Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[C:5]([C:26]1[S:27][C:28]3[CH:34]=[CH:33][CH:32]=[CH:31][C:29]=3[N:30]=1)=[C:6]([CH:24]=[O:25])[N:7]2[CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH2:20][CH:21]2[CH2:23][CH2:22]2)[CH:14]=1)C.NC1C=CC=CC=1S.Cl.[CH3:44][CH2:45][OH:46]>>[CH2:45]([O:46][C:24]([C:6]1[N:7]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH2:20][CH:21]3[CH2:22][CH2:23]3)[CH:14]=2)[C:8]2[C:4]([C:5]=1[C:26]1[S:27][C:28]3[CH:34]=[CH:33][CH:32]=[CH:31][C:29]=3[N:30]=1)=[CH:3][CH:11]=[CH:10][CH:9]=2)=[O:25])[CH3:44]
Reactant: CCc1cccc2c1c(-c1nc3ccccc3s1)c(C=O)n2Cc1cccc(OCC2CC2)c1
Reactant: CCO
Agent: Cl
Agent: Nc1ccccc1S
Product: CCOC(=O)c1c(-c2nc3ccccc3s2)c2ccccc2n1Cc1cccc(OCC2CC2)c1
Temperature: 25 °C
Yield: 71 %

Procedure:
Ethyl-3-benzthiazol-2-yl-1-(3-cyclopropylmethoxybenzyl)-1H-indole-2-carboxaldehyde (Example 41, 0.42 g, 1.1 mmol) was taken up in EtOH (30 mL) at room temperature. 2-aminothiophenol (0.15 g, 1.05 eq.) was added, followed by conc. HCl (0.5 mL), and the reaction mixture was heated to reflux for 24 hours. The mixture was cooled to room temperature, quenched with water and extracted with diethyl ether (3×50 mL.) The organic layers were separated, dried over sodium sulfate, and concentrated in vacuo to give the desired product (0.38 g, 71%) which was taken to the hydrolysis step without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]([NH:16][CH3:17])=[O:15])=[C:12]([CH3:18])[N:11]=[CH:10][CH:9]=2)=[C:4](F)[CH:3]=1.[H-].[Na+]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]2[C:8]3[C:13](=[C:12]([CH3:18])[N:11]=[CH:10][CH:9]=3)[C:14](=[O:15])[N:16]([CH3:17])[C:4]=2[CH:3]=1
Reactant: CNC(=O)c1c(-c2ccc(Cl)cc2F)ccnc1C
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1nccc2c1c(=O)n(C)c1cc(Cl)ccc21
Reaction time: 4 h
Yield: 80.6 %

Procedure:
To a solution of 4-(4-chloro-2-fluorophenyl)-N,2-dimethylnicotinamide (40 mg, 0.144 mmol) in THF (3 mL) cooled to 0° C. was added NaH (10.33 mg, 0.431 mmol) and the reaction mixture was stirred for 4 h. After the reaction completion, the reaction mixture was quenched with ice water and the product was extracted with ethyl acetate (20 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure to afford 8-chloro-4,6-dimethylbenzo[c][2,7]naphthyridin-5(6H)-one (30 mg, 0.116 mmol, 81% yield) as an off-white solid. LC/MS, (ESI) m/z 259.2 [(M+H)+, calcd for C14H12ClN2O 259.1]; LC/MS retention time (Method D): tR=0.65 min.
Reaction SMILES: [O:1]1[CH2:15][CH:2]1[CH2:3][O:4]/[N:5]=[C:6]1\[CH2:7][CH2:8][CH2:9][C:10]2[S:11][CH:12]=[CH:13][C:14]\1=2.[CH3:16][N:17]([CH3:21])[CH2:18][CH2:19][NH2:20]>>[OH:1][CH:2]([CH2:15][NH:20][CH2:19][CH2:18][N:17]([CH3:21])[CH3:16])[CH2:3][O:4]/[N:5]=[C:6]1\[CH2:7][CH2:8][CH2:9][C:10]2[S:11][CH:12]=[CH:13][C:14]\1=2
Reactant: CN(C)CCN
Reactant: c1cc2c(s1)CCC/C2=N\OCC1CO1
Product: CN(C)CCNCC(O)CO/N=C1\CCCc2sccc21
Yield: 28 %

Procedure:
This compound is prepared by the procedure described in Example 1 by condensing E-4-(2,3-epoxypropoxy)imino-4,5,6,7-tetrahydrobenzo[b]thiophene with β-dimethylaminoethylamine. Dioxalate: white crystals; m.p. 222° C. (recrystallised from methanol/water); yield: 28% of theory.
Reaction SMILES: [C:1]([O-:10])(=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([O-:8])=[O:7].[Na+].[Na+].S(=O)(=O)(O)O.S([O-])([O-])(=O)=O.[Na+].[Na+]>>[C:1]([OH:10])(=[O:9])[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([OH:8])=[O:7]
Reactant: O=C([O-])CCCCC(=O)[O-]
Agent: O=S(=O)(O)O
Agent: O=S(=O)([O-])[O-]
Agent: [Na+]
Product: O=C(O)CCCCC(=O)O
Yield: 97.9 %

Procedure:
85 g Sodium adipate were reacted as a 10% solution (after filtration as in Example 2) analogously to Example 6 with sulfuric acid to form 64 g of adipic acid and sodium sulfate.
Reaction SMILES: COC(OC)N(C)C.[NH:9]1[CH2:20][CH2:19][NH:18][CH2:17][CH2:16][NH:15][CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.[C:21]1([N:27]=[C:28]=[O:29])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[OH-].[Na+]>C1(C)C=CC=CC=1.O.C(O)C>[C:21]1([NH:27][C:28]([N:9]2[CH2:20][CH2:19][NH:18][CH2:17][CH2:16][NH:15][CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[O:29])[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: C1CNCCNCCNCCN1
Reactant: O=C=Nc1ccccc1
Agent: COC(OC)N(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Solvent: O
Solvent: CCO
Product: O=C(Nc1ccccc1)N1CCNCCNCCNCC1
Temperature: 0 °C
Reaction time: 12 h

Procedure:
15.9 g (133.5 mmol) of dimethylformamide-dimethylacetal (under nitrogen) is added to 20.0 g (116.1 mmol) of 1,4,7,10-tetraazacyclododecane in 200 ml of absolute toluene. It is refluxed slowly and the solvent is distilled off in this way. Then, it is concentrated by evaporation under reduced pressure. The residue is cooled to 0° C. 16.6 g (139.32 mmol) of phenyl isocyanate is instilled under a nitrogen atmosphere and heated slowly to 100° C. It is stirred for 12 hours at this temperature. It is cooled to room temperature and a mixture of 160 ml of ethanol/40 ml of water is added. Then, it is stirred for 10 minutes at room temperature. Then, 18.58 g (464.4 mmol) of sodium hydroxide is added and it is stirred for 24 hours at 40° C. It is evaporated to dryness in a vacuum and the residue is taken up in 400 ml of water. The aqueous phase is extracted 5 times with 200 ml of methylene chloride, the organic phase is dried on magnesium sulfate and concentrated by evaporation in a vacuum. The residue is chromatographed on silica gel (mobile solvent=methyl-tert-butyl ether/methanol/conc. aqu. ammonia=6/3/1).
Reaction SMILES: [N+](=[CH2:3])=[N-].[C:4]([O:8][C:9]([C:11]1[CH:24]=[CH:23][CH:22]=[C:21]2[C:12]=1[S:13][C:14]1[C:15]([CH2:28][C:29]([OH:31])=[O:30])=[CH:16][CH:17]=[C:18]([CH2:26][NH2:27])[C:19]=1[N:20]2[CH3:25])=[O:10])([CH3:7])([CH3:6])[CH3:5]>C(Cl)Cl>[C:4]([O:8][C:9]([C:11]1[CH:24]=[CH:23][CH:22]=[C:21]2[C:12]=1[S:13][C:14]1[C:15]([CH2:28][C:29]([O:31][CH3:3])=[O:30])=[CH:16][CH:17]=[C:18]([CH2:26][NH2:27])[C:19]=1[N:20]2[CH3:25])=[O:10])([CH3:7])([CH3:5])[CH3:6]
Reactant: CN1c2cccc(C(=O)OC(C)(C)C)c2Sc2c(CC(=O)O)ccc(CN)c21
Reactant: C=[N+]=[N-]
Solvent: ClCCl
Product: COC(=O)Cc1ccc(CN)c2c1Sc1c(C(=O)OC(C)(C)C)cccc1N2C
Reaction time: 1.5 h
Yield: 91 %

Procedure:
1 ml of diazomethane solution (~0.3N in diethyl ether) was added dropwise while cooling with ice to a solution of 80 mg (0.19 mmol) of (6-tert-butoxycarbonyl-aminomethyl-10-methylphenothiazin-4-yl)-acetic acid in 4 ml of methylene chloride. The reaction mixture was brought to room temperature, stirred for 1.5 hours and evaporated. The residue was crystallized from ethyl acetate/hexane, whereupon, after drying in a high vacuum, 72 mg (91%) of methyl (6-tert-butoxycarbonyl-aminomethyl-10-methyl-phenothiazin-4-yl)-acetate were obtained as a white solid. MS 414 (M+, 64), 358 (100), 343 (15), 314 (15), 238 (15), 57 (16).
Reaction SMILES: [CH3:1][N:2]1[C:6]([C:7]2[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:9][CH:8]=2)=[C:5]([N+:20]([O-])=O)[CH:4]=[N:3]1.[Cl-].[NH4+]>C(O)C.O.[Fe]>[NH2:20][C:5]1[CH:4]=[N:3][N:2]([CH3:1])[C:6]=1[C:7]1[CH2:12][CH2:11][N:10]([C:13]([O:15][C:16]([CH3:18])([CH3:17])[CH3:19])=[O:14])[CH2:9][CH:8]=1
Reactant: Cn1ncc([N+](=O)[O-])c1C1=CCN(C(=O)OC(C)(C)C)CC1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: CCO
Product: Cn1ncc(N)c1C1=CCN(C(=O)OC(C)(C)C)CC1
Temperature: 100 °C
Yield: 64.4 %

Procedure:
To a solution of tert-butyl 4-(1-methyl-4-nitro-1H-pyrazol-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate (0.15 g, 0.48 mmol) in ethanol (10 mL) and water (1 mL) was added ammonium chloride (0.131 g, 2.44 mmol) and iron powder (0.109 g, 1.95 mmol). The mixture was heated at 100° C. for 1 hr. The mixture was cooled and filtered through celite and washed with EtOAc. The organic layer was washed with water, separated and dried over MgSO4. The solvent was removed under reduced pressure to yield tert-butyl 4-(4-amino-1-methyl-1H-pyrazol-5-yl)-5,6-dihydropyridine-1(2H)-carboxylate as a brown oil (86 mg, 64%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([O:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH2:25][CH2:26][CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[C:19]=2[CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH:10]=1)[C:5](O)=[O:6].F[P-](F)(F)(F)(F)F.Br[P+](N1CCCC1)(N1CCCC1)[N:49]1[CH2:53]CC[CH2:50]1.CNC.C1COCC1.CCN(C(C)C)C(C)C>ClCCl.O>[CH2:31]([O:30][C:28](=[O:29])[CH2:27][CH2:26][CH2:25][O:24][C:20]1[CH:21]=[CH:22][CH:23]=[C:18]([CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][O:11][C:9]2[CH:8]=[C:4]([C:5](=[O:6])[N:49]([CH3:53])[CH3:50])[CH:3]=[C:2]([Br:1])[CH:10]=2)[C:19]=1[CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH3:32]
Reactant: Br[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Reactant: CCOC(=O)CCCOc1cccc(CCCCCCOc2cc(Br)cc(C(=O)O)c2)c1CCC(=O)OCC
Agent: CNC
Agent: F[P-](F)(F)(F)(F)F
Solvent: O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)CCCOc1cccc(CCCCCCOc2cc(Br)cc(C(=O)N(C)C)c2)c1CCC(=O)OCC
Reaction time: 36 h
Yield: 89.7 %

Procedure:
To a solution of 3-bromo-5-{6-[2-(2-ethoxycarbonyl-ethyl)-3-(3-ethoxycarbonyl-propoxy)-phenyl]-hexyloxy}-benzoic acid (808 mg, 1.33 mmol), bromotripyrrolidinophosphonium hexafluorophosphate (PyBroP) (745 mg, 1.6 mmol) in dichloromethane (15 mL) were added dimethylamine in THF (800 μL, 1.6 mmol, 2 M solution) and DIPEA (463 μL, 2.66 mmol) at room temperature. The resulting clear solution was stirred for 36 h. Then, the reaction mixture was diluted with water (100 mL) and dichloromethane (50 mL). The two layers were separated and the aqueous layer was extracted with dichloromethane (50 mL). The combined organic extracts were washed with brine solution (200 mL) and dried over anhydrous magnesium sulfate. Filtration of the drying agent and concentration of the filtrate in vacuo gave the crude product which was purified by using an ISCO™ (40 g) column chromatography eluting with 40-60% ethyl acetate in hexanes to afford 4-{3-[6-(3-bromo-5-dimethylcarbamoyl-phenoxy)-hexyl]-2-(2-ethoxycarbonyl-ethyl)-phenoxy}-butyric acid ethyl ester (757 mg, 90%) as a colorless oil
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:16]([CH2:17][C:18]([OH:20])=O)[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:4][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH2:33]([NH:36][CH2:37][CH2:38][CH3:39])[CH2:34][CH3:35]>O1CCCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:16]([CH2:17][C:18]([N:36]([CH2:37][CH2:38][CH3:39])[CH2:33][CH2:34][CH3:35])=[O:20])[C:11]3=[N:12][CH:13]=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:6][CH:7]=1
Reactant: CCCNCCC
Reactant: O=C(O)Cn1c(-c2ccc(Br)cc2)nc2cccnc21
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: C1CCOC1
Product: CCCN(CCC)C(=O)Cn1c(-c2ccc(Br)cc2)nc2cccnc21
Temperature: 25 °C
Reaction time: 6 h

Procedure:
Under nitrogen bubbling, a mixture of 2-(4-bromophenyl)-3H-imidazo[4,5-b]pyridine-3-acetic acid (13.28 g, 0.04 mole) and 1,1' carbonyldiimidazole (7.14 g, 0.044 mole) in 300 ml of tetrahydrofuran was stirred at room temperature for 6 hrs. Then, under nitrogen atmosphere, dipropylamine (12.12 g, 0.12 mole) was added and the reaction mixture was heated at reflux for 3 hrs. The reaction mixture was filtered and the filtrate was evaporated to dryness. The solid was dried under vacuum overnight and was recrystallized from isopropyl alcohol-water. The crystalline solid was collected by filtration, washed with water, and dried under high vacuum over the weekend to give 9.0 g (54%), mp 153°-55° C.
Reaction SMILES: [OH:1][C:2]([CH2:4][C:5]1([NH:15][C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=2)=[O:17])[C:13]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[NH:7][C:6]1=[O:14])=[O:3].[H-].[Na+].[CH2:28](Br)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1.[Cl-].[Na+]>CS(C)=O>[CH2:28]([N:7]1[C:8]2[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:5]([CH2:4][C:2]([OH:1])=[O:3])([NH:15][C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=2)=[O:17])[C:6]1=[O:14])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1
Reactant: BrCc1ccccc1
Reactant: Cc1ccc(NC(=O)NC2(CC(=O)O)C(=O)Nc3ccccc32)cc1
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Product: Cc1ccc(NC(=O)NC2(CC(=O)O)C(=O)N(Cc3ccccc3)c3ccccc32)cc1
Reaction time: 0.25 h

Procedure:
To a solution of 0.404 g of (RS)-3-(hydroxycarbonylmethyl)-3-(N'-(4-methylphenyl)ureido)indolin-2-one in 20 ml of dry dimethyl sulfoxide was added 2.5 ml of a 1M solution of sodium hydride in dry dimethyl sulfoxide at room temperature under a nitrogen atmosphere. After stirring the mixture for 15 minutes, 0.19 ml of benzyl bromide was added thereto, followed by stirring at the same temperature for 30 minutes. The reaction mixture was poured into an aqueous solution of sodium chloride and extracted with ethyl ether. The ethyl ether layer was dried over anhydrous magnesium sulfate and concentrated to give (RS)-1-benzyl-3-(hydroxycarbonylmethyl)-3-(N'-(4-methylphenyl)ureido)indolin-2-one.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:10]=[N:11][N:12]([C:15]3[CH:23]=[CH:22][C:18]([C:19](O)=[O:20])=[CH:17][N:16]=3)[C:13]=2[OH:14])=[C:5]([CH3:24])[CH:4]=1)#[N:2].C1N=CN(C(N2C=NC=C2)=O)C=1.[CH2:37]([N:39]1[CH2:44][CH2:43][NH:42][CH2:41][CH2:40]1)[CH3:38].Cl>C1COCC1.CN(C1C=CN=CC=1)C.CS(C)=O.O>[CH2:37]([N:39]1[CH2:44][CH2:43][N:42]([C:19]([C:18]2[CH:22]=[CH:23][C:15]([N:12]3[C:13]([OH:14])=[C:9]([C:6]4[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][C:5]=4[CH3:24])[CH:10]=[N:11]3)=[N:16][CH:17]=2)=[O:20])[CH2:41][CH2:40]1)[CH3:38]
Reactant: CCN1CCNCC1
Reactant: Cc1cc(C#N)ccc1-c1cnn(-c2ccc(C(=O)O)cn2)c1O
Agent: CN(C)c1ccncc1
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: O
Solvent: CS(C)=O
Solvent: C1CCOC1
Product: CCN1CCN(C(=O)c2ccc(-n3ncc(-c4ccc(C#N)cc4C)c3O)nc2)CC1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 90 %

Procedure:
Combined 6-(4-(4-cyano-2-methylphenyl)-5-hydroxy-1H-pyrazol-1-yl)nicotinic acid (0.524 g, 1.636 mmol) in THF (3 mL) and added DMSO (1 mL) and DMAP (3.00 mg, 0.025 mmol) followed by a dropwise addition of a solution of CDI (0.292 g, 1.80 mmol) in DMSO (1 mL). The resulting clear solution was stirred at ambient temperature for 45 minutes and an additional portion of CDI (73.0 mg, 0.450 mmol) was added. The mixture was stirred for a total of 2 hours and 1-ethylpiperazine (0.270 mL, 2.127 mmol) was added. The resulting mixture was stirred for 4.5 hours and then diluted with water (6 mL, dropwise), acidified to pH=7 with 6N aqueous hydrochloric acid, and then further diluted with water (4 mL) to give a solid. The solid was filtered and dried in vacuum to give the title compound (0.613 g, 90%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.06 (t, J=7.07 Hz, 3H) 2.43 (s, 3H) 2.53-2.63 (m, 4H) 3.57 (br. s., 6H) 7.61 (d, J=8.08 Hz, 1H) 7.67 (s, 1H) 7.90 (d, J=8.08 Hz, 1H) 8.02 (dd, J=8.59, 2.27 Hz, 1H) 8.06 (s, 1H) 8.42 (d, J=8.59 Hz, 1H) 8.52 (d, J=1.77 Hz, 1H); MS (M+H)+417.
Reaction SMILES: [Cl:1][Si:2]([SiH:5]([Si:10]([Cl:13])([Cl:12])[Cl:11])[Si:6]([Cl:9])([Cl:8])[Cl:7])([Cl:4])[Cl:3].[CH:14]([C-:16]1[CH:20]=[CH:19][CH:18]=[CH:17]1)=[CH2:15].[CH-:21]1[CH:25]=[CH:24][CH:23]=[CH:22]1.[Fe+2:26]>C1(C)C=CC=CC=1.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.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Rh]>[Cl:11][Si:10]([Si:5]([CH:15]=[CH:14][C-:16]1[CH:20]=[CH:19][CH:18]=[CH:17]1)([Si:6]([Cl:9])([Cl:8])[Cl:7])[Si:2]([Cl:1])([Cl:3])[Cl:4])([Cl:13])[Cl:12].[CH-:21]1[CH:25]=[CH:24][CH:23]=[CH:22]1.[Fe+2:26]
Reactant: C=C[c-]1cccc1
Reactant: Cl[Si](Cl)(Cl)[SiH]([Si](Cl)(Cl)Cl)[Si](Cl)(Cl)Cl
Agent: [Fe+2]
Agent: [Rh]
Agent: [Cl-]
Solvent: Cc1ccccc1
Product: Cl[Si](Cl)(Cl)[Si](C=C[c-]1cccc1)([Si](Cl)(Cl)Cl)[Si](Cl)(Cl)Cl

Procedure:
Tris(trichlorosilyl)silane prepared in Example 9 is dissolved in toluene with a molar equivalent of vinylferrocene and tris(triphenylphoshine)rhodium chloride (Wilkinson's catalyst) and heated for >4 hours to form tris(trichlorosilyl)silylvinylferrocene by dehydrogenative coupling. This intermediate can be reduced to form 2-(2-ferrocenylethenyl)isotetrasilane (formula (15)), as described in Example 3.
Reaction SMILES: C([Li])CCC.[CH2:6]([O:13][C:14]1[CH:30]=[CH:29][C:17]([CH2:18][C:19]2[CH:28]=[C:27]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=[CH:26]3)[CH:20]=2)=[CH:16][C:15]=1Br)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[CH2:32]([O:39][C@@H:40]1[C@@H:46]([O:47][CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)[C@H:45]([O:55][CH2:56][C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)[C@@H:44]([CH2:63][O:64][CH2:65][C:66]2[CH:71]=[CH:70][CH:69]=[CH:68][CH:67]=2)[O:43][C:41]1=[O:42])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[Cl-].[NH4+]>C1COCC1.CCCCCC>[CH:20]1[C:21]2[C:27]([CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:28][C:19]=1[CH2:18][C:17]1[CH:29]=[CH:30][C:14]([O:13][CH2:6][C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)=[C:15]([C:41]2([O:43][C@H:44]([CH2:63][O:64][CH2:65][C:66]3[CH:67]=[CH:68][CH:69]=[CH:70][CH:71]=3)[C@@H:45]([O:55][CH2:56][C:57]3[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=3)[C@H:46]([O:47][CH2:48][C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=3)[C@H:40]2[O:39][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[OH:42])[CH:16]=1
Reactant: Brc1cc(Cc2cc3cccccc-3c2)ccc1OCc1ccccc1
Reactant: O=C1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: OC1(c2cc(Cc3cc4cccccc-4c3)ccc2OCc2ccccc2)O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Reaction time: 0.17 h
Yield: 468.1 %

Procedure:
A 1.6 M n-hexane solution of n-butyl lithium (0.32 ml) was added dropwise to a solution of 2-[4-(benzyloxy)-3-bromobenzyl]azulene (0.17 g) in THF (3.0 ml) at −55° C. and the mixture was stirred at the same temperature for 10 minutes. A solution of 2,3,4,6-tetra-O-benzyl-glucono-1,5-lactone (0.12 g) in THF (3.0 ml) was added dropwise to the reaction mixture and the mixture was stirred at the same temperature for 30 minutes. Saturated aqueous solution of ammonium chloride was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel column chromatography (ethyl acetate-n-hexane) to obtain 1-C-[5-(azulen-2-ylmethyl)-2-(benzyloxy)phenyl]-2,3,4,6-tetra-O-benzyl-D-glucopyranose (0.9 g).
Reaction SMILES: [F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([NH:13][C:14]([N:16]2[CH2:21][CH2:20][N:19]([C:22]3[C:26](Cl)=[N:25][S:24][N:23]=3)[CH2:18][CH2:17]2)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:30][N:31]([CH3:40])[C:32]1[CH:33]=[C:34]([CH2:38][OH:39])[CH:35]=[CH:36][CH:37]=1.C(C(CCC)[O-])(C)(C)C.[K+].C(O)(C)(C)C>>[F:1][C:2]([F:29])([F:28])[C:3]1[CH:4]=[C:5]([NH:13][C:14]([N:16]2[CH2:21][CH2:20][N:19]([C:22]3[C:26]([O:39][CH2:38][C:34]4[CH:35]=[CH:36][CH:37]=[C:32]([N:31]([CH3:40])[CH3:30])[CH:33]=4)=[N:25][S:24][N:23]=3)[CH2:18][CH2:17]2)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1
Reactant: O=C(Nc1cc(C(F)(F)F)cc(C(F)(F)F)c1)N1CCN(c2nsnc2Cl)CC1
Reactant: CN(C)c1cccc(CO)c1
Agent: CCCC([O-])C(C)(C)C
Agent: [K+]
Solvent: CC(C)(C)O
Product: CN(C)c1cccc(COc2nsnc2N2CCN(C(=O)Nc3cc(C(F)(F)F)cc(C(F)(F)F)c3)CC2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 49.7 %

Procedure:
To a round bottom flask equipped with a magnetic stir bar was added 4-(4-Chloro-[1,2,5]thiadiazol-3-yl)-piperazine-1-carboxylic acid (3,5-bis-trifluoromethyl-phenyl)-amide (0.1 g, 0.21 mmol, 1.0 eq.), (3-Dimethylamino-phenyl)-methanol (0.065 g, 0.062 mL, 0.43 mmol, 2.0 eq) and 1M potassium tert-butyl butoxide in t-butanol (0.65 ml, 0.65 mmol, 3.0 eq). The mixture was stirred at room temperature overnight. After removal of solvent in vacuo, the crude mixture was purified on preparative HPLC, affording the title compound N-[3,5-bis(trifluoromethyl)phenyl]-4-[4-({[3-(dimethylamino)phenyl]methyl}oxy)-1,2,5-thiadiazol-3-yl]piperazine-1-carboxamide as a white solid (0.06 g, 55% yield). 1H NMR (DMSO-d6) 9.23 (s, 1H), 8.18 (s, 2H), 7.59 (s, 1H), 7.22 (m, 1H), 6.89 (s, 1H), 6.78 (m, 2H), 5.39 (m, 4H), 3.61 (m, 4H), 3.53 (m, 4H), 2.92 (s, 6H) ppm.
Reaction SMILES: [NH2:1][C:2]1[C:6]2=[N:7][CH:8]=[CH:9][CH:10]=[C:5]2[S:4][C:3]=1[C:11]([O:13][CH3:14])=[O:12].C(N(CC)CC)C.[C:22](Cl)(Cl)=[O:23].C1(C)C=CC=CC=1>C1COCC1>[N:1]([C:2]1[C:6]2=[N:7][CH:8]=[CH:9][CH:10]=[C:5]2[S:4][C:3]=1[C:11]([O:13][CH3:14])=[O:12])=[C:22]=[O:23]
Reactant: COC(=O)c1sc2cccnc2c1N
Reactant: O=C(Cl)Cl
Solvent: Cc1ccccc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: COC(=O)c1sc2cccnc2c1N=C=O
Temperature: -78 °C
Reaction time: 2 h

Procedure:
Methyl 3-aminothieno[3,2-b]pyridine-2-carboxylate (0.624 g, 3.00 mmol), prepared as described in (Journal of Heterocyclic Chemistry, 24: 85 (1987), and triethylamine (0.84 mL, 6.0 mmol) in THF (20 mL) at −78° C. was treated with a 1.93M solution of phosgene in toluene (1.7 mL, 3.3 mmol), stirred for 2 hours at −78° C., concentrated, and used in subsequent steps without further purification.
Reaction SMILES: C(OC(=O)O[C@H:6]1[CH2:10][C@@H:9]([N:11]2[CH:19]=[N:18][C:17]3[C:12]2=[N:13][C:14]([Cl:21])=[N:15][C:16]=3[Cl:20])[CH:8]=[CH:7]1)C.ClC1N=C2C(N=CN2[C@@H]2C[C@H](O)C=C2)=C(Cl)N=1.[C:40]([O:44][C:45](=[O:51])[NH:46][C:47](=[O:50])[CH2:48][CH3:49])([CH3:43])([CH3:42])[CH3:41].C(N(C(OC(C)(C)C)=O)[C@H]1C[C@@H](N2C=NC3C2=NC(Cl)=NC=3Cl)C=C1)(OC(C)(C)C)=O>>[C:40]([O:44][C:45](=[O:51])[N:46]([C@H:6]1[CH2:10][C@@H:9]([N:11]2[CH:19]=[N:18][C:17]3[C:12]2=[N:13][C:14]([Cl:21])=[N:15][C:16]=3[Cl:20])[CH:8]=[CH:7]1)[C:47](=[O:50])[CH2:48][CH3:49])([CH3:42])([CH3:41])[CH3:43]
Reactant: CCOC(=O)O[C@@H]1C=C[C@H](n2cnc3c(Cl)nc(Cl)nc32)C1
Reactant: CCC(=O)NC(=O)OC(C)(C)C
Agent: CC(C)(C)OC(=O)N(C(=O)OC(C)(C)C)[C@@H]1C=C[C@H](n2cnc3c(Cl)nc(Cl)nc32)C1
Agent: O[C@@H]1C=C[C@H](n2cnc3c(Cl)nc(Cl)nc32)C1
Product: CCC(=O)N(C(=O)OC(C)(C)C)[C@@H]1C=C[C@H](n2cnc3c(Cl)nc(Cl)nc32)C1

Procedure:
The title compound is prepared from carbonic acid (1S,4R)-4-(2,6-dichloro-purin-9-yl)-cyclopent-2-enyl ester ethyl ester (an intermediate for preparing the compound of Example 4) and propionyl-carbamic acid tert-butyl ester (see preparation of intermediates) using a procedure analogous to that of di-Boc-[(1S,4R)-4-(2,6-dichloro-purin-9-yl)-cyclopent-2-enyl]-amine (another intermediate for preparing the compound of Example 4). 1H nmr (CDCl3, 400 MHz); 8.70(s, 1H), 6.15(m, 1H), 5.85(m, 1H), 5.80(m, 1H), 5.60(m, 1H), 3.15(m, 1H), 2.75(q, 2H), 2.10(m, 1H), 1.55(s, 9H), 1.15(t, 3H), MS (ES+) m/e 426 (MH+).
Reaction SMILES: O1CCCC1.C(N(CC)CC)C.[C:13]([C:17]#[CH:18])([CH3:16])([CH3:15])[CH3:14].[CH3:19][C:20]1[CH:26]=[C:25](I)[C:24]([CH3:28])=[CH:23][C:21]=1[NH2:22]>[Cu](I)I.C(OCC)(=O)C.O>[CH3:19][C:20]1[CH:26]=[C:25]([C:18]#[C:17][C:13]([CH3:16])([CH3:15])[CH3:14])[C:24]([CH3:28])=[CH:23][C:21]=1[NH2:22]
Reactant: C#CC(C)(C)C
Reactant: Cc1cc(I)c(C)cc1N
Agent: I[Cu]I
Solvent: C1CCOC1
Solvent: O
Solvent: CCN(CC)CC
Product: Cc1cc(C#CC(C)(C)C)c(C)cc1N
Temperature: 50 °C
Reaction time: 15 h

Procedure:
Tetrahydrofuran (5 ml), 5 ml of triethylamine, 216 mg of tert-butylacetylene, 71 mg of palladium chloride-ditriphenylphosphine complex, and 19 mg of copper iodide were added to 0.5 q of 2,5-dimethyl-4-iodoaniline, and the mixture was stirred at 50° C. for 15 hours. After completion of the reaction, water was added to the reaction solution, and extraction was performed 3 times with ethyl acetate. The organic layer was collected, washed with a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=10:1), thereby obtaining 0.31 g of 2,5-dimethyl-4-(3,3-dimethyl-1-butynyl)aniline (Compound 4-25).