (69.8 mmol) of 3,3-diethoxy-1-propyne in 210 ml of absolute tetrahydrofuran. The mixture was stirred at -78° for 30 minutes and treated at -40° with 13.70 g (69.8 mmol) of 3,4,5-trimethoxybenzaldehyde in 60 ml of tetrahydrofuran. The reaction mixture was stirred at 0° for 1 hour and treated with 100 ml of saturated ammonium chloride solution and 150 ml of ether. The aqueous phase was extracted twice with ether. The combined organic phases were dried over magnesium sulphate and evaporated. The residue was dissolved in 100 ml of methylene chloride and added dropwise at 0° to a suspension of 176.8 g of manganese dioxide in 300 ml of methylene chloride. The reaction mixture was stirred at 0° for 20 minutes, filtered over magnesium sulphate and evaporated. The residue was crystallized from iso-octane at 0° and there is obtained 4,4-diethoxy-1-(3,4,5-trimethoxyphenyl)-2-butyn-1-one of melting point 52°-54°.
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[C:4]([CH3:9])[CH:3]=1.[CH2:10]([O:12][C:13]([N:15]=[C:16]=[S:17])=[O:14])[CH3:11]>ClCCl>[Br:1][C:2]1[N:7]=[C:6]([NH:8][C:16]([NH:15][C:13]([O:12][CH2:10][CH3:11])=[O:14])=[S:17])[CH:5]=[C:4]([CH3:9])[CH:3]=1
Reactant: CCOC(=O)N=C=S
Reactant: Cc1cc(N)nc(Br)c1
Solvent: ClCCl
Product: CCOC(=O)NC(=S)Nc1cc(C)cc(Br)n1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of 6-bromo-4-methyl-pyridin-2-ylamine (0.5 g, 2.67 mmol) in dichloromethane (20 ml) cooled to 5° C. was added ethoxycarbonyl isothiocyanate (0.32 ml, 2.67 mmol) dropwise over 15 min. The reaction mixture was then allowed to warm to room temperature at which it was stirred for 16 h. Evaporation in vacuo gave a solid that was collected by filtration and thoroughly washed with cyclohexane to give the desired product. Yield 0.59 g, 69%. LCMS MI: 317.92+319.94, RT: 5.05 min, Method: 2
Reaction SMILES: [C:1]([NH:4][C@@H:5]1[CH2:11][C@:10]2([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:12](CC3C=CC=CC=3)[C@H:6]1[CH2:7][CH2:8][C@H:9]2[O:26][CH2:27][C:28]1[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[C:30]([C:38]([F:41])([F:40])[F:39])[CH:29]=1)(=[O:3])[CH3:2].[ClH:42]>CO.C(OCC)C.[OH-].[Pd+2].[OH-]>[ClH:42].[C:1]([NH:4][C@@H:5]1[CH2:11][C@:10]2([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)[NH:12][C@H:6]1[CH2:7][CH2:8][C@H:9]2[O:26][CH2:27][C:28]1[CH:29]=[C:30]([C:38]([F:39])([F:40])[F:41])[CH:31]=[C:32]([C:34]([F:36])([F:35])[F:37])[CH:33]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)N[C@@H]1C[C@@]2(c3ccccc3)[C@H](OCc3cc(C(F)(F)F)cc(C(F)(F)F)c3)CC[C@@H]1N2Cc1ccccc1
Agent: [Pd+2]
Agent: Cl
Agent: [OH-]
Solvent: CCOCC
Solvent: CO
Product: CC(=O)N[C@@H]1C[C@]2(c3ccccc3)N[C@H]1CC[C@H]2OCc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reaction time: 1 h

Procedure:
(1R*,2R*,5S*,6R*)-6-Acetamido-8-benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octane (Example 118; 66 mg, 0.11 mmol) was dissolved in methanol (5 ml) and 2N hydrochloric acid (1 ml) and 10% palladium hydroxide (20 mg) added. The reaction mixture was hydrogenated at 40 psi for 1 hour. The mixture was then filtered and concentrated in vacuo then the oil basified (saturated sodium hydrogen carbonate solution) and extracted with dichloromethane (×3), dried (MgSO4) and concentrated in vacuo to give a clear oil. The oil was purified by thin layer chromatography [10% methanol in dichloromethane] to give a white solid. The hydrochloride salt was made by adding 1 equivalent of hydrogen chloride in diethyl ether (1.0M) to a solution in diethyl ether and the title compound-filtered and dried in vacuo at 60° C.
Reaction SMILES: C[O:2][C:3](=[O:32])[C:4]([CH3:31])([CH3:30])[CH2:5][C:6]1[N:7]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)[C:8]2[C:13]([C:14]=1[S:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[CH:12][C:11]([O:20][CH3:21])=[CH:10][CH:9]=2.C1COCC1.[Li+].[OH-]>CO>[Cl:29][C:26]1[CH:27]=[CH:28][C:23]([CH2:22][N:7]2[C:8]3[C:13](=[CH:12][C:11]([O:20][CH3:21])=[CH:10][CH:9]=3)[C:14]([S:15][C:16]([CH3:19])([CH3:17])[CH3:18])=[C:6]2[CH2:5][C:4]([CH3:31])([CH3:30])[C:3]([OH:32])=[O:2])=[CH:24][CH:25]=1
Reactant: COC(=O)C(C)(C)Cc1c(SC(C)(C)C)c2cc(OC)ccc2n1Cc1ccc(Cl)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: COc1ccc2c(c1)c(SC(C)(C)C)c(CC(C)(C)C(=O)O)n2Cc1ccc(Cl)cc1
Temperature: 80 °C

Procedure:
The compound from Step A was hydrolysed using 325 mL of THF, 600 mL of MeOH and 325 mL of 1.0M LiOH. The solution was heated to 80° C. for 3 h. The solution was acidified with 1N HC1 and extracted with 3×200 mL of EtOAc. The organic phase was washed with water (2×150 mL) and dried over MgSO4. The solution was evaporated to dryness to provide the title compound. m.p. 190°-191° C. Anal C, H, N: Calc. C 65.27; H 6.57; N 3.04, Found C 65.28; H 6.58; N 3.04
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([CH3:8])[NH:5][C:4]2=[CH:9][C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[N:11][C:3]=12.[NH2:18][CH2:19][CH2:20][N:21]1[CH2:26][CH2:25][O:24][CH2:23][CH2:22]1.C([O-])([O-])=O.[K+].[K+]>O>[CH3:8][C:6]1[NH:5][C:4]2[C:3]([N:11]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:9]=2)=[C:2]([NH:18][CH2:19][CH2:20][N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)[N:7]=1
Reactant: NCCN1CCOCC1
Reactant: Cc1nc(Cl)c2nc(-c3ccccc3)cc-2[nH]1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Product: Cc1nc(NCCN2CCOCC2)c2nc(-c3ccccc3)cc-2[nH]1
Yield: 43.4 %

Procedure:
This compound was prepared according to the method described in Example 26 by employing 4-chloro-2-methyl-6-phenylpyrrolo[3,2-d]pyrimidine (Example 1(e)) (0.10 g, 0.41 mmol), 4-(2-aminoethyl)morpholine (Aldrich Chemical Company) (0.270 g, 2.06 mmol) and K2CO3 (0.36 g, 2.60 mmol) in H2O (2.5 mL) to give crude pink solids. Recrystallization from EtOAc/MeOH gave 0.060 g (43%) of the title compound as a white solid. Mp: >280° C. 1H NMR (DMSO-d6; 500 MHz): δ 2.39 (s, 3), 3.61 (t, 4, J=4.5), 3.65 (q, 2, J=6.1), 4.04 (s, 2), 6.75 (s, 1), 6.81 (br s, 1), 7.38 (t, 1, J=7.4), 7.51 (t, 2, J=7.6), 7.78 (d, 2, J=7.6), 11.39 (s, 1). 13C NMR (CD3OD, 100 MHz): δ 26.3, 39.2, 55.9, 60.1, 68.8, 99.9, 127.3, 128.3, 130.6, 131.2, 134.0, 143.1, 149.8, 151.1, 161.5. MS m/z: 338 (M+1). Anal. Calcd for C19H23N5O. 0.25H2O: C, 66.74; H, 6.93; N, 20.48. Found: C, 66.84; H, 6.83; N, 20.39.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[C:9]=2[CH:14]([OH:18])[CH2:15][CH:16]=[CH2:17])=[CH:4][CH:3]=1.[CH2:19]([O:21][C:22]([C:24]1([C:27]2[CH:32]=[CH:31][C:30](B3OC(C)(C)C(C)(C)O3)=[CH:29][CH:28]=2)[CH2:26][CH2:25]1)=[O:23])[CH3:20]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH2:19]([O:21][C:22]([C:24]1([C:27]2[CH:32]=[CH:31][C:30]([C:2]3[CH:7]=[CH:6][C:5]([C:8]4[O:12][N:11]=[C:10]([CH3:13])[C:9]=4[CH:14]([OH:18])[CH2:15][CH:16]=[CH2:17])=[CH:4][CH:3]=3)=[CH:29][CH:28]=2)[CH2:25][CH2:26]1)=[O:23])[CH3:20]
Reactant: CCOC(=O)C1(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)CC1
Reactant: C=CCC(O)c1c(C)noc1-c1ccc(Br)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Product: C=CCC(O)c1c(C)noc1-c1ccc(-c2ccc(C3(C(=O)OCC)CC3)cc2)cc1

Procedure:
Prepared according to the procedure described in Example 3, Step 5, using dichlorobis(triphenylphosphine)palladium(II) as the catalyst and using 1-[5-(4-bromo-phenyl)-3-methyl-isoxazol-4-yl]-but-3-en-1-ol and 1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclopropanecarboxylic acid ethyl ester.
Reaction SMILES: CO[C:3](=[O:17])[C:4]([C:6]1[CH:7]=[C:8]([CH3:16])[CH:9]=[C:10]2[C:14]=1[N:13]([CH3:15])[CH:12]=[CH:11]2)=[O:5].[F:18][C:19]1[CH:27]=[C:26]2[C:22]([C:23]([CH2:28][C:29]([NH2:31])=[O:30])=[CH:24][NH:25]2)=[CH:21][CH:20]=1.CC(C)([O-])C.[K+].C1COCC1.Cl>CN(C=O)C>[CH3:15][N:13]1[C:14]2[C:10](=[CH:9][C:8]([CH3:16])=[CH:7][C:6]=2[C:4](=[O:5])[C:3]([NH:31][C:29](=[O:30])[CH2:28][C:23]2[C:22]3[C:26](=[CH:27][C:19]([F:18])=[CH:20][CH:21]=3)[NH:25][CH:24]=2)=[O:17])[CH:11]=[CH:12]1
Reactant: COC(=O)C(=O)c1cc(C)cc2ccn(C)c12
Reactant: NC(=O)Cc1c[nH]c2cc(F)ccc12
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: Cc1cc(C(=O)C(=O)NC(=O)Cc2c[nH]c3cc(F)ccc23)c2c(ccn2C)c1
Temperature: 25 °C
Reaction time: 11 h
Yield: 21.7 %

Procedure:
To a mixture of (1,5-dimethyl-1H-indol-7-yl)-oxo-acetic acid methyl ester (0.51 g, 2.21 mmol) and 2-(6-fluoro-1H-indol-3-yl)-acetamide (0.38 g, 2 mmol) in DMF (20 mL) was added a solution of potassium tert-butoxide in THF (1.0 M, 8.0 mL, 8.0 mmol) at room temperature. The reaction mixture was stirred at room temperature for 11 h, treated with concentrated hydrochloric acid (2 mL) and then heated at 50° C. for 2 h. The mixture was cooled to room temperature, extracted with ethyl acetate and the extract was washed with water, saturated aqueous sodium bicarbonate and brine dried (sodium sulfate), filtered and evaporated. Flash column chromatography on silica gel eluting with chloroform and acetone gave 2-(1,5-dimethyl-1H-indol-7-yl)-N-[2-(6-fluoro-1H-indol-3-yl)-acetyl]-2-oxo-acetamide (170 mg, 23%) and 3-(1,5-dimethyl-1H-indol-7-yl)-4-(6-fluoro-1H-indol-3-yl)-pyyrole-2,5-dione (340 mg, 45.5%). 1H NMR (d6-DMSO, 400 MHz) δ 2.26 (s, 3H), 3.58 (s, 3H), 6.36 (d, J=3.13 Hz, 1H), 6.40˜6.45 (m, 2H), 6.73 (s, 1H), 7.11 (dd, J1=2.34 Hz, J2=9.38 Hz, 1H), 7.16 (d, J=3.13 Hz, 1H), 7.7.39 (s, 1H), 7.80 (d, J=3.13 Hz, 1H), 11.14 (s, 1H), 11.82 (s, 1H); MS (ES, m/z): C22H16FN3O2: 374.2 (M++1); 372.2 (M+−1).
Reaction SMILES: [CH:1](=O)[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.[N:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=1.C(OC(=O)C)(=O)C>O>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([CH:1]=[CH:17][C:14]2[CH:15]=[CH:16][N:11]=[CH:12][CH:13]=2)=[CH:3][CH:4]=1
Reactant: Cc1ccncc1
Reactant: COc1ccc(C=O)cc1
Solvent: O
Solvent: CC(=O)OC(C)=O
Product: COc1ccc(C=Cc2ccncc2)cc1
Yield: 54.9 %

Procedure:
The photo-bleachable compound expressed by the structural formula (II-14) was prepared in the following manner. Thus, a reaction mixture was prepared by dissolving 6.81 g (0.05 mole) of p-anisaldehyde and 4.66 g (0.05 mole) of γ-picoline in 10.21 g (0.10 mole) of acetic anhydride and the mixture was heated under reflux for 16 hours to effect the reaction. After acetic acid and the unreacted acetic anhydride were evaporated from the reaction mixture, the residual reaction mixture was poured into water so that a crystalline material was precipitated therein. The reaction mixture was filtered and the collected precipitates were washed with water. Recrystallization of the precipitates from a mixture of methyl alcohol and water gave 5.80 g of 4-[2-(4-methoxyphenyl)ethenyl]pyridine, the yield of which was 55% of the theoretical value.
Reaction SMILES: C(N(C(C)C)CC)(C)C.[CH2:10]([C@@H:17]1[CH2:21][O:20][C:19](=[O:22])[N:18]1[C:23](=[O:29])[CH2:24]P(=O)([O-])[O-])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Cl-].[Li+].[CH2:32]([O:39][CH2:40][CH:41]=O)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C(#N)C>[CH2:10]([C@@H:17]1[CH2:21][O:20][C:19](=[O:22])[N:18]1[C:23](=[O:29])/[CH:24]=[CH:41]/[CH2:40][O:39][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: O=CCOCc1ccccc1
Reactant: O=C(CP(=O)([O-])[O-])N1C(=O)OC[C@H]1Cc1ccccc1
Agent: [Cl-]
Agent: [Li+]
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: O=C(/C=C/COCc1ccccc1)N1C(=O)OC[C@H]1Cc1ccccc1
Temperature: 0 °C

Procedure:
Diisopropylethylamine (51 mL, 290 mmol) was added slowly to a mechanically stirred, 0° C. slurry composed of {2-[(4R)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-2-oxoethyl}phosphonate (94.8 g, 267 mmol; see Shapiro, G; Chengzhi, C. Tetrahedron Lett. 1992, 33, 2447) and dry lithium chloride (12.5 g, 280 mmol) in acetonitrile (260 mL). After stirring for 10 min, a solution of 2-benzyloxyacetaldehyde (40.0 g, 267 mmol) in acetonitrile (20 mL) was added dropwise over 10 min. The cooling bath was then removed and the reaction mixture was stirred at rt for 12 h before being partitioned between ether and water and the layers separated The aqueous phase was extracted with additional ether and the combined organic phases (700 mL total) were stirred at rt with 2M HCl (350 mL) for 1 h. The organic phase was then washed with saturated NaCl and NaHCO3 aqueous solutions, followed by drying over a mixture of Na2SO4 and MgSO4, and concentration in vacuo. Flash chromatography of the residue on silica gel eluting with 10/90 acetone/benzene yielded (4R)-4-benzyl-3-[(2E)-4-(benzyloxy)but-2-enoyl]-1,3-oxazolidin-2-one as a colorless solid upon trituration with ether. 1H NMR (500 MHz, d6-acetone) δ 7.57 (1H, d, J= 15.6 Hz), 7.43-7.27 (10H, m), 7.21-7.15 (1H, m), 4.84 (1H, t, J= 8.2 Hz), 4.64 (2H, s), 4.43 (1H, t, J= 8.5 Hz), 4.32 (2H, m), 4.29 (1H, dd, J= 2.9, 8.9 Hz), 3.24 (1H, dd, J= 3.1, 13.5 Hz), 3.03 (1H, dd, J= 8.4, 13.5 Hz).
Reaction SMILES: [CH2:1]([S:8][C:9]1[S:19][C:12]2=[N:13][C:14](I)=[CH:15][C:16](=[O:17])[N:11]2[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:20]([Si:22]([CH3:25])([CH3:24])[CH3:23])#[CH:21]>C(N(CC)CC)C.O1CCCC1.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>[CH2:1]([S:8][C:9]1[S:19][C:12]2=[N:13][C:14]([C:21]#[C:20][Si:22]([CH3:25])([CH3:24])[CH3:23])=[CH:15][C:16](=[O:17])[N:11]2[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C#C[Si](C)(C)C
Reactant: O=c1cc(I)nc2sc(SCc3ccccc3)nn12
Agent: Cl[Pd]Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: C[Si](C)(C)C#Cc1cc(=O)n2nc(SCc3ccccc3)sc2n1
Reaction time: 4 h

Procedure:
In a mixture of 30 ml of triethylamine and 60 ml of tetrahydrofurane, 7.0 g of the thus obtained 55% pure 2-benzylthio-7-iodo-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one was dissolved, and 0.68 g of bis(triphenylphosphine)palladium (II) chloride and 0.18 g of cuprous iodide were added to the solution. A solution of 3.8 g of ethynyltrimethylsilane in 20 ml of triethylamine was added dropwise to the above solution, the resulting solution was heated to 68°-70° C. and stirred for 4 hours. After cooling, the reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was separated by silica gel column chromatography using an ethyl acetate/hexane mixture as an eluent, and thus 4.2 g of 2-benzylthio-7-trimethylsilylethynyl-5H-1,3,4-thiadiazolo[3,2-a]pyrimidin-5-one was obtained.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.Br[C:10]1[CH:15]=[CH:14][C:13]([I:16])=[CH:12][N:11]=1.C([O-])([O-])=O.[Cs+].[Cs+].CCOC(C)=O>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C:10]2[CH:15]=[CH:14][C:13]([I:16])=[CH:12][N:11]=2)=[CH:4][CH:3]=1
Reactant: Oc1ccc(F)cc1
Reactant: Brc1ccc(I)cn1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Fc1ccc(Oc2ccc(I)cn2)cc1
Temperature: 120 °C
Reaction time: 4 h

Procedure:
A mixture of 4-fluorophenol (1.12 g, 10 mmol), 2-bromo-5-iodopyridine (2.84 g, 10 mmol) and Cs2CO3 (3.83 g, 10 mmol) in DMF was stirred at 120° C. for 4 hrs. The reaction was worked up with EtOAc to give 2-(4-fluoro-phenoxy)-5-iodo-pyridine which was used for next step without further purification (crude yield 100%, yellowish solid). LC/MS: m/z=317 [M+H]+.