Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1[CH2:3][C:4]2[C:9]([CH:10]=1)=[C:8]([CH:11]([CH3:13])[CH3:12])[CH:7]=[CH:6][C:5]=2[CH3:14].C([Li])CCC.[Cl-].[CH3:21][SiH:22]([CH3:36])[CH:23]1[C:35]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[C:29]2[C:24]1=[CH:25][CH:26]=[CH:27][CH:28]=2.[Cl-].[NH4+]>CCOCC.CCCCCC>[CH3:21][Si:22]([CH3:36])([CH:3]1[C:4]2[C:9](=[C:8]([CH:11]([CH3:12])[CH3:13])[CH:7]=[CH:6][C:5]=2[CH3:14])[CH:10]=[C:2]1[CH3:1])[CH:23]1[C:35]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[C:29]2[C:24]1=[CH:25][CH:26]=[CH:27][CH:28]=2
Reactant: CC1=Cc2c(C(C)C)ccc(C)c2C1
Reactant: C[SiH](C)C1c2ccccc2-c2ccccc21
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCCCCC
Solvent: CCOCC
Product: CC1=Cc2c(C(C)C)ccc(C)c2C1[Si](C)(C)C1c2ccccc2-c2ccccc21
Temperature: -78 °C
Yield: 46 %

Procedure:
A 100 ml four-necked flask equipped with a reflux tube, a thermometer and a dropping funnel was thoroughly purged with nitrogen and dried. To the flask, 2-methyl-4-i-propyl-7-methylindene (1.50 g, 8.06 mmol) and dehydrated ether (25 ml) were introduced. Under stirring at −78° C., a hexane solution of n-butyllithium (8.46 mmol) was dropwise added. After the dropwise addition, the temperature of the system was allowed to spontaneously and slowly rise to room temperature. The reaction mixture was stirred at room temperature over night, whereby a colourless solution came, through a white slurry and a light yellow slurry, to a yellow slurry. To the slurry, the dimethyl(9-fluorenyl)silane chloride (2.06 g, 8.06 mmol) synthesized above was added under stirring at 0° C., followed by stirring at room temperature for 1.5 hours. After ether (100 ml) and a saturated ammonium chloride aqueous solution (100 ml) were added, the resulting mixture was introduced into a separatory funnel to separate out an organic phase. The organic phase was washed with a saturated ammonium chloride aqueous solution, water and a saturated sodium chloride aqueous solution, and dried over anhydrous magnesium sulfate. After the solvent was removed, the obtained product (a yellow oil) was purified by column chromatography (developer: hexane) to obtain 1.50 g so a yellow oil (yield: 46%).
Reaction SMILES: [Cl:1][C:2]1[CH:14]=[C:13]([O:15][CH2:16][CH:17]=[C:18]([Cl:20])[Cl:19])[CH:12]=[C:11]([Cl:21])[C:3]=1[O:4][CH2:5][CH2:6][CH2:7][CH2:8]C=O.Cl.[C:23]([O:27][NH2:28])([CH3:26])([CH3:25])[CH3:24].Cl.N1C=CC=C[CH:31]=1>>[C:23]([O:27][N:28]=[CH:8][CH2:7][CH2:6][CH:5]([O:4][C:3]1[C:11]([Cl:21])=[CH:12][C:13]([O:15][CH2:16][CH:17]=[C:18]([Cl:19])[Cl:20])=[CH:14][C:2]=1[Cl:1])[CH3:31])([CH3:26])([CH3:25])[CH3:24]
Reactant: CC(C)(C)ON
Reactant: c1ccncc1
Reactant: O=CCCCCOc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl
Agent: Cl
Product: CC(CCC=NOC(C)(C)C)Oc1c(Cl)cc(OCC=C(Cl)Cl)cc1Cl
Temperature: 25 °C
Reaction time: 24 h
Yield: 50 %

Procedure:
To a mixture of 0.37 g of 5-(2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)pentanal and 10 ml of pyridine was added 0.13 g of O-tert-butylhydroxylamine hydrochloride. After stirring at room temperature for 24 hours, the reaction mixture was poured into diluted hydrochloric acid, and extracted twice with diethyl ether. The diethyl ether layers were combined, washed with water, dried over anhydrous magnesium sulfate, and concentrated to give a crude product. This crude product was subjected to silica gel chromatography, which afforded 0.22 g (yield, 50%) of 4-(2,6-dichloro-4-(3,3-dichloro-2-propenyloxy)phenoxy)pentanal O-tert-butyloxime, nD25.2 1.5275.
Reaction SMILES: I[CH2:2][CH2:3][CH2:4][C:5]1[CH:6]=[C:7]([CH:15]=[CH:16][CH:17]=1)[O:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11].[C:18]1([CH:24]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH2:25][CH2:26][NH2:27])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CN(C=O)C.CCOC(C)=O>[C:28]1([CH:24]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH2:25][CH2:26][NH:27][CH2:2][CH2:3][CH2:4][C:5]2[CH:6]=[C:7]([CH:15]=[CH:16][CH:17]=2)[O:8][CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1
Reactant: CCOC(=O)COc1cccc(CCCI)c1
Reactant: NCCC(c1ccccc1)c1ccccc1
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCOC(=O)COc1cccc(CCCNCCC(c2ccccc2)c2ccccc2)c1
Reaction time: 8 h
Yield: 40.3 %

Procedure:
To a solution of ethyl [3-(3-iodopropyl)phenoxy]acetate (2.5 g) in DMF (50 mL) was added (3,3-diphenylpropyl)amine (1.7 g) at ambient temperature. The reaction mixture was stirred for 8 hours at the same temperature. The resulting mixture was diluted with EtOAc and washed successively with saturated NaHCO3 aqueous solution, water and brine. The organic layer was dried over anhydrous MgSO4, filtered and evaporated in vacuo. The residue was purified by silica gel column chromatography (chloroform:MeOH=100:0-95:5) to give ethyl (3-{3-[(3,3-diphenylpropyl)amino]propyl}phenoxy)acetate (1.25 g).
Reaction SMILES: Cl.[NH2:2][C:3]1[S:4][C:5]([Cl:8])=[CH:6][N:7]=1.Cl[S:10]([C:13]1[CH:14]=[CH:15][C:16]([C:19]([O:21]C)=[O:20])=[N:17][CH:18]=1)(=[O:12])=[O:11].Cl.[OH-].[Na+]>N1C=CC=CC=1.O>[Cl:8][C:5]1[S:4][C:3]([NH:2][S:10]([C:13]2[CH:14]=[CH:15][C:16]([C:19]([OH:21])=[O:20])=[N:17][CH:18]=2)(=[O:11])=[O:12])=[N:7][CH:6]=1
Reactant: COC(=O)c1ccc(S(=O)(=O)Cl)cn1
Reactant: Nc1ncc(Cl)s1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: c1ccncc1
Solvent: O
Product: O=C(O)c1ccc(S(=O)(=O)Nc2ncc(Cl)s2)cn1
Temperature: 25 °C
Yield: 7.4 %

Procedure:
2-Amino-5-chlorothiazole hydrochloride (2.63 g, 15.4 mmol, 3.96 eq) was dissolved in pyridine (10 ml) and stirred at room temperature for 10 minutes before the addition of methyl 5-(chlorosulfonyl)pyridine-2-carboxylate (Preparation 16, 915 mg, 3.8 mmol, 1 eq) portionwise and the resulting reaction mixture stirred at room temperature for a further hour. The mixture was dropped slowly into 6M HCl (20 ml), extracted into ethyl acetate (15 ml), washed with saturated sodium hydrogen carbonate (15 ml), dried over sodium sulphate, filtered and evaporated in vacuo. The residue was suspended in dioxane (5 ml), a solution of sodium hydroxide (300 mg, 7.5 mmol, 1.9 eq) in water (2 ml) was added and the reaction mixture stirred at room temperature for 30 minutes. The reaction mixture was washed with ethyl acetate (10 ml). The remaining aqueous phase diluted with brine (10 ml), acidified to pH 1, extracted into ethyl acetate (10 ml), dried over sodium sulphate, filtered and evaporated in vacuo to yield the title compound as an orange solid (90 mg, 0.28 mmol, 7%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6](/[C:9](/[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:10]\[CH:11]=[CH:12]\[C:13]([OH:15])=[O:14])=[CH:5][CH:4]=1.[N+:22]([C:25]1[CH:30]=[CH:29][C:28](O)=[CH:27][CH:26]=1)([O-:24])=[O:23].C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)(Cl)(Cl)Cl.ClCCl>[N+:22]([C:25]1[CH:30]=[CH:29][C:28]([O:14][C:13](=[O:15])/[CH:12]=[CH:11]/[CH:10]=[C:9](\[C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)/[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[CH:27][CH:26]=1)([O-:24])=[O:23]
Reactant: COc1ccc(/C(=C\C=C\C(=O)O)c2ccccc2)cc1
Reactant: O=[N+]([O-])c1ccc(O)cc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: ClC(Cl)(Cl)Cl
Solvent: ClCCl
Product: COc1ccc(/C(=C\C=C\C(=O)Oc2ccc([N+](=O)[O-])cc2)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 82.2 %

Procedure:
As in Example 115, (2E,4Z)-5-(4-methoxyphenyl)-5-phenyl-2,4-pentadienoic acid (0.85 g) and 4-nitrophenol (0.5 g) in 5 mL of carbon tetrachloride and 5 mL of dichloromethane was treated with 1,3-dicyclohexylcarbodiimide (0.62 g). The mixture was stirred at room temperature for 18 hours and the usual work up furnished 1.0 g of (2E,4Z)-5-(4-methoxyphenyl)-5-phenyl-2,4-pentadienoic acid 4-nitrophenyl ester as an oil.
Reaction SMILES: [CH3:1][CH2:2][CH2:3][CH2:4][CH2:5][C@H:6]([OH:25])/[CH:7]=[CH:8]/[C@@H:9]1[C@@H:13]([CH2:14]/[CH:15]=[CH:16]\[CH2:17][CH2:18][CH2:19][C:20]([OH:22])=O)[C@@H:12]([OH:23])[CH2:11][C@H:10]1[OH:24].C(N(CC)CC)C.C(OC(Cl)=O)C.[CH:39]1[C:44]([OH:45])=[CH:43][C:42]2[C:46]([CH2:49][CH2:50][NH2:51])=[CH:47][NH:48][C:41]=2[CH:40]=1.Cl>C(Cl)Cl.C(OCC)(=O)C>[OH:45][C:44]1[CH:43]=[C:42]2[C:41](=[CH:40][CH:39]=1)[NH:48][CH:47]=[C:46]2[CH2:49][CH2:50][NH:51][C:20](=[O:22])[CH2:19][CH2:18][CH2:17]/[CH:16]=[CH:15]\[CH2:14][C@H:13]1[C@@H:12]([OH:23])[CH2:11][C@@H:10]([OH:24])[C@@H:9]1/[CH:8]=[CH:7]/[C@@H:6]([OH:25])[CH2:5][CH2:4][CH2:3][CH2:2][CH3:1]
Reactant: CCCCC[C@H](O)/C=C/[C@@H]1[C@@H](C/C=C\CCCC(=O)O)[C@@H](O)C[C@H]1O
Reactant: NCCc1c[nH]c2ccc(O)cc12
Agent: CCOC(=O)Cl
Agent: Cl
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: CCCCC[C@H](O)/C=C/[C@@H]1[C@@H](C/C=C\CCCC(=O)NCCc2c[nH]c3ccc(O)cc23)[C@@H](O)C[C@H]1O
Temperature: 0 °C
Yield: 67.9 %

Procedure:
A solution of the protected prostaglandin F2α (500 mg, 0.825 mmol) in CH2Cl2 (4.5 mL) was treated with triethylamine (290 μL, 2.06 mmol) with stirring and cooled to 0° C. Ethylchloroformate (87 μL, 0.907 mmol) was then added and after 15 minutes the reaction was warmed to room temperature. Serotonin hydrochloride (211 mg, 0.99 mmol) was added and stirred for 16 hours. The reaction was then diluted with ethyl acetate and washed with HCl (1 N), saturated sodium bicarbonate, and brine. The organic portion was dried (MgSO4), filtered and concentrated in vacuo. The residue was diluted with methanol and pyridinium p-toluenesulfonate (PPTs) (100 mg) was added and the solution was stirred for 24 hours. The solvent was then removed in vacuo, and the residue was diluted with ethyl acetate and washed with HCl (1 N), saturated sodium bicarbonate, and brine. The organic portion was dried (MgSO4), filtered and concentrated in vacuo. Flash column chromatography (silica gel, 19:1 ethyl acetate:methanol) gave (Z)-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-((E)-(S)-3-hydroxy-oct-1-enyl)-cyclopentyl]-hept-5-enoic acid [2-(5-hydroxy-1H-indol-3-yl)-ethyl]-amide (Compound 3) (287 mg, 68%).
Reaction SMILES: [Cl:1][C:2]1[C:3]([F:33])=[C:4]([CH:8]2[C:12]([C:15]3[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=3[F:22])([C:13]#[N:14])[CH:11]([CH2:23][C:24]([CH:27]3[CH2:29][CH2:28]3)([CH3:26])[CH3:25])[NH:10][CH:9]2[C:30](O)=[O:31])[CH:5]=[CH:6][CH:7]=1.CC1(C)[O:39][C@@H:38]([CH2:40][CH2:41][NH2:42])[CH2:37][O:36]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.Cl>C(Cl)Cl.O1CCCC1>[OH:39][C@H:38]([CH2:37][OH:36])[CH2:40][CH2:41][NH:42][C:30]([CH:9]1[CH:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=2[F:33])[C:12]([C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=2[F:22])([C:13]#[N:14])[CH:11]([CH2:23][C:24]([CH:27]2[CH2:28][CH2:29]2)([CH3:25])[CH3:26])[NH:10]1)=[O:31]
Reactant: CC(C)(CC1NC(C(=O)O)C(c2cccc(Cl)c2F)C1(C#N)c1ccc(Cl)cc1F)C1CC1
Reactant: CC1(C)OC[C@H](CCN)O1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CC(C)(CC1NC(C(=O)NCC[C@H](O)CO)C(c2cccc(Cl)c2F)C1(C#N)c1ccc(Cl)cc1F)C1CC1
Yield: 68.5 %

Procedure:
In a manner similar to the method described in Examples 42c and 42d, rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2-cyclopropyl-2-methyl-propyl)-pyrrolidine-2-carboxylic acid prepared in Example 99c (0.41 g, 0.83 mmol) was reacted with 2-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-ethylamine (0.36 g, 2.5 mmol), HATU (0.57 g, 1.5 mmol) and iPr2NEt (0.43 mL, 2.5 mmol) in CH2Cl2 at room temperature for 20 h, then reacted with aqueous HCl solution in tetrahydrofuran at room temperature for 2 h to give rac-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2-cyclopropyl-2-methyl-propyl)-pyrrolidine-2-carboxylic acid ((S)-3,4-dihydroxy-butyl)-amide as a white solid (0.33 g, 70%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([S:10]([N:13]([CH2:15][C:16]2[O:20][CH:19]=[C:18]([C:21](O)=[O:22])[CH:17]=2)[CH3:14])(=[O:12])=[O:11])=[C:5]([CH3:24])[CH:4]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[N:37]1[CH:42]=[CH:41][C:40]([CH2:43][CH2:44][N:45]2[CH2:50][CH2:49][NH:48][CH2:47][CH2:46]2)=[CH:39][CH:38]=1>ClCCCl>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[C:6]([S:10]([N:13]([CH3:14])[CH2:15][C:16]2[O:20][CH:19]=[C:18]([C:21]([N:48]3[CH2:49][CH2:50][N:45]([CH2:44][CH2:43][C:40]4[CH:39]=[CH:38][N:37]=[CH:42][CH:41]=4)[CH2:46][CH2:47]3)=[O:22])[CH:17]=2)(=[O:11])=[O:12])=[C:5]([CH3:24])[CH:4]=1
Reactant: c1cc(CCN2CCNCC2)ccn1
Reactant: COc1cc(C)c(S(=O)(=O)N(C)Cc2cc(C(=O)O)co2)c(C)c1
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: ClCCCl
Product: COc1cc(C)c(S(=O)(=O)N(C)Cc2cc(C(=O)N3CCN(CCc4ccncc4)CC3)co2)c(C)c1

Procedure:
The title compound was prepared according to general procedure AA using 5-({[(4-Methoxy-2,6-dimethylphenyl)sulfonyl](methyl)amino}methyl)furan-3-carboxylic acid (63 mg, 0.18 mmol), CDI (58 mg, 0.36 mmol) and 1-[2-(pyridin-4-yl)ethyl]piperazine (57 mg, 0.30 mmol) in DCE (4.5 mL). The crude product was purified using Ambersep and PL-MIA resins, then using prep method A.
Reaction SMILES: [Br:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:13][CH2:14][CH:15]([CH3:17])[CH3:16])=[C:7]([NH2:12])[CH:8]=[N:9]2)=[CH:4][CH:3]=1.[CH2:18]([O:20][CH2:21][C:22](Cl)=O)[CH3:19]>N1C=CC=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]3[N:13]([CH2:14][CH:15]([CH3:17])[CH3:16])[C:19]([CH2:18][O:20][CH2:21][CH3:22])=[N:12][C:7]=3[CH:8]=[N:9][C:10]=2[CH:11]=1
Reactant: CC(C)CNc1c(N)cnc2cc(Br)ccc12
Reactant: CCOCC(=O)Cl
Solvent: c1ccncc1
Product: CCOCc1nc2cnc3cc(Br)ccc3c2n1CC(C)C
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 41.1 %

Procedure:
A solution of 7-bromo—N4-isobutylquinoline-3,4-diamine (85 g, prepared according to Part F of Example 1) in anhydrous pyridine (413 mL) was immersed in an ice bath, and ethoxyacetyl chloride (36.9 g, 300 mmol) was added. The reaction was allowed to warm to room temperature and was then heated in an oil bath held at 85° C. for 3.5 h. The reaction mixture was concentrated under vacuum, and the residue was taken up in diethyl ether and washed with 2M Na2CO3 (2×) followed by H2O (1×). The organic layer was dried (MgSO4), filtered, and concentrated. Recrystallization of the resulting solid from boiling 15% ethyl acetate in hexanes afforded 43.0 g of 7-bromo-2-ethoxymethyl-1-isobutyl-1H-imidazo[4,5-c]quinoline as brown crystals.
Reaction SMILES: [N:1]([C:4]1[S:8][C:7]2[CH2:9][CH2:10][CH2:11][CH2:12][C:6]=2[C:5]=1[C:13]([O:15]CC)=O)=[C:2]=[S:3].[CH3:18][C:19]1[N:23]([CH2:24][CH2:25][CH2:26][NH2:27])[CH:22]=[N:21][CH:20]=1>>[CH3:18][C:19]1[N:23]([CH2:24][CH2:25][CH2:26][N:27]2[C:13](=[O:15])[C:5]3[C:6]4[CH2:12][CH2:11][CH2:10][CH2:9][C:7]=4[S:8][C:4]=3[NH:1][C:2]2=[S:3])[CH:22]=[N:21][CH:20]=1
Reactant: CCOC(=O)c1c(N=C=S)sc2c1CCCC2
Reactant: Cc1cncn1CCCN
Product: Cc1cncn1CCCn1c(=S)[nH]c2sc3c(c2c1=O)CCCC3

Procedure:
The compound was synthesized starting from ethyl 4,5,6,7-tetrahydro-2-isothiocyanatobenzo[b]thiophene-3-carboxylate (0.175 g. 0.66 mmol) and 3-(5-methyl-1H-imidazol-1-yl)propan-1-amine (5) (0.09 g, 0.66 mmol) as described above.
Reaction SMILES: [CH2:1](OCC)C.[N:6]1([C:12]2[C:17]([CH:18]=[O:19])=[CH:16][CH:15]=[C:14]([C:20]([F:23])([F:22])[F:21])[N:13]=2)[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1.C[Mg]Cl>C1COCC1>[N:6]1([C:12]2[C:17]([CH:18]([OH:19])[CH3:1])=[CH:16][CH:15]=[C:14]([C:20]([F:23])([F:21])[F:22])[N:13]=2)[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1
Reactant: O=Cc1ccc(C(F)(F)F)nc1N1CCOCC1
Reactant: CCOCC
Agent: C[Mg]Cl
Solvent: C1CCOC1
Product: CC(O)c1ccc(C(F)(F)F)nc1N1CCOCC1
Reaction time: 0.5 h

Procedure:
To a diethylether (7.0 ml) solution of 2-morpholin-4-yl-6-(trifluoromethyl)pyridine-3-carbaldehyde (Jornal of Medicinal Chemistry, 2005, 48, p 71-90, 0.88 g, 3.4 mmol) was added THF solution of methylmagnesiumchloride (3.0M, 1.36 ml) at 0° C. and the mixture was stirred for 0.5 h. The same procedure as described in Example 9C was performed to give the title compound as a colorless oil (quant. 0.9 g).
Reaction SMILES: [Cl-:1].[Cl-].[C:3](=[Zr+2:6]([CH:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:22]([Si](C)(C)C)=[CH:21]1)[CH:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([Si](C)(C)C)=[CH:8]1)([CH3:5])[CH3:4].C[Si](C)(C)[C:35]1[C:43]2C(=CC=CC=2)C(C(C2C3C(=CC=CC=3)C([Si](C)(C)C)=C2)(C)C)[CH:36]=1.[Li][Li].[CH:64](C1C2C(=CC=CC=2)C(C(C2C3C(=CC=CC=3)C(C(C)C)=C2)(C)C)C=1)([CH3:66])[CH3:65]>>[Cl-:1].[Cl-:1].[C:3](=[Zr+2:6]([CH:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:22]([CH:64]([CH3:66])[CH3:65])=[CH:21]1)[CH:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([CH:35]([CH3:43])[CH3:36])=[CH:8]1)([CH3:5])[CH3:4]
Reactant: CC(C)=[Zr+2](C1C=C([Si](C)(C)C)c2ccccc21)C1C=C([Si](C)(C)C)c2ccccc21
Reactant: CC(C)(C1C=C([Si](C)(C)C)c2ccccc21)C1C=C([Si](C)(C)C)c2ccccc21
Reactant: CC(C)C1=CC(C(C)(C)C2C=C(C(C)C)c3ccccc32)c2ccccc21
Agent: [Cl-]
Agent: [Li][Li]
Product: CC(C)=[Zr+2](C1C=C(C(C)C)c2ccccc21)C1C=C(C(C)C)c2ccccc21

Procedure:
It was worked according to the procedure described at point (c) of example 1 except that, instead of 2,2-bis(3-trimethylsilyl-indenyl)propane, 20 mmol of the dilithium salt of 2,2-bis(3-isopropyl-indenyl)propane was used, and that the product was recrystallized from DME. Pure rac-isopropylidene-bis(3-isopropyl-indenyl)zirconium dichloride was obtained. 1H-NMR (toluene-d8, 30° C.) δ: 7.34 (m.4H); 6.98 (m,2H); 6,69 (m,2H); 5.78 (s,2H); 3.14 (sept,2H); 1.81 (s,6H); 1.20 (d,12H).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)[C@@H:10]([OH:37])[CH2:11][C@@H:12]([NH:26]C(=O)OCC1C=CC=CC=1)[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=2)=[CH:16][CH:15]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl>CO.C(OCC)(=O)C.[OH-].[OH-].[Pd+2]>[NH2:26][C@@H:12]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=2)=[CH:16][CH:15]=1)[CH2:11][C@H:10]([OH:37])[C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[CH2:38][C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)[C@@H](O)C[C@H](Cc1ccc(-c2ccccn2)cc1)NC(=O)OCc1ccccc1
Agent: [Pd+2]
Agent: Cl
Agent: [OH-]
Solvent: CO
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)N[C@@H](Cc1ccccc1)[C@@H](O)C[C@@H](N)Cc1ccc(-c2ccccn2)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A solution of the product of Example 1C (4.2 g, 7.0 mmol) in a mixture of methanol (35 mL) and ethyl acetate (35 mL) was treated with Pd(OH)2 on carbon (1.4 g, 20% Pd by wt.) and HCl solution (1.8 mL, 4N in dioxane), and the reaction was stirred under a hydrogen atmosphere (balloon pressure) for 16 hours at 25° C. The reaction mixture was filtered through a bed of celite®, rinsed with methanol and concentrated to give the title compound as the hydrochloride salt (3.7 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([S:8]([CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1.Cl[C:18]1[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][N:19]=1.CCN(C(C)C)C(C)C>O1CCOCC1>[Cl:1][C:2]1[CH:3]=[C:4]([S:8]([CH:11]2[CH2:16][CH2:15][N:14]([C:18]3[CH:23]=[CH:22][C:21]([N+:24]([O-:26])=[O:25])=[CH:20][N:19]=3)[CH2:13][CH2:12]2)(=[O:10])=[O:9])[CH:5]=[CH:6][CH:7]=1
Reactant: O=S(=O)(c1cccc(Cl)c1)C1CCNCC1
Reactant: O=[N+]([O-])c1ccc(Cl)nc1
Solvent: CCN(C(C)C)C(C)C
Solvent: C1COCCO1
Product: O=[N+]([O-])c1ccc(N2CCC(S(=O)(=O)c3cccc(Cl)c3)CC2)nc1
Yield: 27.6 %

Procedure:
Using the procedure from Example 7A, 4-[(3-chlorophenyl)sulfonyl]piperidine (100 mg, 0.38 mmol) was reacted with 2-chloro-5-nitropyridine (122 mg, 0.76 mmol), DIEA (0.2 ml, 1.14) and 1,4-dioxane (0.3 ml) to afford the title compound (40 mg), a yellow solid, in 28% yield.
Reaction SMILES: CS(O[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]/[CH:14]=[CH:15]\[CH2:16]/[CH:17]=[CH:18]\[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])(=O)=O.[Br-:24].[Mg+2].[Br-].O>CCOCC>[CH2:6]([Br:24])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]/[CH:14]=[CH:15]\[CH2:16]/[CH:17]=[CH:18]\[CH2:19][CH2:20][CH2:21][CH2:22][CH3:23]
Reactant: CCCCC/C=C\C/C=C\CCCCCCCCOS(C)(=O)=O
Reactant: [Br-]
Agent: [Mg+2]
Solvent: O
Solvent: CCOCC
Product: CCCCC/C=C\C/C=C\CCCCCCCCBr
Reaction time: 21 h
Yield: 109.6 %

Procedure:
A mixture of linoleyl methane sulfonate (6.2 g, 18 mmol) and magnesium bromide etherate (17 g, 55 mmol) in anhydrous ether (300 mL) was stirred under argon overnight (21 hours). The resulting suspension was poured into 300 mL of chilled water. Upon shaking, the organic phase was separated. The aqueous phase was extracted with ether (2×150 mL). The combined ether phase was washed with water (2×150 mL), brine (150 mL), and dried over anhydrous Na2SO4. The solvent was evaporated to afford 6.5 g of colourless oil. The crude product was purified by column chromatography on silica gel (230-400 mesh, 300 mL) and eluted with hexanes. This gave 6.2 g (approximately 100%) of linoleyl bromide (II). 1H NMR (400 MHz, CDCl3) δ: 5.27-5.45 (4H, m, 2×CH═CH), 3.42 (2H, t, CH2Br), 2.79 (2H, t, C═C—CH2-C═C), 2.06 (4H, q, 2× allylic CH2), 1.87 (2H, quintet, CH2), 1.2-1.5 (16H, m), 0.90 (3H, t, CH3) ppm.
Reaction SMILES: [C:1]([C:5]1[N:6]=[C:7]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:8]2[N:13]=[N:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[Cl:21])[C:9]=2[N:10]=1)([CH3:4])([CH3:3])[CH3:2].C(C1N=C(Cl)C2N=NN(CC3C=CC=CC=3Cl)C=2N=1)(C)(C)C.N1CC[O:53][CH:52](CO)C1>>[C:1]([C:5]1[N:6]=[C:7]([N:22]2[CH2:27][CH2:26][O:25][CH:24]([CH2:52][OH:53])[CH2:23]2)[C:8]2[N:13]=[N:12][N:11]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[Cl:21])[C:9]=2[N:10]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: OCC1CNCCO1
Reactant: CC(C)(C)c1nc(N2CCOCC2)c2nnn(Cc3ccccc3Cl)c2n1
Agent: CC(C)(C)c1nc(Cl)c2nnn(Cc3ccccc3Cl)c2n1
Product: CC(C)(C)c1nc(N2CCOC(CO)C2)c2nnn(Cc3ccccc3Cl)c2n1

Procedure:
In analogy to the procedure described for the synthesis of 5-tert-butyl-3-(2-chloro-benzyl)-7-morpholin-4-yl-3H-[1,2,3]triazolo[4,5-d]pyrimidine (example 1, step c), the title compound was prepared from 5-tert-butyl-7-chloro-3-(2-chlorobenzyl)-3H-[1,2,3]triazolo[4,5-d]pyrimidine and morpholin-2-ylmethanol and isolated as light-yellow gum (11.8 mg, 60%). MS (m/e): 417.5 (MH+).
Reaction SMILES: [CH3:1][C:2]1[N:3]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH3:14])[N:9]=2)[C:4]([CH3:7])=[CH:5][CH:6]=1.[Li][CH2:16]CCC.CI>C1COCC1>[CH3:7][C:4]1[N:3]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([CH2:14][CH3:16])[N:9]=2)[C:2]([CH3:1])=[CH:6][CH:5]=1
Reactant: [Li]CCCC
Reactant: Cc1cccc(-n2c(C)ccc2C)n1
Solvent: CI
Solvent: C1CCOC1
Product: CCc1cccc(-n2c(C)ccc2C)n1
Temperature: -30 °C
Yield: 60 %

Procedure:
To a solution of the product from Example 2a (6.82 g, 36.6 mmol) in 75 mL of dry THF cooled to 40° C. under a N2 atmosphere was added dropwise n-BuLi as a 2.5M solution in hexanes (16 mL, 40 mmol). The resulting solution was stirred at low temperature for thirty minutes then treated with CH3I (2.4 mL, 38.6 mmol). On completion of the addition the mixture was allowed to warm to −30° C. and after 20 min to room temperature. The reaction was subsequently quenched by pouring into brine solution, the product isolated by extraction with EtOAc. Dried over MgSO4, filtered and concentration under vacuum. Purified by silica gel column chromatography eluting with EtOAc/hexane gave the title compound (4.42 g, 60%).
Reaction SMILES: [F:1][C:2]([F:27])([F:26])[C:3]1[CH:4]=[C:5]([S:9]([O:12][C:13]2[CH:14]=[CH:15][C:16]([NH:22][C:23]([NH2:25])=[O:24])=[C:17]([N+:19]([O-])=O)[CH:18]=2)(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1.[H][H]>CO.COCCO.[Ni]>[F:26][C:2]([F:1])([F:27])[C:3]1[CH:4]=[C:5]([S:9]([O:12][C:13]2[CH:14]=[CH:15][C:16]([NH:22][C:23]([NH2:25])=[O:24])=[C:17]([CH:18]=2)[NH2:19])(=[O:11])=[O:10])[CH:6]=[CH:7][CH:8]=1
Reactant: [H][H]
Reactant: NC(=O)Nc1ccc(OS(=O)(=O)c2cccc(C(F)(F)F)c2)cc1[N+](=O)[O-]
Agent: [Ni]
Solvent: CO
Solvent: COCCO
Product: NC(=O)Nc1ccc(OS(=O)(=O)c2cccc(C(F)(F)F)c2)cc1N

Procedure:
61.5 g of 5-(3-trifluoromethylphenylsulfonyloxy)-2-ureidonitrobenzene in 200 ml of methanol and 200 ml of 2-methoxyethanol are hydrogenated under normal pressure with a catalytic amount of Raney nickel. After hydrogen uptake is complete, the catalyst is filtered off with suction, washed with methanol and the solution is evaporated under reduced pressure, 1 liter of water is added, and the solid is filtered off with suction, washed with water and dried over NaOH, melting point 172° C., decomposition.