Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [I-].[K+].Cl[CH2:4][C:5]1[N:9]2[C:10]3[CH:25]=[CH:24][CH:23]=[CH:22][C:11]=3[C:12]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=3[Cl:21])=[N:13][CH2:14][C:8]2=[N:7][N:6]=1.[CH:26]1([NH2:29])[CH2:28][CH2:27]1>O1CCCC1>[CH:26]1([NH:29][CH2:4][C:5]2[N:9]3[C:10]4[CH:25]=[CH:24][CH:23]=[CH:22][C:11]=4[C:12]([C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=4[Cl:21])=[N:13][CH2:14][C:8]3=[N:7][N:6]=2)[CH2:28][CH2:27]1
Reactant: ClCc1nnc2n1-c1ccccc1C(c1ccccc1Cl)=NC2
Reactant: NC1CC1
Agent: [I-]
Agent: [K+]
Solvent: C1CCOC1
Product: Clc1ccccc1C1=NCc2nnc(CNC3CC3)n2-c2ccccc21

Procedure:
In the manner given in Example 1, potassium iodide and 1-(chloromethyl)-6-(o-chlorophenyl)-4H-s-triazolo-[4,3-a][1,4]benzodiazepine in tetrahydrofuran is treated with cyclopropylamine to give 1-[(cyclopropylamino)-methyl]-6-(o-chlorophenyl)-4H-s-triazolo[4,3-a][1,4]-benzodiazepine.
Reaction SMILES: C([O:8][C:9]1[C:27]([C:28]([CH3:31])([CH3:30])[CH3:29])=[CH:26][C:12]([CH2:13][N:14]2[C:22]3[C:21](=[O:23])[NH:20][C:19]([CH2:24][CH3:25])=[N:18][C:17]=3[N:16]=[CH:15]2)=[CH:11][C:10]=1[C:32]([CH3:35])([CH3:34])[CH3:33])C1C=CC=CC=1.[H][H]>CO.[C].[Pd]>[CH2:24]([C:19]1[NH:20][C:21](=[O:23])[C:22]2[N:14]([CH2:13][C:12]3[CH:26]=[C:27]([C:28]([CH3:29])([CH3:31])[CH3:30])[C:9]([OH:8])=[C:10]([C:32]([CH3:35])([CH3:34])[CH3:33])[CH:11]=3)[CH:15]=[N:16][C:17]=2[N:18]=1)[CH3:25]
Reactant: [H][H]
Reactant: CCc1nc2ncn(Cc3cc(C(C)(C)C)c(OCc4ccccc4)c(C(C)(C)C)c3)c2c(=O)[nH]1
Agent: [Pd]
Solvent: CO
Product: CCc1nc2ncn(Cc3cc(C(C)(C)C)c(O)c(C(C)(C)C)c3)c2c(=O)[nH]1
Yield: 88.1 %

Procedure:
0.2 g of 10% palladium carbon was added to a solution of 0.9 g (1.90 mmol) of the resulting hypoxanthine compound in 50 ml of methanol and the mixture was stirred overnight in a hydrogen atmosphere. Palladium carbon was removed by filtration and the residue was concentrated under vacuum to obtain 0.64 g of 2-ethyl-7-(4-hydroxy-3,5-di-t-butylbenzyl)hypoxanthine (yield 100%).
Reaction SMILES: [CH3:1][Si:2]([C:5]#[CH:6])([CH3:4])[CH3:3].C([Li])CCC.B(F)(F)F.CCOCC.[CH:21](=[O:30])/[CH:22]=[CH:23]\[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH3:29]>C1COCC1>[OH:30][CH:21]([CH2:22]/[CH:23]=[CH:24]\[CH2:25][CH2:26][CH2:27][CH2:28][CH3:29])[C:6]#[C:5][Si:2]([CH3:4])([CH3:3])[CH3:1]
Reactant: CCCCCC/C=C\C=O
Reactant: C#C[Si](C)(C)C
Agent: FB(F)F
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: C1CCOC1
Product: CCCCC/C=C\CC(O)C#C[Si](C)(C)C
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 60 %

Procedure:
Trimethylsilylacetylene (6.9 g, 48.6 mmole) is dissolved in 125 ml dry THF in a flamed dried 500 ml 3-neck round bottom flask under nitrogen at -78° C. The solution is treated with n-butyllithium (29.9 ml, 46.3 mmole) slowly dropwise over 10 minutes and stirred 30 minutes at -78° C. The reaction mixture is subsequently treated slowly dropwise with boron trifluoride etherate (6.0 ml, 48.8 mmole) and the resultant mixture is stirred 20 minutes at -78° C. 3-Z-Nonenal (6.2 g, 44 mmole), in 3×12 ml dry THF, is added rapidly dropwise to the reaction mixture at -78° C. The reaction is warmed to 0° C. and stirred an additional 20 minutes. The mixture is quenched with 100 ml saturated sodium chloride, the layers separated, and the aqueous phase extracted with 3×60 ml diethyl ether. The organics are combined, dried over magnesium sulfate, and concentrated in vacuo to a dark yellow oil (10.5 g). The crude oil is chromatographed over 200 g silica gel (230-400 mesh), eluting with 6% ethyl acetate/hexane and collecting 60 ml fractions. Fractions 8-16 are combined and concentrated to afford 6.3 g of the title compound as a pale yellow oil. Following the above procedure gives the title compound having the physical characteristic described below:
Reaction SMILES: [Cl:1][C:2]1[C:10]([O:11][CH2:12][CH2:13][CH2:14][NH:15]C(OC(C)(C)C)=O)=[CH:9][C:8]([I:23])=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:24].Cl.CO.C(OC(C)C)(C)C>CO>[ClH:1].[Cl:1][C:2]1[C:10]([O:11][CH2:12][CH2:13][CH2:14][NH2:15])=[CH:9][C:8]([I:23])=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:24]
Reactant: CC(C)(C)OC(=O)NCCCOc1cc(I)c2c(c1Cl)CNC2=O
Agent: Cl
Solvent: CC(C)OC(C)C
Solvent: CO
Product: NCCCOc1cc(I)c2c(c1Cl)CNC2=O
Temperature: 60 °C
Reaction time: 1 h
Yield: 193 %

Procedure:
4-Chloro-5-[3-(tert-butoxycarbonylamino)propoxy]-7-iodoisoindolinone (101 mg, 0.216 mmol) was suspended in methanol (1.5 mL), and the suspension was added with 10% hydrogen chloride-methanol solution (1.5 mL), followed by stirring at 60° C. for 1.0 hour. The reaction mixture was added with diisopropylether. The obtained solid was collected by filtration and washed with diisopropylether, followed by drying under reduced pressure to obtain 4-chloro-5-(3-aminopropoxy)-7-iodoisoindolinone hydrochloride (84.0 mg, yield 96%).
Reaction SMILES: [C:1]1([CH:7]([N:9]2[C:13]([C:14]([NH2:16])=O)=[CH:12][N:11]=[CH:10]2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.P(Cl)(Cl)(Cl)=O>N1C=CC=CC=1>[C:1]1([CH:7]([N:9]2[C:13]([C:14]#[N:16])=[CH:12][N:11]=[CH:10]2)[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(c1ccccc1)n1cncc1C(N)=O
Solvent: c1ccncc1
Solvent: O=P(Cl)(Cl)Cl
Product: CC(c1ccccc1)n1cncc1C#N
Temperature: 25 °C

Procedure:
To a stirred and cooled (-10° C.) solution of 3.7 parts of (+)-1-(1-phenylethyl)-1H-imidazole-5-carboxamide in 50 parts of pyridine are added dropwise, during a 15 minute period, 3.4 parts of phosphoryl chloride. The mixture is allowed to reach room temperature; then heated in a boiling water-bath for 1.5 hrs. The reaction mixture is cooled to room temperature and poured onto 250 parts of ice-water. The precipitated product is filtered off, washed with water and dissolved in trichloromethane. The solution is dried, filtered and evaporated. The solid residue is crystallized from a mixture of 2,2'-oxybispropane and ethanol, yielding (+)-1-(1-phenylethyl)-1H-imidazole-5 -carbonitrile; m.p. 129.3° C.; [α] = +40.56° (c = 1% CH3OH).
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]=[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[S:6][C:7]=1[CH3:8].[OH:15][C:16]1[CH:23]=[CH:22][C:19]([CH:20]=[O:21])=[CH:18][CH:17]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[CH3:8][C:7]1[S:6][C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:4][C:3]=1[CH2:2][O:15][C:16]1[CH:23]=[CH:22][C:19]([CH:20]=[O:21])=[CH:18][CH:17]=1
Reactant: O=Cc1ccc(O)cc1
Reactant: Cc1sc(-c2ccccc2)nc1CCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1sc(-c2ccccc2)nc1COc1ccc(C=O)cc1
Temperature: 80 °C
Reaction time: 3 h
Yield: 92.9 %

Procedure:
A mixture of 4-chloromethyl-5-methyl-2-phenylthiazole (5.40 g), 4-hydroxybenzaldehyde (2.91 g), anhydrous potassium carbonate (4.95 g) and N,N-dimethylformamide (50 mL) was stirred at 80° C. for 3 hrs. The reaction mixture was poured into water, and the precipitated solid was collected by filtration, and dried with air to give crystals (6.85 g, 93%) of 4-[(5-methyl-2-phenyl-4-thiazolyl)methoxy]benzaldehyde. Recrystallization from ethyl aceetate-hexane gave colorless prism crystals. melting point: 18-119° C.
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[S:5][C:6]2[CH:32]=[CH:31][CH:30]=[CH:29][C:7]=2[N:8]([CH2:12][C:13]2[CH:18]=[CH:17][C:16]([NH:19][C:20](=[O:28])[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[CH3:27])=[CH:15][CH:14]=2)[C:9](=[O:11])[CH:10]=1.[CH3:33][O:34][C:35]1[CH:42]=[C:41]([O:43][CH3:44])[CH:40]=[CH:39][C:36]=1[CH:37]=O.C([BH3-])#N.[Na+].[OH-].[Na+]>CO.C(O)(=O)C>[CH3:33][O:34][C:35]1[CH:42]=[C:41]([O:43][CH3:44])[CH:40]=[CH:39][C:36]=1[CH2:37][NH:1][CH2:2][CH2:3][C:4]1[S:5][C:6]2[CH:32]=[CH:31][CH:30]=[CH:29][C:7]=2[N:8]([CH2:12][C:13]2[CH:14]=[CH:15][C:16]([NH:19][C:20](=[O:28])[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[CH3:27])=[CH:17][CH:18]=2)[C:9](=[O:11])[CH:10]=1
Reactant: COc1ccc(C=O)c(OC)c1
Reactant: Cc1ccccc1C(=O)Nc1ccc(CN2C(=O)C=C(CCN)Sc3ccccc32)cc1
Agent: [BH3-]C#N
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: CO
Product: COc1ccc(CNCCC2=CC(=O)N(Cc3ccc(NC(=O)c4ccccc4C)cc3)c3ccccc3S2)c(OC)c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A mixture of Compound 7 as prepared in Example 31 (0.105 g, 0.24 mM), 2,4-dimethoxybenzaldehyde (0.040 g, 0.240 mM) and acetic acid (0.05 ml) in methanol was stirred at room temperature for three hours and 2.5 equivalence of sodium cyanoborohydride was added. The mixture was stirred at room temperature for an additional 4 hours and a 6N NaOH (0.5 ml; adjusted to pH8) was added. The methanol was removed under reduced pressure and the residue diluted with water (50 ml) and extracted with ethyl acetate (2×5 ml). The ethyl acetate extracts were dried (MgSO4), evaporated in vacuo and purified by flash column chromatography (EM silica gel 60; 5% MeOH in CH2Cl2) to give a white solid product. m/z (MH+) 596.
Reaction SMILES: [NH2:1][C:2]1[N:3]=[N:4][N:5]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:6]=1.[CH:14]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH:23]([CH3:25])[CH3:24])[C:18]=1[N:26]=[C:27]=[O:28])([CH3:16])[CH3:15].C(N(CC)CC)C>C(Cl)Cl>[CH3:16][CH:14]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH:23]([CH3:24])[CH3:25])[C:18]=1[NH:26][C:27]([NH:1][C:2]1[N:3]=[N:4][N:5]([CH2:7][C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:6]=1)=[O:28])[CH3:15]
Reactant: CC(C)c1cccc(C(C)C)c1N=C=O
Reactant: Nc1nnn(Cc2ccccc2)n1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)c1cccc(C(C)C)c1NC(=O)Nc1nnn(Cc2ccccc2)n1
Temperature: 25 °C
Reaction time: 96 h

Procedure:
5-Amino-2-benzyltetrazole (1.55 g, 8.84 mmol) was dissolved in 20 mL methylene chloride after which 2,6-diisopropylphenyl isocyanate (2.25 mL, 10.6 mmol) and 1.5 mL triethylamine was added. The mixture was stirred at room temperature for 4 days then quenched with 5 mL 2N sulfuric acid and extracted with 50 mL ethyl acetate. The organic layer was washed with water and a saturated aqueous solution of sodium carbonate, dried over magnesium sulfate, filtered, and evaporated, leaving a white solid which was recrystallized from ethyl acetate/ether to give the title compound, m.p. 180-181° C.
Reaction SMILES: [F:1][C:2]([F:33])([F:32])[C:3]1[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:4]=1[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([CH:15]=[C:16]3[S:20][C:19](SC)=[N:18][C:17]3=[O:23])=[CH:12][CH:13]=2)[CH:8]=[N:7]1.[NH:34]1[CH2:39][CH2:38][CH:37](NC(=O)C)[CH2:36][CH2:35]1>>[F:32][C:2]([F:1])([F:33])[C:3]1[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:4]=1[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([CH:15]=[C:16]3[S:20][C:19]([N:34]4[CH2:35][CH2:36][CH:37]([CH2:16][C:17]([NH2:18])=[O:23])[CH2:38][CH2:39]4)=[N:18][C:17]3=[O:23])=[CH:12][CH:13]=2)[CH:8]=[N:7]1
Reactant: CSC1=NC(=O)C(=Cc2ccc3c(cnn3Cc3ccc(C(F)(F)F)cc3C(F)(F)F)c2)S1
Reactant: CC(=O)NC1CCNCC1
Product: NC(=O)CC1CCN(C2=NC(=O)C(=Cc3ccc4c(cnn4Cc4ccc(C(F)(F)F)cc4C(F)(F)F)c3)S2)CC1

Procedure:
N—(1-{5-[1-(2,4-Bis-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-4-oxo-4,5-dihydro-thiazol-2-yl}-piperidin-4-ylacetamide was prepared from 5-[1-(2,4-Bis-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-methylsulfanyl-thiazol-4-one and N-Piperidin-4-yl-acetamide following General Procedure B.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]=[CH:3][CH2:2]1.CN1CCOCC1.[O:14](C(OC(C)(C)C)=O)[C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=O>C(Cl)Cl>[C:15]([N:1]1[CH2:6][CH2:5][CH:4]=[CH:3][CH2:2]1)([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:14]
Reactant: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Reactant: C1=CCNCC1
Solvent: CN1CCOCC1
Solvent: ClCCl
Product: CC(C)(C)OC(=O)N1CC=CCC1
Temperature: 25 °C
Reaction time: 36 h

Procedure:
To 1.66 g of 1,2,5,6-tetrahydropyridine in 25 ml of CH2Cl2, 2.02 g of N-methylmorpholine are added, the mixture obtained is treated with a solution of 4.36 g (BOC)2O in 30 ml of CH2Cl2 and the mixture obtained is stirred for ca. 36 hours at RT. N-BOC-1,2,5,6-tetrahydropyridine is obtained. 1H-NMR: 5.82(m,1H,HIV), 5.64(m,1H,HIII), 3.86(b,2H,HII), 3.47(t,2H,HVI), 2.12(b,1H,HV), 1.46(m,9H,(CH3)3).
Reaction SMILES: [Li+].CC([N-]C(C)C)C.[CH:9]1([N:15]2[CH2:20][CH2:19][CH2:18][CH2:17][C:16]2=[O:21])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.[Cl:22][C:23]1[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:24]=1[CH2:30]Cl>C1COCC1.C(OCC)(=O)C>[Cl:22][C:23]1[CH:28]=[C:27]([Cl:29])[CH:26]=[CH:25][C:24]=1[CH2:30][CH:17]1[CH2:18][CH2:19][CH2:20][N:15]([CH:9]2[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]2)[C:16]1=[O:21]
Reactant: O=C1CCCCN1C1CCCCC1
Reactant: ClCc1ccc(Cl)cc1Cl
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: O=C1C(Cc2ccc(Cl)cc2Cl)CCCN1C1CCCCC1
Reaction time: 0.25 h
Yield: 242 %

Procedure:
Add 1.8 M LDA (0.9 mL, 1.7 mmol) to solution of 1-cyclohexylpiperidin-2-one (300 mg, 1.7 mmol) in THF (5 mL) at −78° C. and stir for 15 minutes. Add 2,4-dichloro-1-(chloromethyl)benzene (640 mg, 3.3 mmol) and warm the reaction to room temperature. Quench the reaction with water and dilute with ethyl acetate. Dry the organic layer with sodium sulfate, filter and concentrate. Purify the residue by biotage chromatography to afford the title compound as a white solid (1.4 g, 81%): MS (APCI-pos mode) m/z (rel intensity): 340.2 (M+H).
Reaction SMILES: [CH3:1][C:2]([C:13]1[CH:18]=[CH:17][C:16]([N:19]2[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]2)=[CH:15][CH:14]=1)(C(OCC)=O)[C:3]([O:5]CC)=[O:4]>Cl>[CH3:25][N:22]1[CH2:21][CH2:20][N:19]([C:16]2[CH:15]=[CH:14][C:13]([CH:2]([CH3:1])[C:3]([OH:5])=[O:4])=[CH:18][CH:17]=2)[CH2:24][CH2:23]1
Reactant: CCOC(=O)C(C)(C(=O)OCC)c1ccc(N2CCN(C)CC2)cc1
Agent: Cl
Product: CC(C(=O)O)c1ccc(N2CCN(C)CC2)cc1
Yield: 68.5 %

Procedure:
A solution of diethyl 2-methyl-2-(4-(4-methylpiperazin-1-yl)phenyl)malonate (3.50 g, 10.0 mmol) in cone. HCl (20 ml) was stirred for 18 h at reflux in a sealed tube. The reaction mixture was concentrated and co-distilled with toluene to afford (1.7 g, 70%) of 2-(4-(4-methylpiperazin-1-yl)phenyl)propanoic acid as dark brown solid.
Reaction SMILES: [CH2:1]([P+:3]([CH2:8]O)([CH2:6]O)[CH2:4]O)O.[Cl-:10].[NH:11]1[CH2:15][CH2:14][NH:13][C:12]1=[O:16]>C1(C)C=CC=CC=1>[Cl-:10].[O:16]=[C:12]1[NH:13][CH2:14][CH2:15][N:11]1[CH2:8][P+:3]([CH2:1][N:11]1[CH2:15][CH2:14][NH:13][C:12]1=[O:16])([CH2:4][N:11]1[CH2:15][CH2:14][NH:13][C:12]1=[O:16])[CH2:6][N:11]1[CH2:15][CH2:14][NH:13][C:12]1=[O:16]
Reactant: O=C1NCCN1
Reactant: OC[P+](CO)(CO)CO
Agent: [Cl-]
Solvent: Cc1ccccc1
Product: O=C1NCCN1C[P+](CN1CCNC1=O)(CN1CCNC1=O)CN1CCNC1=O
Yield: 96.1 %

Procedure:
Reaction of THPC (9.53 g, 0.05mol) with 2-imidazolidinone (17.22 g, 0.2 mol) in toluene (75 ml), following Example 1, gave 22.23 g (96.1%) of tetrakis[(2-oxo-1-imidazolidinyl)methyl]phosphonium chloride (I, R, R'=CH2CH2, R"=H, X=Cl) as a white solid, mp 220° C. The product was soluble in dilute sodium hydroxide and insoluble in water or organic solvents.
Reaction SMILES: [CH2:1]([C:15]1[CH:20]=[CH:19][C:18]([S:21](Cl)(=[O:23])=[O:22])=[CH:17][CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14].[S:25]1[CH:29]=[N:28][N:27]=[C:26]1[NH2:30].Cl>N1C=CC=CC=1>[CH2:1]([C:15]1[CH:20]=[CH:19][C:18]([S:21]([NH:30][C:26]2[S:25][CH:29]=[N:28][N:27]=2)(=[O:23])=[O:22])=[CH:17][CH:16]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: CCCCCCCCCCCCCCc1ccc(S(=O)(=O)Cl)cc1
Reactant: Nc1nncs1
Agent: Cl
Solvent: c1ccncc1
Product: CCCCCCCCCCCCCCc1ccc(S(=O)(=O)Nc2nncs2)cc1
Temperature: 25 °C
Reaction time: 6 h
Yield: 46.6 %

Procedure:
To a solution of p-tetradecylbenzenesulfonyl chloride (440 mg, 1.18 mmol) in pyridine (8 mL) was added 1,3,4-thiadiazol-2-amine (179 mg, 1.77 mmol). The reaction mixture was stirred at room temperature for 6 hours, then 2 M HCl (40 mL) was added to quench the reaction. The mixture was extracted with ethyl acetate (3×50 mL), the organic layer was washed with water (40 mL) and brine (40 mL), dried over anhydrous Na2SO4 and concentrated. The residue was purified by chromatography over silica gel (70-230 mesh) eluted with methanol:DCM 1:19 to give the product as a solid (240 mg, 0.55 mmol, 47% yield), mp 116-117° C.; 1H NMR (300 MHz, CDCl3) δ 0.88 (t, 3H, J=6.9 Hz), 1.25 (m, 22H), 1.60 (m, 2H), 2.64 (t, 2H, J=7.2 Hz), 7.29 (d, 2H, J=8.4 Hz), 7.84 (d, 2H, J=8.4 Hz), 8.23 (s, 1H); 13C NMR (75 MHz, CDCl3) 14.1, 22.6, 29.2, 29.3, 29.4, 29.5, 29.6, 31.1, 31.9, 35.9, 126.5, 128.9, 138.1, 142.6, 148.6, 167.4; MS (LCQ, ESI+) Calcd for C22H36N3O2S2 438.2, found 438.3 (M+H)+; HRMS (ESI+, m/z) Calcd for C22H36N3O2S2 438.2243, found 438.2243 (M+H)+.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[O:11][CH2:10][CH:9]([CH2:12][NH2:13])[O:8][C:7]=2[CH:14]=1.Br[CH2:16][CH2:17][CH2:18][O:19][C:20]1[CH:29]=[C:28]2[C:23]([CH:24]=[CH:25][CH:26]=[N:27]2)=[CH:22][CH:21]=1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[N:27]1[C:28]2[C:23](=[CH:22][CH:21]=[C:20]([O:19][CH2:18][CH2:17][CH2:16][NH:13][CH2:12][CH:9]3[O:8][C:7]4[CH:14]=[C:3]([O:2][CH3:1])[CH:4]=[CH:5][C:6]=4[O:11][CH2:10]3)[CH:29]=2)[CH:24]=[CH:25][CH:26]=1
Reactant: BrCCCOc1ccc2cccnc2c1
Reactant: COc1ccc2c(c1)OC(CN)CO2
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COc1ccc2c(c1)OC(CNCCCOc1ccc3cccnc3c1)CO2
Temperature: 80 °C
Yield: 28.2 %

Procedure:
2,3-Dihydro-7-methoxy-1,4-benzodioxin-2-methanamine (2.7 g, 14 mmole), 7-(3-bromopropoxy)quinoline (3.86 g, 14 mmole), and diisopropylethylamine (6.5 g, 50 mmole) were combined in 100 ml of DMF and heated at 80° C. for 24 hours under a nitrogen atmosphere. The solvent was then removed in vacuum and replaced with 500 ml of dichloromethane. The mixture was washed with 250 ml each of saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, dried over sodium sulfate, filtered, and concentrated in vacuum. The residue was column chromatographed on 200 g of silica gel using 4% methanolchloroform as eluant. The product-containing fractions were combined and concentrated in vacuum and the residue recrystallized from 50 ml of ethanol with the addition of 8 ml of 4N isopropanolic HCl to give 1.5 g of the title compound as a yellow solid dihydrochloride monohydrate, m.p. 135°-142° C.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][C:3]([NH:6][C:7](=[O:9])[CH3:8])=[N:2]1.[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[N+:10]([C:4]1[C:3]([NH:6][C:7](=[O:9])[CH3:8])=[N:2][NH:1][CH:5]=1)([O-:12])=[O:11]
Reactant: CC(=O)Nc1cc[nH]n1
Reactant: O=[N+]([O-])O
Agent: O=S(=O)(O)O
Product: CC(=O)Nc1n[nH]cc1[N+](=O)[O-]
Yield: 64.7 %

Procedure:
A solution of N-1H-pyrazol-3-ylacetamide (Liebigs annalen der chemie., 1967, 707, 147; 0.500 g, 4.0 mmol) was stirred in a mixture of nitric acid (d=1.52, 0.2 ml, 4.8 mmol) and sulphuric acid (d=1.83, 2 ml) at 0° C. for 2.5 hours. The mixture was poured onto ice and the resultant precipitate was filtered, washed with water and then a 2:1 mixture of diethyl ether:methanol and then with diethyl ether. The residue was dried in vacuo to give N-(4-nitro-1H-pyrazol-3-yl)acetamide (0.44 g, 65% yield):
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:19]=[CH:18][C:9]([CH:10]=NC2C=CC=CC=2)=[CH:8][CH:7]=1)[CH2:2][CH2:3][CH3:4].[CH3:20][S:21]([CH2:24][S:25]([CH3:28])(=[O:27])=[O:26])(=[O:23])=[O:22].C(OC(=O)C)(=O)C>CC1C=CC(C)=CC=1>[CH2:1]([O:5][C:6]1[CH:7]=[CH:8][C:9]([CH:10]=[C:24]([S:25]([CH3:28])(=[O:27])=[O:26])[S:21]([CH3:20])(=[O:23])=[O:22])=[CH:18][CH:19]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CS(=O)(=O)CS(C)(=O)=O
Reactant: CCCCOc1ccc(C=Nc2ccccc2)cc1
Solvent: Cc1ccc(C)cc1
Solvent: CC(=O)OC(C)=O
Product: CCCCOc1ccc(C=C(S(C)(=O)=O)S(C)(=O)=O)cc1
Temperature: 120 °C
Yield: 54.1 %

Procedure:
A mixture of 2.5 g (0.01 mol) of N-(4-butoxybenzylidene)aniline, 1.9 g (0.011 mol) of di(methylsulfonyl) methane, 1.1 mL of acetic anhydride, and 60 mL of p-xylene were heated at 120° C. for 3 days. Upon cooling, the contents of the reaction were chromatographed on silica gel, using dichloromethane as the eluent. Crystallization from toluene afforded 1.8 g (54%) of (6) as a white solid.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][CH:7]=2)=[N:2]1.C(=O)([O-])[O-].[K+].[K+].[CH2:19]([O:26][C:27]([NH:29][CH2:30][CH2:31]OS(C)(=O)=O)=[O:28])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CS(C)=O>[CH2:19]([O:26][C:27](=[O:28])[NH:29][CH2:30][CH2:31][O:12][C:9]1[CH:10]=[CH:11][C:6]([C:3]2[CH:4]=[CH:5][NH:1][N:2]=2)=[CH:7][CH:8]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: Oc1ccc(-c2cc[nH]n2)cc1
Reactant: CS(=O)(=O)OCCNC(=O)OCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: O=C(NCCOc1ccc(-c2cc[nH]n2)cc1)OCc1ccccc1
Temperature: 70 °C
Yield: 61 %

Procedure:
A round-bottomed flask was charged with 4-pyrazol-3-yl-phenol (840 mg, 5.25 mmol), potassium carbonate (2.17 g, 15.7 mmol), and methanesulfonic acid 2-benzyloxycarbonylamino-ethyl ester (C. A. Townsend, et al., Tetrahedron, 47, 2591 (1991)) (2.86 g, 10.5 mmol) in 10.5 ml of dry dimethylsulfoxide. The resulting solution was heated to about 70° C. for about four days. The reaction mixture was then poured into 1 N HCL, and the aqueous phase was extracted twice with ethyl acetate. The combined organic extracts were washed with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude material was purified by column chromatography (methylene chloride to 2% methanol/methylene chloride) to afford 1.09 g (61% yield) of desired product. LRMS ([M+H+])=338.1.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:19])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([OH:18])[CH:14]=[C:15]([CH2:16]Br)[C:7]1=2)[CH3:2].[N-:20]=[N+:21]=[N-:22].[Na+]>CC#N.O>[CH2:1]([O:3][C:4](=[O:19])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([OH:18])[CH:14]=[C:15]([CH2:16][N:20]=[N+:21]=[N-:22])[C:7]1=2)[CH3:2]
Reactant: [N-]=[N+]=[N-]
Reactant: CCOC(=O)CC1OB(O)c2cc(O)cc(CBr)c21
Agent: [Na+]
Solvent: O
Solvent: CC#N
Product: CCOC(=O)CC1OB(O)c2cc(O)cc(CN=[N+]=[N-])c21
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a crude (4-bromomethyl-1,6-dihydroxy-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl)-acetic acid ethyl ester in CH3CN/H2O (10/2 mL) was added sodium azide (3.1 g, 48 mmol). The solution was stirred overnight at r.t. The crude solution was purified by HPLC, yielded 450 mg of the title compound. 1H NMR (300 MHz, CD3CN) δ 7.21 (s, 1H), 6.99 (s, 1H), 5.61 (dd, 1H), 4.31-4.56 (dd, 2H), 4.10 (q, 2H), 3.02-3.14 (dd, 1H), 2.37-2.43 (m, 1H), 1.21 (t, 3H).
Reaction SMILES: [F-].C([N+](CCCC)(CCCC)CCCC)CCC.[Si]([O:26][CH2:27][CH2:28][CH2:29][CH2:30][O:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[CH:43]=[CH:42][C:41]([C:44]([O:46][CH2:47][CH3:48])=[O:45])=[CH:40][CH:39]=2)=[CH:34][C:33]=1[C:49]1[CH:58]=[CH:57][C:56]2[C:55]([CH3:60])([CH3:59])[CH2:54][CH2:53][C:52]([CH3:62])([CH3:61])[C:51]=2[CH:50]=1)(C(C)(C)C)(C)C.O>O1CCCC1>[OH:26][CH2:27][CH2:28][CH2:29][CH2:30][O:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[CH:43]=[CH:42][C:41]([C:44]([O:46][CH2:47][CH3:48])=[O:45])=[CH:40][CH:39]=2)=[CH:34][C:33]=1[C:49]1[CH:58]=[CH:57][C:56]2[C:55]([CH3:60])([CH3:59])[CH2:54][CH2:53][C:52]([CH3:61])([CH3:62])[C:51]=2[CH:50]=1
Reactant: CCOC(=O)c1ccc(-c2ccc(OCCCCO[Si](C)(C)C(C)(C)C)c(-c3ccc4c(c3)C(C)(C)CCC4(C)C)c2)cc1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)c1ccc(-c2ccc(OCCCCO)c(-c3ccc4c(c3)C(C)(C)CCC4(C)C)c2)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 93.2 %

Procedure:
6.8 ml (6.8 mmol) of a solution of tetrabutylammonium fluoride (1M) are added to a solution of 2.8 g (4.5 mmol) of ethyl 4′-[4-(tert-butyldimethylsilanyloxy)butoxy]-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)biphenyl-4-carboxylate in 20 ml of tetrahydrofuran. The reaction mixture is stirred for 4 h at ambient temperature. The reaction is stopped by adding 20 ml of water and the mixture is then extracted with ethyl acetate. The organic phases are combined, washed with a saturated aqueous solution of sodium chloride, and dried over magnesium sulfate. The solvents are evaporated off. The crude obtained in the form of an oil is chromatographed on silica gel (heptane/ethyl acetate: 70/30), to give 2.10 g of ethyl 4′-(4-hydroxybutoxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)biphenyl-4-carboxylate in the form of a colorless oil (yield=93%).