Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([F:12])([F:11])[F:10])=[CH:5][C:4]=1[C:13](=[O:15])[CH3:14].B(Br)(Br)Br>ClCCl.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[OH:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]([F:10])([F:11])[F:12])=[CH:5][C:4]=1[C:13](=[O:15])[CH3:14]
Reactant: COc1ccc(C(F)(F)F)cc1C(C)=O
Agent: BrB(Br)Br
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [I-]
Solvent: ClCCl
Product: CC(=O)c1cc(C(F)(F)F)ccc1O
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 35.2 %

Procedure:
To a stirred solution of 1-[2-methoxy-5-(trifluoromethyl)phenyl]ethanone (35 g, 0.16 mol) in dry dichloromethane (400 mL) at 0° C. was added solid tetrabutylammonium iodide (2.96 g, 0.008 mol) followed by boron tribromide (33.96 mL, 0.35 mol) drop-wise. After addition, the reaction mixture was stirred at ambient temperature for 1.5 hours. The reaction mixture was cooled to 0° C. and quenched with ice. The mixture was extracted with diethyl ether (1 L). The organic layer was washed with water (2 L) and then saturated aqueous sodium chloride (1 L). After concentration of the organic layer at ambient temperature in vacuo, the crude product was purified by silica gel column chromatography (2% diethyl ether in hexane elution) to afford the title compound as a colourless oil (11.5 g, 35%).
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[C:13]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])(=[O:15])[CH3:14].[O:21]=[C:22]1[CH:27]=[C:26]([C:28](=[O:31])[CH2:29][CH3:30])[CH:25]=[CH:24][NH:23]1>O1CCCC1.O>[C:17]([O:16][C:13](=[O:15])[CH2:14][C:28]([OH:31])([C:26]1[CH:25]=[CH:24][NH:23][C:22](=[O:21])[CH:27]=1)[CH2:29][CH3:30])([CH3:20])([CH3:19])[CH3:18]
Reactant: CC(=O)OC(C)(C)C
Reactant: CCC(=O)c1cc[nH]c(=O)c1
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: O
Solvent: C1CCOC1
Product: CCC(O)(CC(=O)OC(C)(C)C)c1cc[nH]c(=O)c1
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
A solution of diisopropylamine (35 ml, 250 mmol) in anhydrous tetrahydrofuran (275 ml) is treated dropwise at 0° C., under argon, with n-butyllithium (2.5 M in hexane, 100 ml, 250 mmol). The resulting mixture is agitated at 0° C. for 15 min, then cooled down to −78° C. and treated with tert-butyl acetate (33.8 ml, 250 mmol). After agitation at −78° C. for 15 min, the resulting lithiated reagent is added dropwise, over 1 hour, using a transfer canula, to a solution of 1-(2-oxo-1,2-dihydro-4-pyridinyl)-1-propanone (obtained according to 1.g, 15.2 g, 100 mmol) at −78° C. in anhydrous tetrahydrofuran (330 ml) and the resulting mixture is maintained at −78° C. for 15 min, then allowed to return to 0° C. for 1 hour. The reaction medium is hydrolyzed by the addition of water (60 ml) then the volatiles are evaporated off under reduced pressure. The residue is taken up in ethyl acetate and the resulting solution is washed with water, dried and concentrated. The residue is suspended in diethyl ether and filtered in order to produce after drying 21.5 g (80%) of a white solid, m.p. 167° C.
Reaction SMILES: [F:1][C:2]([F:14])([F:13])[C:3]1[CH:12]=[CH:11][C:6]([C:7]([NH:9][NH2:10])=[O:8])=[CH:5][CH:4]=1.Cl.[C:16](=[NH:21])(OCC)[CH3:17]>>[NH:21]=[C:16]([NH:10][NH:9][C:7](=[O:8])[C:6]1[CH:11]=[CH:12][C:3]([C:2]([F:13])([F:14])[F:1])=[CH:4][CH:5]=1)[CH3:17]
Reactant: NNC(=O)c1ccc(C(F)(F)F)cc1
Reactant: CCOC(C)=N
Agent: Cl
Product: CC(=N)NNC(=O)c1ccc(C(F)(F)F)cc1

Procedure:
4.78 g (23.4 mmol) 4-(trifluoromethyl)benzoic acid hydrazide and 5.21 g (42.1 mmol) ethyl acetimidate hydrochloride are reacted as described for intermediate product 1a).
Reaction SMILES: Cl[CH2:2][CH2:3][N:4]([CH2:6][CH2:7]Cl)[CH3:5].C(#N)[CH:10]([CH2:12][C:13]#[N:14])O.C(=O)([O-])[O-].[K+].[K+].C(#[N:24])C>>[CH3:5][N:4]1[CH2:6][CH2:7][C:12]([C:10]#[N:24])([C:13]#[N:14])[CH2:2][CH2:3]1
Reactant: CC#N
Reactant: N#CCC(O)C#N
Reactant: CN(CCCl)CCCl
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CN1CCC(C#N)(C#N)CC1

Procedure:
A mixture of 31.2 g of bis(chloroethyl)methylamine, 13.2 g of malonitrile, 55.28 g of potassium carbonate and 800 ml of acetonitrile is refluxed on a steam bath for 24 hours, then filtered while hot. The filtrate is evaporated and the residue crystallized with charcoal treatment from 100 ml of ethanol, giving 10.6 g of 1-methylpiperidine-4,4-dicarbonitrile, as colorless crystals.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[NH:10][C@H:11]1[CH2:14][C@H:13]([NH:15][C:16]2[C:21]([NH2:22])=[CH:20][CH:19]=[CH:18][N:17]=2)[CH2:12]1.[C:23](Cl)(=O)[CH2:24][CH3:25].C(N(CC)CC)C>ClCCl>[CH2:24]([C:25]1[N:15]([C@H:13]2[CH2:12][C@H:11]([NH:10][C:2]3[S:1][C:5]4[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=4[N:3]=3)[CH2:14]2)[C:16]2=[N:17][CH:18]=[CH:19][CH:20]=[C:21]2[N:22]=1)[CH3:23]
Reactant: CCC(=O)Cl
Reactant: Nc1cccnc1N[C@H]1C[C@H](Nc2nc3ccccc3s2)C1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCc1nc2cccnc2n1[C@H]1C[C@H](Nc2nc3ccccc3s2)C1
Temperature: 100 °C
Reaction time: 1 h

Procedure:
N2-(Trans-3-(benzo[d]thiazol-2-ylamino)cyclobutyl)pyridine-2,3-diamine (0.075 g, 0.241 mmol) was suspended in dichloromethane (20 mL) and treated with propionyl chloride (0.03 ml, 0.357 mmol). Triethylamine (0.050 ml, 0.359 mmol) was added and the reaction stirred for 1 hour. The mixture was evaporated to dryness under reduced pressure and the crude redissolved in propionic acid (5 mL). The solution was heated at 100° C. for 16 hours. The mixture was evaporated to dryness under reduced pressure and purified using silica chromatography (0-10% methanol in dichloromethane gradient) followed by reverse phase HPLC gave the desired N-(trans-3-(2-ethyl-3H-imidazo[4,5-b]pyridin-3-yl)cyclobutyl)benzo[d]thiazol-2-amine (0.045 g, 0.129 mmol, 53.5% yield). M+1: 350.1. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.31 (t, J=7.53 Hz, 3 H) 2.46 (br. s., 1 H) 2.52-2.68 (m, 2 H) 2.79 (q, J=7.63 Hz, 2 H) 3.61-3.84 (m, 2 H) 4.47-4.68 (m, 1 H) 5.12 (quin, J=8.20 Hz, 1 H) 7.03 (t, J=7.53 Hz, 1 H) 7.12 (dd, J=7.92, 4.79 Hz, 1 H) 7.18-7.32 (m, 1 H) 7.52 (dd, J=21.91, 8.00 Hz. 2 H) 7.88 (dd, J=8.02, 1.37 Hz. 1 H) 8.26 (dd, J=4.69, 1.37 Hz. 1 H).
Reaction SMILES: [Li]CCCC.C([Mg]Cl)CCC.Br[C:13]1[CH:14]=[N:15][CH:16]=[C:17]([Br:19])[CH:18]=1.[O:20]=[C:21]1[CH2:25][CH2:24][CH:23]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:22]1>[NH4+].C1(C)C=CC=CC=1.C1COCC1>[Br:19][C:17]1[CH:18]=[C:13]([C:21]2([OH:20])[CH2:25][CH2:24][CH:23]([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:22]2)[CH:14]=[N:15][CH:16]=1
Reactant: Brc1cncc(Br)c1
Reactant: CCOC(=O)C1CCC(=O)C1
Agent: CCCC[Mg]Cl
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Product: CCOC(=O)C1CCC(O)(c2cncc(Br)c2)C1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of THF:toluene (2.11 mL:2.11 mL) and n-BuLi (0.923 ml, 1.48 mmol) was cooled to −10° C. The reaction mixture was purged/filled with argon (3×). n-Butyl magnesium chloride (0.369 ml, 0.739 mmol) was added to the reaction mixture and stirred for 30 minutes. 3,5-Dibromopyridine (0.5 g, 2.111 mmol) was added to the reaction mixture over the course of 30 minutes, keeping bath below −10° C. and stirred for 1 hour. Ethyl 3-oxocyclopentanecarboxylate (0.330 g, 2.111 mmol) was added to the reaction mixture and stirred at −10° C. for ˜5 minutes. The reaction mixture was warmed to room temperature, diluted with saturated ammonium, extracted DCM (3×), and combined organic layers were concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/hexanes) to afford ethyl 3-(5-bromopyridin-3-yl)-3-hydroxycyclopentanecarboxylate. MS ESI calc'd for C13H17BrNO3 [M+H]+ 314 and 316. found 314 and 316.
Reaction SMILES: [CH2:1]1[O:6][C:4](=[O:5])[NH:3][C@@H:2]1[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[Li]CCCC.[Br:19][CH2:20][C:21](Br)=[O:22].CCOC(C)=O.CCCCCC>C1COCC1.C(OCC)(=O)C>[CH2:7]([C@@H:2]1[CH2:1][O:6][C:4](=[O:5])[N:3]1[C:21](=[O:22])[CH2:20][Br:19])[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: O=C(Br)CBr
Reactant: O=C1N[C@H](Cc2ccccc2)CO1
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: CCCCCC
Product: O=C(CBr)N1C(=O)OC[C@H]1Cc1ccccc1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 78.9 %

Procedure:
To a solution of R-(−)-4-benzyl-2-oxazolidinone (15.0 g, 84.65 mmol) in THF (200 mL) was added nBuLi (2.5M in hexanes, 34 mL, 84.65 mmol) dropwise at −78° C. The solution was stirred at −78° C. for 30 min and then bromo acetyl bromide (18.65 g, 7.8 nL, 124.15 mmol) was added. The solution was allowed to warm to 25° C. overnight (19 h). An aliquot was taken and TLC (1:2 EtOAc-hexane) indicated that reaction was complete. It was diluted in ethyl acetate (200 mL) and the organic layer was washed with saturated aqueous NaRCO3 (2×50 mL). The organic layer was dried over MgSO4, filtered and concentrated to obtain a crude brown oil (24.6 g). The crude product was purified by flash chromatography, eluent: 1:4 EtOAc-hexane, to furnish (4R)-4-benzyl-3-(bromoacetyl)-1,3-oxazolidin-2-one as a colorless oil (19.9 g, 79.6%). Mass Spectrum (+ESI): 300, 299 (M+H)+.
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([NH:13][C:14]2[CH:19]=[CH:18][C:17]([N:20]3[CH2:25][CH2:24][CH:23]([N:26]4[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]4)[CH2:22][CH2:21]3)=[C:16]([CH3:33])[CH:15]=2)[C:5]([C:10]([NH2:12])=[O:11])=[N:6][C:7]=1[CH2:8][CH3:9].[NH2:34][CH2:35][CH:36]1[CH2:39][N:38]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:37]1.C(=O)([O-])[O-].[K+].[K+].CN1CCCC1=O>O.C(OCC)(=O)C>[C:10]([C:5]1[N:6]=[C:7]([CH2:8][CH3:9])[C:2]([NH:34][CH2:35][CH:36]2[CH2:39][N:38]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:37]2)=[N:3][C:4]=1[NH:13][C:14]1[CH:19]=[CH:18][C:17]([N:20]2[CH2:25][CH2:24][CH:23]([N:26]3[CH2:31][CH2:30][N:29]([CH3:32])[CH2:28][CH2:27]3)[CH2:22][CH2:21]2)=[C:16]([CH3:33])[CH:15]=1)(=[O:11])[NH2:12]
Reactant: CCc1nc(C(N)=O)c(Nc2ccc(N3CCC(N4CCN(C)CC4)CC3)c(C)c2)nc1Cl
Reactant: CC(C)(C)OC(=O)N1CC(CN)C1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CN1CCCC1=O
Product: CCc1nc(C(N)=O)c(Nc2ccc(N3CCC(N4CCN(C)CC4)CC3)c(C)c2)nc1NCC1CN(C(=O)OC(C)(C)C)C1
Yield: 27.8 %

Procedure:
A mixture of 5-chloro-6-ethyl-3-({3-methyl-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazine-2-carboxamide (350 mg), tert-butyl 3-(aminomethyl)azetidine-1-carboxylate (266 mg), potassium carbonate (154 mg), and N-methylpyrrolidone (7 mL) was reacted at 100° C. for 11.5 hours. To the mixture were added ethyl acetate and water, followed by liquid separation. The organic phase was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and then the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (eluent; chloroform:methanol=1:0-9:1) to obtain tert-butyl 3-({[5-carbamoyl-3-ethyl-6-({3-methyl-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl}amino)pyrazin-2-yl]amino}methyl)azetidine-1-carboxylate (128 mg) as a yellow solid.
Reaction SMILES: [C:1]1([S:7]([C:10]2[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=2N)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N([O-])=O.[Na+].[S:21]([O-:25])([O-])(=O)=[O:22].S(=O)(O)[O-].[Na+].[ClH:31]>O>[C:1]1([S:7]([C:10]2[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=2[S:21]([Cl:31])(=[O:25])=[O:22])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Cl
Reactant: Nc1ccccc1S(=O)(=O)c1ccccc1
Reactant: O=S(=O)([O-])[O-]
Agent: O=N[O-]
Agent: O=S([O-])O
Agent: [Na+]
Solvent: O
Product: O=S(=O)(Cl)c1ccccc1S(=O)(=O)c1ccccc1
Reaction time: 0.25 h
Yield: 66 %

Procedure:
To a solution of 2-(phenylsulfonyl)aniline (2.33 g, (10 mmol) in 30% aqueous hydrochloric acid (4 mL) was added 40% aqueous sodium nitrite (4 mL) at 0-5° C. After 15 minute, to the diazo solution were added 30% aqueous hydrochloric acid (10 mL), cooper sulfate (50 mg) and 40% aqueous sodium bisulfite (10 mL) at 5-10° C. The mixture was stirred for 30 minutes and additional water (30 mL) was added. The mixture was extracted into dichloromethane (3×40 mL) and the dichloromethane solution was washed with brine (40 mL) and dried over Na2SO4. After removing the solvent in vacuo, the residue was purified by flash column chromatography (dichloromethane) to give the title compound as a white solid (2.1 g, 66%). 1H-NMR (300 MHz, CDCl3) δ8.62 (d, J=7.8 Hz, 1H), 8.34 (d, J=7.9 Hz, 1H), 7.85-7.98 (m, 4H), 7.48-7.63 (m, 3H).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([NH:9]C(=O)C)[CH:5]=[CH:6][C:7]=1[CH3:8].[Cl:13][C:14]1[N:19]=[C:18]([N:20]2[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[CH:17]=[CH:16][N:15]=1.O>CN(C=O)C>[ClH:13].[CH3:8][C:7]1[C:2]([NH:1][C:14]2[N:19]=[C:18]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[CH:17]=[CH:16][N:15]=2)=[CH:3][C:4]([NH2:9])=[CH:5][CH:6]=1
Reactant: Clc1nccc(N2CCOCC2)n1
Reactant: CC(=O)Nc1ccc(C)c(N)c1
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ccc(N)cc1Nc1nccc(N2CCOCC2)n1
Product: Cl
Temperature: 100 °C
Reaction time: 8 h
Yield: 38.8 %

Procedure:
To a solution of N-(3-amino-4-methyl-phenyl) acetamide (5 g, 41 mmol) in DMF (5 ml) was added 4-(2-chloro-pyrimidin-4-yl)-morpholine (8.1 g, 40 mmol) and KI (0.5 g, 3 mmol), which was stirred at 100° C. overnight, cooled to 10° C. and added to H2O (100 mL). The resulting mixture was extracted with CH2Cl2 (2×100 mL), the combined organic layers dried (Na2SO4) and concentrated in vacuo. The residue was dissolved in conc. HCl (10 mL), stirred at 80° C. for 2 h and concentrated in vacuo to yield 6-methyl-N1-(4-morpholinopyrimidin-2-yl)benzene-1,3-diamine hydrochloride (5.0 g, 65%). 1H NMR (DMSO-d6): 8.00 (d, J=7.2 Hz, 1H), 7.57 (brs, 1H), 7.36 (d, J=8.4 Hz, 1H), 7.14 (dd, J=8.4, 1.6 Hz, 1H), 6.65 (d, J=7.2 Hz, 1H), 3.69 (s, 4H), 3.66 (s, 4H), 2.25 (s, 3H). MS (ESI) m/e: 286 (M++1).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)CC)(C)C.F[P-](F)(F)(F)(F)F.CN(C)C(F)=[N+](C)C.[NH:43]1[C:47]2=[N:48][CH:49]=[CH:50][CH:51]=[C:46]2[CH2:45][C@H:44]1[C:52]([O:54][CH2:55][CH3:56])=[O:53]>C(Cl)Cl>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH:13]1[CH2:18][CH2:17][O:16][CH2:15][CH2:14]1)[C:10]([N:43]1[C:47]2=[N:48][CH:49]=[CH:50][CH:51]=[C:46]2[CH2:45][C@H:44]1[C:52]([O:54][CH2:55][CH3:56])=[O:53])=[O:12])=[O:7])([CH3:2])([CH3:3])[CH3:4]
Reactant: CCOC(=O)[C@@H]1Cc2cccnc2N1
Reactant: CC(C)(C)OC(=O)N[C@H](C(=O)O)C1CCOCC1
Agent: CN(C)C(F)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CCOC(=O)[C@@H]1Cc2cccnc2N1C(=O)[C@@H](NC(=O)OC(C)(C)C)C1CCOCC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 48.8 %

Procedure:
In a 100 mL round-bottomed flask, (S)-2-(tert-butoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetic acid (270 mg, 1.04 mmol, Eq: 1.00) was combined with DCM (10 mL) to give a colorless solution. Diisopropylethylamine (0.73 mL, 4.16 mmol, Eq: 4) was added followed by N,N,N′,N′-tetramethylfluoroformamidinium hexafluorophosphate (824 mg, 3.12 mmol, Eq: 3). The reaction was stirred at rt for 1 h and then (S)-ethyl 2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate (200 mg, 1.04 mmol, Eq: 1.00) was added. After stirring overnight at rt, the reaction mixture was washed with saturated aqueous NaHCO3 (50 mL), dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 24 g, 0% to 30% EtOAc in hexanes) to give (S)-ethyl 1-((S)-2-(tert-butoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetyl)-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-2-carboxylate (220 mg), m/z=434 (M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:19]=[CH:18][C:5]2[O:6][C:7]3[CH:17]=[CH:16][CH:15]=[CH:14][C:8]=3[CH2:9][N:10]([C:11](Cl)=[O:12])[C:4]=2[CH:3]=1.CCN(CC)CC.[NH2:27][CH2:28][C:29]#[N:30]>C(Cl)Cl>[Cl:1][C:2]1[CH:19]=[CH:18][C:5]2[O:6][C:7]3[CH:17]=[CH:16][CH:15]=[CH:14][C:8]=3[CH2:9][N:10]([C:11]([NH:30][CH2:29][C:28]#[N:27])=[O:12])[C:4]=2[CH:3]=1
Reactant: O=C(Cl)N1Cc2ccccc2Oc2ccc(Cl)cc21
Reactant: N#CCN
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: N#CCNC(=O)N1Cc2ccccc2Oc2ccc(Cl)cc21
Yield: 80.6 %

Procedure:
By the method of Example 18, the title compound of Example 2 (5.24 g, 17.8 mmol) in 100 mL of CH2Cl2 with molecular sieves #5A (10 g) and Et3N (2.5 mL, 18.0 mmol) was reacted with aminoacetonitrile (1.0 g, 17.8 mmol) to produce 4.5 g of the title product.
Reaction SMILES: C([Li])(CC)C.Br[C:7]1[N:8]([Si:16]([CH:23]([CH3:25])[CH3:24])([CH:20]([CH3:22])[CH3:21])[CH:17]([CH3:19])[CH3:18])[C:9]2[C:14]([CH:15]=1)=[CH:13][CH:12]=[CH:11][CH:10]=2.[CH2:26]([N:29]1[C@H:33]([CH2:34][CH2:35][CH3:36])[CH2:32]OS1(=O)=O)[CH2:27][CH3:28].Cl>O1CCCC1.C1CCCCC1.CCCCCC>[CH:17]([Si:16]([CH:23]([CH3:25])[CH3:24])([CH:20]([CH3:22])[CH3:21])[N:8]1[C:9]2[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:15]([CH2:32][C@H:33]([NH:29][CH2:26][CH2:27][CH3:28])[CH2:34][CH2:35][CH3:36])=[CH:7]1)([CH3:19])[CH3:18]
Reactant: CCC[C@@H]1COS(=O)(=O)N1CCC
Reactant: CC(C)[Si](C(C)C)(C(C)C)n1c(Br)cc2ccccc21
Agent: Cl
Agent: [Li]C(C)CC
Solvent: CCCCCC
Solvent: C1CCCCC1
Solvent: C1CCOC1
Product: CCCN[C@H](CCC)Cc1cn([Si](C(C)C)(C(C)C)C(C)C)c2ccccc12
Temperature: -70 °C
Yield: 72.9 %

Procedure:
Under an argon atmosphere, s-butyl lithium (a 0.99 mol/L cyclohexane/n-hexane solution, 68.7 mL) was added to a solution of 2-bromo-1-triisopropylsilylindole (11.99 g) in tetrahydrofuran (85 mL) under stirring at −70° C. and then stirred at −70° C. for 30 minutes. A solution of (R)-3,4-dipropyl-1,2,3-oxathiazolidine 2,2-dioxide (7.05 g) in tetrahydrofuran (17 mL) was added to the resulting solution under stirring at −20° C. and then stirred for 13 hours, while the temperature was raised to room temperature. An aqueous 4 mol/L hydrochloric acid solution (34 mL) was added to the solution under water-cooling and stirring, and then vigorously stirred at room temperature for 1 hour. The organic layer was separated, washed with a saturated aqueous sodium hydrogen carbonate solution (30 mL), dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was subjected to column chromatography (NH-DM1020, from Hexane to AcOEt/Hexane=1/7) and then further purified by column chromatography (NH-DM1020, from AcOEt/Hexane=1/9 to AcOEt/MeOH=9/1) to give (R)-1-(1-triisopropylsilylindole-3-yl)-2-propylaminopentane (9.94 g, 73% yield) as a red oil.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[C:8]([CH3:10])[C:7]([CH:11]=[CH:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[C:6]([CH3:20])[CH:5]=1>C(O)C.C1COCC1.[Pd]>[CH3:1][O:2][C:3](=[O:21])[C:4]1[CH:9]=[C:8]([CH3:10])[C:7]([CH2:11][CH2:12][C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])=[C:6]([CH3:20])[CH:5]=1
Reactant: COC(=O)c1cc(C)c(C=CC(=O)OC(C)(C)C)c(C)c1
Agent: [Pd]
Solvent: CCO
Solvent: C1CCOC1
Product: COC(=O)c1cc(C)c(CCC(=O)OC(C)(C)C)c(C)c1
Temperature: 25 °C
Reaction time: 16 h
Yield: 95.7 %

Procedure:
To a solution of 4-(2-tert-butoxycarbonyl-vinyl)-3,5-dimethyl-benzoic acid methyl ester (11.2 g, 38.6 mmol) in ethanol (50 mL) and THF (50 mL), Pd/C (1.0 g, 10% Pd) is added. The mixture is stirred for 16 h at rt under 2.5 bar of H2. The catalyst is filtered off and the filtrate is concentrated and dried under HV to give 4-(2-tert-butoxycarbonyl-ethyl)-3,5-dimethyl-benzoic acid methyl ester (10.8 g) as a colourless oil; LC-MS: tR=1.08 min.
Reaction SMILES: [SH:1][CH2:2][CH2:3][CH:4]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[C:5]([O-:7])=[O:6].C(=O)(O)[O-].[Na+].CCCCCCC.[CH3:26][Sn:27](Cl)(Cl)[CH3:28]>O>[SH:1][CH2:2][CH2:3][CH:4]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[C:5]([O-:7])=[O:6].[SH:1][CH2:2][CH2:3][CH:4]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13])[C:5]([O-:7])=[O:6].[CH3:26][Sn+2:27][CH3:28]
Reactant: C[Sn](C)(Cl)Cl
Agent: CCCCCCC(CCS)C(=O)[O-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCCCCCC
Product: C[Sn+2]C
Reaction time: 1 h

Procedure:
Into a 2 liter flask is placed 204 gm (1.0 mole) 2-mercapto-ethylcaprylate, 200 ml water, 84 gm (1.0 mole) sodium bicarbonate and 300 ml heptane. To the above stirred mixture is added dropwise, at 30°-40° C., 110 gms (0.5 mole) dimethyltin dichloride dissolved in 200 ml water. Stir for 1 hour at 30°-40° C. and allow the layers to separate. The organic layer is washed with 200 ml water and then stripped under vacuum at about 100° C. A yield of 273 gm of dimethyltin bis(2-mercaptoethyl caprylate) is obtained. nD25 1.5060.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1Br.Br[C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13](Br)=[CH:12][CH:11]=1.[CH:21]1[C:34]2[C:25](=[CH:26][C:27]3[C:32]([C:33]=2B(O)O)=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:24]=[CH:23][CH:22]=1>>[CH:4]1[C:3]2[C:2](=[CH:15][C:14]3[C:19]([C:18]=2[C:10]2[C:19]4[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=4)[C:13]([C:33]4[C:34]5[C:25]([CH:26]=[C:27]6[C:32]=4[CH:31]=[CH:30][CH:29]=[CH:28]6)=[CH:24][CH:23]=[CH:22][CH:21]=5)=[CH:12][CH:11]=2)=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH:7]=[CH:6][CH:5]=1
Reactant: Brc1ccccc1Br
Reactant: OB(O)c1c2ccccc2cc2ccccc12
Reactant: Brc1ccc(Br)c2ccccc12
Product: c1ccc2c(-c3ccc(-c4c5ccccc5cc5ccccc45)c4ccccc34)c3ccccc3cc2c1

Procedure:
Procedure analogous to Example 3a. Instead of 149.0 ml (1.2 mol) of 1,2-dibromobenzene and 98.0 g (308 mmol) of 9,10-anthracenediboronic acid ethylene glycol ester, 28.6 g (100 mmol) of 1,4-dibromonaphthalene and 68.0 g (306 mmol) of 9-anthraceneboronic acid are used. After cooling, the solid is filtered off with suction and washed twice with 500 ml of boiling ethanol each time. Yield: 33.0 g (69 mmol), 68.7% of theory; purity: 98% according to 1H-NMR.
Reaction SMILES: CI.N12CCCN=C1CCCC[CH2:4]2.[O:14]=[C:15]1[CH2:20][CH2:19][CH:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:17]([C:27]([OH:29])=[O:28])=[CH:16]1>CC(C)=O>[O:14]=[C:15]1[CH2:20][CH2:19][CH:18]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:17]([C:27]([O:29][CH3:4])=[O:28])=[CH:16]1
Reactant: O=C1C=C(C(=O)O)C(c2ccccc2)CC1
Reactant: C1CCC2=NCCCN2CC1
Solvent: CC(C)=O
Solvent: CI
Product: COC(=O)C1=CC(=O)CCC1c1ccccc1
Temperature: 10 °C
Yield: 92.8 %

Procedure:
358 g (2.52 mol) of methyl iodide and 361 g (2.38 mol) of 1,8-diazabicyclo[5.4.0]undec-7-ene were successively added to a solution of 428 g (1.98 mol) of (RS)-3-oxo-6-phenylcyclohex-1-ene-1-carboxylic acid, which was obtained according to J. Org. Chem., 1971, 36, 3707, in 4.5 cm3 of acetone and then the reaction mixture was brought to reflux for five hours. The acetone was subsequently distilled off and then the residue was stirred with 2.5 dm3 of water. After cooling to 10° C., the precipitate formed was filtered off, washed with ice-cold water and then dried at 30° C. 423 g (93%) of methyl (RS)-3-oxo-6-phenylcyclohex-1-ene-1-carboxylate were thus obtained in the form of a yellow powder, the characteristics of which were as follows:
Reaction SMILES: Br[CH2:2][CH2:3][CH:4]=[CH2:5].[C:6]1(=[O:16])[NH:10][C:9](=[O:11])[C:8]2=[CH:12][CH:13]=[CH:14][CH:15]=[C:7]12.[K]>CN(C=O)C.CCOCC>[CH2:2]([N:10]1[C:6](=[O:16])[C:7]2[C:8](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:9]1=[O:11])[CH2:3][CH:4]=[CH2:5]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: C=CCCBr
Agent: [K]
Solvent: CN(C)C=O
Solvent: CCOCC
Product: C=CCCN1C(=O)c2ccccc2C1=O
Temperature: 70 °C
Reaction time: 18 h

Procedure:
To a stirred solution of 4-bromo-1-butene (5-3, 20 g, 148 mmol) in DMF (150 mL) was added potassium phthalimide (5-4, 25 g, 133 mmol) and the mixture stirred for 18 hours at 70° C. After cooling to RT, the mixture was diluted with ether, washed with water and brine, dried over MgSO4, and concentrated to give 5-5 as a white solid.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:14][CH2:13][CH2:12][N:11]([CH:15]3[CH2:17][CH2:16]3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[C:18]([NH:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1)(=[O:20])[CH3:19]>>[ClH:1].[ClH:1].[CH:15]1([N:11]2[CH2:12][CH2:13][CH2:14][N:8]([C:5]3[N:6]=[N:7][C:2]([C:25]4[CH:26]=[CH:27][C:22]([NH:21][C:18](=[O:20])[CH3:19])=[CH:23][CH:24]=4)=[CH:3][CH:4]=3)[CH2:9][CH2:10]2)[CH2:17][CH2:16]1
Reactant: CC(=O)Nc1ccc(B(O)O)cc1
Reactant: Clc1ccc(N2CCCN(C3CC3)CC2)nn1
Product: CC(=O)Nc1ccc(-c2ccc(N3CCCN(C4CC4)CC3)nn2)cc1
Product: Cl

Procedure:
The title compound was prepared by a similar procedure to that described in Example 68, starting from 1-(6-chloro-pyridazin-3-yl)-4-cyclopropyl-perhydro-1,4-diazepine and 4-acetamidophenylboronic acid. 1H NMR (400 MHz, CD3OD) δ 8.47 (d, 1H), 8.08 (d, 1H), 7.94 (d, 2H), 7.85 (d, 2H), 4.33 (broad m, 1H), 4.12 (broad m, 1H), 3.91 (broad m, 4H), 3.62 (broad m, 2H), 2.97 (hept, 1H), 2.55 ((broad m, 1H), 2.43 (broad m, 1H), 2.17 (s, 3H), 1.24 (broad m, 2H), 1.01 (d, 2H).