Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O.[Na].[SH:3][C:4]1[N:8]([CH3:9])[N:7]=[N:6][N:5]=1.S(/[CH:13]=[CH:14]\[C:15](=[O:17])[CH3:16])C#N>C(O)C>[SH:3][C:4]1[N:8]([CH3:9])[N:7](/[CH:13]=[CH:14]\[C:15](=[O:17])[CH3:16])[NH:6][N:5]=1
Reactant: Cn1nnnc1S
Reactant: CC(=O)/C=C\SC#N
Agent: [Na]
Solvent: CCO
Solvent: O
Product: CC(=O)/C=C\N1NN=C(S)N1C
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a stirred solution of 5-mercapto-1-methyltetrazole sodium salt hydrate (1.1 g., 0.008 mole) in aqueous ethanol (15 ml), a solution of cis-4-thiocyano-3-buten-2-one (Compound 28) in ethanol was added dropwise over 5 minutes. A solid suspension was observed forming over the next 2 hours which was stirred at 25° C. for 18 hours. The volatiles were removed in vacuo and the residue was extracted into ethyl acetate and washed thoroughly with water. After drying (MgSO4), the solution was concentrated. The solid residue was purified via column chromatography on silica gel using hexanes/ethyl acetate (3:2) as eluant to yield 1.1 g of a white solid, mp 112°-114° C. IR (nujol) uc=o 1660 cm-1.
Reaction SMILES: [CH3:1][C:2]([CH3:7])([CH2:5][OH:6])[CH2:3][OH:4].[S:8](Cl)(Cl)=[O:9]>ClCCl>[CH3:1][C:2]1([CH3:7])[CH2:5][O:6][S:8](=[O:9])[O:4][CH2:3]1
Reactant: O=S(Cl)Cl
Reactant: CC(C)(CO)CO
Solvent: ClCCl
Product: CC1(C)COS(=O)OC1
Temperature: 40 °C
Reaction time: 3 h

Procedure:
To a solution of 2,2-dimethyl-propane-1,3-diol (1 g) in dichloromethane (5 mL) is added dropwise at 0° C. thionylchloride (735 μL). The mixture is stirred for 3 hours at 40° C. and then partitioned between saturated aqueous NaHCO3 solution and dichloromethane. The organic phase is washed with brine and dried (MgSO4). The solvent is evaporated to give the title compound. Yield: 1 g; TLC: rf=0.65 (silicagel, cyclohexane/ethyl acetate 3:1).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH2:13][C:14]3[CH:19]=[CH:18][C:17](CCC(O)=O)=[CH:16][CH:15]=3)[C:11]3[CH:25]=[C:26]([F:30])[C:27]([F:29])=[CH:28][C:10]=3[N:9]=2)=[C:4](OCC2CCCC2)[CH:3]=1.[CH3:38][O:39][C:40](=[O:58])C1C=CC=CC=1C1NC2C=C(F)C(F)=CC=2N=1.BrCC1CCCCC1>>[CH3:38][O:39][C:40](=[O:58])[C:4]1[CH:3]=[CH:2][CH:7]=[CH:6][C:5]=1[C:8]1[N:12]([CH2:13][CH:14]2[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]2)[C:11]2[CH:25]=[C:26]([F:30])[C:27]([F:29])=[CH:28][C:10]=2[N:9]=1
Reactant: COC(=O)c1ccccc1-c1nc2cc(F)c(F)cc2[nH]1
Reactant: O=C(O)CCc1ccc(Cn2c(-c3ccc(Cl)cc3OCC3CCCC3)nc3cc(F)c(F)cc32)cc1
Agent: BrCC1CCCCC1
Product: COC(=O)c1ccccc1-c1nc2cc(F)c(F)cc2n1CC1CCCCC1

Procedure:
The title compound was prepared in analogy to Example 19, intermediate b, from 2-(5,6-difluoro-1H-benzoimidazol-2-yl)-benzoic acid methyl ester and bromomethyl-cyclohexane (2550-36-9). Off-white powder (15%). MS (Turbo Spray): m/z=384.8 (M+H).
Reaction SMILES: [NH2:1][C:2]1[CH:6]=[C:5]([C:7]([CH3:10])([CH3:9])[CH3:8])[NH:4][N:3]=1.Cl[C:12]([O:14][CH2:15][CH3:16])=[O:13]>O1CCOCC1>[C:7]([C:5]1[NH:4][N:3]=[C:2]([NH:1][C:12](=[O:13])[O:14][CH2:15][CH3:16])[CH:6]=1)([CH3:10])([CH3:9])[CH3:8]
Reactant: CC(C)(C)c1cc(N)n[nH]1
Reactant: CCOC(=O)Cl
Solvent: C1COCCO1
Product: CCOC(=O)Nc1cc(C(C)(C)C)[nH]n1
Yield: 25.9 %

Procedure:
2.8 g of Compound [II] was dissolved in 30 ml of dioxane, and 2.2 g of ethyl chloroformate was added to the solution. The mixture was then allowed to react for 5 hours under refluxing. After completion of the reaction, the solvent was distilled off, and hexane and a potassium carbonate aqueous solution were added to the residue to form crystals. The crystals were collected by filtration and washed with water and hexane to obtain 1.1 g of ethyl N-(5-t-butyl-3-pyrazolyl)carbamate.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:29]=[CH:28][C:6]([CH2:7][O:8][C:9]2[C:10](OS(C(F)(F)F)(=O)=O)=[CH:11][C:12]([CH2:15][O:16][C:17](=[O:19])[CH3:18])=[N:13][CH:14]=2)=[CH:5][CH:4]=1.C(N(CC)CC)C.[CH3:37][Si:38]([C:41]#[CH:42])([CH3:40])[CH3:39].O>C(#N)C.[Cu](I)I>[CH3:1][O:2][C:3]1[CH:29]=[CH:28][C:6]([CH2:7][O:8][C:9]2[C:10]([C:42]#[C:41][Si:38]([CH3:40])([CH3:39])[CH3:37])=[CH:11][C:12]([CH2:15][O:16][C:17](=[O:19])[CH3:18])=[N:13][CH:14]=2)=[CH:5][CH:4]=1
Reactant: C#C[Si](C)(C)C
Reactant: COc1ccc(COc2cnc(COC(C)=O)cc2OS(=O)(=O)C(F)(F)F)cc1
Agent: I[Cu]I
Solvent: CC#N
Solvent: O
Solvent: CCN(CC)CC
Product: COc1ccc(COc2cnc(COC(C)=O)cc2C#C[Si](C)(C)C)cc1
Temperature: 45 °C
Reaction time: 8 h
Yield: 504.6 %

Procedure:
(5-[(4-Methoxybenzyl)oxy]-4-{[(trifluoromethyl)sulfonyl]oxy}pyridin-2-yl)methylacetate (1.2 g, 2.78 mmol) was dissolved in acetonitrile (9.3 mL), added copper iodide (53 mg, 278 μmol), ditriphenylphosphine palladium (II) dichloride (98 mg, 139 μmol), triethylamine (8.0 mL) and trimethylsilyl acetylene (819 mg, 8.34 mmol) under an argon atmosphere, and under ice-cold conditions, and the mixture was stirred at 45° C. overnight. This operation was conducted for 4 lots, and the following treatments were conducted as a whole. The reaction solution was added water, and filtered through a pad of celite. The obtained filtrate was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. A crude product of the title compound (5.38 g) was obtained as a yellow oil.
Reaction SMILES: [C:1]1([CH:7]([C:9]2[CH:18]=[C:17]3[C:12]([CH:13]=[CH:14][CH:15]=[N:16]3)=[CH:11][CH:10]=2)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(Cl)([Cl:21])=O>ClCCl>[Cl:21][CH:7]([C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[C:9]1[CH:18]=[C:17]2[C:12]([CH:13]=[CH:14][CH:15]=[N:16]2)=[CH:11][CH:10]=1
Reactant: OC(c1ccccc1)c1ccc2cccnc2c1
Reactant: O=S(Cl)Cl
Solvent: ClCCl
Product: ClC(c1ccccc1)c1ccc2cccnc2c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 98.5 %

Procedure:
A mixture of 3.2 parts of intermediate 2, namely α-phenyl-7-quinolinemethanol, 8 parts of thionyl chloride and 65 parts of dichloromethane was stirred for 4 hours at room temperature. The reaction mixture was evaporated and the residue was poured into water. The product was extracted with dichloromethane (3×39 parts) and the combined extracts were dried, filtered and evaporated, yielding 3.4 parts (98.5%) of 7-(chlorophenylmethyl)quinoline (interm. 23). In a similar manner there were also prepared the intermediates listed in Table 2.
Reaction SMILES: [NH2:1][C@H:2]([CH2:6][CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C:3]([OH:5])=[O:4].O.Cl[C:17]([O:19][CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:18].Cl>C1COCC1.CCOC(C)=O>[CH2:20]([O:19][C:17]([NH:1][C@H:2]([CH2:6][CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C:3]([OH:5])=[O:4])=[O:18])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: O=C(Cl)OCc1ccccc1
Reactant: CC(C)(C)OC(=O)CC[C@@H](N)C(=O)O
Agent: Cl
Solvent: O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)CC[C@@H](NC(=O)OCc1ccccc1)C(=O)O
Temperature: 0 °C
Reaction time: 2.5 h

Procedure:
(R)-2-amino-5-(tert-butoxy)-5-oxopentanoic acid (1.00 g, 4.92 mmol) was suspended in THF (18.45 ml)/Water (6.15 ml) and cooled to 0° C. using an ice bath. To the cold slurry was slowly added benzyl chloroformate (0.773 mL, 5.41 mmol) and the reaction mixture was allowed to stir for 2.5 h. The slurry was diluted with 50 mL of EtOAc before being acidified to pH 3 using an aqueous 1N HCl solution. The crude product was extracted three times with EtOAc. The organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The crude product was obtained as a clear oil and was subjected to silica gel chromatography using 100% Hexanes to 100% ethyl acetate as eluant. The product, (R)-2-(((benzyloxy)carbonyl)amino)-5-(tert-butoxy)-5-oxopentanoic acid, was obtained as a colorless oil (1.41 g, 71%). 1H NMR (400 MHz, chloroform-d) δ 7.44-7.29 (m, 5H), 5.53 (d, J=7.5 Hz, 1H), 5.13 (s, 2H), 4.41 (d, J=5.1 Hz, 1H), 2.56-2.30 (m, 2H), 2.21 (dd, J=13.5, 6.5 Hz, 1H), 2.06-1.88 (m, 2H), 1.45 (s, 9H).
Reaction SMILES: [Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8](O)([CH3:10])[CH3:9])=[CH:4][CH:3]=1.S(=O)(=O)(O)O.[NH4+].[OH-:18].[CH3:19][C:20]#[N:21]>O>[Cl:1][C:2]1[N:7]=[CH:6][C:5]([C:8]([NH:21][C:20](=[O:18])[CH3:19])([CH3:10])[CH3:9])=[CH:4][CH:3]=1
Reactant: CC(C)(O)c1ccc(Cl)nc1
Reactant: CC#N
Reactant: [OH-]
Agent: O=S(=O)(O)O
Agent: [NH4+]
Solvent: O
Product: CC(=O)NC(C)(C)c1ccc(Cl)nc1
Temperature: 25 °C
Reaction time: 60 h

Procedure:
A solution of the product from Step A, 1-A, (33.42 g, 195 mmol) in CH3CN (250 mL) was cooled to 0° C. using an ice-water bath. Sulfuric acid (72.7 mL, 1363 mmol) was slowly added and the reaction mixture was allowed to warm to rt and was stirred between 48-72 h. The reaction mixture was cooled to 0° C. using an ice-water bath, diluted with H2O (100 mL) and subsequently treated slowly with aq. 29% NH4OH (203 mL). The quenched mixture was extracted with MTBE and the organic layer was separated. The aqueous layer was extracted with MTBE and the combined organic layers were concentrated under reduced pressure until a solid was present. The solids were treated with hexanes, collected by vacuum filtration and dried under high vacuum. HPLC/MS: 213.0 (M+1); Rt=1.71 min.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:21])[CH2:5][S:6]([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:16][C:17]#[C:18][CH2:19][CH3:20])=[CH:11][CH:10]=1)(=[O:8])=[O:7])[CH3:2].[Br:22][C:23]1[CH:36]=[CH:35][C:26]([CH2:27][N:28]([CH2:32][CH2:33]Cl)[CH2:29][CH2:30]Cl)=[CH:25][CH:24]=1>>[CH2:1]([O:3][C:4]([C:5]1([S:6]([C:9]2[CH:10]=[CH:11][C:12]([O:15][CH2:16][C:17]#[C:18][CH2:19][CH3:20])=[CH:13][CH:14]=2)(=[O:7])=[O:8])[CH2:30][CH2:29][N:28]([CH2:27][C:26]2[CH:35]=[CH:36][C:23]([Br:22])=[CH:24][CH:25]=2)[CH2:32][CH2:33]1)=[O:21])[CH3:2]
Reactant: ClCCN(CCCl)Cc1ccc(Br)cc1
Reactant: CCC#CCOc1ccc(S(=O)(=O)CC(=O)OCC)cc1
Product: CCC#CCOc1ccc(S(=O)(=O)C2(C(=O)OCC)CCN(Cc3ccc(Br)cc3)CC2)cc1

Procedure:
1-(4-Bromo-benzyl)-4-(4-pent-2-ynyloxy-benzenesulfonyl)-piperidine-4-carboxylic acid ethyl ester was prepared according to the general method as outlined in Example 1 (Step 6). Starting from (4-pent-2-ynyloxy-benzenesulfonyl)-acetic acid ethyl ester (4 g, 12.9 mmol) and (4-bromo-benzyl)-bis-(2-chloro-ethyl)-amine (5.83 g, 16.8 mmol, 2.85 g of the product was isolated. Yield 2.85 g (31%); low melting white solid; MS: 549.9 (M+H)+
Reaction SMILES: [N:1]1[C:2]2[N:3]([N:7]=[C:8]3[CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][C:9]=23)[N:4]=[CH:5][CH:6]=1.FC(F)(F)C(O)=O>ClCCl>[N:1]1[C:2]2[N:3]([N:7]=[C:8]3[CH2:12][NH:11][CH2:10][C:9]=23)[N:4]=[CH:5][CH:6]=1
Reactant: CC(C)(C)OC(=O)N1Cc2nn3nccnc3c2C1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: c1cnn2nc3c(c2n1)CNC3
Reaction time: 1 h

Procedure:
To 77 mg (0.29 mmol) of the product from Step A in dichloromethane (1 mL) was added trifluoroacetic acid (1 mL) and the reaction mixture stirred for 1 h. The solvent was evaporated in vacuo and the residue purified by flash chromatography on a Biotage Horizon® system (silica gel, 0 to 20% ethyl acetate/methanol containing 10% NH4OH gradient) to yield the title compound as a yellow solid. LC/MS 162.2 (M+1).
Reaction SMILES: C([O:3][C:4](=[O:30])[C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:14]=[C:15]3[C:20](=[C:21]([CH:23]4[CH2:25][CH2:24]4)[CH:22]=2)[O:19][C:18]([CH3:27])([CH3:26])[CH2:17][C:16]3([CH3:29])[CH3:28])=[CH:7][CH:6]=1)C.CO.[OH-].[Na+].O>C(#N)C>[CH:23]1([C:21]2[CH:22]=[C:13]([C:12]#[C:11][C:8]3[CH:7]=[CH:6][C:5]([C:4]([OH:30])=[O:3])=[CH:10][CH:9]=3)[CH:14]=[C:15]3[C:20]=2[O:19][C:18]([CH3:26])([CH3:27])[CH2:17][C:16]3([CH3:29])[CH3:28])[CH2:24][CH2:25]1
Reactant: CCOC(=O)c1ccc(C#Cc2cc(C3CC3)c3c(c2)C(C)(C)CC(C)(C)O3)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CC#N
Solvent: O
Solvent: CO
Product: CC1(C)CC(C)(C)c2cc(C#Cc3ccc(C(=O)O)cc3)cc(C3CC3)c2O1

Procedure:
Following general procedure L and using 4-(8-cyclopropyl-2,2,4,4-tetramethyl-chroman-6-yl-ethynyl)-benzoic acid ethyl ester (Compound 33, 0.135 g, 0.34 mmol), 5 mL of methanol and 1M sodium hydroxide solution (2 mL) followed by preparative reverse phase HPLC using 10% water in acetonitrile as the mobile phase, the title compound was obtained as a solid (0.093 g, 73%).
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([F:10])[C:3]=1[C:4]#[N:5].[S:11](Cl)(=[O:14])(=[O:13])[NH2:12]>>[C:4]([C:3]1[C:6]([F:10])=[CH:7][CH:8]=[CH:9][C:2]=1[NH:1][S:11]([NH2:12])(=[O:14])=[O:13])#[N:5]
Reactant: NS(=O)(=O)Cl
Reactant: N#Cc1c(N)cccc1F
Product: N#Cc1c(F)cccc1NS(N)(=O)=O

Procedure:
Prepared as in Example 77a from 2-amino-6-fluorobenzonitrile and sulfamoyl chloride
Reaction SMILES: [CH3:1][C:2]([CH3:20])([CH2:18][CH3:19])[C:3](=[O:17])[C:4]([N:6]1[CH2:10][CH2:9][CH2:8][CH:7]1[C:11](=[O:16])[CH2:12][CH2:13][CH:14]=[CH2:15])=[O:5].[CH2:21]([O:28][C:29]1[CH:34]=[CH:33][C:32](Br)=[CH:31][CH:30]=1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(N(CC)CC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][C:2]([CH3:20])([CH2:18][CH3:19])[C:3](=[O:17])[C:4]([N:6]1[CH2:10][CH2:9][CH2:8][CH:7]1[C:11](=[O:16])[CH2:12][CH2:13][CH:14]=[CH:15][C:32]1[CH:33]=[CH:34][C:29]([O:28][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:30][CH:31]=1)=[O:5]
Reactant: Brc1ccc(OCc2ccccc2)cc1
Reactant: C=CCCC(=O)C1CCCN1C(=O)C(=O)C(C)(C)CC
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: Cc1ccccc1P(c1ccccc1C)c1ccccc1C
Solvent: CCN(CC)CC
Product: CCC(C)(C)C(=O)C(=O)N1CCCC1C(=O)CCC=Cc1ccc(OCc2ccccc2)cc1
Yield: 60.1 %

Procedure:
A solution of 3,3-dimethyl-1-(2-pent-4-enoylpyrrolidinyl)pentane-1,2-dione (1.73 g; 6.20 mmol), 4-benzyloxybromobenzene (1.80 g; 6.83 mmol), palladium (II) acetate (70 mg; 0.31 mmol), and tri(orthotolyl)phosphine (380 mg; 1.24 mmol) in triethylamine (23 ml) was refluxed overnight. The mixture was concentrated in vacuo and purified on a silica gel column, eluting with a gradient from 10% ethyl acetate/hexane to 20% ethyl acetate/hexane, to obtain 1.72 g (60%) of 3,3-dimethyl-1-(2-{5-[4-(phenylmethoxy)phenyl]pent-4-enoyl}pyrrolidinyl)pentane-1,2-dione as a yellow oil.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:17]=1[NH:16][CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([BH3-])#N.[Na+].[OH-].[Na+]>C(O)(=O)C.C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:17]=1[NH:16][CH2:15][CH2:14]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: c1ccc(COc2cccc3cc[nH]c23)cc1
Agent: [BH3-]C#N
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: c1ccc(COc2cccc3c2NCC3)cc1
Reaction time: 4 h
Yield: 87.3 %

Procedure:
A magnetically stirred solution of 7-benzyloxyindole (16.0 g, 71.66 mmol) in glacial acetic acid (200 ml) at 10° C. under nitrogen was treated with sodium cyanoborohydride (10.0 g, 0.159 mol) in portions via a powder funnel maintaining an addition temperature of below 17° C. Resulting white suspension was stirred below 20° C. for 4 h and quenched with water (300 ml). Evaporation in vacuo gave a colourless oil which was diluted with ethyl acetate (300 ml) treated with 2M sodium hydroxide (400 ml) and stirred vigorously for 16 h. The organic layer was separated, the aqueous was extracted with ethyl acetate (3×100 ml), the combined organic phases were washed with aqueous 2M NaOH(aq) (200 ml) brine (2×200 ml), dried (Na2SO4) and evaporation of the solvent gave the crude product as an oily white solid. Column chromatography (ethyl acetate-light petroleum (b.p. 40-60° C.), 1:9) provided the title compound (14.1 g, 89%) as white crystals. Crystallised from ethyl acetate and light petroleum (b.p. 40-60° C.) as colourless plates (m.p. 58-60° C.). (Found: C, 80.04; H, 6.58; N; 6.19. C15H15NO requires C, 79.97; H, 6.71; N, 6.22%); νmax (nujol)/cm−1 3332, 30338, 1885, 1618, 1591; δH (270 MHz) 3.02 (2H, 2×2-H, 3J2,3=8.4 Hz); 3.51 (2H, 2×3-H, 3J3.2=8.6 Hz); 3.80 (1H, bs, N-H); 5.02 (2H, s, CH2Ph); 6.65 (2H, m, 4-H, 5-H); 6.80 (1H, m, 6-H); 7.33 (5H, m, Ph). δc (67.8 MHz) 30.3 (2-C); 47.62 (3-C); 70.1 (OCH2Ph); 110.8 (6-C); 117.5 (5-C); 118.9 (4-C); 130.4 (3a-C); 137.2 (7a-C); 140.9 (benzyl ipso-C); 144.4 (7-C). Remaining signals lie between 127.3-128.4 ppm; m/z 225.2 (17.24, M+), 134.1 (100), 116.1 (14.06), 91.1 (29.15).
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([Cl:12])=[N:7]2.[F:13][C:14]1[CH:19]=[CH:18][C:17]([S:20](Cl)(=[O:22])=[O:21])=[CH:16][CH:15]=1>N1C=CC=CC=1>[Cl:12][C:6]1[CH:5]=[CH:4][C:3]2[C:8](=[CH:9][CH:10]=[CH:11][C:2]=2[NH:1][S:20]([C:17]2[CH:18]=[CH:19][C:14]([F:13])=[CH:15][CH:16]=2)(=[O:22])=[O:21])[N:7]=1
Reactant: Nc1cccc2nc(Cl)ccc12
Reactant: O=S(=O)(Cl)c1ccc(F)cc1
Solvent: c1ccncc1
Product: O=S(=O)(Nc1cccc2nc(Cl)ccc12)c1ccc(F)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
5-Amino-2-chloroquinoline (1.0 g, 5.6 mmol) was dissolved in 10 mL pyridine and 4-fluorobenzenesulphonylchloride (1.1 g, 5.7 mmol) was added. The reaction mixture was stirred at room temperature overnight and quenched by addition of 100 mL water and 6.8 mL acetic acid. The mixture was extracted three times with ethyl acetate (100 mL each). The organic phases ware pooled, dried with sodium sulfate, filtered and evaporated. The residue was purified by flash chromatography on silica gel (cyclohexane/ethyl acetate 100:0->50:50 gradient). N-(2-Chloro-quinolin-5-yl)-4-fluoro-benzenesulfonamide was obtained as a brown solid (762 mg, 40%), MS:
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][NH2:5].C(N(CC)CC)C.[N+:13]([C:16]1[CH:24]=[CH:23][C:19]([C:20](Cl)=[O:21])=[CH:18][CH:17]=1)([O-:15])=[O:14]>C(Cl)Cl>[Cl:1][CH2:2][CH2:3][CH2:4][NH:5][C:20](=[O:21])[C:19]1[CH:18]=[CH:17][C:16]([N+:13]([O-:15])=[O:14])=[CH:24][CH:23]=1
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Reactant: NCCCCl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: O=C(NCCCCl)c1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A solution of 6.43 g (49 mmol) 3-chloropropylamine and 13.6 ml (98 mmol) triethylamine in 220 ml methylene chloride was cooled by an ice bath and 9 g (48.5 mmol) 4-nitrobenzoyl chloride were added fractionwise. After one hour stirring at room temperature the organic phase was washed twice with water, dried over MgSO4 and concentrated in vacuo to afford 10.68 g (91%). of beige crystals. 1H NMR was consistent with the desired structure.
Reaction SMILES: [CH3:1][C:2]1[N:11]([C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)[C:10](=[O:19])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1.[N:20]1([CH2:26][CH2:27]O)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>O1CCCC1>[CH3:1][C:2]1[N:11]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:27][CH2:26][N:20]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)=[CH:14][CH:13]=2)[C:10](=[O:19])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1
Reactant: OCCN1CCCCC1
Reactant: Cc1nc2ccccc2c(=O)n1-c1ccc(O)cc1
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: Cc1nc2ccccc2c(=O)n1-c1ccc(OCCN2CCCCC2)cc1
Temperature: 25 °C
Reaction time: 48 h
Yield: 86 %

Procedure:
2-methyl-3-(4-hydroxyphenyl)-4-(3H)quinazolinone synthesized according to Example 1-(1) and -(2) (100 mg, 0.40 mmol), 2-(1-piperidinyl)ethanol (89 mg, 0.50 mmol) and triphenylphosphine (125 mg, 0.50 mmol) were dissolved in dry tetrahydrofuran (2 mL) and cooled on an ice bath. Diethylazodicarboxylate (75 uL, 0.50 mmol) was dripped in at 0° C. and stirred at room temperature for 48 hours. The solvent was distilled off under reduced pressure, ether was added, the solid precipitate was filtered off and the filtrate was concentrated. The residue was purified by silica gel column chromatography (chloroform/methanol=30/1) and the title compound (124 mg, 86%) was obtained as a light brown oily substance.
Reaction SMILES: [N:1]([C@@H:4]1[CH2:8][N:7]([CH2:9][C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:6][C@H:5]1[OH:16])=[N+]=[N-].[H][H].[C:19](OC(=O)C)(=[O:21])[CH3:20]>CO.[Ni]>[CH2:9]([N:7]1[CH2:6][C@@H:5]([OH:16])[C@H:4]([NH:1][C:19](=[O:21])[CH3:20])[CH2:8]1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: CC(=O)OC(C)=O
Reactant: [N-]=[N+]=N[C@@H]1CN(Cc2ccccc2)C[C@H]1O
Reactant: [H][H]
Agent: [Ni]
Solvent: CO
Product: CC(=O)N[C@@H]1CN(Cc2ccccc2)C[C@H]1O
Reaction time: 0.25 h
Yield: 85.4 %

Procedure:
To a solution of (trans)-4-azido-1-benzyl-pyrrolidin-3-ol (0.6 g, 3 mmol) (prepared as described in J. Med. Chem 1990, 33, 5, 1344) in MeOH (10 ml) was added Rainey nickel (0.5 g) and the reaction was stirred under one atmosphere of hydrogen for 1 h. The reaction was then filtered through Hyflo and concentrated. The residue was redissolved in CH2Cl2 (5 ml) and added to saturated NaHCO3 (5 ml) and stirred vigorously while acetic anhydride (0.2 ml, 2 mmol) was added. The reaction was stirred for 15 minutes after which time the organic was separated, were dried (Na2SO4) and concentrated. Purification by flash column chromatography (CH2Cl2:MeOH 9:1) afforded the title product (0.4 g, 68%). MS: 235.1 (MH+).
Reaction SMILES: Cl.[C:2](Cl)(=[O:4])[CH3:3].Cl.[CH2:7](O)[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]CC.C([O-])(=O)C.[Na+]>C(O)(C(F)(F)F)=O.C(OC(=O)C)(=O)C.C(O)CCCCCCC>[CH3:3][CH:2]([OH:4])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CC(=O)Cl
Reactant: CCCCCCCCO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O=C(O)C(F)(F)F
Solvent: CC(=O)OC(C)=O
Product: CCCCCCC(C)O

Procedure:
Assignment of the absolute configuration of the TSL-1 and ES 3,6-dideoxyhexose was achieved by GC/MS analysis of the acetylated glycosides formed from chiral 2-octanol. 3M HCl in both (-)-2 and (+)-2 octanol (available from Sigma) were prepared by the dropwise addition of about 256 μl acetyl chloride (available from Mallinkrodt, Inc., Paris, Ken.) to about 1.2 ml octanol. Derivatizations of TSL-1 and ES antigens were achieved by: (a) hydrolysis in 2M TFA at about 121° C. for about 1 hour (hr); (b) octanolysis in either (-)-2 or (+)-2 3M octanol HCl at about 80° C. for about 3 hr; (c) addition of sodium acetate; and (d) acetylation in acetic anhydride at about 100° C. for about 1 hr. The acetylated octyl glycosides were partitioned into the organic phase between about 1 ml chloroform and about 1 ml water, dried, and extracted into acetone (see, for example, Leontein et al., pp. 359-362, 1978, Carbohyd. Res., Vol. 62). Samples were analyzed by GC/MS as above for alditol acetates (total ion chromatogram) or in the selected ion monitoring mode (selecting m/z's of about 83, 85, 112, 145, and 215). Methyl tyvelose (3,6-dideoxy-D-arabinohexose) and Ascaris suum eggs (containing 3,6-dideoxy-L-arabinohexose) were also subjected to hydrolysis, (-)-2 and (+)-2 octanolysis, and acetylation. GC/MS data from the resulting acetylated 3,6-dideoxyarabinohexose octyl glycoside derivatives were compared to those obtained from the TSL-1 and ES antigen samples. Verification of absolute configuration was achieved by co-injection.
Reaction SMILES: [Cl:1][C:2]1[C:3](F)=[C:4]([F:19])[CH:5]=[C:6]2[C:11]=1[N:10]([CH:12]1[CH2:14][CH2:13]1)[CH:9]=[C:8]([C:15]([OH:17])=[O:16])[C:7]2=[O:18].C(N(CC)CC)C.[CH3:28][C:29]1([CH2:34][NH2:35])[CH2:33][CH2:32][NH:31][CH2:30]1>C(#N)C>[NH2:35][CH2:34][C:29]1([CH3:28])[CH2:33][CH2:32][N:31]([C:3]2[C:2]([Cl:1])=[C:11]3[C:6]([C:7](=[O:18])[C:8]([C:15]([OH:17])=[O:16])=[CH:9][N:10]3[CH:12]3[CH2:14][CH2:13]3)=[CH:5][C:4]=2[F:19])[CH2:30]1
Reactant: O=C(O)c1cn(C2CC2)c2c(Cl)c(F)c(F)cc2c1=O
Reactant: CC1(CN)CCNC1
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CC1(CN)CCN(c2c(F)cc3c(=O)c(C(=O)O)cn(C4CC4)c3c2Cl)C1
Yield: 95 %

Procedure:
To 1.05 g (3.50 mmol) of 8-chloro-1-cyclopropyl-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid was added 15 ml of acetonitrile, 1.0 g (9.9 mmol) of triethylamine and 0.7 g (6 mmol) of the 3-methyl-3-pyrrolidinemethanamine. The mixture was refluxed 18 hours and cooled. Filtration gave 1.31 g of the title compound, mp 189°-191° C.