Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[CH2:2][CH:3]([OH:21])[CH2:4][O:5][C:6]1[CH:7]=[C:8]([C:12]2[NH:13][CH:14]=[C:15]([C:17]([F:20])([F:19])[F:18])[N:16]=2)[CH:9]=[CH:10][CH:11]=1.[OH-].[K+].C(O)(=O)C>CO>[O:21]1[CH2:2][CH:3]1[CH2:4][O:5][C:6]1[CH:7]=[C:8]([C:12]2[NH:13][CH:14]=[C:15]([C:17]([F:20])([F:19])[F:18])[N:16]=2)[CH:9]=[CH:10][CH:11]=1
Reactant: OC(CCl)COc1cccc(-c2nc(C(F)(F)F)c[nH]2)c1
Agent: [K+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CO
Product: FC(F)(F)c1c[nH]c(-c2cccc(OCC3CO3)c2)n1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a solution of 2-[3-(3-chloro-2-hydroxypropoxy)phenyl]-4-trifluoromethylimidazole (3.8 g.) in methanol (150 ml.) is added powdered potassium hydroxide (3. g.) and the mixture is allowed to stir 4 hours at room temperature. Glacial acetic acid (2.75 ml.) is added and the mixture concentrated under reduced pressure 920 mm. Hg.) over steam. The resulting residue is stirred with water, filtered and recrystallized from xylene to yield 2.5 g. of 2-[3-(2,3-epoxypropoxy)phenyl]-4-trifluoromethylimidazole is obtained, m.p. 145°-146.5° C.
Reaction SMILES: [C:1]1([CH2:7][O:8][C:9](=[O:36])[C:10]2[CH:15]=[C:14]([O:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH:13]=[C:12]([OH:35])[CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Br[CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[C:46]([O:50][CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[C:45]=1[O:58][CH2:59][C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1.[I-].[K+].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O.CN(C=O)C>[C:1]1([CH2:7][O:8][C:9](=[O:36])[C:10]2[CH:15]=[C:14]([O:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH:13]=[C:12]([O:35][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][C:44]3[CH:49]=[CH:48][CH:47]=[C:46]([O:50][CH2:51][C:52]4[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=4)[C:45]=3[O:58][CH2:59][C:60]3[CH:61]=[CH:62][CH:63]=[CH:64][CH:65]=3)[CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: BrCCCCCCc1cccc(OCc2ccccc2)c1OCc1ccccc1
Reactant: CCCCCCCCCCCCCCCCCCOc1cc(O)cc(C(=O)OCc2ccccc2)c1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCCCCCCCOc1cc(OCCCCCCc2cccc(OCc3ccccc3)c2OCc2ccccc2)cc(C(=O)OCc2ccccc2)c1
Yield: 76.7 %

Procedure:
A mixture of 1.5 g (3 mmol) of 3-hydroxy-5-(octadecyloxy) benzoic acid phenylmethyl ester, 1.6 g (3.4 mmol) of 1-(6-bromo-hexyl)-2,3-bis(phenylmethoxy)benzene [M. Carson, R.-J. Han and R. A. LeMahieu, U.S. Pat. No. 5,025,036 (1991)], 0.45 g (3 mmol) of potassium iodide and 0.84 g (6 mmol) of potassium carbonate in 40 ml of acetone and 10 ml of DMF was stirred at reflux for 47 hours. The solvents were removed at reduced pressure and the residue was purified by HPLC using 5% ethyl acetate-hexane to give 2.0 g (77% yield) of 3-[[6-[2,3-bis(phenylmethoxy)phenyl]hexyl]oxy]-5-(octadecyloxy)benzoic acid phenylmethyl ester as an oil. The nmr spectrum served to confirm the structure.
Reaction SMILES: Br[C:2]1[N:7]2[N:8]=[C:9]([NH:11][C:12](=[O:19])[C:13]3[CH:18]=[CH:17][CH:16]=[N:15][CH:14]=3)[N:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1.[CH2:20]([NH2:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>>[CH2:20]([NH:27][C:2]1[N:7]2[N:8]=[C:9]([NH:11][C:12](=[O:19])[C:13]3[CH:18]=[CH:17][CH:16]=[N:15][CH:14]=3)[N:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: O=C(Nc1nc2cccc(Br)n2n1)c1cccnc1
Reactant: NCc1ccccc1
Product: O=C(Nc1nc2cccc(NCc3ccccc3)n2n1)c1cccnc1

Procedure:
The title compound was prepared following procedure described for example 30 but starting from N-(5-bromo[1,2,4]triazolo[1,5-a]pyridin-2-yl)nicotinamide ((B2), 100 mg; 0.31 mmol; 1.0 eq.) and benzylamine (1.0 mL) as an oily solid (10 mg, 9%). HPLC, Rt: 2.46 min. (purity 85.8%). LC/MS, M+(ESI): 345.1, M−(ESI): 343.1.
Reaction SMILES: C(O[C:4]([C:6]1[C:11](=[O:12])[N:10]([CH2:13][CH2:14][CH:15]([CH3:17])[CH3:16])[N:9]2[CH:18]=[CH:19][CH:20]=[C:8]2[C:7]=1[OH:21])=O)C.[NH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[S:29]([NH2:32])(=[O:31])=[O:30]>C(O)C>[O:30]=[S:29]1(=[O:31])[C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[NH:22][C:4]([C:6]2[C:11](=[O:12])[N:10]([CH2:13][CH2:14][CH:15]([CH3:16])[CH3:17])[N:9]3[CH:18]=[CH:19][CH:20]=[C:8]3[C:7]=2[OH:21])=[N:32]1
Reactant: CCOC(=O)c1c(O)c2cccn2n(CCC(C)C)c1=O
Reactant: Nc1ccccc1S(N)(=O)=O
Solvent: CCO
Product: CC(C)CCn1c(=O)c(C2=NS(=O)(=O)c3ccccc3N2)c(O)c2cccn21
Temperature: 180 °C
Yield: 50 %

Procedure:
4-Hydroxy-1-(3-methyl-butyl)-2-oxo-1,2-dihydro-pyrrolo[1,2-b]pyridazine-3-carboxylic acid ethyl ester (Example 1f, 0.040 g, 0.14 mmol) was mixed with 2-amino-benzenesulfonamide (0.0235 g, 0.14 mmol) and the resulting mixture was heated to 180° C. for 20 min. The resulting crude oil was allowed to cool to 25° C. and ethanol (0.5 mL) was added and sonicated to afford a tan precipitate, which was collected and dried in vacuo. The crude solid was dissolved in 1.0 M aqueous potassium hydroxide solution (0.3 mL) and heated to 110° C. for 20 h. The reaction mixture was allowed to cool to 25° C. and 10% aqueous hydrochloric acid solution (0.5 mL) was added and the resulting white precipitate was collected. The solid was washed with methanol and dried in vacuo to afford the desired product, 3-(1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-4-hydroxy-1-(3-methyl-butyl)-pyrrolo[1,2-b]pyridazin-2-one (0.028 g, 0.07 mmol, 52% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 0.97 (6H, d, J=6.4 Hz), 1.28 (2H, bs), 1.61 (2H, q, J1=15.2 Hz, J2=6.8 Hz), 1.74 (1H, m), 4.43 (2H, t, J=8.0 Hz), 6.71 (1H, dd, J1=4.4 Hz, J2=2.4 Hz), 7.04 (1H, d, J=4.4 Hz), 7.23 (1H, t, J=8.0 Hz), 7.50 (1H, t, J=7.6 Hz), 7.63 (1H, d, J=8.4 Hz), 7.88 (1H, d, J=8.0 Hz), 7.90 (1H, m); LC-MS (ESI) calcd for C19H20N4O4S 400.45, found 401.28 [M+H+].
Reaction SMILES: [N:1]1([CH2:7][C:8]2[CH:9]=[C:10]([CH2:14][CH:15]3CO3)[CH:11]=[CH:12][CH:13]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[C-]#[N:19].[Na+].[Cl-].[NH4+].[CH2:23]([OH:25])[CH3:24]>>[OH:25][CH:23]([CH:14]([C:10]1[CH:11]=[CH:12][CH:13]=[C:8]([CH2:7][N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[CH:9]=1)[CH3:15])[C:24]#[N:19]
Reactant: [C-]#N
Reactant: c1cc(CC2CO2)cc(CN2CCCCC2)c1
Reactant: CCO
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Product: CC(c1cccc(CN2CCCCC2)c1)C(O)C#N

Procedure:
0.74 g (3.2 mmol) of 2-[3-(1-piperidylmethyl)phenyl]methyl-oxirane, 0.294 g (6 mmol) of sodium cyanide and 0.107 g (2 mmol) of ammonium chloride are boiled in 5 ml ethanol/5 ml water for 6 hours. After substantial concentration of the mother liquor by evaporation under vacuum, the residue is taken up in 10 ml of water, and the solution is adjusted to pH 12 with potassium carbonate and extracted with 3×20 ml of methylene chloride. The organic phase yields 0.82 g of a brown oil after dehydration and evaporation under vacuum.
Reaction SMILES: [Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[F:13][C:14]1[CH:15]=[C:16]([N:21]2[C:26](=[O:27])[C:25]([CH2:28][C:29]3[CH:34]=[CH:33][C:32]([C:35]4[C:36]([C:41]#[N:42])=[CH:37][CH:38]=[CH:39][CH:40]=4)=[CH:31][CH:30]=3)=[C:24]([CH2:43][CH2:44][CH3:45])[N:23]=[C:22]2[CH3:46])[CH:17]=[CH:18][C:19]=1[OH:20]>O.C(OCC)(=O)C>[F:13][C:14]1[CH:15]=[C:16]([N:21]2[C:26](=[O:27])[C:25]([CH2:28][C:29]3[CH:34]=[CH:33][C:32]([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=4[C:41]4[NH:3][C:4](=[O:7])[O:5][N:42]=4)=[CH:31][CH:30]=3)=[C:24]([CH2:43][CH2:44][CH3:45])[N:23]=[C:22]2[CH3:46])[CH:17]=[CH:18][C:19]=1[OH:20]
Reactant: CCCc1nc(C)n(-c2ccc(O)c(F)c2)c(=O)c1Cc1ccc(-c2ccccc2C#N)cc1
Reactant: O=C([O-])O
Reactant: [NH3+]O
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Solvent: CS(C)=O
Product: CCCc1nc(C)n(-c2ccc(O)c(F)c2)c(=O)c1Cc1ccc(-c2ccccc2-c2noc(=O)[nH]2)cc1
Temperature: 40 °C
Reaction time: 0.5 h
Yield: 64.2 %

Procedure:
A mixture of hydroxylammonium chloride (1.40 g), sodium hydrogen carbonate (2.00 g) and dimethyl sulfoxide (10 mL) was stirred at 40° C. for 30 min, 4′-{[1-(3-fluoro-4-hydroxyphenyl)-2-methyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl]methyl}biphenyl-2-carbonitrile (0.91 g) was added, and the mixture was stirred at 90° C. for 18 hr. The reaction mixture was allowed to cool to room temperature, ethyl acetate and water were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was dissolved in tetrahydrofuran (10 mL). N,N′-carbonyldiimidazole (0.39 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.36 mL) were added, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to give the title compound as colorless crystals (0.66 g, 64%).
Reaction SMILES: [C:1](Cl)(=[O:5])[CH:2]([CH3:4])[CH3:3].[N+:7]([C:10]1[CH:11]=[C:12]([CH:14]=[C:15]([N+:17]([O-:19])=[O:18])[CH:16]=1)[NH2:13])([O-:9])=[O:8].N1C=CC=CC=1.O>CN(C)C=O>[N+:7]([C:10]1[CH:11]=[C:12]([CH:14]=[C:15]([N+:17]([O-:19])=[O:18])[CH:16]=1)[NH:13][C:1](=[O:5])[CH:2]([CH3:4])[CH3:3])([O-:9])=[O:8]
Reactant: Nc1cc([N+](=O)[O-])cc([N+](=O)[O-])c1
Reactant: CC(C)C(=O)Cl
Solvent: CN(C)C=O
Solvent: O
Solvent: c1ccncc1
Product: CC(C)C(=O)Nc1cc([N+](=O)[O-])cc([N+](=O)[O-])c1
Temperature: 25 °C

Procedure:
iso-Butyryl chloride (6.3 ml.) was added dropwise during 15 minutes to a stirred solution of 3,5-dinitroaniline (5.5 g.) in a mixture of dimethylformamide (18 ml.) and dry pyridine (18 ml.) maintained at a temperature of 0°-5°C. The reaction mixture was allowed to warm to room temperature during 30 minutes and then added to a mixture of ice and water (200 ml.). The precipitate was filtered off, dissolved in dimethylformamide (50 ml.) and added to a mixture of ice and water (300 ml.) containing concentrated hydrochloric acid (10 ml.). The precipitate was filtered off, washed with saturated aqueous sodium bicarbonate solution and then with water and dried. Crystallisation from aqueous ethanol gave 3',5'-dinitro-iso-butyranilide (5.6 g.), m.p. 165°-168°C.
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:3]=1[C:4](O)=O.CN(C)[CH:16]=[O:17].[C:19](Cl)(=[O:23])[C:20](Cl)=O.[Si](C=[N+]=[N-])(C)(C)C>C(Cl)Cl>[CH3:1][C:2]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][C:3]=1[CH2:4][C:16]([O:23][CH2:19][C:20]1[CH:9]=[CH:10][CH:2]=[CH:3][CH:4]=1)=[O:17]
Reactant: O=C(Cl)C(=O)Cl
Reactant: CN(C)C=O
Reactant: Cc1ccc([N+](=O)[O-])cc1C(=O)O
Agent: C[Si](C)(C)C=[N+]=[N-]
Solvent: ClCCl
Product: Cc1ccc([N+](=O)[O-])cc1CC(=O)OCc1ccccc1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 52 %

Procedure:
In methylene chloride (50 mL) was placed 2-methyl-5-nitrobenzoic acid (3.00 g, 16.6 mmol) and 1 microdrop of dimethylformamide. The solution was cooled to 0° C. and to this was added oxalyl chloride (3.15 g, 24.8 mmol). After 15 minutes the mixture was allowed to warm to RT and stirred a further 2 hours. The mixture evaporated at reduced pressure. This residue was dissolved in THF (60 mL) and cooled to 0° C. To this was added the 2.00N TMS-diazomethane (18.6 mL, 37.3 mmol) and the mixture stirred at 0° C. for 5 hrs. The solution was evaporated at reduced pressure and the new residue was treated with benzyl alcohol (15 mL) and 2,4,6-collidine (10 mL) and warmed to 180° C. for 15 min. After cooling to RT and diluting with ethyl acetate (100 mL), the resulting solution was washed successively with water (2×100 mL), 5% citric acid (100 mL, till pH of aqueous phase is acidic), water (100 mL) and brine (100 mL). The solvent was removed at reduced pressure and the resultant oil was dried on the high vacuum line at 65° C. to remove most excess benzyl alcohol. The oil was purified by chromatography (Biotage Si-40 column, 10-40% ethyl acetate/Hex—1398 mL) to give benzyl 2-(2-methyl-5-nitrophenyl)acetate as an oil (2.465 g, 52% yield) which was used as is.
Reaction SMILES: [CH3:1][C:2]1[CH:6]=[C:5]([CH2:7][CH2:8][CH:9]([CH3:11])[CH3:10])[O:4][N:3]=1.[H][H]>[Pt](=O)=O.C(O)C>[NH2:3][C:2](=[CH:6][C:5](=[O:4])[CH2:7][CH2:8][CH:9]([CH3:10])[CH3:11])[CH3:1]
Reactant: [H][H]
Reactant: Cc1cc(CCC(C)C)on1
Agent: O=[Pt]=O
Solvent: CCO
Product: CC(N)=CC(=O)CCC(C)C

Procedure:
3-Methyl-5-(3-methylbutyl)isoxazole (3.90 g, 25.5 mmol) [synthesis analogous to C. Kashima et al., Bull. Chem. Soc. Jpn. 46, 310-313 (1973)] is introduced into 80 ml of ethanol, platinum (IV) oxide catalyst (390 mg, 1.72 mmol) is added, and the mixture is then hydrogenated under atmospheric pressure hydrogen for 2 h (slightly exothermic reaction). The catalyst is filtered off, the filtrate is concentrated, and the residue is purified by chromatography on a Biotage 40M cartridge (mobile phase: isohexane/ethyl acetate 3:1). The product fractions are concentrated. The resulting residue is an oil, which crystallizes after a short time. Drying in vacuo results in 3.41 g (86% of theory) of the title compound.
Reaction SMILES: [CH2:1]([C:3]1[NH:4][C:5]2[C:10]([CH:11]=1)=[C:9]([O:12][CH3:13])[CH:8]=[CH:7][CH:6]=2)[CH3:2].[H-].[Na+].[CH2:16](Br)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CN(C=O)C.O>[CH2:1]([C:3]1[N:4]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:5]2[C:10]([CH:11]=1)=[C:9]([O:12][CH3:13])[CH:8]=[CH:7][CH:6]=2)[CH3:2]
Reactant: CCc1cc2c(OC)cccc2[nH]1
Reactant: BrCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCc1cc2c(OC)cccc2n1Cc1ccccc1
Reaction time: 1.5 h
Yield: 48.7 %

Procedure:
2-Ethyl-4-methoxy-1H-indole (4.2 g, 24 mmol) was dissolved in 30 mL of DMF and 960 mg (24 mmol) of 60% NaH/minerial oil was added. After 1.5 hours, 2.9 mL(24 mmol) of benzyl bromide was added. After 4 hours, the mixure was diluted with water and extracted twice with ethyl acetate. The combined ethyl acetate was washed with brine, dried (MgSO4) and concentrated at reduced pressure. The residue was chromatographed on silica gel and eluted with 20% EtOAc/hexane to give 3.1 g (49% yield) of 2-ethyl-4-methoxy-1-(phenylmethyl)-1H-indole.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[C:11](=[O:24])[CH2:12][S:13][C:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]=[CH:16][CH:15]=1.[BH4-].[Na+].O.Cl>C(O)C>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH:11]([OH:24])[CH2:12][S:13][C:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]=[CH:16][CH:15]=1
Reactant: O=C(CSc1ccnc2ccccc12)c1ccc2ccccc2c1
Agent: Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: OC(CSc1ccnc2ccccc12)c1ccc2ccccc2c1
Temperature: -15 °C
Reaction time: 2 h
Yield: 36.5 %

Procedure:
4-[2-(2-Naphtyl)-2-oxoethylthio]quinoline (Compound 2; 450 mg, 1.37 mmol) was dissolved in ethanol (50 ml), added at -15° C. with sodium borohydride (70 mg, 3.04 mmol), and stirred at -15° C. for two hours. The reaction mixture was added with water and neutralized by 2N hydrochloric acid. The solvent was removed under reduced pressure. The residue was extracted with ethyl acetate, washed with saturated saline solution and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure and the residue was chromatographed by silica gel column chromatography (hexane:ethyl acetate=1:4) to obtain 165.7 mg of the titled compound (36.5%).
Reaction SMILES: [P:1]([O-:7])([O:5][CH3:6])([O:3][CH3:4])=[O:2].[Na+].P(OC)(OC)(OC)=O.[I-].[Na+].[C:19](Cl)(=[O:21])[CH3:20]>O1CCCC1>[P:1]([O:7][C:19](=[O:21])[CH3:20])([O:5][CH3:6])([O:3][CH3:4])=[O:2]
Reactant: CC(=O)Cl
Reactant: COP(=O)([O-])OC
Agent: [I-]
Agent: [Na+]
Solvent: COP(=O)(OC)OC
Solvent: C1CCOC1
Product: COP(=O)(OC)OC(C)=O
Yield: 80 %

Procedure:
A suspension of sodium dimethyl phosphate (14.8 g, 0.1 mmol, from trimethyl phosphate and sodium iodide and acetyl chloride (7.8 g, 0.1 mmol) in dry tetrahydrofuran (80 mn) was stirred for two days at room temperature in a flask fitted with a drying tube. The reaction solution was filtered and the tetrahydrofuran was removed under reduced pressure. The resulting colorless liquid was Kugelrohr-distilled (Aldrich Kugelrohr apparatus, 55°-60° C. 0.30 torr) to give 14.2 g (80%) of dimethyl acetyl phosphate.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][CH:3]=1.[Mg].[Si:10]([Cl:14])([Cl:13])([Cl:12])[Cl:11]>C(OCC)C>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([Si:10]([Cl:13])([Cl:12])[Cl:11])=[CH:3][CH:4]=1.[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([Si:10]([C:2]2[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][CH:3]=2)([Cl:14])[Cl:11])=[CH:3][CH:4]=1
Reactant: Cl[Si](Cl)(Cl)Cl
Reactant: Clc1ccc(Br)cc1
Agent: [Mg]
Solvent: CCOCC
Product: Clc1ccc([Si](Cl)(Cl)Cl)cc1
Product: Clc1ccc([Si](Cl)(Cl)c2ccc(Cl)cc2)cc1
Yield: 20 %
Yield: 35 %

Procedure:
The Grignard reagent solution prepared, under nitrogen, from 1-bromo-4-chlorobenzene (38.3 g, 0.2 mol) and magnesium (4.867 g, 0.2 g atom) in 300 ml anhydrous diethyl ether, is filtered through a glass filter-stick by nitrogen pressure into a graduated feed-funnel, from which it is fed during 21/4 hours into a stirred solution of redistilled silicon tetrachloride (102 g, 0.6 mol) in 200 ml of dry ether. The solution is heated at reflux temperature an additional 2 hours, then cooled and filtered under nitrogen. If not protected from the air, the solution turns red and reduced yields are obtained. The ether and excess silicon chloride is concentrated in vacuum and the residue distilled in vacuum under nitrogen. 4-Chlorophenyl trichlorosilane (17 g, 35 percent yield), b.p. 84°-85° C/3.4 mm, nD27.5 1.5400, and bis(4-chlorophenyl) dichlorosilane (6.2 g, 20 percent yield), b.p. 146°-150° C/0.4 mm, m.p. 60°-61° C are obtained.
Reaction SMILES: [Br:1][C:2]1[CH:15]=[CH:14][C:5]([C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=O)=[CH:4][CH:3]=1.C(OP([CH2:24][C:25]1[C:26]2[C:31]([C:32]([CH2:39]P(OCC)(OCC)=O)=[C:33]3[C:38]=1[CH:37]=[CH:36][CH:35]=[CH:34]3)=[CH:30][CH:29]=[CH:28][CH:27]=2)(OCC)=O)C.[C:48](O[K])([CH3:51])([CH3:50])[CH3:49].S(=O)(=O)(O)O>O1CCCC1.O>[Br:1][C:2]1[CH:15]=[CH:14][C:5]([C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:39][C:32]2[C:31]3[C:26]([C:25]([CH:24]=[C:49]([C:8]4[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)[C:48]4[CH:51]=[CH:15][C:2]([Br:1])=[CH:3][CH:50]=4)=[C:38]4[C:33]=2[CH:34]=[CH:35][CH:36]=[CH:37]4)=[CH:27][CH:28]=[CH:29][CH:30]=3)=[CH:4][CH:3]=1
Reactant: CCOP(=O)(Cc1c2ccccc2c(CP(=O)(OCC)OCC)c2ccccc12)OCC
Reactant: CC(C)(C)O[K]
Reactant: O=C(c1ccccc1)c1ccc(Br)cc1
Agent: O=S(=O)(O)O
Solvent: O
Solvent: C1CCOC1
Product: Brc1ccc(C(=Cc2c3ccccc3c(C=C(c3ccccc3)c3ccc(Br)cc3)c3ccccc23)c2ccccc2)cc1
Reaction time: 3.5 h

Procedure:
Under an inert atmosphere, 4-bromobenzophenone (3.917 g, 15 mmol), and 9,10-bis-(diethylphosphonomethyl)anthracene (2.942 g, 6.15 mmol) were dissolved in tetrahydrofuran (40 g). At room temperature, tetrahydrofuran (16.38 g) solution of tert-butoxy potassium (2.070 g, 18.45 mmol) was added dropwise for 5 minutes, and successively stirred for 3.5 hours. The reaction mixture was charged into water (100 ml) and neutralized with 5% sulfuric acid. After neutralization, the crystal was filtrated and the dissolved in tetrahydrofuran (300 ml). Then, the solvent was partly distilled off under reduced pressure, and cooled to deposit crystal. The crystal was filtrated and dried to give the desired product. (Yield: 1.10 g, 26%)
Reaction SMILES: [C:1]([CH:3]([CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])[CH3:4])#[N:2].[CH2:15](N)[CH2:16][NH2:17]>C(=S)=S>[CH3:4][CH:3]([C:1]1[NH:2][CH2:15][CH2:16][N:17]=1)[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: CCCCCCCCCCC(C)C#N
Reactant: NCCN
Solvent: S=C=S
Product: CCCCCCCCCCC(C)C1=NCCN1
Yield: 65 %

Procedure:
19.53 g (100 mmoles) of 2-cyanododecane, 8.5ml (127 mmoles) of ethylenediamine and 0.5 ml of carbon disulfide are reacted according to Example 29 and the reaction mixture is worked up as mentioned therein. Distillation of the residue gives 15.5 g (65%) of the product.
Reaction SMILES: [Br:1][C:2]1[C:3](O)=[N:4][C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([S:15]([NH2:18])(=[O:17])=[O:16])=[N:13][CH:14]=2)=[N:6][CH:7]=1.C(N(CC)C1C=CC=CC=1)C.P(Cl)(Cl)([Cl:33])=O>>[Br:1][C:2]1[C:3]([Cl:33])=[N:4][C:5]([NH:8][C:9]2[CH:10]=[CH:11][C:12]([S:15]([NH2:18])(=[O:17])=[O:16])=[N:13][CH:14]=2)=[N:6][CH:7]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: NS(=O)(=O)c1ccc(Nc2ncc(Br)c(O)n2)cn1
Solvent: CCN(CC)c1ccccc1
Product: NS(=O)(=O)c1ccc(Nc2ncc(Br)c(Cl)n2)cn1
Reaction time: 0.5 h

Procedure:
175 mg (0.5 mmol) of 5-(5-bromo-4-hydroxy-pyrimidin-2-ylamino)-pyridine-2-sulfonic acid amide is refluxed with 20 mg of N,N-diethylaniline in 2 ml of phosphorus oxychloride for 3 hours. Then, it is cooled, poured onto ice and stirred for 30 minutes. The precipitated crystals are suctioned off, washed with water and acetonitrile and dried at 50° C. in a vacuum. Yield: 155 mg (85% of theory) of 5-(5-bromo-4-chloro-pyrimidin-2-ylamino)-pyridine-2-sulfonic acid amide.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([Mg]Br)[CH:5]=[CH:6][C:7]=1[Cl:8].C[CH:12]1[CH2:17][CH2:16][C:15](=O)[C:14]([C:19]([OH:21])=[O:20])=[C:13]1[CH3:22].[Cl-].[NH4+].[CH2:25]1COCC1>[Cu]Cl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:15]2[CH2:16][CH2:17][CH2:12][CH:13]([CH3:22])[CH:14]2[C:19]([O:21][CH3:25])=[O:20])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: C1CCOC1
Reactant: CC1=C(C(=O)O)C(=O)CCC1C
Reactant: Clc1ccc([Mg]Br)cc1Cl
Agent: Cl[Cu]
Agent: [Cl-]
Agent: [NH4+]
Product: COC(=O)C1C(C)CCCC1c1ccc(Cl)c(Cl)c1
Temperature: 0 °C

Procedure:
A suspension of copper (I) chloride (164 mg) in THF (4 mL) was stirred at 0° C. and treated with 3,4-dichlorophenylmagnesium bromide (0.5 M in THF, 3.3 mL). The mixture was stirred for 5 min, then was treated with a solution of methyl 2-methyl-6-oxocyclohex-1-enecarboxylic acid (prepared according to the procedure of Belmont, D. T. et al., J. Org. Chem. 1985, 50, 4102; 140 mg) in THF. The mixture was allowed to warm to rt over 30 min, then was cooled to 0° C. and treated with a 9:1 solution of saturated ammonium chloride-concentrated ammonium hydroxide. The mixture was extracted three times with ethyl acetate and the combined organic layers were washed with saturated aqueous ammonium chloride, dried over sodium sulfate and then concentrated under vacuum. The resulting residue was filtered through silica gel to provide methyl 2-(3,4-dichlorophenyl)-6-methylcyclohexanecarboxylate (153 mg). Mass spectrum m/z 316.44 (M+H+).
Reaction SMILES: [NH2:1][C:2]1[C:6]([C:7]#[N:8])=[C:5]([S:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[NH:4][N:3]=1.[CH3:17][C:18](=O)[CH2:19][C:20](=O)[CH3:21]>CC(O)=O>[CH2:10]([S:9][C:5]1[C:6]([C:7]#[N:8])=[C:2]2[N:1]=[C:18]([CH3:17])[CH:19]=[C:20]([CH3:21])[N:3]2[N:4]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: N#Cc1c(N)n[nH]c1SCc1ccccc1
Reactant: CC(=O)CC(C)=O
Solvent: CC(=O)O
Product: Cc1cc(C)n2nc(SCc3ccccc3)c(C#N)c2n1
Temperature: 25 °C
Reaction time: 3 h
Yield: 95.7 %

Procedure:
A slurry of 0.5 g (2.2 mmole) of 3-amino-5-benzylthio-4-cyanopyrazole in 15 ml glacial HOAc was stirred at room temperature as 0.44 g (4.4 mmole) of 2,4-pentanedione was added. The mixture was stirred at room temperature for 3 hours. The white solid was collected by filtration, washed with HOAc, and dried to give 0.62 g (95.4 percent) of product as a white powder, m.p. 140° C. The analytical sample was recrystallized from 2-propanol. 1H NMR (DMSO-d-6): 7.5 (m, 2H, benzene), 7.3 (m, 3H, benzene), 7.1 (s, 1H, pyrazolopyrimidinyl H-6), 4.5 (s, 2H, CH2), 2.7 (s, 3H, CH3), 2.5 (s obscured by DMSO, 3H, CH3). 13C NMR (DMSO-d-6): 163.3, 155.3, 150.5, 146.7, 137.0, 129.1, 128.3, 127.3 112.8, 111.1, 79.0, 34.5, 24.1, 16.3. IR (KBr): 2220, 1615, 1550 cm -1.