Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1I.C(=O)([O-])O.[Na+].[F:27][C:28]([F:39])([F:38])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1B(O)O.CCOCC>C1(C)C=CC=CC=1.C(O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[CH:9][C:8]=2[Cl:18])[N:5]=[C:4]([C:19]#[N:20])[C:3]=1[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][C:29]=1[C:28]([F:39])([F:38])[F:27]
Reactant: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1I
Reactant: OB(O)c1ccccc1C(F)(F)F
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCOCC
Solvent: O
Product: N#Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)c(N)c1-c1ccccc1C(F)(F)F

Procedure:
To a rapidly stirred solution of 5-amino-3-cyano-1-(2,6-dichloro-4-trifluoromethylphenyl)-4-iodopyrazole (0.62 g) in toluene (5 ml) containing tetrakis(triphenylphosphine)palladium(0) (0.056 g) was added saturated aqueous sodium hydrogen carbonate solution (5 m) and a solution of 2-trifluoromethylphenylboronic acid (1.32 g) in ethanol (2.5 ml). The mixture was heated under reflux for 1.5 hours, cooled and then poured into ether (60 ml) and water (50 ml). The layers were separated and the aqueous phase extracted with a second portion of ether (60 ml). The combined organic layers were washed with water (2×40 ml), brine (40 ml) and then dried (Na2SO4) and evaporated. The residue was purified by column chromatography on silica gel (50 g) eluted with dichloromethane. Combination and evaporation of suitable fractions gave the title compound as a white crystalline solid, m.p. 210-2° C.
Reaction SMILES: [NH2:1][C:2]1[CH:8]=[C:7]([Cl:9])[C:6]([S:10](=[O:13])(=[O:12])[NH2:11])=[CH:5][C:3]=1[NH2:4].[C:14](O)(=O)[CH2:15][CH3:16].Cl>>[Cl:9][C:7]1[C:6]([S:10](=[O:12])(=[O:13])[NH2:11])=[CH:5][C:3]2[NH:4][C:14]([CH2:15][CH3:16])=[N:1][C:2]=2[CH:8]=1
Reactant: CCC(=O)O
Reactant: Nc1cc(Cl)c(S(N)(=O)=O)cc1N
Agent: Cl
Product: CCc1nc2cc(Cl)c(S(N)(=O)=O)cc2[nH]1
Yield: 14.2 %

Procedure:
A mixture of 12.0 g of 2-amino-4-chloro-5-sulfamylaniline, 16.1 g of propionic acid, and 54.4 ml of 4 N hydrochloric acid was refluxed for 6 hours. The solid was collected by filtration, dissolved in boiling methanol, charcoal added, and the solution filtered through Celite. Upon adding to 38% ammonium hydroxide with stirring, a pink solid formed. This was collected by filtration, washed with hot water, air dried, and then recrystallized from acetonitrile to provide 2.0 g of crystals, m.p. 240°-242°.
Reaction SMILES: [Na].[CH2:2]([SH:9])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.CS(O[C@H:15]1[CH2:20][CH2:19][C@H:18]2[C@H:21]3[C@H:31]([CH2:32][CH2:33][C@:16]12[CH3:17])[C@:29]1([CH3:30])[C:24](=[CH:25][C:26](=[O:34])[CH:27]=[CH:28]1)[CH2:23][CH2:22]3)(=O)=O.[OH-].[Na+]>C(O)C>[CH2:2]([S:9][C@@H:15]1[CH2:20][CH2:19][C@H:18]2[C@H:21]3[C@H:31]([CH2:32][CH2:33][C@:16]12[CH3:17])[C@:29]1([CH3:30])[C:24](=[CH:25][C:26](=[O:34])[CH:27]=[CH:28]1)[CH2:23][CH2:22]3)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: SCc1ccccc1
Reactant: C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)C=C[C@@]43C)[C@@H]1CC[C@@H]2OS(C)(=O)=O
Agent: [Na+]
Agent: [Na]
Agent: [OH-]
Solvent: CCO
Product: C[C@]12CC[C@H]3[C@@H](CCC4=CC(=O)C=C[C@@]43C)[C@@H]1CC[C@H]2SCc1ccccc1

Procedure:
To 2.25 gm. of sodium metal dissolved in 185 ml. of ethanol is added 8.2 ml. of benzyl mercaptan followed by 3 gm. of 17β-methanesulfonyloxy-1,4-androstadiene-3-one. The reactants are heated to reflux for 48 hours. Pour the reaction mixture into 5% NaOH solution and extract with ethyl acetate. Wash the ethyl acetate extracts with water, dry over Na2SO4, and evaporate to a residue. The residue is purified on a 300 gm. silica gel column eluting with chloroform/ethyl acetate (2:1) to obtain the title compound.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11][CH2:12][CH:13]=[CH2:14])=[CH:7][C:6]=1[N+:15]([O-:17])=[O:16])(=[O:3])[CH3:2].C(Cl)(Cl)Cl.C(OO)(=[O:24])C>CO>[C:1]([NH:4][C:5]1[CH:10]=[CH:9][C:8]([S:11]([CH2:12][CH:13]=[CH2:14])=[O:24])=[CH:7][C:6]=1[N+:15]([O-:17])=[O:16])(=[O:3])[CH3:2]
Reactant: CC(=O)OO
Reactant: C=CCSc1ccc(NC(C)=O)c([N+](=O)[O-])c1
Solvent: CO
Solvent: ClC(Cl)Cl
Product: C=CCS(=O)c1ccc(NC(C)=O)c([N+](=O)[O-])c1

Procedure:
3.0 G. of 1-acetamido-2-nitro-4-(prop-2-en-1-yl-thio)benzene, prepared according to Example I, in 30 ml. chloroform is cooled to -15° C. and treated with a solution of 2.5 g. of 40% peracetic acid in 4 ml. methanol. After the addition, the temperature is allowed to rise slowly to 20° C whereupon the solution is washed with sodium bisulfite solution and then with sodium bicarbonate solution. The product is isolated by evaporation of the solvent and purified to afford 1-acetamido-2-nitro-4-(prop-2-en-1-ylsulfinyl)benzene. This is treated with 20 ml. methanol and 10 ml. 5N aqueous sodium hydroxide at 20°-25° C. for one hour. The mixture is diluted with water and the crude product filtered off. Recrystallization yields 1-amino-2-nitro-4-(prop-2-en-1-ylsulfinyl)benzene.
Reaction SMILES: [Si:1]([O:8][CH2:9][C:10]1[C:11]([F:28])=[C:12]([C:16]2[CH:17]=[N:18][C:19]([N:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)=[N:20][CH:21]=2)[CH:13]=[CH:14][CH:15]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].ClCCl.CCN(C(C)C)C(C)C.Cl[CH2:42][CH2:43][S:44](Cl)(=[O:46])=[O:45]>O.C(Cl)(Cl)Cl>[Si:1]([O:8][CH2:9][C:10]1[C:11]([F:28])=[C:12]([C:16]2[CH:17]=[N:18][C:19]([N:22]3[CH2:23][CH2:24][N:25]([S:44]([CH:43]=[CH2:42])(=[O:46])=[O:45])[CH2:26][CH2:27]3)=[N:20][CH:21]=2)[CH:13]=[CH:14][CH:15]=1)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]
Reactant: CC(C)(C)[Si](C)(C)OCc1cccc(-c2cnc(N3CCNCC3)nc2)c1F
Reactant: O=S(=O)(Cl)CCCl
Solvent: ClC(Cl)Cl
Solvent: O
Solvent: ClCCl
Product: C=CS(=O)(=O)N1CCN(c2ncc(-c3cccc(CO[Si](C)(C)C(C)(C)C)c3F)cn2)CC1
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 58.8 %

Procedure:
5-[3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]-2-(piperazin-1-yl)pyrimidine (500 mg) was mixed with dichloromethane (10 ml), and DIPEA (482 mg) and 2-chloroethanesulfonyl chloride (304 mg) were added thereto at 0° C., followed by stirring at 0° C. for 1.5 hours. CHCl3 and water were added to the reaction mixture, and the organic layer was washed with water and saturated brine, dried over Na2SO4, and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (EtOAc/hexane) to obtain 5-[3-({[tert-butyl(dimethyl)silyl]oxy}methyl)-2-fluorophenyl]-2-[4-(vinylsulfonyl)piperazin-1-yl]pyrimidine (360 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:28]=[CH:29][C:30]=1[Cl:31])[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([S:15]([N:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[O:16])=[C:7]1[C:23]([O:25][CH2:26][CH3:27])=[O:24].[Mn]([O-])(=O)(=O)=[O:33].[K+]>CC(C)=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:28]=[CH:29][C:30]=1[Cl:31])[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([S:15]([N:17]2[CH2:18][CH2:19][O:20][CH2:21][CH2:22]2)(=[O:33])=[O:16])=[C:7]1[C:23]([O:25][CH2:26][CH3:27])=[O:24]
Reactant: CCOC(=O)c1c(S(=O)N2CCOCC2)c2ccccc2n1Cc1ccc(Cl)c(Cl)c1
Reactant: O=[Mn](=O)(=O)[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: O
Product: CCOC(=O)c1c(S(=O)(=O)N2CCOCC2)c2ccccc2n1Cc1ccc(Cl)c(Cl)c1
Reaction time: 18 h
Yield: 82.1 %

Procedure:
To a suspension of ethyl N-(3,4-dichlorobenzyl)-3-morpholinosulphinylindole-2-carboxylate (803 mg) in acetone (40 ml) was added a solution of potassium permanganate (528 mg) in water (15 ml). The resulting mixture was stirred for 18 hours. The mixture was poured into water (20 ml) and extracted with diethyl ether, dried (MgSO4) and concentrated to a gum which was purified by column chromatography using iso-hexane:ethyl acetate (3:1) as eluent to give the desired product (681 mg, 82%); NMR d (CDCl3) 1.3 (t, 3H), 3.2-3.2 (m, 4H), 3.7-3.8 (m, 4H), 5.4 (s, 2H), 6.95 (d, 1H), 7.3-7.4 (m, 5H), 8.05 (d, 1H); M/z (+) 499.2 (MH+), 497.3.
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[C:8]([O:10]CC2C=CC=CC=2)[CH:7]=[C:6]([CH2:18][CH:19]=[CH2:20])[C:5]=1[OH:21])[CH:2]=[CH2:3].Br[CH:23]([C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=1)[C:24]([O:26][CH3:27])=[O:25].C([O-])([O-])=O.[Cs+].[Cs+].CCOCC>CN(C=O)C>[CH2:18]([C:6]1[CH:7]=[C:8]([OH:10])[CH:9]=[C:4]([CH2:1][CH:2]=[CH2:3])[C:5]=1[O:21][CH:23]([C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=1)[C:24]([O:26][CH3:27])=[O:25])[CH:19]=[CH2:20]
Reactant: C=CCc1cc(OCc2ccccc2)cc(CC=C)c1O
Reactant: COC(=O)C(Br)c1ccc(Cl)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: CCOCC
Product: C=CCc1cc(O)cc(CC=C)c1OC(C(=O)OC)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 15 h

Procedure:
To a solution of 2,6-diallyl-4-benzyloxyphenol (200 mg, 1.0 eq) in DMF (8 mL) were added methyl α-bromo-4-chlorobenzeneacetate (190 mg, 1.0 eq) and Cs2CO3 (285 mg, 1.2 eq). The reaction mixture was stirred at room temperature for 15 h, poured into ether, washed with water and brine, dried over MgSO4, filtered, and concentrated in vac. Purification by chromatography (SiO2, EtOAc/Hexanes 1:20) afforded the desired methyl α-(2,6-diallyl-4-hydroxyphenoxy)-4-chlorobenzeneacetate.
Reaction SMILES: C(C1N(C[C:13]2[CH:18]=[CH:17][C:16]([C:19]([O:21]CC)=[O:20])=[CH:15][C:14]=2Cl)C(C=O)=CN=1)CCC.C(C1C=CC(C2NC(C=O)=CN=2)=CC=1)(OCC)=O.[CH2:43]([C:47]1[N:48](CC2C=CC=CC=2Cl)[C:49](/[CH:52]=[C:53](\[CH2:57][C:58]2[S:59][CH:60]=[CH:61][CH:62]=2)/[C:54]([OH:56])=[O:55])=[CH:50][N:51]=1)[CH2:44][CH2:45][CH3:46]>>[CH2:43]([C:47]1[N:48]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([OH:21])=[O:20])=[CH:15][CH:14]=2)[C:49](/[CH:52]=[C:53](\[CH2:57][C:58]2[S:59][CH:60]=[CH:61][CH:62]=2)/[C:54]([OH:56])=[O:55])=[CH:50][N:51]=1)[CH2:44][CH2:45][CH3:46]
Reactant: CCCCc1ncc(C=O)n1Cc1ccc(C(=O)OCC)cc1Cl
Reactant: CCCCc1ncc(/C=C(\Cc2cccs2)C(=O)O)n1Cc1ccccc1Cl
Agent: CCOC(=O)c1ccc(-c2ncc(C=O)[nH]2)cc1
Product: CCCCc1ncc(/C=C(\Cc2cccs2)C(=O)O)n1-c1ccc(C(=O)O)cc1

Procedure:
The title compound was prepared following the procedure of Example 42 replacing 2-n-butyl-1-[(4-carboethoxy-2-chlorophenyl)methy]imidazole-5-aldehyde with 2-n-butyl-[(4-carboethoxyphenyl]imidazole-5-aldehyde; mp 260°-265° C.(d).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[Cl:9][C:10]1[C:16](Cl)=[CH:15][C:13]([NH2:14])=[C:12]([N+:18]([O-:20])=[O:19])[CH:11]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[Cl:9][C:10]1[C:16]([O:8][C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)=[CH:15][C:13]([NH2:14])=[C:12]([N+:18]([O-:20])=[O:19])[CH:11]=1
Reactant: Nc1cc(Cl)c(Cl)cc1[N+](=O)[O-]
Reactant: Oc1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: Nc1cc(Oc2ccc(F)cc2)c(Cl)cc1[N+](=O)[O-]
Temperature: 90 °C
Reaction time: 8 h
Yield: 48.8 %

Procedure:
To a solution of 4-fluorophenol (1.63 g, 14.54 mmol) in DMSO (20 ml) was added 4,5-dichloro-2-nitroaniline (3 g, 14.49 mmol) and potassium carbonate (4 g, 28.94 mmol) with stirring overnight at 90° C. The reaction was then quenched by the addition of water (200 ml), extracted with ethyl acetate (3×100 ml) and dried over anhydrous magnesium sulfate. The solids were filtered out and the filtrate was concentrated under vacuum to give a residue, which was purified by a silica gel column with 2% to 10% ethyl acetate in petroleum ether to produce 4-chloro-5-(4-fluorophenoxy)-2-nitroaniline as a yellow solid (2.0 g, 49%). Next, to a solution of 4-chloro-5-(4-fluorophenoxy)-2-nitroaniline (2 g, 7.08 mmol) and hydrogen chloride (1.8 ml) and ethanol (25 ml) was added Zn powder (2.8 g) in portions at room temperature. The resulting solution was stirred for 4 h at 85° C. and then concentrated under vacuum. The residue was dissolved in water (300 ml), pH adjusted to 8 with aqueous sodium bicarbonate and extracted with ethyl acetate (3×80 ml). The combined organic layers were dried and concentrated under reduced pressure to give a residue, which was purified by a silica gel column with 10% ethyl acetate in petroleum ether to produce 4-chloro-5-(4-fluorophenoxy)benzene-1,2-diamine as red oil (1 g, 83%). Finally, a solution of 4-chloro-5-(4-fluorophenoxy)benzene-1,2-diamine (400 mg, 1.58 mmol) in 2,2-difluoro-3,3-dimethylbutanoic acid (4 ml) was stirred overnight at 95° C. in an oil bath. Then the solution was poured into water (100 ml), adjusted to pH 8 with saturated aqueous sodium bicarbonate and extracted with ethyl acetate (3×50 ml). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under vacuum to give a residue, which was purified by a silica gel column with 10% ethyl acetate in petroleum ether to produce 5-chloro-6-(4-fluorophenoxy)-2-(pentafluoroethyl)-1H-1,3-benzodiazole as a white solid (19.9 mg, 3%).
Reaction SMILES: Br[C:2]1[C:3]([CH3:11])=[C:4]([C:7]([F:10])=[CH:8][CH:9]=1)[C:5]#[N:6].[CH2:12]([Sn](CCCC)(CCCC)C=C)[CH2:13]CC.[Li+].[Cl-]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:12]([C:2]1[C:3]([CH3:11])=[C:4]([C:7]([F:10])=[CH:8][CH:9]=1)[C:5]#[N:6])=[CH2:13]
Reactant: Cc1c(Br)ccc(F)c1C#N
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [Cl-]
Agent: [Li+]
Solvent: Cc1ccccc1
Product: C=Cc1ccc(F)c(C#N)c1C
Temperature: 105 °C

Procedure:
A mixture of 3-bromo-6-fluoro-2-methylbenzonitrile (8.8 g, 41 mmol), tributyl(vinyl)tin (14.3 g, 45.2 mmol), LiCl (5.20 g, 123 mmol) and Pd(PPh3)4 (2.3 g, 2.0 mmol) in toluene (200 mL) was heated at 100-110° C. under N2 overnight. The mixture was concentrated and the residue was purified by column chromatography to obtain 3-ethenyl-6-fluoro-2-methylbenzonitrile.
Reaction SMILES: [CH:1]([O:8][CH2:9][CH3:10])([O:5][CH2:6][CH3:7])OCC.[P:11]([O:18]Cl)([O:15][CH2:16][CH3:17])[O:12][CH2:13][CH3:14]>>[CH2:13]([O:12][P:11]([CH:1]([O:5][CH2:6][CH3:7])[O:8][CH2:9][CH3:10])(=[O:18])[O:15][CH2:16][CH3:17])[CH3:14]
Reactant: CCOC(OCC)OCC
Reactant: CCOP(OCl)OCC
Product: CCOC(OCC)P(=O)(OCC)OCC
Temperature: 135 °C
Yield: 83.3 %

Procedure:
To a flask containing triethyl orthoformate (23.6 gm; 0.16 mole) equipped with a magnetic stirrer, condensor, and nitrogen atmosphere, is added diethyl chloro phosphite (25 gm; 0.16 mole) over 15-30 minutes and an extremely exothermic reaction occurs. The reaction solution is then heated at 135° C. for 3 hours. The resulting solution is distilled using a Kugelrohr distillation apparatus at 80° C. (0.01 mm Hg) to yield 32 gm of diethoxymethylphosphonic acid diethyl ester (31P NMR 13.2 ppm).
Reaction SMILES: FC1C=CC([S:8]([Cl:11])(=[O:10])=[O:9])=CC=1OC.N[C:15]1[CH:16]=[C:17]([C:23]#[N:24])[C:18](=[CH:21][CH:22]=1)[C:19]#[N:20]>>[C:23]([C:17]1[CH:16]=[C:15]([S:8]([Cl:11])(=[O:10])=[O:9])[CH:22]=[CH:21][C:18]=1[C:19]#[N:20])#[N:24]
Reactant: N#Cc1ccc(N)cc1C#N
Reactant: COc1cc(S(=O)(=O)Cl)ccc1F
Product: N#Cc1ccc(S(=O)(=O)Cl)cc1C#N

Procedure:
The titled compound is prepared analogously to 4-fluoro-3-methoxy-benzenesulfonyl chloride (Intermediate 102a) by replacing 4-fluoro-3-methoxyaniline with 4-amino-phthalonitrile.
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][CH2:16][N:17]=[N+:18]=[N-:19])[CH2:10][CH2:9]1)(OC(C)(C)C)=O.C(O)(C(F)(F)F)=O>CO.C(Cl)Cl>[N:17]([CH2:16][CH2:15][CH2:14][N:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1)=[N+:18]=[N-:19]
Reactant: CC(C)(C)OC(=O)N1CCN(CCCN=[N+]=[N-])CC1
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: [N-]=[N+]=NCCCN1CCNCC1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
3.5 g 1-Boc-4-(3-azidopropyl)-piperazine was dissolved in 30 ml MeOH/DCM (3/1) and 10 ml TFA were added. The reaction mixture was stirred at room temperature for 20 min and the product precipitated by the addition of 150 ml tert-Butyl-methyl ether. Yield 2.3 g.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][CH:11]=[C:10]2[C:5]=1[CH:6]=[N:7][NH:8][C:9]2=[O:14])([O-:3])=[O:2].[C:15](=O)([O-])[O-].[K+].[K+].CI.O>CN(C=O)C>[CH3:15][N:8]1[N:7]=[CH:6][C:5]2[C:10](=[CH:11][CH:12]=[CH:13][C:4]=2[N+:1]([O-:3])=[O:2])[C:9]1=[O:14]
Reactant: O=C([O-])[O-]
Reactant: O=c1[nH]ncc2c([N+](=O)[O-])cccc12
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Solvent: O
Product: Cn1ncc2c([N+](=O)[O-])cccc2c1=O
Reaction time: 8 h
Yield: 91.4 %

Procedure:
1.6 g of 5-nitro-phthalazin-1-one and 2.31 g of potassium carbonate are stirred for 10 minutes at room temperature in 60 ml of DMF. 1.1 ml of methyl iodide is added, and it is stirred overnight. It is added to water, extracted several times with ethyl acetate, and the organic phase is washed with water and brine. It is dried, and the solvent is removed in a vacuum. 1.57 g of 2-methyl-5-nitro-phthalazin-1-one is obtained as a yellow solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[C:9]([N:16]2[CH:20]=[N:19][CH:18]=[N:17]2)[C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:4][CH:3]=1.S(O)(O)(=O)=O.[CH3:26][S:27]C(=N)N.C(=O)(O)[O-].[Na+]>C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([S:27][CH3:26])[CH:9]([N:16]2[CH:20]=[N:19][CH:18]=[N:17]2)[C:10](=[O:15])[C:11]([CH3:14])([CH3:13])[CH3:12])=[CH:4][CH:3]=1
Reactant: CC(C)(C)C(=O)C(=Cc1ccc(Cl)cc1)n1cncn1
Reactant: CSC(=N)N
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CCO
Product: CSC(c1ccc(Cl)cc1)C(C(=O)C(C)(C)C)n1cncn1
Temperature: 25 °C
Yield: 24.9 %

Procedure:
289 g (1 mol) of 1-(4-chlorophenyl)-4,4-dimethyl-2-(1,2,4-triazol-1-yl)-pent-1-en-3-one (E,Z isomer mixture) and 139 g (0.5 mol) of S-methylisothiourea sulphate were suspended in 2.5 liters of ethanol and 336 g (4 mol) of sodium bicarbonate were added in portions, while stirring. The mixture was heated under reflux for 4 hours, cooled to room temperature and poured onto water. The organic constituents were extracted with methylene chloride. The organic phase was dried over sodium sulphate, filtered and evaporated down. The resulting oil was caused to crystallize by stirring it with diisopropyl ether, and the crystals were recrystallized from ethanol. 42 g (12% of theory) of 1-(4-chlorophenyl)-4,4-dimethyl-1-methylthio-2-(1,2,4-triazol-1-yl)-pentan-3-one of melting point 145° C. were obtained. ##STR13## Process variant (c):
Reaction SMILES: [CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([CH:18]=O)[N:14]3[CH3:17])=[C:10]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)[N:9]=2)[C:6]2[CH:26]=[CH:27][CH:28]=[CH:29][C:5]=2[N:4]=1)[CH3:2].[CH3:30][S:31]([CH2:34][CH2:35][N:36]1[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1)(=[O:33])=[O:32].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH2:1]([C:3]1[N:7]([C:8]2[N:16]=[C:15]3[C:11]([N:12]=[C:13]([CH2:18][N:39]4[CH2:38][CH2:37][N:36]([CH2:35][CH2:34][S:31]([CH3:30])(=[O:32])=[O:33])[CH2:41][CH2:40]4)[N:14]3[CH3:17])=[C:10]([N:20]3[CH2:21][CH2:22][O:23][CH2:24][CH2:25]3)[N:9]=2)[C:6]2[CH:26]=[CH:27][CH:28]=[CH:29][C:5]=2[N:4]=1)[CH3:2]
Reactant: CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(C=O)n(C)c2n1
Reactant: CS(=O)(=O)CCN1CCNCC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Product: CCc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(CN3CCN(CCS(C)(=O)=O)CC3)n(C)c2n1
Reaction time: 16 h

Procedure:
A mixture of 2-(2-ethylbenzoimidazol-1-yl)-9-methyl-6-morpholin-4-yl-9H-purine-8-carbaldehyde (65 mg, 0.17 mmol) and 1-(2-methanesulfonylethyl)piperazine (38 mg, 0.20 mmol) in DCE (4 mL) was stirred at room temperature for 1.5 h before the addition of sodium triacetoxyborohydride (70 mg, 0.33 mmol). The reaction mixture was stirred for 16 h then partitioned between brine and DCM. The organic phase was dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, MeOH:EtOAc, 0-20%). The resulting oil was loaded onto an Isolute® SCX-2 cartridge which was washed with MeOH/DCM and the product eluted with 2M NH3/MeOH affording 312 as a cream solid (29 mg, 30%). LCMS (Method G): RT 5.97 min [M+H]+ 568.3. 1H NMR (CDCl3, 400 MHz): δ 8.03-7.99 (m, 1 H); 7.78-7.73 (m, 1 H); 7.30-7.24 (m, 2 H); 4.35 (m, 4 H); 3.90-3.83 (m, 7 H); 3.77 (s, 2 H); 3.36 (q, J=7.5 Hz, 2 H); 3.22-3.11 (m, 2H); 3.04 (s, 3 H); 2.91 (t, J=6.4 Hz, 2 H); 2.59 (m, 8 H) and 1.45 (t, J=7.5 Hz, 3 H)
Reaction SMILES: C([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][N:17]([N:26]2[CH:30]=[N:29][N:28]=[CH:27]2)[C:18]2[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=2)=[CH:11][CH:10]=1)C1C=CC=CC=1.C(O)C.C(OCC)(=O)C>C1COCC1.[Pd]>[OH:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][N:17]([N:26]2[CH:27]=[N:28][N:29]=[CH:30]2)[C:18]2[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][CH:19]=2)=[CH:11][CH:10]=1
Reactant: N#Cc1ccc(N(CCc2ccc(OCc3ccccc3)cc2)n2cnnc2)cc1
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Solvent: CCO
Product: N#Cc1ccc(N(CCc2ccc(O)cc2)n2cnnc2)cc1
Reaction time: 72 h

Procedure:
To a stirred solution of 4-{[2-(4-benzyloxyphenyl)ethyl]-[1,2,4]triazol-4-yl-amino}benzonitrile (536 mg, 1.355 mmol) in distilled THF (15 mL) was added in succession absolute ethanol (30 mL) and Pd/C (10%, 54 mg). The black suspension was then stirred under an atmosphere of hydrogen (balloon) for 3 days. Upon removal by filtration and washings of the supported catalyst exhaustively with distilled THF, the filtrate was evaporated to give a pale yellow syrup which solidified upon standing at room temperature to a light yellow wax (192 mg). This crude was fractionated by flash chromatography (ethyl acetate) and the second fraction that separated gave 4-{[2-(4-hydroxyphenyl)ethyl]-[1,2,4]triazol-4-yl-amino}benzonitrile as a pale yellow waxy residue (115 mg, 376.6 μmol, 28%); Rf 0.46 (neat ethyl acetate), c.f. 0.59 (S.M.); δH (400 MHz, DMSO-d6) 2.70 (2H, t, J 7.4 Hz, CH2CH2N), 4.01 (2H, t, J˜7.6 Hz, CH2N), 6.59 (2H, AA′BB′), 6.69 (2H, AA′BB′), 7.06 (2H, AA′BB′), 7.71 (2H, AA′BB′), 8.78 (2H, s, C3′-H and C5′-H) and 9.29 (1H, s, exchanged with D2O, OH); LRMS (FAB+): 611.2[12, (2M+H)+], 459.1[8, (M+H+NBA)+], 306.0[100, (M+H)+]; (FAB−): 763.5[18, (2M+NBA)−], 609.4[45, (2M−H)−], 184.0[100, (HOPhCH2CH2)−]; HRMS (FAB+) 306.13477 C17H16N5O requires 306.13549.
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:13]3[N:12]([OH:19])[C:11]=2[C:20]2[CH:25]=[CH:24][N:23]=[CH:22][CH:21]=2)=[CH:6][CH:5]=1.[CH3:26][O:27][CH2:28]Cl.[Cl-].[NH4+]>CN(C)C=O>[F:3][C:4]1[CH:5]=[CH:6][C:7]([C:10]2[C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:13]3[N:12]([O:19][CH2:26][O:27][CH3:28])[C:11]=2[C:20]2[CH:21]=[CH:22][N:23]=[CH:24][CH:25]=2)=[CH:8][CH:9]=1
Reactant: On1c(-c2ccncc2)c(-c2ccc(F)cc2)c2ncccc21
Reactant: COCCl
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: CN(C)C=O
Product: COCOn1c(-c2ccncc2)c(-c2ccc(F)cc2)c2ncccc21
Reaction time: 0.5 h
Yield: 52.8 %

Procedure:
Sodium hydride (30 mg, 0.72 mmole 60% in oil) is added to a solution of 200 mg (0.65 mmole) of 3-(4-Fluoro-phenyl)-2-pyridin-4-yl-pyrrolo[3,2-b]pyridin-1-ol in 6 mL of dimethylformamide at room temperature. After 30 min. at room temperature, 65 mg of chloromethyl methyl ether is added to the reaction mixture. After 1 hour at room temperature, the reaction mixture is poured into ammonium chloride solution and extracted with ethyl acetate. The organic phase is washed with water and dried over magnesium sulfate. The solid residue is purified by chromatography on silica gel (ethylacetate) to give 120 mg of 3-(4-Fluoro-phenyl)-1-methoxymethoxy-2-pyridin-4-yl-1H-pyrrolo[3,2-b]pyridine as white crystals.