Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: S.[Cl:2][C:3]1[CH:4]=[C:5]([CH2:10][C:11]#[N:12])[CH:6]=[CH:7][C:8]=1[Cl:9].C(N(CC)CC)C.C(N)(=[S:22])C>C(O)C>[Cl:2][C:3]1[CH:4]=[C:5]([CH2:10][C:11]([NH2:12])=[S:22])[CH:6]=[CH:7][C:8]=1[Cl:9]
Reactant: CC(N)=S
Reactant: N#CCc1ccc(Cl)c(Cl)c1
Agent: S
Solvent: CCN(CC)CC
Solvent: CCO
Product: NC(=S)Cc1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 55 %

Procedure:
Hydrogen sulfide (gas) was bubbled into a solution of (3,4-dichloro-phenyl)-acetonitrile (1.86 g, 10 mmol, 1.0 eq)) and triethyl amine (10 mmol, 1 eq) in ethanol (10 ml) for about 1 hour. After 1 hour the reaction mixture capped and stirred at room temperature overnight. TLC showed that most of nitrile was converted to thioacteamide. Excess of H2S was removed by bubbling nitrogen into the reaction mixture for 30 min. The reaction mixture was then concentrated and purified by silica gel chromatography (ISCO system, 30-60% ethylacetate/hexane) to give the title compound (1213) (55% yield).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16](O)=[O:17])=[C:11]([CH3:19])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:20][NH:21][CH3:22].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16]([N:21]([CH3:22])[CH3:20])=[O:17])=[C:11]([CH3:19])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CNC
Reactant: Cc1cc(OCc2ccccc2)ccc1CC(=O)O
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1cc(OCc2ccccc2)ccc1CC(=O)N(C)C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
[4-(benzyloxy)-2-methylphenyl]acetic acid (1.1 g, 4.29 mmol) was dissolved in DMF (5 ml) and dimethylamine (6.44 ml, 12.88 mmol), DIEA (2.25 ml, 12.88 mmol), and HATU (3.26 g, 5.58 mmol) added. The mixture was stirred at RT for overnight. The residue was purified by column chromatography using a Biotage RP C18 cartridge (30 g) using a gradient eluant of 10-100% water:acetonitrile+0.05% formic acid. to afford the title compound. LC/MS (m/z): 284 (M+H)+.
Reaction SMILES: O[N:2]=[C:3]([C:9]([C:11]1[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=1)=O)[C:4]([O:6][CH2:7][CH3:8])=[O:5].[N+:18]([C:21]1[CH:28]=[CH:27][C:24]([CH2:25][NH2:26])=[CH:23][CH:22]=1)([O-:20])=[O:19]>>[CH3:17][C:14]1[CH:15]=[CH:16][C:11]([C:9]2[NH:26][C:25]([C:24]3[CH:23]=[CH:22][C:21]([N+:18]([O-:20])=[O:19])=[CH:28][CH:27]=3)=[N:2][C:3]=2[C:4]([O:6][CH2:7][CH3:8])=[O:5])=[CH:12][CH:13]=1
Reactant: NCc1ccc([N+](=O)[O-])cc1
Reactant: CCOC(=O)C(=NO)C(=O)c1ccc(C)cc1
Product: CCOC(=O)c1nc(-c2ccc([N+](=O)[O-])cc2)[nH]c1-c1ccc(C)cc1
Yield: 77.7 %

Procedure:
Ethyl 2-hydroxyimino-3-(4-methylphenyl)-3-oxopropionate (50.0 g) and 4-nitrobenzylamine (50.0 g) were reacted and treated in the same manner as in Starting Material Synthetic Example 1 to give ethyl 5-(4-methylphenyl)-2-(4-nitrophenyl)imidazole-4-carboxylate (58.0 g), which was dissolved in ethyl alcohol (1200 ml). Thereto was added 1 M sodium hydroxide solution (300 ml) and the mixture was reacted and treated in the same manner as in Starting Material Synthetic Example 2 to give 5-(4-methylphenyl)-2-(4-nitrophenyl)imidazole-4-carboxyic acid (37.6 g), melting point 212° C. (decomposition).
Reaction SMILES: Br[CH2:2][C:3]1[CH:12]=[CH:11][C:10]2[C:9]([CH3:14])([CH3:13])[CH2:8][CH2:7][C:6]([CH3:16])([CH3:15])[C:5]=2[CH:4]=1.[OH:17][C:18]1[CH:28]=[CH:27][C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:20][CH:19]=1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH3:13][C:9]1([CH3:14])[CH2:8][CH2:7][C:6]([CH3:16])([CH3:15])[C:5]2[CH:4]=[C:3]([CH2:2][O:17][C:18]3[CH:19]=[CH:20][C:21]([C:22]([O:24][CH2:25][CH3:26])=[O:23])=[CH:27][CH:28]=3)[CH:12]=[CH:11][C:10]1=2
Reactant: CC1(C)CCC(C)(C)c2cc(CBr)ccc21
Reactant: CCOC(=O)c1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)c1ccc(OCc2ccc3c(c2)C(C)(C)CCC3(C)C)cc1
Yield: 50.8 %

Procedure:
10 g (36 mmol) of 2-bromomethyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene, 6 g (36 mmol) of ethyl 4-hydroxybenzoate and 7.2 g (52 mmol) of anhydrous potassium carbonate in 60 ml of dimethylformamide were refluxed for 5.25 h. The mixture was then poured into water and extracted several times with ether, and the organic phase was washed with water, dried over Na2SO4 and concentrated. Recrystallization from methanol resulted in 6.7 g of the title compound of melting point 109°-11° C.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[CH2:12]([O:14][C:15](=[O:27])/[CH:16]=[CH:17]/[CH2:18][C@@H:19]([CH3:26])[CH2:20][CH2:21][CH:22]=[C:23]([CH3:25])[CH3:24])[CH3:13]>C(Cl)Cl>[CH2:12]([O:14][C:15](=[O:27])[CH:16]=[CH:17][CH2:18][C@H:19]([CH3:26])[CH2:20][CH2:21][CH:22]1[C:23]([CH3:25])([CH3:24])[O:9]1)[CH3:13]
Reactant: CCOC(=O)/C=C/C[C@@H](C)CCC=C(C)C
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CCOC(=O)C=CC[C@H](C)CCC1OC1(C)C
Temperature: 0 °C
Yield: 101.3 %

Procedure:
13.54 g of 3-chloro-perbenzoic acid (MCPBA, 70%) was dissolved in 30 ml of CH2Cl2 and cooled to 0°. 8.84 g of (E)-(S)-5,9-dimethyl-deca-2,8-dienoic acid ethyl ester dissolved in 15 ml of CH2Cl2, was slowly added and the mixture kept for an additional 0.5 h in the ice bath. The reaction was then quenched by pouring onto crushed ice/sodium pyrosulfite, extracted twice with AcOEt, washed with 2N NaOH, water and brine, dried over sodium sulfate and evaporated to dryness to yield 9.59 g of (5R)-7-((RS)-3,3-dimethyl-oxiranyl)-5-methyl-hept-2-enoic acid ethyl ester as 1/1 epimeric mixture, sufficiently pure for the next step.
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:6](=[C:7]([OH:12])[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]([NH:15][C@H:16]([C:25]([NH:27][CH2:28][CH2:29][C:30]2[CH:37]=[CH:36][C:34]([OH:35])=[C:32]([OH:33])[CH:31]=2)=[O:26])[CH2:17][C:18](=[O:24])[O:19]C(C)(C)C)=[O:14])[CH:3]=1.C([SiH](C(C)C)C(C)C)(C)C>>[OH:1][C:2]1[C:11]2[C:6](=[C:7]([OH:12])[CH:8]=[CH:9][CH:10]=2)[N:5]=[C:4]([C:13]([NH:15][C@H:16]([C:25]([NH:27][CH2:28][CH2:29][C:30]2[CH:37]=[CH:36][C:34]([OH:35])=[C:32]([OH:33])[CH:31]=2)=[O:26])[CH2:17][C:18](=[O:19])[OH:24])=[O:14])[CH:3]=1
Reactant: CC(C)(C)OC(=O)C[C@H](NC(=O)c1cc(O)c2cccc(O)c2n1)C(=O)NCCc1ccc(O)c(O)c1
Agent: CC(C)[SiH](C(C)C)C(C)C
Product: O=C(O)C[C@H](NC(=O)c1cc(O)c2cccc(O)c2n1)C(=O)NCCc1ccc(O)c(O)c1
Yield: 5.6 %

Procedure:
The title compound was prepared by hydrolysis of the tert-butyl protective group of N-[Nα-(4,8-dihydroxyquinoline-2-carbonyl)-Oγ-tert-butyl-L-aspartyl]dopamine prepared in example 62, step B (121 mg, 2.4 mmol) using the indications of general procedure C in the presence of triisopropylsilane (187 mg, 1.2 mmol). Purification by flash chromatography using 50% EtOAc/CH2Cl2/1% AcOH yielded the desired product as a yellow powder (61 mg, 57%).
Reaction SMILES: [F:1][C:2]([F:17])([F:16])[C:3](=O)[CH2:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([S:13][CH3:14])=[CH:9][CH:8]=1)=O.Cl.[C:19]1([NH:25][NH2:26])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C(O)C>[CH3:14][S:13][C:10]1[CH:11]=[CH:12][C:7]([C:5]2[N:25]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[N:26]=[C:3]([C:2]([F:17])([F:16])[F:1])[CH:4]=2)=[CH:8][CH:9]=1
Reactant: NNc1ccccc1
Reactant: CSc1ccc(C(=O)CC(=O)C(F)(F)F)cc1
Agent: Cl
Solvent: CCO
Product: CSc1ccc(-c2cc(C(F)(F)F)nn2-c2ccccc2)cc1

Procedure:
A solution of 4,4,4-trifluoro-(4-methylsulfanylphenyl)-butane-1,3-dione (3.0 g) and phenyl hydrazine hydrochloride (1.18 g) in ethanol (20 mL) was refluxed for 7 h. The solvent was evaporated and the residue was chromatographed over silicagel using 20% ethyl acetate in petroleum ether as eluent yielding 2.25 g (% yield=83, Mol. Weight=334) of product as a gum.
Reaction SMILES: [OH:1][C:2]1[C:7](=[O:8])[CH:6]=[CH:5][NH:4][C:3]=1[CH3:9].C(=O)([O-])[O-].[K+].[K+].[C:16]([CH:20](OC(F)(F)F)[OH:21])([F:19])([F:18])[F:17]>CO.C(OCC)(=O)C>[OH:1][C:2]1[C:7](=[O:8])[C:6]([CH:20]([OH:21])[C:16]([F:19])([F:18])[F:17])=[CH:5][NH:4][C:3]=1[CH3:9]
Reactant: OC(OC(F)(F)F)C(F)(F)F
Reactant: Cc1[nH]ccc(=O)c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: CCOC(C)=O
Product: Cc1[nH]cc(C(O)C(F)(F)F)c(=O)c1O

Procedure:
A mixture of 3-hydroxy-2-methyl-1H-pyridin-4-one (6.1 g, 48.7 mmol), potassium carbonate (17 g, 123 mmol), and CF3CH(OH)OCF3 (25 mL, 0.25 mol) was heated to reflux under a blanket of nitrogen for 30 h. The progress of the reaction was monitored by HPLC Method 1 (Example 24), which indicated 63% (peak percent area) of conversion to the product. The reaction mixture was diluted with methanol (50 mL), then filtered to remove solid particulates. The filtrate was evaporated to dryness to afford an oil. The oily residue was taken up in ethyl acetate (150 mL) and washed with a saturated ammonium chloride solution (80 mL). The organic fraction was collected and set aside. The pH of the aqueous fraction was adjusted to 6 with a dilute hydrochloric acid solution, and the resulting aqueous solution was extracted with ethyl acetate (2×40 mL). All the organic fractions were combined, then washed with saturated ammonium chloride, dried over Na2SO4, filtered and then evaporated to dryness to give an oil. On trituration with ether, 3-hydroxy-2-methyl-5-(2,2,2-trifluoro-1-hydroxy-ethyl)-1H-pyridin-4-one separated as a solid product and was collected by suction filtration (3.5 g, 33%). NMR data is described in Part C above.
Reaction SMILES: [Br:1][C:2]1[N:6]=[C:5]([Br:7])[NH:4][N:3]=1.[I-].[K+].[CH3:10][O:11][C:12]1[CH:19]=[CH:18][C:15]([CH2:16]Cl)=[CH:14][CH:13]=1.C(N(CC)C(C)C)(C)C>C(#N)C>[Br:1][C:2]1[N:6]=[C:5]([Br:7])[N:4]([CH2:16][C:15]2[CH:18]=[CH:19][C:12]([O:11][CH3:10])=[CH:13][CH:14]=2)[N:3]=1
Reactant: COc1ccc(CCl)cc1
Reactant: Brc1n[nH]c(Br)n1
Agent: [I-]
Agent: [K+]
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc(Cn2nc(Br)nc2Br)cc1
Yield: 78 %

Procedure:
3,5-dibromo-1H-1,2,4-triazole (1.5 g, 6.61 mmol, Eq: 1.00), potassium iodide (110 mg, 661 μmol, Eq: 0.10), 4-methoxybenzyl chloride (1.14 g, 990 μl, 7.27 mmol, Eq: 1.1) and N,N-diisopropylethylamine (1.71 g, 2.31 ml, 13.2 mmol, Eq: 2.0) was stirred in acetonitrile (23.0 ml) overnight at room temperature. The crude material was applied on silica gel and purified by column to give 3,5-Dibromo-1-(4-methoxy-benzyl)-1H-[1,2,4]triazole (1.79 g, 78%) as white solid. MS: m/z=348.1 (M+H+)
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][N:9]=[C:10]([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)[CH2:11][CH2:12][CH2:13][C:14](O)=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]>[Pd].CO>[F:23][C:20]1[CH:21]=[CH:22][C:17]([CH:10]2[CH2:11][CH2:12][CH2:13][C:14](=[O:15])[N:9]2[NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:18][CH:19]=1
Reactant: CC(C)(C)OC(=O)NN=C(CCCC(=O)O)c1ccc(F)cc1
Agent: [Pd]
Solvent: CO
Product: CC(C)(C)OC(=O)NN1C(=O)CCCC1c1ccc(F)cc1
Reaction time: 5 h
Yield: 54.9 %

Procedure:
Step AAG (2): 10% Palladium on carbon (0.5 g) was carefully added to a solution of 5-(2-(tert-Butoxycarbonyl)hydrazono)-5-(4-fluorophenyl)pentanoic acid (2.3 g, 7.09 mmol) in MeOH (30 mL) in a Parr hydrogenation bottle under nitrogen. The bottle was repeatedly evacuated and flushed with H2 gas (50 psi). The mixture was shaken for 5 h. The vessel was flushed with nitrogen. The reaction contents were filtered through diatomaceous earth (Celite®). The plug and vessel were washed with fresh methanol. The filtrates were combined and concentrated in vacuo. The crude product was purified using silica gel column chromatography (10-80, EtOAc/chloroform, linear gradient) to afford tert-butyl 2-(4-fluorophenyl)-6-oxopiperidin-1-ylcarbamate (1.2 g, 55% yield). 1H NMR (500 MHz, chloroform-d) δ ppm 7.13-7.20 (an, 2 H) 7.06 (t, J=8.55 Hz, 2 H) 6.40 (br. s., 1 H) 4.91 (br. s., 1 H) 2.52-2.75 (m, 2 H) 2.20-2.40 (m, 1 H) 1.77-1.93 (m, 3 H) 1.44 (s, 9 H).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:12]3[S:13][C:14]([C:23]4[N:27]=[CH:26][N:25]([CH:28]5[CH2:33][CH2:32][CH2:31][CH2:30][O:29]5)[N:24]=4)=[C:15]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[N:16]=3)=[C:9]([CH3:11])[N:10]=2)[CH:7]=1.[F:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([O:41][CH3:42])[C:36]=1B(O)O.C(=O)([O-])[O-].[Cs+].[Cs+].CCOC(C)=O>COCCOC.O>[F:34][C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([O:41][CH3:42])[C:36]=1[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:12]3[S:13][C:14]([C:23]4[N:27]=[CH:26][N:25]([CH:28]5[CH2:33][CH2:32][CH2:31][CH2:30][O:29]5)[N:24]=4)=[C:15]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=4)[N:16]=3)=[C:9]([CH3:11])[N:10]=2)[CH:7]=1
Reactant: COc1cccc(F)c1B(O)O
Reactant: Cc1nc2ccc(Br)cn2c1-c1nc(-c2ccccc2)c(-c2ncn(C3CCCCO3)n2)s1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: COCCOC
Solvent: CCOC(C)=O
Product: COc1cccc(F)c1-c1ccc2nc(C)c(-c3nc(-c4ccccc4)c(-c4ncn(C5CCCCO5)n4)s3)n2c1
Temperature: 95 °C
Reaction time: 2 h
Yield: 91.8 %

Procedure:
To a suspension of 6-bromo-2-methyl-3-{4-phenyl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-1,3-thiazol-2-yl}imidazo[1,2-a]pyridine (157 mg, 0.3 mmol) obtained in Example 117-B(i) in DME (10 mL) and water (2 mL) were added (2-fluoro-6-methoxyphenyl)boronic acid (102 mg, 0.6 mmol), [1,1-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane complex (51 mg, 0.06 mmol) and cesium carbonate (293 mg, 0.9 mmol) under a nitrogen atmosphere, and the mixture was stirred at 95° C. for 2 h. The reaction mixture was allowed to cool to rt, and then were added water (40 mL) and EtOAc (40 mL). The aqueous layer was extracted with EtOAc (40 mL), and the combined organic layer was dried over anhydrous magnesium sulfate. Insoluble materials were removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (EtOAc/hexane=10/90→50/50) to give the title compound (156 mg, 92%) as a yellow solid.
Reaction SMILES: [CH3:1][N:2]1[CH:8]2[CH2:9][CH2:10][CH:3]1[CH2:4][N:5]([S:11]([NH2:14])(=[O:13])=[O:12])[CH2:6][CH2:7]2.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:55]([O:57][C:58](=[O:79])[C@H:59]([O:61][C:62]1[CH:67]=[C:66](Cl)[N:65]=[C:64]([S:69][CH2:70][C:71]2[CH:76]=[CH:75][CH:74]=[C:73]([F:77])[C:72]=2[F:78])[N:63]=1)[CH3:60])[CH3:56]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:78][C:72]1[C:73]([F:77])=[CH:74][CH:75]=[CH:76][C:71]=1[CH2:70][S:69][C:64]1[N:63]=[C:62]([O:61][C@H:59]([CH3:60])[C:58]([O:57][CH2:55][CH3:56])=[O:79])[CH:67]=[C:66]([NH:14][S:11]([N:5]2[CH2:6][CH2:7][CH:8]3[N:2]([CH3:1])[CH:3]([CH2:10][CH2:9]3)[CH2:4]2)(=[O:13])=[O:12])[N:65]=1
Reactant: CCOC(=O)[C@@H](C)Oc1cc(Cl)nc(SCc2cccc(F)c2F)n1
Reactant: CN1C2CCC1CN(S(N)(=O)=O)CC2
Agent: [Pd]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: CCOC(=O)[C@@H](C)Oc1cc(NS(=O)(=O)N2CCC3CCC(C2)N3C)nc(SCc2cccc(F)c2F)n1
Temperature: 100 °C

Procedure:
To a solution of 9-methyl-3,9-diazabicyclo[4.2.1]nonane (0.56 g) in 1,4-dioxane (10 ml) was added sulfamide (0.37 g) and the reaction mixture was then heated at reflux in 1,4-dioxane for 72 h. The reaction mixture was purified by loading onto SCX and eluting with 7N NH3/MeOH (200 ml). The eluent was then reduced in vacuo to yield 9-methyl-3,9-diazabicyclo[4.2.1]nonane-3-sulfonamide (0.13 g) as a yellow solid. A mixture of 9-methyl-3,9-diazabicyclo[4.2.1]nonane-3-sulfonamide (0.13 g), tris(dibenzylideneacetone)dipalladium (0) (50 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (XPHOS) (50 mg), cesium carbonate (0.31 g) and 2-[[6-chloro-2-[[(2,3-difluorophenyl)methyl]thio]-4-pyrimidinyl]oxy]-(2R)-propanoic acid ethyl ester (the product of example 5 step i), 0.25 g) in 1,4-dioxane (10 mL) was heated at reflux in a microwave at 100° C., 300 W, open vessel with cooling for 30 min. The reaction mixture was then reduced in vacuo and the residue was partitioned between EtOAc (150 ml) and H2O (100 ml). The organics were separated and the aqueous layer was re-extracted with EtOAc (2×150 ml). Organics were combined, dried (MgSO4) and reduced in vacuo to give the subtitle compound as a yellow solid. Yield 0.35 g
Reaction SMILES: [CH2:1]([NH2:6])[CH2:2][CH2:3][CH2:4][CH3:5].Cl.[N-:8]([C:11]#[N:12])[C:9]#[N:10].[Na+]>CC(O)C>[CH2:1]([NH:6][C:11]([NH:8][C:9]#[N:10])=[NH:12])[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: N#C[N-]C#N
Reactant: CCCCCN
Agent: Cl
Agent: [Na+]
Solvent: CC(C)O
Product: CCCCCNC(=N)NC#N
Yield: 67.9 %

Procedure:
Pentylamine (17.43 g, 0.20 mol) in 2-propanol (175 ml) was acidified with conc. HCl (17 ml, 0.204 mol) and then treated with sodium dicyanamide (23.15 g, 0.26 mol). The mixture was refluxed for 20 hours, allowed to cool and filtered through Celite. The filtrate was concentrated in vacuo and the residue dissolved in chloroform. This solution was washed with water and dried over magnesium sulfate. Filtration and evaporation in vacuo gave 20.93 g (67.9%) of off-white solid; mass spec.: M+ at 154.
Reaction SMILES: [OH-:1].[K+].[Cl:3][C:4]1[CH:5]=[C:6]([CH:33]=[CH:34][C:35]=1[O:36][CH3:37])[O:7][C@@H:8]1[CH2:12][CH2:11][N:10]([C:13]([CH3:32])([CH3:31])[CH2:14][CH2:15][C:16]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:17]#[N:18])[CH2:9]1>CC(O)(CC)CC>[Cl:3][C:4]1[CH:5]=[C:6]([CH:33]=[CH:34][C:35]=1[O:36][CH3:37])[O:7][C@@H:8]1[CH2:12][CH2:11][N:10]([C:13]([CH3:32])([CH3:31])[CH2:14][CH2:15][C:16]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:17]([NH2:18])=[O:1])[CH2:9]1
Reactant: COc1ccc(O[C@@H]2CCN(C(C)(C)CCC(C#N)(c3ccccc3)c3ccccc3)C2)cc1Cl
Reactant: [OH-]
Agent: CCC(C)(O)CC
Agent: [K+]
Product: COc1ccc(O[C@@H]2CCN(C(C)(C)CCC(C(N)=O)(c3ccccc3)c3ccccc3)C2)cc1Cl
Temperature: 25 °C
Yield: 33 %

Procedure:
Potassium hydroxide (140 mg, 2.49 mmol) was added to a solution of the product of example 27 (61 mg, 0.125 mmol) in 3-methyl-3-pentanol (5 mL) and the mixture was heated under reflux for 16 hours. The solution was cooled to room temperature, concentrated in vacuo and the residue was partitioned between dichloromethane (10 mL) and water (5 mL), aqueous was extracted with dichloromethane (3×10 mL). Combined organics were concentrated under reduced pressure and the residue purified by column chromatography on silica gel, eluting with ethyl acetate:methanol:0.88 ammonia, 90:10:1. The product containing fractions were evaporated under reduced pressure to afford the title compound as a colourless gum in 33% yield, 21 mg.
Reaction SMILES: C[Li].C1(C)C=CC(S(NN=[C:14]2[CH2:19][CH2:18][C@H:17]3[C@H:20]4[C@H:30]([C@H:31]([N:33]([CH3:35])[CH3:34])[CH2:32][C@:15]23[CH3:16])[C@:28]2([CH3:29])[C@H:23]([CH2:24][C@H:25]([OH:39])[C@@H:26]([O:36][CH2:37][CH3:38])[CH2:27]2)[CH2:22][CH2:21]4)(=O)=O)=CC=1>CCOCC.O1CCCC1>[CH3:34][N:33]([C@@H:31]1[CH2:32][C@@:15]2([CH3:16])[C@@H:17]([CH2:18][CH:19]=[CH:14]2)[C@H:20]2[C@H:30]1[C@:28]1([CH3:29])[C@@H:23]([CH2:22][CH2:21]2)[CH2:24][C@H:25]([OH:39])[C@@H:26]([O:36][CH2:37][CH3:38])[CH2:27]1)[CH3:35]
Reactant: CCO[C@H]1C[C@@]2(C)[C@@H](CC[C@@H]3[C@@H]2[C@H](N(C)C)C[C@]2(C)C(=NNS(=O)(=O)c4ccc(C)cc4)CC[C@@H]32)C[C@@H]1O
Agent: [Li]C
Solvent: C1CCOC1
Solvent: CCOCC
Product: CCO[C@H]1C[C@@]2(C)[C@@H](CC[C@@H]3[C@@H]2[C@H](N(C)C)C[C@]2(C)C=CC[C@@H]32)C[C@@H]1O
Reaction time: 72 h

Procedure:
A 1.5 M solution of methyl lithium in ether (20 ml) was added to a cooled solution of 11α-N,N-dimethylamino-2β-ethoxy-3α-hydroxy-5α-androstan-17-one 17-p-toluenesulphonylhydrazone (1.2 g) in dry tetrahydrofuran (100 ml). The mixture was kept at room temperature for three days and then most of the solvent was evaporated in vacuo. The residue was acidified with 2 N-hydrochloric acid, washed with ether, and the aqueous layer was then basified with 2 N-sodium hydroxide and extracted into ether. The washed and dried (Na2SO4) extract was evaporated in vacuo and the residue was purified by chromatography over silica (ethyl acetate-petroleum ether 1:1) and crystallization from aqueous methanol to give the title compound m.p. 51°-54°, [α]D -23.8°.
Reaction SMILES: Br[C:2]1[N:7]=[N:6][C:5]([NH2:8])=[N:4][C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[C:15]1([OH:21])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>>[O:21]([C:2]1[N:7]=[N:6][C:5]([NH2:8])=[N:4][C:3]=1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: Oc1ccccc1
Reactant: Nc1nnc(Br)c(-c2ccccc2)n1
Product: Nc1nnc(Oc2ccccc2)c(-c2ccccc2)n1
Yield: 14.8 %

Procedure:
6-Phenoxy-5-phenyl-1,2,4-triazin-3-amine (78 mg, 14%) was prepared from 6-bromo-5-phenyl-1,2,4-triazin-3-amine (0.5 g, 1.99 mmol) and phenol (0.74 g, 7.90 mmol) according to the general procedure of Example 3.
Reaction SMILES: [H-].[Na+].[H][H].[Br-].[CH2:6]([PH3+])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15].BrC1C=CC=CC=1C(C1C=CC=CC=1)=O.BrC1C=C(C(OC)=O)C(OC)=C(C=1)C(C1C=C(Br)C=C(C(OC)=O)C=1OC)=O.[Cl-].[NH4+]>CCCCCC.CS(C)=O.O>[CH2:6]=[CH:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: CCCCCCCCCC[PH3+]
Reactant: [H][H]
Agent: COC(=O)c1cc(Br)cc(C(=O)c2cc(Br)cc(C(=O)OC)c2OC)c1OC
Agent: O=C(c1ccccc1)c1ccccc1Br
Agent: [Br-]
Solvent: O
Solvent: CS(C)=O
Solvent: CCCCCC
Product: C=CCCCCCCCC
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
Sodium hydride (79.6 mg, 1.99 mmol, 60% dispersion in mineral oil) was washed with n-hexane (3×2 mL). Dimethyl sulfoxide (2 mL) was introduced via a syringe and the mixture was heated at 75° C. until the evolution of hydrogen ceased. The clear solution was cooled in an ice-water bath and a solution of the n-decylphosphonium bromide (874 mg, 1.99 mmol) in DMSO (4 mL) was added dropwise. The resulting solution was stirred at room temperature for 15 minutes. A solution of the bromobenzophenone, 5,5'dibromo-2,2'-dimethoxy-3,3'dicarbomethoxybenzophenone, (642 mg, 1.24 mmol) in warm DMSO (5 mL) was added dropwise and the reaction mixture heated at 55° C. for 22 hours. It was cooled in an ice-water bath. A solution of ammonium chloride (200 mg) in water (5 mL) was added and the reaction mixture was extracted with ethyl ether (5×5 mL). The organic extracts were washed twice with brine, dried over sodium sulfate, and evaporated in vacuo. A flash chromatography on silica gel (230-400 mesh), elution with n-hexane/ethyl acetate, 4:1, yielded decene, 1,1-[di(5'-bromo-2'-methoxy-3'-methoxycarbonyl) phenyl]-1-undecene, (466 mg, 64%) as an oil: IR (KBr) 3072, 2925, 2853, 1736, 1570, 1436, 1285, 1253, 1195, 1164, 1149, 1006 cm- 1 ; 1H NMR (CDCl3, 200 MHz) δ7.88 (d, J=2.5 Hz, 1H), 7.79 (d, J =2.5 Hz, 1H), 7.55 (d, J=2.5 Hz, 1H), 7.50 (d, J=2.5 Hz, 1H), 6.07 (t, J=7.3 Hz, 1H), 3.88 (s, 3H), 3.87 (s, 3H), 3.52 (s, 3H), 3.49 (s, 3H), 2.09 (m, 2H), 1.26 (m, 14H), 0.88 (t, J=6.3 Hz, 3H); CIMS m/e (relative intensity) 641 (MH+, 4), 609 (MH+ -MeOH, 100).