Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([OH:9])=[CH:5][C:4]=1[N+:10]([O-:12])=[O:11].C(=O)([O-])[O-].[K+].[K+].Br[CH2:20][CH2:21][Cl:22]>C(#N)C>[Cl:22][CH2:21][CH2:20][O:9][C:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[C:4]([N+:10]([O-:12])=[O:11])[CH:5]=1
Reactant: COc1ccc(O)cc1[N+](=O)[O-]
Reactant: ClCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: COc1ccc(OCCCl)cc1[N+](=O)[O-]
Temperature: 25 °C

Procedure:
4-Methoxy-3-nitrophenol (0.8 g, 4.7 mmol) was dissolved in acetonitrile (13 ml). Potassium carbonate (1.63 g, 11.8 mmol) was added, followed by 1-bromo-2-chloroethane (3.93 ml, 47.2 mmol). The reaction was heated and stirred at reflux for 20 h. The reaction was cooled to room temperature, the solid was then filtered off and the solvent evaporated under reduced pressure to give the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([CH2:10][CH2:11][OH:12])=[CH:7][C:6]=2[CH:13]=1.C(N(CC)CC)C.[C:21]1([CH3:31])[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1>CN(C)C1C=CN=CC=1.ClCCl>[CH3:31][C:21]1[CH:26]=[CH:25][C:24]([S:27]([O:12][CH2:11][CH2:10][C:8]2[O:9][C:5]3[CH:4]=[CH:3][C:2]([Br:1])=[CH:13][C:6]=3[CH:7]=2)(=[O:29])=[O:28])=[CH:23][CH:22]=1
Reactant: OCCc1cc2cc(Br)ccc2o1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1ccc(S(=O)(=O)OCCc2cc3cc(Br)ccc3o2)cc1
Temperature: 50 °C
Yield: 48.1 %

Procedure:
The product from Example 4A (1.21 g, 5.0 mmol), 4-dimethylaminopyridine (0.06 g, 0.5 mmol), and triethylamine (1.5 mL, 10.5 mmol) were combined in dichloromethane (20 mL) stirred briefly and treated with para-toluenesulfonyl chloride (1.91 g, 10.0 mmol) in dichloromethane (2 mL) over about 5 minutes. After stirring at about 22° C. for 3 hours, the mixture was then washed with saturated NaHCO3 solution (20 mL, 2×), brine (20 mL), dried over Na2SO4, and distilled to dryness. The residue in acetonitrile (˜5 mL) was heated at 50° C. to effect dissolution, allowed to cool to room temperature slowly, and then cooled to about 0° C. The slurry was filtered and the obtained solid dried under reduced pressure at 40° C. to provide the title compound (0.95 g, 48% yield). MS-DCI (M+NH4)+ observed m/z at 412, 414; 1H NMR (CDCl3 at 400 MHz) δ 2.38 (s, 3H), 3.11 (m, 2H), 4.35 (m, 2H), 6.35 (m, 1H), 7.1-7.18 (m, 3H), 7.27 (dd, 1H), 7.56 (d, 1H), 7.64-7.67 (m, 2H); 13C NMR (CDCl3 at 100 MHz) δ 21.9, 28.8, 67.1, 103.7, 112.0, 115.5, 122.9, 126.3, 127.4, 129.4, 130.1, 132.3, 144.4, 153.0, 154.2 with 2 peaks overlapping.
Reaction SMILES: [CH3:1][C:2]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[C:5]([CH3:13])[N:4]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][NH:22][C:23](=O)[O:24]C3C=CC=CC=3)=[CH:16][CH:15]=2)[N:3]=1.[F:32][C:33]1[CH:34]=[C:35]([S:40]([NH2:43])(=[O:42])=[O:41])[CH:36]=[CH:37][C:38]=1[F:39]>>[CH3:1][C:2]1[C:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[C:5]([CH3:13])[N:4]([C:14]2[CH:19]=[CH:18][C:17]([CH2:20][CH2:21][NH:22][C:23]([NH:43][S:40]([C:35]3[CH:36]=[CH:37][C:38]([F:39])=[C:33]([F:32])[CH:34]=3)(=[O:41])=[O:42])=[O:24])=[CH:16][CH:15]=2)[N:3]=1
Reactant: NS(=O)(=O)c1ccc(F)c(F)c1
Reactant: Cc1nn(-c2ccc(CCNC(=O)Oc3ccccc3)cc2)c(C)c1-c1ccccc1
Product: Cc1nn(-c2ccc(CCNC(=O)NS(=O)(=O)c3ccc(F)c(F)c3)cc2)c(C)c1-c1ccccc1

Procedure:
The title compound was prepared according to the procedure described in step 1 of Example 42 from phenyl 2-[4-(3,5-dimethyl-4-phenyl-1H-pyrazol-1-yl)phenyl]ethylcarbamate (step 1 of Example 22) and 3,4-difluorobenzenesulfonamide: 1H-NMR (CDCl3) δ 7.84-7.70 (2H, m), 7.47-7.21 (10H, m), 6.07 (1H, br.s), 3.50-3.43 (2H, m), 2.85 (2H, t, J=6.3 Hz), 2.32 (3H, s), 2.22 (3H, s).
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10]/[C:11](=[C:18]2\[C:19](=[O:30])[NH:20][C:21]3[C:26]\2=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][CH:22]=3)/[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:6][CH:5]=1.[CH:31](=O)[CH:32]([CH3:34])[CH3:33].C([BH3-])#N.[Na+]>CO>[CH2:31]([N:2]([CH2:3][C:4]1[CH:5]=[CH:6][C:7]([NH:10]/[C:11](=[C:18]2\[C:19](=[O:30])[NH:20][C:21]3[C:26]\2=[CH:25][C:24]([N+:27]([O-:29])=[O:28])=[CH:23][CH:22]=3)/[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)=[CH:8][CH:9]=1)[CH2:3][CH:4]([CH3:9])[CH3:5])[CH:32]([CH3:34])[CH3:33]
Reactant: NCc1ccc(N/C(=C2\C(=O)Nc3ccc([N+](=O)[O-])cc32)c2ccccc2)cc1
Reactant: CC(C)C=O
Agent: Cl
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: CC(C)CN(Cc1ccc(N/C(=C2\C(=O)Nc3ccc([N+](=O)[O-])cc32)c2ccccc2)cc1)CC(C)C

Procedure:
Prepared analogously to Example 159 from (Z)-3-[1-(4-aminomethyl-phenylamino)-1-phenyl-methylidene]-5-nitro-2-indolinone-hydrochloride, isobutyraldehyde and sodium cyanoborohydride in methanol.
Reaction SMILES: [CH3:1][C:2]1([CH3:9])[CH:7]([OH:8])[C:5](=[O:6])[O:4][CH2:3]1.C(=O)([O-])[O-:11].[Li+:14].[Li+].C(=O)=O>O>[OH2:4].[C:5]([O-:11])(=[O:6])[C@@H:7]([C:2]([CH2:3][OH:4])([CH3:9])[CH3:1])[OH:8].[Li+:14]
Reactant: O=C([O-])[O-]
Reactant: CC1(C)COC(=O)C1O
Agent: O=C=O
Agent: [Li+]
Solvent: O
Product: CC(C)(CO)[C@@H](O)C(=O)[O-]

Procedure:
A slurry of 1.00 kilogram of racemic DL-pantolactone and 300 grams of lithium carbonate in 1.5 liters of water was continuously stirred and heated at boiling temperature in a flask provided with a stirrer and reflux condenser for 1.5 hours. After all the evolved carbon dioxide had been expelled, the reaction mixture was filtered while hot and 25 grams of lithium carbonate was thus recovered therefrom. When the filtrate was cooled and stirred, 700 grams of crystals of racemic DL-lithium pantoate monohydrate having a melting point of 107°-110° C. amounting to 53.0% of the theoretical yield, separated and was collected. By evaporation of the mother liquor a further amount of DL-lithium pantoate, equivalent to 42% of the original DL-pantolactone, was recovered.
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6](Br)[C:3]=1[C:4]#[N:5].C([O-])(=O)C.[K+].[C:16]1(B(O)O)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C1(C)C=CC=CC=1>[NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:3]=1[C:4]#[N:5]
Reactant: N#Cc1c(N)cccc1Br
Reactant: OB(O)c1ccccc1
Agent: CC(=O)[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: N#Cc1c(N)cccc1-c1ccccc1
Temperature: 110 °C
Reaction time: 17 h

Procedure:
2-Amino-6-bromo-benzonitrile (1.0 Kg, 5.07 moles) and toluene (10 L, 10 vol) were added to a 20 L glass-lined reactor equipped with mechanical stirrer under inert atmosphere. Potassium acetate (996 g, 10.16 moles) and phenylboronic acid (866, 7.10 moles) were added into the solution and the solution was degassed with nitrogen for 30 min. After this time, dichloro-bis(triphenylphosphine) palladium (II) (17.8 g, 0.025 moles) was added to the reaction mixture at ambient temperature. The mixture was heated to 110° C., where it stirred for 17 h. At the conclusion of this period, the reaction progress was monitored by HPLC, which indicated the reaction was completed. The reaction mixture was filtered through a celite bed. The filtrate was transferred back to the reactor and concentrated hydrochloric acid (˜35%, 2 L, 2 vol) was charged to the reactor at ambient temperature. The HCl salt of the title compound precipitated out from the reaction and was collected by filtration. The HCl salt was transferred into the 20 L reactor and then made basic with 10% NaOH solution (pH 8-9). The resulting product was extracted with ethyl acetate (10 L, 10 vol). The ethyl acetate layer was washed with water (5 L, 5 vol) and then the solvent was evaporated under vacuum to give a residue. Hexanes (5 L, 5 vol) were added to the residue at 35-40° C., and the resulting slurry was cooled to ambient temperature. Once at the prescribed temperature, the product was collected by filtration to provide a pale yellow solid (802 g, 81.4%, 99% by HPLC). 1H NMR (DMSO-D6, 400 MHz, δ ppm); 7.43-7.52 (m, 5H), 7.33-7.37 (m, 1H), 6.83 (d, J=8 Hz, 1H), 6.62 (d, J=8 Hz, 1H), 6.1 (s, 2H). ES-MS: [M++1]=194.23.
Reaction SMILES: [C:1]1([N:7]=[C:8]=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[NH2:11][C:12]1[CH:13]=[C:14]2[C:24]([CH2:25][CH:26]=1)=[C:17]1[NH:18][C:19](=[O:23])[C:20](=[O:22])[NH:21][C:16]1=[CH:15]2.C(N(CC)CC)C>CN(C)C=O>[C:1]1([NH:7][C:8](=[O:9])[NH:11][C:12]2[CH:13]=[C:14]3[C:24]([CH2:25][CH:26]=2)=[C:17]2[NH:18][C:19](=[O:23])[C:20](=[O:22])[NH:21][C:16]2=[CH:15]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: NC1=CCC2=c3[nH]c(=O)c(=O)[nH]c3=CC2=C1
Reactant: O=C=Nc1ccccc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: O=C(NC1=CCC2=c3[nH]c(=O)c(=O)[nH]c3=CC2=C1)Nc1ccccc1
Reaction time: 8 h

Procedure:
1.92 ml of phenyl isocyanate are added at a temperature in the region of 20° C. to a solution of 1.5 g of 7-amino-1,4-dihydro-5H-indeno [1,2-b]pyrazine-2,3-dione hydrochloride and 2.48 ml of triethylamine in 20 ml of dimethylformamide. After overnight stirring at the same temperature, the precipitate formed is filtered off, washed with water and dried under a partial vacuum (1 mm Hg; 0.13 kPa) at 40° C. to yield 1.4 g of 7-(3-phenylureido)-1,4-dihydro-5H-indeno[1,2-b]pyrazine-2,3-dione in the form of a greenish solid, the melting point of which is above 260° C. (Analysis C18H14N4O3 ; 4.0 H2O; % calculated C: 64.66; H: 4.22; N: 16.76; % found C: 64.4; H: 4.5; N: 16.8; 1H NMR spectrum [250 MHz, (CD3)2SO-d6, δ in ppm]: 3.58 (s, 2H CH2 9); 7.00 (t, J=7.5 Hz, 1H: aromatic H of the phenyl at para with respect to the ureido); 7.30 (t, J=7.5 Hz, 2H: aromatic H of the phenyl at meta with respect to the ureido); 7.50 (d, J=7.5 Hz, 2H: aromatic H of the phenyl at ortho with respect to the ureido); from 7.20 to 7.60 (mt, 2H: H 5 and H 6); 7.72 (s broad, 1H: H 8); 8.80 (s broad, 2H: ArNHCONH); 12.00 and 12.28 (2 unres. comp. 1H each: NHCOCONH).
Reaction SMILES: [NH2:1][C:2]1[C:11]2[O:12][CH2:13][O:14][C:10]=2[CH:9]=[C:8]2[C:3]=1[C:4](=[O:20])[C:5]([C:17]([OH:19])=[O:18])=[N:6][N:7]2[CH2:15][CH3:16].[N:21]([O-])=O.[Na+].[ClH:25]>O>[Cl-:25].[C:17]([C:5]1[C:4](=[O:20])[C:3]2[C:2]([N+:1]#[N:21])=[C:11]3[O:12][CH2:13][O:14][C:10]3=[CH:9][C:8]=2[N:7]([CH2:15][CH3:16])[N:6]=1)([OH:19])=[O:18]
Reactant: Cl
Reactant: CCn1nc(C(=O)O)c(=O)c2c(N)c3c(cc21)OCO3
Reactant: O=N[O-]
Agent: [Na+]
Solvent: O
Product: CCn1nc(C(=O)O)c(=O)c2c([N+]#N)c3c(cc21)OCO3
Product: [Cl-]
Temperature: 25 °C
Reaction time: 5 h
Yield: 74.5 %

Procedure:
A mixture of 5-amino-1-ethyl-4-oxo-1,4-dihydro-[1,3]dioxolo[4,5-g]cinnoline-3-carboxylic acid (3.6 g, 12.99 mmol) in hydrochloric acid (conc) (20 ml) was stirred at room temperature and sodium nitrite (0.986 g, 14.28 mmol) in water (7 mL) was added dropwise to maintain the temperature bellow 45° C. Stirring continued for 5 h. The solution was poured into 50 ml of water and was allowed to stand overnight in the refrigerator. Precipitate was collected by filtration and dried over drierite in a desiccator to yield 3-Carboxy-1-ethyl-4-oxo-1,4-dihydro-[1,3]dioxolo[4,5-g]cinnoline-5-diazonium chloride (3.15 g, 9.67 mmol, 74.5% yield). LCMS: (M+H)+: 326.2
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([C:13]([F:16])([F:15])[F:14])=[CH:11][C:10]([C:17]3[C:21]([CH3:23])([CH3:22])[C:20](=[O:24])[NH:19][N:18]=3)=[N:9]2)=[N:6][CH:7]=1.[CH3:25]CN(C(C)C)C(C)C.ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl>C(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([C:13]([F:15])([F:16])[F:14])=[CH:11][C:10]([C:17]3[C:21]([CH3:22])([CH3:23])[C:20](=[O:24])[N:19]([CH3:25])[N:18]=3)=[N:9]2)=[N:6][CH:7]=1
Reactant: CCN(C(C)C)C(C)C
Reactant: CC1(C)C(=O)NN=C1c1cc(C(F)(F)F)n(-c2ccc(Br)cn2)n1
Agent: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: ClCCl
Product: CN1N=C(c2cc(C(F)(F)F)n(-c3ccc(Br)cn3)n2)C(C)(C)C1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 78 %

Procedure:
Step-3: 1′-(5-Bromopyridin-2-yl)-4,4-dimethyl-5′-(trifluoromethyl)-1H, 1′H-[3,3′-bipyrazol]-5(4H)-one: To a stirred and (0° C.) cooled solution of step-2 intermediate (2.0 g, 4.76 mmol) and DIPEA (1.66 mL, 9.52 mmol) in DCM (20 mL) was added a solution of triphosgene (560 mg, 1.90 mmol) in DCM (5 mL) over a period of 10 min. The reaction mixture was warmed to room temperature and then stirred overnight. Reaction was cooled down to 0° C. and then quenched with ice water (5 mL). Water (25 mL) was added to the reaction followed by DCM (50 mL). The layers were separated and the aqueous layer was extracted with DCM (2×50 mL). The combined organic layers were washed with brine (50 mL), dried (Na2SO4) and filtered. The filtrate was rotary evaporated to afford 1.50 g (78%) of the title compound as semisolid. 1HNMR (400 MHz, CDCl3) δ 8.85 (s, 1H, D2O exchangeable), 8.59 (d, J=2.0 Hz, 1H), 8.02 (dd, J=2.0 & 8.0 Hz, 1H), 7.78 (d, J=8.0 Hz, 1H), 7.31 (s, 1H), 1.60 (s, 6H); ESI-MS (m/z) 402, 404 [(MH)+, Br79,81].
Reaction SMILES: C(NC(C)C)(C)C.CC(C)([O-])C.[K+].[F:14][CH:15]1[C:21](=[O:22])[C:20]2[CH:23]=[CH:24][CH:25]=[CH:26][C:19]=2[N:18]([S:27]([C:30]2[CH:36]=[CH:35][C:33]([CH3:34])=[CH:32][CH:31]=2)(=[O:29])=[O:28])[CH2:17][CH2:16]1.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:47])(=O)=O)=CC=1.Cl>O1CCCC1.CCCCCC>[F:14][C:15]1([F:47])[C:21](=[O:22])[C:20]2[CH:23]=[CH:24][CH:25]=[CH:26][C:19]=2[N:18]([S:27]([C:30]2[CH:31]=[CH:32][C:33]([CH3:34])=[CH:35][CH:36]=2)(=[O:29])=[O:28])[CH2:17][CH2:16]1
Reactant: Cc1ccc(S(=O)(=O)N2CCC(F)C(=O)c3ccccc32)cc1
Reactant: O=S(=O)(c1ccccc1)N(F)S(=O)(=O)c1ccccc1
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CCCCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: Cc1ccc(S(=O)(=O)N2CCC(F)(F)C(=O)c3ccccc32)cc1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 30.4 %

Procedure:
To 300 ml of tetrahydrofuran solution containing 2.62 g of diisopropylamine and 2.91 g of potassium t-butoxide was added dropwise 16.2 ml of 1.6N n-hexane solution of n-butyllithilum at -78° C., followed by 30 minutes of stirring at -78° C. To this reaction solution was added 70 ml of tetrahydrofuran solution containing 7.2 g of 4-fluoro-1-tosyl-2,3,4,5-tetrahydro-1H-1-benzazepin-5-one, followed by 1 hour of stirring at -78° C. The reaction solution was mixed with 70 ml of tetrahydrofuran solution containing 10.22 g of N-fluorobenzenesulfonimide, and the mixture was stirred for 2 hours at -78° C. and then for 1 hour at room temperature. The reaction solution was mixed with 500 ml of 0.1N hydrochloric acid aqueous solution and the mixture was extracted with ethyl acetate. The resulting organic layer was washed with 10% sodium thiosulfate, 1N sodium hydroxide and saturated sodium chloride aqueous solution in that order and dried over anhydrous magnesium sulfate, subsequently evaporating the solvent. The resulting residue was applied to silica gel column chromatography, which was eluted with a mixed solvent of n-hexane and ethyl acetate (4:1, v/v) to obtain 2.31 g of 4,4-difluoro-1-tosyl-2,3,4,5-tetrahydro-1H-1-benzazepin-5-one.
Reaction SMILES: C1C[C@@H:5]([NH2:7])[C@H:4](N)CC1.[C:9]1(C=O)[C:18]2C(=CC=CC=2)C=C[CH:10]=1.C1[O:25][C:24]2[CH:26]=[C:27]([CH:30]=O)[CH:28]=[CH:29][C:23]=2[O:22]1.C(C1(C)CCC2CC1C2(C)C)=O>>[C:24]1([C@H:5]([NH2:7])[CH3:4])[C:26]2[C:27](=[CH:30][CH:10]=[CH:9][CH:18]=2)[CH:28]=[CH:29][CH:23]=1.[CH3:26][C:24](=[O:25])[C:23](=[O:22])[CH3:29]
Reactant: O=Cc1ccc2c(c1)OCO2
Reactant: O=Cc1cccc2ccccc12
Reactant: N[C@@H]1CCCC[C@H]1N
Agent: CC1(C=O)CCC2CC1C2(C)C
Product: CC(=O)C(C)=O
Product: C[C@@H](N)c1cccc2ccccc12

Procedure:
10 g of toluene, 1 mmol of a zinc compound such as diethylzinc (Examples 1 to 6 and 9), phenylzinc hydride (Example 7) or zinc hydride (Example 8), and 1 mmol of one of the ligands of the secondary diimine type shown in Table 1 overleaf were added to a 100 ml three-necked flask. The mixture was stirred for 10 min at 20° C., following which 12 g (100 mmol) of acetophenone were added. 6.5 g (100 mmol) of PMHS were then added over a period of 10 minutes, and the solution was stirred continuously for 8 h at 20° C. The complete disappearance of the acetophenone was traced by chromatography. The reaction solution was slowly poured onto an aqueous 30% soda solution (0.15 mol of NaOH). The aqueous phase was decanted, the toluene was evaporated from the organic solution, and the alcohol produced was vacuum-distilled. The enantiomeric excess of the product was determined by chromatographic analysis in the gaseous phase on a chiral column of the Chirasil® type. The Schiff base diimine ligands were prepared by reacting 1 equivalent of commercially available (1R,2R)-(−)diaminocyclohexane with 2 equivalents of 1-naphthaldehyde (Example 1), heliotropin (Example 2), mesitylaldehyde (Example 3) and 2-formylpinane (Example 4) in accordance with Krasik and Alper's description, Tetrahedron, 1994, 50, 4347. The diimine ligands of Examples 5 to 8 were obtained by condensing 2 equivalents of (R)-α-naphthylethylamine (Example 5) or (R)-(α)-phenylethylamine with 1 equivalent of 2,3-butanedione in accordance with Dieck and Dietrich's description, Chem. Ber., 1984, 117, 694. The pyridinyl-imine ligand of Example 9 was prepared by condensing 2-pyridyl carboxaldehyde and (R)-α-phenylethylamine in accordance with Brunner, Reiter and Riepel's method, Chem. Ber., 1984, 117, 1130.
Reaction SMILES: FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:10]=[CH:11][C:12]2[S:16][C:15]([S:17]([N:20]3[CH2:25][CH2:24][NH:23][CH2:22][C:21]3=[O:26])(=[O:19])=[O:18])=[N:14][C:13]=2[CH:27]=1.[CH:28]([O:41][C:42]([NH:44][C:45]1[NH:46][C:47](=[O:58])[C:48]2[N:49]=[CH:50][N:51]([CH2:54][C:55](O)=[O:56])[C:52]=2[N:53]=1)=[O:43])([C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1>>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]2[S:16][C:15]([S:17]([N:20]3[CH2:25][CH2:24][N:23]([C:55](=[O:56])[CH2:54][N:51]4[CH:50]=[N:49][C:48]5[C:47](=[O:58])[NH:46][C:45]([NH:44][C:42]([O:41][CH:28]([C:35]6[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=6)[C:29]6[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=6)=[O:43])=[N:53][C:52]4=5)[CH2:22][C:21]3=[O:26])(=[O:19])=[O:18])=[N:14][C:13]=2[CH:27]=1
Reactant: O=C(O)Cn1cnc2c(=O)[nH]c(NC(=O)OC(c3ccccc3)c3ccccc3)nc21
Reactant: O=C1CNCCN1S(=O)(=O)c1nc2cc(Cl)ccc2s1
Solvent: O=C(O)C(F)(F)F
Product: O=C(Nc1nc2c(ncn2CC(=O)N2CCN(S(=O)(=O)c3nc4cc(Cl)ccc4s3)C(=O)C2)c(=O)[nH]1)OC(c1ccccc1)c1ccccc1

Procedure:
The title compound was synthesized by the reaction of 1-(5-chloro-benzothiazole-2-sulfonyl)-piperazin-2-one trifluoroacetic acid salt with [2-N-(benzhydryloxycarbonyl)-guanin-9-yl]-acetic acid as per the procedure of Example 52. 1H NMR (500 MHz; DMSO-d6) δ 11.62 (brs, H), 11.25 (brs, 1H), 8.42–8.39 (m, 1H), 7.96 (s, 0.6H), 7.82 (s, 0.4H), 7.78 (m, 1H), 7.46 (d, 4H), 7.39 (t, 4H), 7.31 (t, 2H), 6.87 (s, 1H), 5.17 (s, 1.2H), 5.06 (s, 0.8H), 4.53 (s, 0.8H), 4.29 (s, 1.2H), 4.25 (t, 1.2H), 4.08–4.06 (m, 2H), 3.87 (t, 0.8H).
Reaction SMILES: [Li]CCCC.[CH3:6][N:7]1[CH:11]=[N:10][NH:9][C:8]1=[S:12].[Cl:13][C:14]1[CH:42]=[CH:41][C:17]([C:18]([C:20]2[CH:32]=[C:30]3[C:31]4[N:26]([CH2:27][CH2:28][CH2:29]3)[C:25](=[O:33])[CH:24]=[C:23]([C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([Cl:40])[CH:35]=3)[C:22]=4[CH:21]=2)=[O:19])=[CH:16][CH:15]=1>C1COCC1>[OH2:19].[Cl:40][C:36]1[CH:35]=[C:34]([C:23]2[C:22]3[CH:21]=[C:20]([C:18]([C:17]4[CH:16]=[CH:15][C:14]([Cl:13])=[CH:42][CH:41]=4)([OH:19])[C:11]4[N:7]([CH3:6])[C:8]([SH:12])=[N:9][N:10]=4)[CH:32]=[C:30]4[CH2:29][CH2:28][CH2:27][N:26]([C:25](=[O:33])[CH:24]=2)[C:31]=34)[CH:39]=[CH:38][CH:37]=1
Reactant: O=C(c1ccc(Cl)cc1)c1cc2c3c(c1)c(-c1cccc(Cl)c1)cc(=O)n3CCC2
Reactant: Cn1cn[nH]c1=S
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: Cn1c(S)nnc1C(O)(c1ccc(Cl)cc1)c1cc2c3c(c1)c(-c1cccc(Cl)c1)cc(=O)n3CCC2
Product: O
Temperature: 0 °C
Reaction time: 1 h
Yield: 39.8 %

Procedure:
n-BuLi (0.0166 mol) was added slowly at −78° C. to a solution of 2,4-dihydro-4-methyl-3H-1,2,4-triazole-3-thione (0.0082 mol) in THF (50 ml) under N2 flow. The mixture was stirred at 0° C. for 1 hour, then cooled to −78° C. 9-(4-chlorobenzoyl)-7-(3-chlorophenyl)-2,3-dihydro-1H,5H-benzo[ij]quinolizin-5-one (described in International Application WO98/40383) (0.0046 mol) was added portionwise. The mixture was stirred at room temperature for 4 hours, poured out on ice and extracted with EtOAc. The organic layer was separated, dried (MgSO4), filtered, and the solvent was evaporated. The residue (2.32 g) was purified by column chromatography over silica gel (15-40 μm) (eluent: CH2Cl2/CH3OH/NH4OH 98/2/0.1 to 96/4/0.1). The pure fractions were collected and the solvent was evaporated. The residue (1 g, 40%). was crystallized from acetonitril. The precipitate was filtered off and dried, yielding 0.52 g (21%) of 7-(3-chlorophenyl)-9-[(4-chlorophenyl)hydroxy(5-mercapto-4-methyl-4H-1,2,4-triazol-3-yl)methyl]-2,3-dihydro-1H,5H-benzo[ij]quinolizin-5-one hydrate (1:1), melting point 160° C. (intermediate 7).
Reaction SMILES: [C:1]([CH:4]1[C:9](C)([CH3:10])[NH:8][C:7](C)([CH3:12])[CH:6]([C:14](=[O:20])[CH2:15][CH2:16][CH2:17][CH2:18][Cl:19])[CH:5]1[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[C:22]=1[Cl:28])(=[O:3])[CH3:2].[I-].[Na+].Cl.[C:32]1([C:38]2([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C(O)(C)C.C(OCC)C>[ClH:19].[C:1]([C:4]1[CH:5]([C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[C:22]=2[Cl:28])[C:6]([C:14](=[O:20])[CH2:15][CH2:16][CH2:17][CH2:18][N:41]2[CH2:40][CH2:39][C:38]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)[CH2:43][CH2:42]2)=[C:7]([CH3:12])[NH:8][C:9]=1[CH3:10])(=[O:3])[CH3:2]
Reactant: c1ccc(C2(c3ccccc3)CCNCC2)cc1
Reactant: CC(=O)C1C(c2cccc(Cl)c2Cl)C(C(=O)CCCCCl)C(C)(C)NC1(C)C
Agent: Cl
Agent: [I-]
Agent: [Na+]
Solvent: CCOCC
Solvent: CC(C)O
Product: CC(=O)C1=C(C)NC(C)=C(C(=O)CCCCN2CCC(c3ccccc3)(c3ccccc3)CC2)C1c1cccc(Cl)c1Cl

Procedure:
5 g (12 mmol) 5-acetyl-4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-2,6-dimethyl-3-(5-chloropentanoyl)-pyridine are reacted first with 3.6 g (24 mmol) sodium iodide and then with 6.9 g (24 mmol) 4,4-diphenylpiperidine hydrochloride, as described for starting compound B. Working up is carried out as described for starting compound B. The crude product is chromatographed with toluene/acetone=7/3. The product thus obtained is taken up in 20 ml isopropanol and the mixture is diluted with 5 ml diethyl ether. The title compound is precipitated by addition of ethereal hydrochloric acid. Yield: 2.3 g (30%). M.p. 258°-259° C. decomp. (acetonitrile).
Reaction SMILES: [N:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][CH:2]2O.[C:10]([O:13]C(=O)C)(=[O:12])[CH3:11]>>[C:10]([O:13][CH:3]1[CH:4]2[CH2:7][CH2:8][N:1]([CH2:6][CH2:5]2)[CH2:2]1)(=[O:12])[CH3:11]
Reactant: CC(=O)OC(C)=O
Reactant: OC1CC2CCN1CC2
Product: CC(=O)OC1CN2CCC1CC2

Procedure:
The thus obtained (+) quinuclidinol was esterified with acetic anhydride to yield in a quantitative manner the desired novel (+) 3-acetoxy quinuclidine. The hydrochloride was obtained from a solution of hydrogen chloride in anhydrous ether, M.P. = 175° C.
Reaction SMILES: [OH-].[K+].[F:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=O)=[CH:6][CH:5]=1.[CH:12]([C:15]([CH3:17])=[O:16])([CH3:14])[CH3:13].C(O)(=O)C>CO.O>[F:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[CH:17][C:15](=[O:16])[CH:12]([CH3:14])[CH3:13])=[CH:6][CH:5]=1
Reactant: O=Cc1ccc(F)cc1
Reactant: CC(=O)C(C)C
Agent: [K+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: CC(=O)O
Product: CC(C)C(=O)C=Cc1ccc(F)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
75 ml of 15% strength potassium hydroxide solution are added dropwise to 198.4 g (1.6 mol) of freshly distilled 4-fluorobenzaldehyde and 137.6 g (1.6 mol) of methyl isopropyl ketone in 300 ml of methanol and stirred overnight at room temperature. The mixture is then neutralized using 10 ml of acetic acid, 1 l of water is added and the mixture is extracted with two 500 ml portions of ether. The combined organic phases are washed with 500 ml of saturated sodium chloride solution and dried over sodium sulphate. After removing the solvent, the residue is distilled under high vacuum.