Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]([C:12](N(OC)C)=[O:13])[C:9]([N:18]2[CH2:22][CH2:21][C@@H:20]([OH:23])[CH2:19]2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.[CH3:24][Mg]Br>O1CCCC1>[Cl:1][C:2]1[CH:11]=[C:10]([C:12](=[O:13])[CH3:24])[C:9]([N:18]2[CH2:22][CH2:21][C@@H:20]([OH:23])[CH2:19]2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2
Reactant: CON(C)C(=O)c1cc(Cl)c2cccnc2c1N1CC[C@@H](O)C1
Reactant: C[Mg]Br
Solvent: C1CCOC1
Product: CC(=O)c1cc(Cl)c2cccnc2c1N1CC[C@@H](O)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 95 %

Procedure:
To a mixture of 5-chloro-8-[(3R)-3-hydroxypyrrolidin-1-yl]-N-methoxy-N-methylquinoline-7-carboxamide (115 mg, 0.342 mmol) in tetrahydrofuran (0.5 mL) was added 1.40 M methylmagnesium bromide in tetrahydrofuran (1.5 mL, 2.0 mmol). The reaction was stirred at room temperature overnight, quenched with saturated ammonium chloride, and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, and then concentrated to dryness under reduced pressure. The resultant residue was purified on silica gel, eluting with 0 to 10% MeOH in dichloromethane, to give the desired product (95 mg, 95%). LCMS calculated for C15H16ClN2O2(M+H)+: m/z=291.1; found: 291.1.
Reaction SMILES: [CH:1]1[C:5]2=[C:6]([OH:15])[C:7]3[CH:14]=[CH:13][C:11](=[O:12])[O:10][C:8]=3[CH:9]=[C:4]2[O:3][CH:2]=1.Cl[CH2:17][CH2:18][CH2:19][C:20]#[N:21].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CC(=O)CC>[C:20]([CH2:19][CH2:18][CH2:17][O:15][C:6]1[C:7]2[CH:14]=[CH:13][C:11](=[O:12])[O:10][C:8]=2[CH:9]=[C:4]2[O:3][CH:2]=[CH:1][C:5]=12)#[N:21]
Reactant: O=c1ccc2c(O)c3ccoc3cc2o1
Reactant: N#CCCCCl
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CCC(C)=O
Product: N#CCCCOc1c2ccoc2cc2oc(=O)ccc12
Reaction time: 0.29 h

Procedure:
800 mg (3.956 mmol) of 5-hydroxypsoralen and 0.7 ml (655.5 mg, 6.33 mmol) of 4-chlorobutyronitrile were refluxed in 50 ml of 2-butanone in the presence of an excess (2.6 g) of anhydrous potassium carbonate and catalytic amounts of potassium iodide for 48 hours. The progress of the reaction was monitored by thin layer chromatography. After 48 hours the reaction mixture was concentrated under reduced pressure. The residual oily layer was cooled, diluted with water and acidified with concentrated hydrochloric acid to pH 1. The slurry was stirred for 15-20 min and then filtered. The solids were washed with water to neutral pH, dried bysuction and then further washed with petroleum ether. The dried solids were dissolved in refluxing methanol, treated with charcoal and recrystallized from methanol.
Reaction SMILES: C[O:2][C:3](=[O:20])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH:11]=[CH:12][C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][CH:14]=1.O.[OH-].[K+]>CO>[Cl:19][C:16]1[CH:15]=[CH:14][C:13]([CH:12]=[CH:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][C:3]([OH:20])=[O:2])=[CH:18][CH:17]=1
Reactant: COC(=O)CCCCCCCC=Cc1ccc(Cl)cc1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=C(O)CCCCCCCC=Cc1ccc(Cl)cc1
Reaction time: 2 h
Yield: 103.7 %

Procedure:
To a solution of 1.62 g of 10-(4-chlorophenyl)-dec-9-enoic acid methyl ester in 200 mL of 4:1 methanol:water is added 5.4 g of KOH. The solution is stirred for 2 hours and extracted three times with diethyl ether. The aqueous layer is acidified with concentrated hydrochloric acid, and extracted three times with diethyl ether. The organic layers are combined, washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo to give a yellow oil. The residue is purified via flash chromatography on a 40 mm×150 mm silica column eluting with 40% ethyl acetate/hexane to give 1.6 g (100%) of pure 10-(4-chlorophenyl)dec-9-enoic acid as a mixture of E and Z isomers.
Reaction SMILES: [Cl:1][CH:2]([CH2:12][S:13]([F:18])([F:17])([F:16])([F:15])[F:14])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][S:8]([OH:11])(=[O:10])=[O:9].[OH-].[Na+:20]>C(O)C>[Cl:1][CH:2]([CH2:12][S:13]([F:18])([F:17])([F:14])([F:15])[F:16])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][S:8]([O-:11])(=[O:10])=[O:9].[Na+:20]
Reactant: O=S(=O)(O)CCCCCC(Cl)CS(F)(F)(F)(F)F
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=S(=O)([O-])CCCCCC(Cl)CS(F)(F)(F)(F)F

Procedure:
10g (29.35 mmol; 1 eq) of sulfonic acid from Example 6b are suspended in 130 ml of ethanol, and 1.4 9 (35.22 mmol; 1.2 eq) of sodium hydroxide are added. The reaction mixture is heated under reflux for 1 h. The solid is filtered off at RT.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:11]([OH:13])=[O:12])=[CH:3]1.C(N1C=CN=C1)(N1C=CN=C1)=O.[N:26]12[CH2:33][C:30]([CH2:34]O)([CH2:31][CH2:32]1)[CH2:29][CH2:28][CH2:27]2.C([Li])CCC.CCCCCC>O1CCCC1>[N:26]12[CH2:33][C:30]([CH2:34][O:12][C:11]([C:4]3[C:5]4[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=4)[N:2]([CH3:1])[CH:3]=3)=[O:13])([CH2:31][CH2:32]1)[CH2:29][CH2:28][CH2:27]2
Reactant: Cn1cc(C(=O)O)c2ccccc21
Reactant: OCC12CCCN(CC1)C2
Agent: O=C(n1ccnc1)n1ccnc1
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: Cn1cc(C(=O)OCC23CCCN(CC2)C3)c2ccccc21
Reaction time: 1 h
Yield: 57.6 %

Procedure:
A solution of 1-methyl-1H-indole-3-carboxylic acid (1.75 g, 10 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen was treated with 1,1'-carbonyldiimidazole (1.79 g, 11 mmol), stirred for one hour, and degassed under a stream of nitrogen over 10 minutes. Meanwhile a cooled (-10° C.) solution of 1-azabicyclo[3.2.1]octane-5-methanol (1.55 g, 11 mmol) in anhydrous tetrahydrofuran (10 mL) under nitrogen was treated (via syringe) with 2.5N n-butyllithium/hexane (10.5 mmol), stirred for 30 minutes, concentrated in vacuo, and taken up in anhydrous tetrahydrofuran (10 mL) under nitrogen. The suspension of the acid/1,1'-carbonyldiimidazole adduct was transferred into this solution, and the mixture was stirred 18 hours at room temperature and 4 hours at 55° C., and concentrated in vacuo. The residue was partitioned between toluene (150 mL) containing some 2-propanol and saturated aqueous sodium carbonate (100 mL). The organic layer was separated and the aqueous solution was extracted with toluene (2×100 mL) containing some 2-propanol. The combined organic solution was dried (Na2SO4), concentrated in vacuo, and filtered through alumina (eluted with 20% methanol/tetrahydrofuran). The filtrate was concentrated in vacuo, triturated with petroleum ethers (30°-60°), and recrystallized from ether/petroleum ethers (2 crops) to afford 1.72 g (58%) of colorless solid; mp 94.5°-96.5° C.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2(O)[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]3=[N:17][CH2:18][CH2:19][N:9]23)=[CH:4][CH:3]=1>CC(O)=O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]3=[N:17][CH:18]=[CH:19][N:9]23)=[CH:4][CH:3]=1
Reactant: OC1(c2ccc(Br)cc2)c2ccccc2C2=NCCN21
Solvent: CC(=O)O
Product: Brc1ccc(C2c3ccccc3-c3nccn32)cc1
Temperature: 25 °C

Procedure:
A solution of 5-(4-bromophenyl)-2,5-dihydro-3H-imidazo[2,1-a]isoindol-5-ol (20.5 g) in AcOH (210 mL) was heated at 125° C. under nitrogen for 6.5 h. The reaction mixture was the cooled to room temperature and concentrated. The resulting residue was partitioned between EtOAc and saturated aqueous NaHCO3 solution. Aqueous layer was extracted with EtOAc (2×). Combined organic layers were washed with brine, dried over Na2SO4 and concentrated. Flash chromatography using a linear gradient of 0-4% MeOH in EtOAc-hexanes (1:1, v/v) afforded title compound as a light yellow solid. Mass. found (M+H)+, 311.0.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7](=[O:20])[C:8]#[C:9]C2(O[Si](C)(C)C)CCCC2)=[CH:3][CH:2]=1.CC1C=CC(S(O)(=O)=O)=CC=1>C(Cl)Cl.O>[N:1]1[CH:6]=[CH:5][C:4]([C:7](=[O:20])[C:8]#[CH:9])=[CH:3][CH:2]=1
Reactant: C[Si](C)(C)OC1(C#CC(=O)c2ccncc2)CCCC1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: ClCCl
Product: C#CC(=O)c1ccncc1
Reaction time: 1 h
Yield: 84.3 %

Procedure:
To a stirred solution of 1-(pyridin-4-yl)-3-(1-(trimethylsilyloxy)cyclopentyl) prop-2-yn-1-one (1.1 g, 3.8 mmol) in DCM (15 mL) was added PTSA (0.87 g, 4.6 mmol) at RT and the reaction mixture was stirred for 1 h. The reaction mixture was diluted with water (2 mL), the organic layer was washed with a saturated NaHCO3 solution, water, dried over Na2SO4, filtered and then concentrated in vacuo to afford 341-hydroxycyclopentyl)-1-(pyridin-4-yl) prop-2-yn-1-one (0.42 g, 51%) as an oil.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([N:17]2[CH2:22][CH2:21][CH2:20][N:19](CC(O)=O)[C:18]2=[O:27])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[K+].BrCC(OC(C)(C)C)=O>O1CCCC1.ClCCl.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][CH:14]([N:17]2[CH2:22][CH2:21][CH2:20][NH:19][C:18]2=[O:27])[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)CN1CCCN(C2CCN(C(=O)OCc3ccccc3)CC2)C1=O
Agent: CC(C)(C)OC(=O)CBr
Agent: CC(C)(C)[O-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: ClCCl
Solvent: C1CCOC1
Product: O=C(OCc1ccccc1)N1CCC(N2CCCNC2=O)CC1
Reaction time: 0.58 h

Procedure:
1-Benzyloxycarbonyl-4-(3-carboxymethyl-2-oxoperhydropyrimidin-1-yl)piperidine. Potassium tert-butoxide (52 mL, 1 M in tert-butanol) was added to l-benzyloxycarbonyl-4-(2-oxoperhydropyrimidin-1-yl)piperidine (15.0 g), and the solution was stirred for 35 minutes. tert-Butyl bromoacetate (7.65 mL) was then added, and the mixture was stirred overnight. The reaction mixture was diluted with tetrahydrofuran (20 mL) and dichloromethane (10 mL) followed by the addition of tetrabutylammonium iodide (1.74 g), potassium tert-butoxide (52 mL, 1 M in tert-butanol), and tert-butyl bromoacetate (7.65 mL). After being stirred overnight, the reaction mixture was diluted with dichloromethane and washed with water. The separated organic layer was dried, evaporated to an oil, and dissolved in 1 N hydrochloric acid (700 mL), tetrahydrofuran (200 mL), and methanol (200 mL). After being stirred overnight, the reaction mixture was concentrated in vacuo to remove the organic solvents. The resulting aqueous solution was extracted with dichloromethane, acidified with 2 N hydrochloric acid to a pH of 2, and extracted with dichloromethane. The first organic extract was concentrated to give unreacted 1-benzyloxycarbonyl-4-(2-oxoperhydropyrimidin-1-yl)piperidine (7.0 g). The second organic extract was washed with water, dried, and evaporated. The crude product was triturated from ether and filtered to give the title compound as a white solid (8.3 g); MS: m/z=376(M+1); NMR (CDCl3): 7.35 (m,5), 5.12 (s,2), 4.48 (m,1), 4.28 (m,2), 4.02 (s,2), 3.35 (m,2), 3.18 (m,2), 2.87 (m,2), 1.97 (m,2), 1.65 (m,4).
Reaction SMILES: [CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]([NH:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([N+:17]([O-])=O)[CH:12]=2)=[O:8])[CH:3]=1.O.O.[Sn](Cl)(Cl)(Cl)Cl.Cl>O1CCCC1.C(OCC)(=O)C>[CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]([NH:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([NH2:17])[CH:12]=2)=[O:8])[CH:3]=1
Reactant: Cc1cc(C(=O)NCc2cccc([N+](=O)[O-])c2)no1
Agent: Cl
Agent: Cl[Sn](Cl)(Cl)Cl
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Solvent: O
Product: Cc1cc(C(=O)NCc2cccc(N)c2)no1
Temperature: 25 °C
Reaction time: 18 h
Yield: 86.5 %

Procedure:
To a solution containing 260 mg (1.00 mmol) of N-(5-methylisoxaz-3-oyl)-3-nitrobenzylamine in 20 mL of tetrahydrofuran was added 674 mg (3.00 mmol) of tin chloride dihydrate, followed by 2 ml of concentrated hydrochloric acid. The reaction was stirred at room temperature for 18 hours and then diluted with 100 mL of ethyl acetate. The organic solution was washed with saturated aqueous sodium bicarbonate, dried over sodium sulfate, filtered, and concentrated to give 200 mg (86%) of the title compound as a yellow foam. MS(FD) m/z 231 (M+).
Reaction SMILES: Cl.[Cl:2][C@@H:3]([C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=1)[CH2:4][CH2:5][NH:6][CH:7]([C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:12]=[CH:11][CH:10]=1)[CH3:8].C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[CH3:8][C@@H:7]([NH:6][CH2:5][CH2:4][CH2:3][C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:26])([F:27])[F:28])[CH:20]=1)[C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=12.[ClH:2]
Reactant: CC(NCC[C@@H](Cl)c1cccc(C(F)(F)F)c1)c1cccc2ccccc12
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Product: C[C@@H](NCCCc1cccc(C(F)(F)F)c1)c1cccc2ccccc12
Temperature: 20 °C
Yield: 82.6 %

Procedure:
(R)-3-chloro-N-(1-(naphthalen-1-yl)ethyl)-3-(3-(trifluoromethyl)phenyl)propan-1-amine hydro-chloride (X) (15.0 g, 35.021 mmol) is suspended in toluene (90 ml) at 15°-20° C. and sat. aq. sodium bicarbonate (75.6 g, X72 mmol) is charged drop-wise, under vigorous stirring, until pH=8-9 of the aqueous layer. The mixture is layered upon standing few minutes and then the organic phase is separated, washed with water (2×75 ml) and transferred into an autoclave. 5% Palladium on carbon (50% moisture content) is added (0.373 g, 0.088 mmol), followed by methanol (15 ml), the mixture is exposed to inert atmosphere, then pressurized with 100 kPa hydrogen gas, upon stirring at 20° C. Hydrogen pressure is maintained until positive IPC (via HPC, about 4-5 hrs), then the reaction mixture is filtered through a Celite® pad. Methanol is distilled off the filtered solution and isopropyl acetate (IPAC) (90 ml) is added. The resulting suspension is heated up to 70° C. and stirred for 30 minutes, then cooled down slowly to 0° C. Cinacalcet hydrochloride is isolated as a white powder upon filtration, washing with IPAC (2×15 ml) and exsiccation at 60*-65° C. under vacuum (11.4 g, 28.944 mmol; yield: 82.6%).
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[C:8]([C:9]([OH:11])=O)=[N:7][CH:6]=[CH:5][N:4]=1.[Cl:14][C:15]1[CH:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:16]=1[CH2:22][CH:23]([NH2:25])[CH3:24].Cl.C(N=C=NCCCN(C)C)C.O>CN(C)C1C=CN=CC=1.C(Cl)(Cl)Cl>[Cl:14][C:15]1[CH:20]=[C:19]([Cl:21])[CH:18]=[CH:17][C:16]=1[CH2:22][CH:23]([NH:25][C:9]([C:8]1[C:3]([C:2]([F:1])([F:13])[F:12])=[N:4][CH:5]=[CH:6][N:7]=1)=[O:11])[CH3:24]
Reactant: O=C(O)c1nccnc1C(F)(F)F
Reactant: CC(N)Cc1ccc(Cl)cc1Cl
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClC(Cl)Cl
Solvent: O
Product: CC(Cc1ccc(Cl)cc1Cl)NC(=O)c1nccnc1C(F)(F)F
Temperature: 25 °C
Reaction time: 12 h
Yield: 63.1 %

Procedure:
To a solution of 2-trifluoromethylpyrazine-3-carboxylic acid (0.25 g, 1.3 mmol), [2-(2,4-dichlorophenyl)-1-methylethyl]amine (0.27 g, 1.3 mmol) and 4-dimethylaminopyridine (0.19 g, 1.6 mmol) in chloroform (10 ml) was added 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.3 g, 1.6 mmol) and the mixture was stirred at room temperature for 12 hrs. After adding water and chloroform, the mixture was partitioned, and the organic layer was washed successively with water and saturated brine and dried over anhydrous sodium sulfate. The mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to give a desired compound (yield; 0.31 g, 63%).
Reaction SMILES: CO[C:3]([C:5]1[O:9][N:8]=[C:7]([O:10][CH2:11][C:12]2[C:13]([C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)=[N:14][O:15][C:16]=2[CH2:17][OH:18])[CH:6]=1)=[O:4].[NH2:26][CH:27]1[CH2:32][CH2:31][O:30][CH2:29][CH2:28]1>>[O:30]1[CH2:31][CH2:32][CH:27]([NH:26][C:3]([C:5]2[O:9][N:8]=[C:7]([O:10][CH2:11][C:12]3[C:13]([C:19]4[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=4)=[N:14][O:15][C:16]=3[CH2:17][OH:18])[CH:6]=2)=[O:4])[CH2:28][CH2:29]1
Reactant: COC(=O)c1cc(OCc2c(-c3ccc(F)cc3)noc2CO)no1
Reactant: NC1CCOCC1
Product: O=C(NC1CCOCC1)c1cc(OCc2c(-c3ccc(F)cc3)noc2CO)no1
Yield: 46 %

Procedure:
As described for example 43 g, 3-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-ylmethoxy]-isoxazole-5-carboxylic acid methyl ester (100 mg, 0.29 mmol) was converted, using 4-aminotetrahydropyran instead of isopropylamine, to the title compound (55 mg, 46%) which was obtained as a white solid after purification by chromatography (silica, dichloromethane:methanol=1:0 to 9:1). MS: m/e=416.1 [M−H]−.
Reaction SMILES: [CH2:1]([CH:9]1[CH2:14][C:13](=[O:15])[O:12][C:10]1=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[CH2:16]([OH:23])[C:17]([NH2:22])([CH2:20][OH:21])[CH2:18]O.N#N>>[OH:21][CH2:20][C:17]1([CH2:16][OH:23])[CH2:18][O:15][C:13]([CH2:14][CH:9]([C:10]2[O:12][CH2:18][C:17]([CH2:20][OH:21])([CH2:16][OH:23])[N:22]=2)[CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])=[N:22]1
Reactant: CCCCCCCCC1CC(=O)OC1=O
Reactant: NC(CO)(CO)CO
Agent: N#N
Product: CCCCCCCCC(CC1=NC(CO)(CO)CO1)C1=NC(CO)(CO)CO1
Yield: 100 %

Procedure:
10 parts n-octylsuccinic anhydride and 12 parts tris(hydroxymethyl)aminomethane were heated neat 3 hrs. at 180° C. under a rapid flow of N2. The product was obtained as a colorless glass in 100% yield. The following spectral properties confirm the structure shown below: ir (neat) 3300 (OH), 1600 (C=N); nmr (CDCl3) δ 4.40 (broad s, 4.0 H, 2 CH2 's in rings), δ 4.25 (broad s, 3.7 H, 4 OH, addition of D2O eliminates peak), δ 3.55 (broadened 10 Hz AB, 7.2 H, 4 CH2O), δ 2.5 (broad s, 3.0 H, CH--CH), δ 1.4 (broad s with t shoulder at 0.9, 17 H, n-C8H17).
Reaction SMILES: [C@@H:1]1([N:9]2[CH:16]=[CH:15][C:13]([NH2:14])=[N:12][C:10]2=[O:11])[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3](O)[CH2:2]1.[OH-].[Na+].C(O)(=O)C.CC(C)([O-])C.[K+]>C(O)C.CS(C)=O>[C@@H:1]1([N:9]2[CH:16]=[CH:15][C:13]([NH2:14])=[N:12][C:10]2=[O:11])[O:8][C@H:5]([CH2:6][OH:7])[CH:3]=[CH:2]1
Reactant: Nc1ccn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)n1
Agent: CC(C)(C)[O-]
Agent: [K+]
Agent: [Na+]
Solvent: CCO
Solvent: CC(=O)O
Solvent: CS(C)=O
Product: Nc1ccn([C@H]2C=C[C@@H](CO)O2)c(=O)n1

Procedure:
Namely, 2',3'-dideoxycytidine can be obtained according to the method of Horwitz et al in a way that N-benzoyl-2'-deoxy-3',5'-di-0-mesylcytidine derivable from 2'-deoxycytidine is refluxed with aqueous solution of sodium hydroxide in ethanol, then this is treated with dilute acetic acid, and further allowed to react with potassium tert-butoxide in dimethyl sulfoxide to obtain 2',3'-dideoxy-2',3'-didehydrocytidine, which is hydrogenated (J. Org. Chem., 32, 817, 1967).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6].[C:13]1(B(O)O)[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[O:1]([C:2]1[CH:3]=[C:4]([CH:10]=[CH:11][CH:12]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: OB(O)c1ccccc1
Reactant: CCOC(=O)c1cccc(O)c1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: c1ccncc1
Solvent: ClCCl
Product: CCOC(=O)c1cccc(Oc2ccccc2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 76.4 %

Procedure:
A mixture of ethyl 3-hydroxybenzoate (0.200 g; 1.20 mmol), benzeneboronic acid (0.294 g; 2.41 mmol), copper acetate (0.437 g; 2.41 mmol) and pyridine (0.195 mL; 2.42 mmol) in dichloromethane (8 mL) was stirred at room temperature overnight. The reaction mixture was filtered and concentrated in vacuo. The crude mixture was purified by flash chromatography on silica gel (eluent 5 to 35% ethyl acetate in heptane) to yield 0.222 g (76%) of the title compound as a colourless oil.
Reaction SMILES: [O:1]([P:8]([O:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)([CH:10]=[CH:11][C@H:12]1[O:32][C@H:31]([CH2:33][O:34]CC2C=CC=CC=2)[C@@H:22]([O:23]CC2C=CC=CC=2)[C@@H:13]1[O:14]CC1C=CC=CC=1)=[O:9])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>[Pd].CO.C(O)(=O)C>[O:1]([P:8]([O:42][C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1)([CH2:10][CH2:11][C@H:12]1[O:32][C@H:31]([CH2:33][OH:34])[C@@H:22]([OH:23])[C@@H:13]1[OH:14])=[O:9])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=P(C=C[C@H]1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1OCc1ccccc1)(Oc1ccccc1)Oc1ccccc1
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CO
Product: O=P(CC[C@H]1O[C@H](CO)[C@@H](O)[C@@H]1O)(Oc1ccccc1)Oc1ccccc1

Procedure:
According to Flowchart C, 2,5-anhydro-D-mannose 24, is protected as the dimethyl acetal 25 which is reacted with sodium hydride in dimethylformamide, followed by benzyl bromide giving 2,5-anhydro-3,4,6-tris-O-(phenylmethyl)-D-mannose, dimethyl acetal 26. Compound 26 is treated with tetrafluoroboric acid in acetonitrile giving 2,5-anhydro-3,4,6-tris-O-(phenylmethyl)-D-mannose 27 which is reacted with diphenyl triphenylphosphoranylidenemethylphosphonate in toluene at reflux, giving 3,6-anhydro-1,2-dideoxy-1-(diphenoxyphosphinyl)-4,5,7-tris-O-(phenylmethyl)-D-manno-hept-1-enitol 28. Compound 28 is hydrogenated over palladium on carbon in methanol and acetic acid, giving 3,6-anhydro-1,2-dideoxy-1-(diphenoxyphosphinyl)-D-manno-heptitol 29, which is reacted with diphenyl chlorophosphate in pyridine, giving 3,6-anhydro-1,2-dideoxy-1-(diphenoxyphosphinyl)-D-manno-heptitol, 7-(diphenyl phosphate) 30, which is then hydrogenated with platinum oxide, giving the product 3,6-anhydro-1,2-dideoxy-1-phosphono-D-manno-heptitol, 7-(dihydrogen phosphate) 31. ##STR11##
Reaction SMILES: [N+:1]([CH:4]=[C:5](SC)[NH:6][CH2:7][CH2:8][S:9][CH2:10][C:11]1[NH:15][CH:14]=[N:13][C:12]=1[CH3:16])([O-:3])=[O:2].[NH2:19][CH2:20][CH2:21][S:22][CH2:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=1>>[N+:1]([CH:4]=[C:5]([NH:19][CH2:20][CH2:21][S:22][CH2:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][N:26]=1)[NH:6][CH2:7][CH2:8][S:9][CH2:10][C:11]1[NH:15][CH:14]=[N:13][C:12]=1[CH3:16])([O-:3])=[O:2]
Reactant: CSC(=C[N+](=O)[O-])NCCSCc1[nH]cnc1C
Reactant: NCCSCCc1ccccn1
Product: Cc1nc[nH]c1CSCCNC(=C[N+](=O)[O-])NCCSCCc1ccccn1

Procedure:
Reaction of 1-nitro-2-methylthio-2-[2-((4-methyl-5-imidazolyl)methylthio)ethylamino]ethylene with 2-[2-(2-aminoethyl)thioethyl]pyridine according to the procedure of Example 1(a)(ii) yields the title compound.
Reaction SMILES: [F:1][C:2]1([F:29])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[NH:11][C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([O:19][CH:20]2[CH2:25][CH2:24][N:23]([CH:26]([CH3:28])[CH3:27])[CH2:22][CH2:21]2)=[CH:14][CH:13]=3)=[O:9])[CH2:4][CH2:3]1.[CH3:30][O:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1B(O)O>>[F:29][C:2]1([F:1])[CH2:7][CH2:6][N:5]([C:8]([C:10]2[N:11]([C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][C:32]=3[O:31][CH3:30])[C:12]3[C:17]([CH:18]=2)=[CH:16][C:15]([O:19][CH:20]2[CH2:25][CH2:24][N:23]([CH:26]([CH3:27])[CH3:28])[CH2:22][CH2:21]2)=[CH:14][CH:13]=3)=[O:9])[CH2:4][CH2:3]1
Reactant: COc1ccccc1B(O)O
Reactant: CC(C)N1CCC(Oc2ccc3[nH]c(C(=O)N4CCC(F)(F)CC4)cc3c2)CC1
Product: COc1ccccc1-n1c(C(=O)N2CCC(F)(F)CC2)cc2cc(OC3CCN(C(C)C)CC3)ccc21

Procedure:
In analogy to the procedure described for the synthesis of example 6, the title compound was synthesized from (4,4-difluoro-piperidin-1-yl)-[5-(1-isopropyl-piperidin-4-yloxy)-1H-indol-2-yl]-methanone (intermediate 1) and 2-methoxyphenylboronic acid. The title compound was obtained in 7% yield as yellow oil. MS (m/e): 512.3 (MH+, 100%).