Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:17][CH2:18][CH:19]([NH2:38])[CH2:20][O:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].[C:39](#[N:42])[CH:40]=[CH2:41].[OH-].[Na+].[OH-].C([N+](CCCC)(CCCC)CCCC)CCC>>[CH2:1]([O:17][CH2:18][CH:19]([NH:38][CH2:41][CH2:40][C:39]#[N:42])[CH2:20][O:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCCCCCCCCCCCOCC(N)COCCCCCCCCCCCCCCCC
Reactant: C=CC#N
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Na+]
Agent: [OH-]
Product: CCCCCCCCCCCCCCCCOCC(COCCCCCCCCCCCCCCCC)NCCC#N
Temperature: 60 °C
Reaction time: 0.25 h
Yield: 36 %

Procedure:
A mixture of 1,3-di(n-hexadecyloxy)-2-aminopropane (500 mg., 0.93 mmoles), acrylonitrile (75 ml.) and 2 wt. % aqueous sodium hydroxide solution (75 ml.) was heated to 60° C. Tetrabutyl ammonium hydroxide (1 ml. of 40 wt. % aqueous solution) was then added and the resulting mixture stirred for 15 minutes at 90° C. The reaction mixture was then cooled, causing precipitation of solids, which were isolated by filtration and found (TLC) to contain a large quantity of unreacted starting material. Using fresh acrylonitrile and aqueous sodium hydroxide solution in each cycle, the solids were treated two more times by the above procedure The third cycle solid product was purified by silica gel chromatography (elution with toluene:ethyl acetate) [200 mg., 36% yield, m.p. 45°-46° C., ir (CHCl3) 2250 cm-1, n.m.r. (CDDl3) δ3.07 (t, 2, --NHCH2CH2CN) and 2.53 (t, 2, --NHCH2CH2CN)].
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:12]3[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]3)[N:9]=[C:10](I)[C:3]=12.[F:25][C:26]1[CH:31]=[C:30]([O:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:29]=[CH:28][C:27]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>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.O>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@@H:12]3[CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]3)[N:9]=[C:10]([C:27]3[CH:28]=[CH:29][C:30]([O:32][C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[CH:31][C:26]=3[F:25])[C:3]=12
Reactant: OB(O)c1ccc(Oc2ccccc2)cc1F
Reactant: CC(C)(C)OC(=O)N1CCC[C@@H](n2nc(I)c3c(N)ncnc32)C1
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: O
Solvent: COCCOC
Product: CC(C)(C)OC(=O)N1CCC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3F)c3c(N)ncnc32)C1
Temperature: 80 °C
Reaction time: 12 h
Yield: 70.5 %

Procedure:
Into a 100 mL 3-necked round-bottom flask purged and maintained under an inert atmosphere of nitrogen, was placed tert-butyl (3R)-3-[4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate (400 mg, 0.90 mmol, 1.00 equiv), (2-fluoro-4-phenoxyphenyl)boronic acid (250 mg, 1.08 mmol, 1.20 equiv), sodium carbonate (190 mg, 1.79 mmol, 1.99 equiv), ethylene glycol dimethyl ether (50 mL), water (15 mL), and Pd(PPh3)4 (52 mg, 0.04 mmol, 0.05 equiv). The resulting solution was stirred for 12 h at 80° C. and then concentrated under vacuum. The residue was loaded onto a silica gel column and eluted with dichloromethane/methanol (100/1) to give 320 mg (70%) of tert-butyl (3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carboxylate as a yellow solid.
Reaction SMILES: Cl[C:2]1[CH:12]=[C:6]2[N:7]([CH3:11])[CH2:8][CH2:9][CH2:10][N:5]2[C:4](=[O:13])[N:3]=1.[C:14]1([CH2:20][CH2:21][SH:22])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C([O-])([O-])=O.[K+].[K+]>CS(C)=O>[CH3:11][N:7]1[CH2:8][CH2:9][CH2:10][N:5]2[C:4](=[O:13])[N:3]=[C:2]([S:22][CH2:21][CH2:20][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[CH:12]=[C:6]12
Reactant: SCCc1ccccc1
Reactant: CN1CCCn2c1cc(Cl)nc2=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: CN1CCCn2c1cc(SCCc1ccccc1)nc2=O
Temperature: 100 °C
Reaction time: 16 h
Yield: 46.4 %

Procedure:
To a solution of 8-chloro-1-methyl-3,4-dihydro-1H-pyrimido[1,6-a]pyrimidin-6(2H)-one (100 mg, 0.501 mmol) and 2-phenylethanethiol (83 mg, 0.601 mmol) in dimethyl sulfoxide (DMSO) (3 mL) was added K2CO3 (208 mg, 1.503 mmol). The reaction mixture was stirred at 100° C. for 16 hr. The crude product was purified by Prep-HPLC to afford 70 mg title product.
Reaction SMILES: [F:1][C:2]([C:5]1[CH:6]=[CH:7][C:8]([O:25][CH3:26])=[C:9]([CH:24]=1)[CH2:10][NH:11][C@H:12]1[CH2:17][CH2:16][CH2:15][NH:14][C@H:13]1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([F:4])[CH3:3].[C:27]([OH:37])(=[O:36])[C@@H:28]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[OH:29]>C(O)C>[C:27]([OH:37])(=[O:36])[CH:28]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[OH:29].[F:1][C:2]([C:5]1[CH:6]=[CH:7][C:8]([O:25][CH3:26])=[C:9]([CH:24]=1)[CH2:10][NH:11][C@H:12]1[CH2:17][CH2:16][CH2:15][NH:14][C@H:13]1[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([F:4])[CH3:3]
Reactant: O=C(O)[C@H](O)c1ccccc1
Agent: COc1ccc(C(C)(F)F)cc1CN[C@H]1CCCN[C@H]1c1ccccc1
Solvent: CCO
Product: O=C(O)C(O)c1ccccc1

Procedure:
To a solution of Compound 36 (179 mg, 0.50 mmol) in ethanol (3 ml) was added (R)-(−)-mandelic acid (75.4 mg, 0.50 mmol) at room temperature. After the solvent was evaporated in vacuo, the residue was recrystallized from ethanol-diethyl ether to give Compound 37 (168 mg, 66%) as a white solid.
Reaction SMILES: [Cl:1][C:2]1[C:3]([Cl:11])=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=[O:8].O.[C:13]1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[CH3:13][O:8][C:7](=[O:9])[C:6]1[CH:10]=[C:2]([Cl:1])[C:3]([Cl:11])=[N:4][CH:5]=1
Reactant: O=C(O)c1cnc(Cl)c(Cl)c1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CO
Product: COC(=O)c1cnc(Cl)c(Cl)c1
Temperature: 25 °C

Procedure:
A solution of 5,6-dichloro-nicotinic acid (1.92 g, 10 mmol, Aldrich) and p-toluenesulfonic acid monohydrate (190 mg, 1.0 mmol, Aldrich) in methanol (5 mL, Aldrich) was heated at reflux for 25 h. The reaction mixture was cooled to room temperature, the solvent was removed in vacuo and the residue was dissolved in EtOAc (50 mL). The solution was washed with satd. NaHCO3 (20 mL) and brine (20 mL), dried over Na2SO4, and filtered. The filtrate was evaporated in vacuo and the residue was purified by silica gel column chromatography, eluting with 30% EtOAc/hexane to give the title compound as a white solid. MS ESI, pos. ion) m/e: 205 (M+1).
Reaction SMILES: [N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]=1[C:10]1[CH:17]=[CH:16][C:13]([CH:14]=O)=[CH:12][CH:11]=1.[C:18]([O:22][C:23]([N:25]1[C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[N:27]=[C:26]1[CH2:34][NH:35][CH:36]1[C:45]2[N:44]=[CH:43][CH:42]=[CH:41][C:40]=2[CH2:39][CH2:38][CH2:37]1)=[O:24])([CH3:21])([CH3:20])[CH3:19].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C1COCC1>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:17]=[CH:16][C:13]([CH2:14][N:35]([CH2:34][C:26]2[N:25]([C:23]([O:22][C:18]([CH3:20])([CH3:21])[CH3:19])=[O:24])[C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=3[N:27]=2)[CH:36]2[C:45]3[N:44]=[CH:43][CH:42]=[CH:41][C:40]=3[CH2:39][CH2:38][CH2:37]2)=[CH:12][CH:11]=1
Reactant: O=Cc1ccc(-c2nc3ccccc3[nH]2)cc1
Reactant: CC(C)(C)OC(=O)n1c(CNC2CCCc3cccnc32)nc2ccccc21
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Product: CC(C)(C)OC(=O)n1c(CN(Cc2ccc(-c3nc4ccccc4[nH]3)cc2)C2CCCc3cccnc32)nc2ccccc21
Temperature: 60 °C
Reaction time: 3 h
Yield: 32.1 %

Procedure:
Using General Procedure B: To a solution 4-(benzimidazol-2-yl)-benzaldehyde (39 mg, 0.175 mmol) and (1-tert-butoxycarbonyl-1H-Benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine (60 mg, 0.16 mmol) in THF (2 mL) was added acetic acid (90 μL) and sodium triacetoxyborohydride (68 mg, 0.32 mmol) and the mixture stirred at 60° C. for 3 h. Purification of the crude product by radial chromatography on silica gel (0.7%MeOH/0.5%NH4OH/CH2Cl2) afforded the desired [4-(1H-benzimidazol-2-yl)-benzyl]-(N-tert-butoxycarbonylbenzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amine (30 mg, 39%) as a flaky white solid. 1H NMR (CDCl3) δ1.72 (s, 10H), 1.97 (m, 2H), 2.26 (m, 1H), 2.73 (m, 2H), 3.80 (d, 1H, J=15.0 Hz), 4.00 (d, 1H, J=15.0 Hz), 4.35 (m, 1H), 4.71 (s, 2H), 7.00 (m, 1H), 7.14 (m, 2H), 7.24 (m, 3H), 7.33 (d, 2H, J=7.2 Hz), 7.47 (br, 1H), 7.53 (d, 1H, J=7.2 Hz), 7.63 (d, 1H, J=7.8 Hz), 7.67 (d, 2H, J=7.8 Hz), 7.79 (br, 1H), 8.39 (d, 1H, J=3.5 Hz), 9.92 (br, 1H (NH)).
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][C:5]([I:8])=[CH:4][CH:3]=1.C([Li])CCC.N#N.[Cl:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][O:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[CH2:32][CH2:33][CH:34]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[CH:35]=O>O1CCCC1>[Cl:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][O:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[CH2:32][CH2:33][C:34]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[CH:35][C:2]1[CH:7]=[CH:6][C:5]([I:8])=[CH:4][CH:3]=1
Reactant: Ic1ccc(I)cc1
Reactant: O=CC(CCc1ccccc1OCCCCCCCCCl)c1ccccc1
Agent: N#N
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: ClCCCCCCCCOc1ccccc1CCC(=Cc1ccc(I)cc1)c1ccccc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a stirred solution of 1,4-diiodobenzene (9.9 g, 30 mmol) in anhydrous tetrahydrofuran (100 ml) was added n-butyllithium (18.75 ml, 1.6M in hexanes, 30 mmol) dropwise under N2 at -78° C., and stirring was continued for 15 min. A solution of 1-(4-(8-chlorooctoxy-phenyl)-2-phenyl-1-butanone (11.18 g, 29 mmol) in tetrahydrofuran (50 ml) was added and stirring continued at -78° C. for 2 h. Then the mixture was allowed to warm to room temperature. After 16 h, the mixture was quenched with saturated ammonium chloride solution (10 ml), poured into ether (100 ml) and washed with brine (50 ml) and water (2×50 ml). The organic layer was dried (MgSO4), and concentrated in vacuo. The residues were dissolved in ethanol (100 ml), concentrated hydrochloric acid (50 ml) was added and the mixture was refluxed for 4 h. The ethanol was removed in vacuo, the residues were dissolved in ether (50 ml), washed with water (3×50 ml), dried (MgSO4) and concentrated in vacuo. The residues were column-chromatographed (silica; eluant: 10% dichloromethane in petrol) to give a mixture of the title compound and the Z Isomer as a viscous colourless oil (13.6 g). Crystalisation from ethanol gave the title compound as white crystals (5.35 g, 31%) mp 64°-66° C. NMR (CDCl3) δ=0.89 (3H,t,J=7.5 Hz), 1.26-1.46 (8H, m), 1.60-1.80 (4H,m), 2.415 (2H,q,J=7.4 Hz), 3.50 (2H,t,J=6.6 Hz), 3.79 (2H,t,J=6.6 Hz), 6.505 (2H,d,J=8.7 Hz), 6.705 (2H,d,J=8.7 Hz), 6.965 (2H,d,J=8.4 Hz), 7.07-7.19 (5H,m), 7.65 (2H,d,J=8.2 Hz). IR (evap, cm-1) 2931, 2857, 1606, 1509. MS(CI) m/e=574 (M+ +1, 10%) Analysis C30H34ClIO requires C 62.89, H 5.98, Cl 6.19, I 22.15; found C 66.92, H 5.95, Cl 6.30, I 22.05%
Reaction SMILES: C1O[C:5]2([CH2:10][CH2:9][N:8]([C:11]3[CH:16]=[CH:15][C:14]([C:17]#[N:18])=[CH:13][CH:12]=3)[CH2:7][CH2:6]2)[O:4]C1C.Cl>CCOCC>[C:17]([C:14]1[CH:13]=[CH:12][C:11]([N:8]2[CH2:9][CH2:10][C:5](=[O:4])[CH2:6][CH2:7]2)=[CH:16][CH:15]=1)#[N:18]
Reactant: CC1COC2(CCN(c3ccc(C#N)cc3)CC2)O1
Agent: Cl
Solvent: CCOCC
Product: N#Cc1ccc(N2CCC(=O)CC2)cc1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
A solution of 34 (915 mg, 3.54 mmol) in ether (6 mL) was treated with 6N aqueous HCl (25 mL). The mixture was stirred at room temperature (2 d). The solvent was removed in vacuo and the residue dissolved in 3N HCl (25 mL) and acetic acid (20 mL). The mixture was stirred at room temperature (2 h). The solvent was removed in vacuo and the residue dissolved in dichloromethane and sodium carbonate solution. The aqueous layer was extracted with two additional portions of dichloromethane and the combined organic extracts were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. PCTLC (SiO2, 4 mm, 10% EtOH-90% CHCl3) afforded the title compound (35).
Reaction SMILES: [N+:1]1([O-:9])[C:2]([CH3:8])=[CH:3][CH:4]=[CH:5][C:6]=1[CH3:7].[F:10][B-:11]([F:14])([F:13])[F:12].[CH3:15][O+](C)C>ClCCl>[F:10][B-:11]([F:14])([F:13])[F:12].[CH3:15][O:9][N+:1]1[C:6]([CH3:7])=[CH:5][CH:4]=[CH:3][C:2]=1[CH3:8]
Reactant: Cc1cccc(C)[n+]1[O-]
Reactant: C[O+](C)C
Agent: F[B-](F)(F)F
Solvent: ClCCl
Product: CO[n+]1c(C)cccc1C
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A solution of 2,6-lutidine N-oxide (24.0 g, 0.20 mol) in anhydrous dichloromethane (400 mL) was added to trimethyloxonium tetrafluoroborate (29.6 g, 0.20 mol) at room temperature under nitrogen atmosphere and the reaction mixture was stirred at room temperature for 3 hours. The mixture was concentrated in vacuo to give the crude product, 1-methoxy-2,6-dimethyl-pyridinium tetrafluoroborate.
Reaction SMILES: C[O:2][C:3]([C:5]1[C:13]([NH:14][C:15]2[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][C:16]=2[Cl:22])=[C:12]([F:23])[C:8]2[N:9]=[CH:10][NH:11][C:7]=2[CH:6]=1)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[Br:21][C:18]1[CH:19]=[CH:20][C:15]([NH:14][C:13]2[C:5]([CH2:3][OH:2])=[CH:6][C:7]3[NH:11][CH:10]=[N:9][C:8]=3[C:12]=2[F:23])=[C:16]([Cl:22])[CH:17]=1
Reactant: COC(=O)c1cc2[nH]cnc2c(F)c1Nc1ccc(Br)cc1Cl
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: OCc1cc2[nH]cnc2c(F)c1Nc1ccc(Br)cc1Cl
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 99.8 %

Procedure:
6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid methyl ester 8b (1.06 g, 2.65 mmol) is suspended in tetrahydrofuran (25 mL) and cooled to −78° C. Lithium aluminum hydride (8.03 mL, 8.03 mmol, 1M solution in tetrahydrofuran) is added dropwise to the reaction mixture. After stirring for 10 minutes at −78° C., the reaction mixture is warmed to 0° C. and becomes a homogeneous solution. The reaction mixture is stirred for 5 minutes at 0° C. and then cooled again to −78° C. The reaction mixture is quenched with MeOH, diluted with Rochelle's salt, warmed to room temperature and stirred for 1 hour. The reaction mixture is then poured into a separatory funnel, diluted with ethyl acetate, and the layers separated. The aqueous phase is extracted with ethyl acetate. The combined ethyl acetate layers are dried (Na2SO4) and concentrated under reduced pressure to yield 0.98 g (100%) of the pure desired product as a pale yellow solid. MS ESI (+) m/z 370, 372 (M+, Br pattern) detected.
Reaction SMILES: [CH2:1](S)[CH2:2][SH:3].S1CCC1S[Sn:10]([S:21][CH:22]1[CH2:25][CH2:24][S:23]1)([S:16]C1CCS1)[S:11][CH:12]1[CH2:15][CH2:14][S:13]1>>[S:23]1[CH2:24][CH2:25][CH:22]1[S:21][Sn:10]1([S:11][CH:12]2[CH2:15][CH2:14][S:13]2)[CH2:1][CH2:2][S:3][S:16]1
Reactant: C1CC(S[Sn](SC2CCS2)(SC2CCS2)SC2CCS2)S1
Reactant: SCCS
Product: C1C[Sn](SC2CCS2)(SC2CCS2)SS1
Temperature: 25 °C
Reaction time: 2 h
Yield: 83.8 %

Procedure:
18.84 g (0.2 mole) of 1,2-ethanedithiol was introduced into 107.9 g (0.2 mole) of tetrakis(thietanylthio)tin prepared in Reference Preparation Example 3, and the resulting mixture was stirred at room temperature (20 degrees centigrade) for 2 hours. In order to remove the by-produced 3-mercaptothietane, methanol was introduced, each time of introducing in an amount of 100 g, and the resulting solution was stirred and washed. In this way, a separation operation was repeatedly carried out 8 times by decantation to precipitate a white solid. The precipitated solid was collected by filtration and dried to obtain 70.6 g (Yield: 84%) of bis(thietanylthio)dithiastannolane as a white crystal.
Reaction SMILES: [Br:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([OH:9])=[C:4]([O:10][CH3:11])[CH:3]=1.FC1C=CC([N+]([O-])=O)=CC=1C(F)(F)F.[F:26][C:27]1[CH:32]=[CH:31][CH:30]=[C:29](F)[N:28]=1>>[Br:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([O:9][C:29]2[CH:30]=[CH:31][CH:32]=[C:27]([F:26])[N:28]=2)=[C:4]([O:10][CH3:11])[CH:3]=1
Reactant: COc1cc(Br)c(F)cc1O
Reactant: Fc1cccc(F)n1
Agent: O=[N+]([O-])c1ccc(F)c(C(F)(F)F)c1
Product: COc1cc(Br)c(F)cc1Oc1cccc(F)n1

Procedure:
According to the procedure of example 20(a) except substituting 2-methoxy-4-propylphenol for 4-bromo-5-fluoro-2-methoxyphenol (441 mg; 2 mmol), and 1-fluoro-4-nitro-2-(trifluoromethyl)benzene for 2,6-Difluoropyridine (0.18 mL; 2 mmol), the title compound was prepared as a yellow oil (246 mg; 39%), after purification on silica gel (cyclohexane/ethyl acetate: 95/5).
Reaction SMILES: [C:1]([C:3]1[N:4]([CH2:28][C:29]2[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][C:30]=2[O:37][CH3:38])[C:5](=[O:27])[N:6]([C:17]2[C:25]3[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=3)[N:19]([CH3:26])[CH:18]=2)[C:7]=1[C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10][CH:9]=1)#[N:2].[H-].[Li+].C(O[C@H:45]1[CH2:50][CH2:49][C@@H:48]([O:51][Si:52]([C:55]([CH3:58])([CH3:57])[CH3:56])([CH3:54])[CH3:53])[CH:47]=[CH:46]1)(=O)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CN(C=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[Cl-].[Li+]>[Si:52]([O:51][C@@H:48]1[CH2:49][CH2:50][C@H:45]([N:10]2[C:11]3[C:16](=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:8]([C:7]3[N:6]([C:17]4[C:25]5[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=5)[N:19]([CH3:26])[CH:18]=4)[C:5](=[O:27])[N:4]([CH2:28][C:29]4[CH:34]=[CH:33][C:32]([O:35][CH3:36])=[CH:31][C:30]=4[O:37][CH3:38])[C:3]=3[C:1]#[N:2])=[CH:9]2)[CH:46]=[CH:47]1)([C:55]([CH3:58])([CH3:57])[CH3:56])([CH3:54])[CH3:53]
Reactant: CC(=O)O[C@@H]1C=C[C@H](O[Si](C)(C)C(C)(C)C)CC1
Reactant: COc1ccc(Cn2c(C#N)c(-c3c[nH]c4ccccc34)n(-c3cn(C)c4ccccc34)c2=O)c(OC)c1
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: [Cl-]
Solvent: CN(C)C=O
Product: COc1ccc(Cn2c(C#N)c(-c3cn([C@@H]4C=C[C@H](O[Si](C)(C)C(C)(C)C)CC4)c4ccccc34)n(-c3cn(C)c4ccccc34)c2=O)c(OC)c1
Temperature: 60 °C
Reaction time: 0.75 h
Yield: 85.5 %

Procedure:
In a flask was added 0.30 g (0.59 mmole) of the product obtained in Example 17 step b), 0.012 g (1.5 mmole) of lithium hydride and 5 ml of dry DMF. The mixture was stirred under nitrogen at 60° C. for 45 min. The solution was degassed, and a solution of 0.16 g (0.59 mmole) of (1S,4R)-1-Acetoxy-4-(tert-butyldimethylsilanyloxy)-2-cyclohexene, 0.030 g (0.033 mmole) of Pd2(dba)3, 0.046 g (0.17 mmole) of triphenylphosphine, 2 mg of lithium chloride in 5 ml of DMF was added rapidly. The resulting solution was degassed again and stirred at 70° C. for 90 minutes. The solution was partitioned between ethyl acetate and water. The organic phase was collected and concentrated. The residue was purified on silica (Heptane:EtOAc 3:2) giving 0.36 g (85%) of the subtitle compound.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[CH2:15][CH2:14][CH2:13][N:12]([C:17](=[O:35])[CH:18]([N:25]4[C:29]([CH3:30])=[CH:28][C:27]([C:31]([F:34])([F:33])[F:32])=[N:26]4)[CH2:19][C:20]([O:22]CC)=[O:21])[C:11]=3[CH:10]=[N:9]2)=[CH:4][CH:3]=1.O[Li].O.C1COCC1.Cl>O.CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[CH2:15][CH2:14][CH2:13][N:12]([C:17](=[O:35])[CH:18]([N:25]4[C:29]([CH3:30])=[CH:28][C:27]([C:31]([F:32])([F:34])[F:33])=[N:26]4)[CH2:19][C:20]([OH:22])=[O:21])[C:11]=3[CH:10]=[N:9]2)=[CH:6][CH:7]=1
Reactant: CCOC(=O)CC(C(=O)N1CCCc2c1cnn2-c1ccc(F)cc1)n1nc(C(F)(F)F)cc1C
Agent: Cl
Agent: [Li]O
Solvent: O
Solvent: CO
Solvent: C1CCOC1
Product: Cc1cc(C(F)(F)F)nn1C(CC(=O)O)C(=O)N1CCCc2c1cnn2-c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 103.9 %

Procedure:
A mixture of ethyl 4-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-3-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]-4-oxo-butanoate (0.030 g, 0.060 mmol), LiOH.H2O (0.020 g, 0.47 mmol), THF (0.4 mL), MeOH (0.4 mL) and H2O (0.2 mL) was stirred for 30 min at rt. It was then acidified with 1 M aq. HCl (2 mL) and extracted with IPA/CHCl3 (1:2, 50 mL). The organic layer was separated, dried over Na2SO4, and concentrated in vacuo to yield 4-[1-(4-fluorophenyl)-6,7-dihydro-5H-pyrazolo[4,3-b]pyridin-4-yl]-3-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]-4-oxo-butanoic acid (0.029 g, 100%).
Reaction SMILES: Cl.[NH2:2][CH:3]1[C:15]2[N:14]3[CH:16]=[CH:17][N:18]=[C:13]3[C:12](=[O:19])[NH:11][C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]1=2.[C:20](Cl)(=[O:23])[CH2:21][CH3:22].C(N(CC)CC)C.O>CN(C)C=O.C(O)(=O)C>[C:20]([NH:2][CH:3]1[C:15]2[N:14]3[CH:16]=[CH:17][N:18]=[C:13]3[C:12](=[O:19])[NH:11][C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]1=2)(=[O:23])[CH2:21][CH3:22]
Reactant: CCC(=O)Cl
Reactant: NC1c2ccccc2-c2[nH]c(=O)c3nccn3c21
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: CC(=O)O
Product: CCC(=O)NC1c2ccccc2-c2[nH]c(=O)c3nccn3c21
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 40.4 %

Procedure:
To a suspension of 0.6 g of 10-amino-5H,10H-imidazo[1,2-a]indeno[1,2-e]pyrazin-4-one hydrochloride in 30 ml of anhydrous dimethylformamide, maintained under a nitrogen atmosphere at a temperature in the region of 0° C., are successively added 0.22 g of propionyl chloride and 0.4 g of triethylamine. The mixture is stirred for 3 hours 30 minutes and 0.22 g of propionyl chloride is added. The mixture is stirred for 1 hour at the same temperature and for 16 hours at a temperature in the region of 20° C. The insoluble material formed is removed by filtration and the filtrate is concentrated to dryness under reduced pressure (10 mmHg; 1.3 kPa) at 100° C. The product obtained (1.14 g) is dissolved at 40° C. in 10 ml of acetic acid and, after addition of 50 ml of distilled water, the solution is stirred for 1 hour at a temperature in the region of 20° C. The insoluble material formed is separated out by filtration, washed twice with 4 ml in total of distilled water and dried under reduced pressure (1 mmHg; 0.13 kPa) at 100° C. 0.26 g of 10-propionamido-5H,10H-imidazo[1,2-a]indeno-[1,2-e]pyrazin-4-one is thus obtained, decomposing without melting above 260° C. [N.M.R. spectrum: [200 MHz; (CD3)2SO d6 ; δ in ppm]: 1.14 (t, J=7.5 Hz, 3H: --CH3 ethyl); 2.28 (q, J=7.5 Hz, 2H: --COCH2 -ethyl); 6.18 (d, J=8.5 Hz, 1H: --CH-- 10); 7.38 and 7.48 (2t broad, J=8 Hz, 1H each: --H7 and --H8); 7.52 and 7.88 (2d broad, J=8 Hz, 1H each: --H6 and --H9); 7.60 and 7.62 (2s, 1H each: --H of the imidazole); 8.48 (d, J=8.5 Hz, 1H: --NHCO-- at 10); 12.43 (broad a, 1H: --CONH-- of the ring)].
Reaction SMILES: [CH3:1][C:2]1([CH3:15])[O:11][C:10]2[C:5](=[CH:6][C:7]([C:12]#[N:13])=[CH:8][CH:9]=2)[CH:4]2[O:14][CH:3]12.[C:16]1([N:22]2[CH:26]=[CH:25][C:24](=[O:27])[NH:23]2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>>[OH:14][CH:3]1[CH:4]([O:27][C:24]2[CH:25]=[CH:26][N:22]([C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)[N:23]=2)[C:5]2[C:10](=[CH:9][CH:8]=[C:7]([C:12]#[N:13])[CH:6]=2)[O:11][C:2]1([CH3:15])[CH3:1]
Reactant: O=c1ccn(-c2ccccc2)[nH]1
Reactant: CC1(C)Oc2ccc(C#N)cc2C2OC21
Product: CC1(C)Oc2ccc(C#N)cc2C(Oc2ccn(-c3ccccc3)n2)C1O

Procedure:
Following the procedure in Example 1, using (±)-2,2-dimethyl-1a,7b-dihydro-2H-1,3-dioxa-cyclopropa[a]naphthalene-6-carbonitrile and 1-phenyl-1,2-dihydro-pyrazol-3-one as starting materials, the title compounds were prepared as white solids.