Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:3]1[CH:4]=[C:5]2[C:14](=[C:15]3[C:20]=1[CH:19]=[CH:18][CH:17]=[CH:16]3)[CH:13]=[CH:12][C:11]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]2=1)[CH3:2].C1C2C=CC3C(=CC([CH:39]=[O:40])=C4C=3C=CC=C4)C=2C=CC=1>C(Cl)Cl>[CH2:1]([C:3]1[C:20]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:14]2[C:5](=[C:6]3[C:11](=[C:12]([CH:39]=[O:40])[CH:13]=2)[CH:10]=[CH:9][CH:8]=[CH:7]3)[CH:4]=1)[CH3:2]
Reactant: O=Cc1cc2c3ccccc3ccc2c2ccccc12
Reactant: CCc1cc2c3ccccc3ccc2c2ccccc12
Solvent: ClCCl
Product: CCc1cc2c3ccccc3c(C=O)cc2c2ccccc12
Yield: 76 %

Procedure:
6-Ethylchrysene (Cambridge Chemical, Inc., 60 g, 0.234 mol) was formylated according to the procedure outlined in 1A, except that CH2Cl2 ( 1 L) was used as the reaction solvent. The crude material was chromatographed on a plug of SiO2 (1 kg) using PhCH3 as the eluting solvent, afforded 50.38 g (76%) of 12-ethyl-6-chrysenecarbaldehyde mp 138°-139°, (C,H).
Reaction SMILES: [C:1]1([C:7]2[O:8][CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([NH2:18])=[CH:14][CH:13]=3)[N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.N1C=CC=CC=1.[Cl:25][C:26]1[CH:34]=[C:33]([Cl:35])[CH:32]=[CH:31][C:27]=1[C:28](Cl)=[O:29]>ClCCl>[Cl:25][C:26]1[CH:34]=[C:33]([Cl:35])[CH:32]=[CH:31][C:27]=1[C:28]([NH:18][C:15]1[CH:14]=[CH:13][C:12]([C:10]2[N:11]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[O:8][CH:9]=2)=[CH:17][CH:16]=1)=[O:29]
Reactant: O=C(Cl)c1ccc(Cl)cc1Cl
Reactant: Nc1ccc(-c2coc(-c3ccccc3)n2)cc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=C(Nc1ccc(-c2coc(-c3ccccc3)n2)cc1)c1ccc(Cl)cc1Cl
Temperature: 25 °C
Reaction time: 1 h
Yield: 19.3 %

Procedure:
to a solution of 4-(2-phenyloxazol-4-yl)benzenamine (299 mg, 1266 μmol) and pyridine (500 μl, 6131 μmol) dissolved in 4 mL dichloromethane at room temperature was added 2,4-dichlorobenzoyl chloride (177 μl, 1266 μmol) all at once. The reaction was stirred at room temperature for 1 hour then concentrated under reduced pressure, taken up in heptane and concentrated again under reduced pressure to afford a yellow solid. The solid was partitioned between dichloromethane and saturated aqueous sodium bicarbonate solution. The organic extract was dried over magnesium sulfate, filtered and the filtrate concentrated under reduced pressure to afford a yellow solid. The product was purified by preparative reversed phase HPLC. Combination of fractions containing product were concentrated under reduced pressure to afford a colorless solid (100 mg, 19%). ESI+ m/z=409.0 [MH]+.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4]Br.[C:6]([C:8]1[CH:33]=[CH:32][C:11]([C:12]([NH:14][C:15]2[CH:16]=[CH:17][C:18]([CH3:31])=[C:19]([NH:21][C:22](=[O:30])[C:23]3[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=3)[CH:20]=2)=[O:13])=[CH:10][CH:9]=1)#[N:7].C(=O)([O-])[O-].[K+].[K+].O>CN(C=O)C>[C:6]([C:8]1[CH:9]=[CH:10][C:11]([C:12]([NH:14][C:15]2[CH:16]=[CH:17][C:18]([CH3:31])=[C:19]([NH:21][C:22](=[O:30])[C:23]3[CH:28]=[CH:27][C:26]([O:29][CH2:4][CH2:3][O:2][CH3:1])=[CH:25][CH:24]=3)[CH:20]=2)=[O:13])=[CH:32][CH:33]=1)#[N:7]
Reactant: COCCBr
Reactant: Cc1ccc(NC(=O)c2ccc(C#N)cc2)cc1NC(=O)c1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COCCOc1ccc(C(=O)Nc2cc(NC(=O)c3ccc(C#N)cc3)ccc2C)cc1
Temperature: 80 °C

Procedure:
2-Bromoethyl methyl ether (0.023 ml) was added to a suspension of N-[5-(4-cyanobenzamido)-2-methylphenyl]-4-hydroxybenzamide (0.06 g) and potassium carbonate (0.045 g) in DMF (3 ml) and the reaction mixture was stirred and heated to 80° C. for 5 hours. The mixture was poured into water and extracted with ethyl acetate. The organic extract was dried (MgSO4) and evaporated. The residue was triturated under diethyl ether and the resultant solid was isolated and dried under vacuum at 55° C. There was thus obtained the title compound (0.038 g); NMR Spectrum: (DMSOd6) 2.19 (s, 3H), 3.27 (s, 3H), 3.66 (s, 2H), 4.17 (m, 2H), 7.04 (d, 2H), 7.24 (d, 1H), 7.57 (d, 1H), 7.82 (s, 1H), 7.96 (m, 4H), 8.1 (d, 2H), 9.71 (s, 1H), 10.44 (s, 1H); Mass Spectrum: M−H− 428.
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][CH:5]([CH2:8][NH:9][C:10]2[S:11][C:12]3[CH2:19][CH2:18][O:17][C:16]4[CH:20]=[CH:21][CH:22]=[CH:23][C:15]=4[C:13]=3[N:14]=2)[CH2:4][CH2:3]1.[C:24](Cl)(=[O:26])[CH3:25].O>N1C=CC=CC=1.C(N(C(C)C)CC)(C)C>[N:14]1[C:13]2[C:15]3[CH:23]=[CH:22][CH:21]=[CH:20][C:16]=3[O:17][CH2:18][CH2:19][C:12]=2[S:11][C:10]=1[NH:9][CH2:8][CH:5]1[CH2:6][CH2:7][CH:2]([NH:1][C:24](=[O:26])[CH3:25])[CH2:3][CH2:4]1
Reactant: CC(=O)Cl
Reactant: NC1CCC(CNc2nc3c(s2)CCOc2ccccc2-3)CC1
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: c1ccncc1
Product: CC(=O)NC1CCC(CNc2nc3c(s2)CCOc2ccccc2-3)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 72.3 %

Procedure:
To a stirred solution of N2-[(4-aminocyclohexyl)methyl]-4,5-dihydrobenzo[2,3]oxepino[4,5-d][1,3]thiazol-2-amine (0.600 g, 1.49 mmol) in anhydrous pyridine (3 ml) and diisopropylethylamine was added acetyl chloride (0.130 ml, 1.83 mmol) dropwise. The solution was stirred for 30 minutes at room temperature and then poured into water (60 ml). The mixture was extracted with EtOAc, and the organic phase evaporated to afford a residue that was chromatographed on silica-gel eluting with EtOAc to yield 72% (400 mg) of the desired product as a light yellow solid: m.p. 69-72° C. 1H-NMR (CDCl3) δ 1.11 (4H, m), 1.60 (1H, broad), 1.73 (1H, broad), 1.83 (2H, m), 1.95 (3H, s), 2.05 (2H, m), 3.14 (4H, m), 3.73 (1H, broad), 4.33 (2H, t, J=4.9 Hz), 5.30 (1H, broad), 7.00 (1H, dd, J=0.9 Hz, 7.7 Hz), 7.12 (2H, m), 8.24 (1H, dd, J=0.9 Hz, 7.8 Hz). ESIMS m/z=372 (MH+).
Reaction SMILES: [N+](=[CH2:3])=[N-].N(CNC(N)=O)=O.[OH-].[K+].[Cl:13][C:14]1[N:22]=[CH:21][CH:20]=[CH:19][C:15]=1[C:16]([OH:18])=[O:17]>C(OCC)C>[Cl:13][C:14]1[N:22]=[CH:21][CH:20]=[CH:19][C:15]=1[C:16]([O:18][CH3:3])=[O:17]
Reactant: C=[N+]=[N-]
Reactant: O=C(O)c1cccnc1Cl
Agent: NC(=O)NCN=O
Agent: [K+]
Agent: [OH-]
Solvent: CCOCC
Product: COC(=O)c1cccnc1Cl
Reaction time: 8 h

Procedure:
To a cold diethyl ether solution containing about 2.8 g. (0.067 mole) of diazomethane generated from 10 g. of nitrosomethyl urea and 30 cc. of 40% potassium hydroxide (see Organic Synthesis, Col. 1, Vol. II, page 166) was added in portions 9.45 g. (0.06 mole) of 2-chloronicotinic acid. After the evolution of nitrogen had ceased the reaction mixture was allowed to stand at room temperature overnight. The solvent was removed in a rotary evaporator leaving 2-chloro-nicotinic acid, methyl ester as a residual oil whose infrared spectrum indicated no OH absorption was present. The oil was used directly in the next step. The above compound has also been described by F. G. Mann and J. A. Reid, J. Chem. Soc., 1952, 2057.
Reaction SMILES: C([O:4][C:5]1[C:22]2[C@@H:21]3[C@H:12]([C@H:13]4[C@@:17]([CH2:19][CH2:20]3)([CH3:18])[C:16](=[O:23])[CH2:15][CH2:14]4)[CH2:11][CH2:10][C:9]=2[CH:8]=[C:7]([O:24][CH3:25])[CH:6]=1)(=O)C.O.Cl>[OH-].[K+]>[OH:4][C:5]1[C:22]2[C@@H:21]3[C@H:12]([C@H:13]4[C@@:17]([CH2:19][CH2:20]3)([CH3:18])[C:16](=[O:23])[CH2:15][CH2:14]4)[CH2:11][CH2:10][C:9]=2[CH:8]=[C:7]([O:24][CH3:25])[CH:6]=1
Reactant: COc1cc2c(c(OC(C)=O)c1)[C@H]1CC[C@]3(C)C(=O)CC[C@H]3[C@@H]1CC2
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: COc1cc(O)c2c(c1)CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12

Procedure:
A solution of 1-acetoxy-3-methoxyestra-1,3,5(10)-trien-17-one (7.0 g, 20.5 mM) in 150 ml of 5% anhydrous methanolic potassium hydroxide is stirred at room temperature for 1 hr. The resulting dark purple solution is added to 700 ml of cold H2O and acidified with 10% HCl to give a white solid which is filtered and recrystallized from acetone-H2O to give 1-hydroxy-3-methoxyestra-1,3,5(10)-trien-17-one, yield 5.4 g (88%), m.p. 220°-222°. Further recrystallization from ethyl acetate gives a product with a m.p. 226°-229°.
Reaction SMILES: S(=O)(=O)(O)O.[CH3:6][C:7]1[CH:12]=[C:11]([CH3:13])[CH:10]=[C:9]([C:14](=[O:23])[C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH2:16])[C:8]=1[OH:24]>>[CH3:13][C:11]1[CH:12]=[C:7]([CH3:6])[C:8]([OH:24])=[C:9]2[C:10]=1[CH2:16][CH:15]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:14]2=[O:23]
Reactant: C=C(C(=O)c1cc(C)cc(C)c1O)c1ccccc1
Agent: O=S(=O)(O)O
Product: Cc1cc(C)c2c(c1O)C(=O)C(c1ccccc1)C2
Temperature: 0 °C
Yield: 70.3 %

Procedure:
Into 15 ml of concentrated sulfuric acid, under ice-cooled condition with stirring, 3.0 g of 2,4-dimethyl-6-(2-phenylacryloyl)phenol was added gradually, then the whole mixture was stirred at room temperature for 1 hour. The reaction mixture was poured in 100 g of ice and extracted with 200 ml of methylene chloride. The extract was washed with water and dried with anhydrous magnesium sulfate, then was concentrated under a reduced pressure to obtain the residue. The residue was recrystallized from ethanol to obtain 2.11 g of 2,3-dihydro-4,6-dimethyl-2-phenyl-7-hydroxy-1H-inden-1-one.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:12]=[CH:13][C:14]=1[O:15][C@@H:16]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH3:17])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([O-])=O.[H][H]>[Pt]=O.C(O)C>[NH2:1][C:4]1[CH:5]=[C:6]([CH:12]=[CH:13][C:14]=1[O:15][C@@H:16]([CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH3:17])[C:7]([O:9][CH2:10][CH3:11])=[O:8]
Reactant: CCCCCC[C@@H](C)Oc1ccc(C(=O)OCC)cc1[N+](=O)[O-]
Reactant: [H][H]
Agent: O=[Pt]
Solvent: CCO
Product: CCCCCC[C@@H](C)Oc1ccc(C(=O)OCC)cc1N
Yield: 97.3 %

Procedure:
A mixture of 1.7 g of ethyl 3-nitro-4-[(R)-2-octyloxy]benzoate and 50 ml of ethyl alcohol was hydrogenated over 0.1 g of platinum(II) oxide until the uptake of hydrogen had finished. The catalyst was filtered off and the filtrate was concentrated. Chromatography of the residue on silica gel with dichloromethane gave 1.5 g of ethyl 3-amino-4-[(R)-2-octyloxy]benzoate as a colourless oil.
Reaction SMILES: [CH:1]1([C:6]([C:8]2[CH:13]=[C:12]([O:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=3)[CH:11]=[CH:10][C:9]=2[C:24]2[CH:29]=[C:28]([O:30][CH3:31])[CH:27]=[CH:26][C:25]=2[F:32])=[O:7])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:33][Si]([N-][Si](C)(C)C)(C)C.[Li+].IC.[Cl-].[NH4+]>C1COCC1>[F:32][C:25]1[CH:26]=[CH:27][C:28]([O:30][CH3:31])=[CH:29][C:24]=1[C:9]1[CH:10]=[CH:11][C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][C:19]([O:22][CH3:23])=[CH:18][CH:17]=2)=[CH:13][C:8]=1[C:6]([C:1]1([CH3:33])[CH2:5][CH2:4][CH2:3][CH2:2]1)=[O:7]
Reactant: COc1ccc(COc2ccc(-c3cc(OC)ccc3F)c(C(=O)C3CCCC3)c2)cc1
Reactant: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Cl-]
Agent: [Li+]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CI
Product: COc1ccc(COc2ccc(-c3cc(OC)ccc3F)c(C(=O)C3(C)CCCC3)c2)cc1
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
To a solution of cyclopentyl(2′-fluoro-5′-methoxy-4-((4-methoxybenzyl)oxy)biphenyl-2-yl)methanone (178 mg) in THF (5 mL) was added a solution (1 M, 0.82 mL) of lithium bis(trimethylsilyl)amide in THF at 0° C., and the mixture was stirred at 0° C. for 10 min. To the reaction mixture was added iodomethane (0.26 mL), and the mixture was stirred at room temperature for 30 min. To the reaction mixture was added saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (128 mg) as a colorless oil.
Reaction SMILES: [CH:1]1[C:14]2[CH2:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[O:6][C:5]=2[CH:4]=[CH:3][CH:2]=1.[Na].[H-].[Na+].[CH3:18][N:19]([CH2:23][CH2:24]Cl)[CH2:20][CH2:21][Cl:22].Cl>CS(C)=O.CCOCC.O>[ClH:22].[CH3:18][N:19]1[CH2:23][CH2:24][C:13]2([C:12]3[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=3[O:6][C:5]3[C:14]2=[CH:1][CH:2]=[CH:3][CH:4]=3)[CH2:21][CH2:20]1
Reactant: c1ccc2c(c1)Cc1ccccc1O2
Reactant: CN(CCCl)CCCl
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Solvent: CCOCC
Product: CN1CCC2(CC1)c1ccccc1Oc1ccccc12
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of xanthene (9.1 g.) in dimethyl sulphoxide (75 ml.) is added dropwise over 20 minutes at room temperature to a solution of sodium methylsulphinylmethide [prepared in the usual way from sodium hydride (8 g. of a 60 % dispersion in mineral oil) and dimethyl sulphoxide (100 ml.)] with stirring in an atmosphere of nitrogen. The blood-red mixture is stirred at room temperature for a further 30 minutes, cooled to 0° C., and a solution of N-methyldi-(2-chloroethyl)amine (9.6 g.) in dimethyl sulphoxide (20 ml.) is then added dropwise during 15 minutes, keeping the temperature below 20° C. Water (500 ml.) is added to the now colourless mixture, and the mixture is extracted three times with ether. The combined ether extracts are dried over MgSO4, evaporated to dryness and the gummy residue (12.2 g.) is chromatographed on basic alumina (Brockmann Grade III), eluting with increasing concentrations of chloroform in light petroleum (b.p. 60-80° C.). Elution with 5% chloroform in light petroleum gives, on evaporation of the solvent, a gum which is dissolved in ether and treated with ethereal hydrochloric acid. The solid is recrystallised from ethanol-ether to give 1'-methylxanthene-9-spiro-4'-piperidine hydrochloride, m.p. 220°-222° C.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][C:3]([C:6]2[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=2)=[N:2]1.N1C=CC=CC=1.[N:18]1([C:24](Cl)=[O:25])[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1>O1CCCC1.CN(C1C=CN=CC=1)C>[O:21]1[CH2:22][CH2:23][N:18]([C:24]([N:1]2[CH:5]=[CH:4][C:3]([C:6]3[CH:7]=[N:8][CH:9]=[CH:10][CH:11]=3)=[N:2]2)=[O:25])[CH2:19][CH2:20]1
Reactant: O=C(Cl)N1CCOCC1
Reactant: c1cncc(-c2cc[nH]n2)c1
Agent: CN(C)c1ccncc1
Solvent: C1CCOC1
Solvent: c1ccncc1
Product: O=C(N1CCOCC1)n1ccc(-c2cccnc2)n1
Temperature: 80 °C

Procedure:
To a stirred solution of 3-(1H-pyrazol-3-yl)pyridine (0.435 g, 3 mmol) in tetrahydrofuran (15 ml) was added pyridine (0.367 ml, 4.50 mmol), DMAP (18.33 mg, 0.150 mmol). The solution was treated with 4-morpholinecarbonyl chloride (0.368 ml, 3.15 mmol). The reaction was heated to 80° C. for 20 hours. THF was removed by vacuum, the residue was partitioned between DCM and water. The organic phase was dried over MgSO4 and filtered. After evaporation the crude product was chromatographed in petroleumether:EtOAc=2:1. (Yield: 174 mg, 21%).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([O:11][CH2:12][C:13]([O:15]CC2C=CC=CC=2)=[O:14])[N:8]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:7]=1)=[O:5])[CH3:2]>C(OCC)(=O)C.[Pd]>[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([O:11][CH2:12][C:13]([OH:15])=[O:14])[N:8]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:7]=1)=[O:5])[CH3:2]
Reactant: CCOC(=O)c1cc(OCC(=O)OCc2ccccc2)n(-c2ccccc2)n1
Agent: [Pd]
Solvent: CCOC(C)=O
Product: CCOC(=O)c1cc(OCC(=O)O)n(-c2ccccc2)n1
Reaction time: 24 h

Procedure:
To a solution of 15.5 g 5-benzyloxycarbonylmethoxy-1-phenyl-1H-pyrazole-3-carboxylic acid ethyl ester in 100 ml ethyl acetate was added 1 g Pd/C (10%) and the resulting suspension stirred under an atmosphere of hydrogen (1 bar) for 24 h. The reaction mixture was filtered over a plug of Celite, washed with ethyl acetate and methanol giving the crude product after evaporation of the solvents. Yield: 9.5 g colorless platelets.
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[S:3]([O:6]S(C(F)(F)F)(=O)=O)(=[O:5])=[O:4].[Br:16][C:17]1[CH:22]=[C:21]([CH3:23])[C:20](O)=[C:19]([CH3:25])[CH:18]=1.N1C=CC=CC=1.Cl>C(Cl)Cl.C(OCC)(=O)C>[F:1][C:2]([F:15])([F:14])[S:3]([O:6][C:20]1[C:21]([CH3:23])=[CH:22][C:17]([Br:16])=[CH:18][C:19]=1[CH3:25])(=[O:5])=[O:4]
Reactant: Cc1cc(Br)cc(C)c1O
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Agent: Cl
Solvent: c1ccncc1
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: Cc1cc(Br)cc(C)c1OS(=O)(=O)C(F)(F)F
Temperature: 0 °C

Procedure:
Trifluoromethanesulfonic anhydride (1.004 mL) was added to an ice-cooled mixture of 4-bromo-2,6-dimethylphenol (1.00 g) and pyridine (0.482 mL) in methylene chloride (5 mL) with stirring. After being stirred for 10 minutes, the reaction mixture was poured into a mixture of 1 mol/L hydrochloric acid and ethyl acetate. The organic layer was separated, washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: diethyl ether/n-hexane=1/20) to afford 4-bromo-2,6-dimethylphenyl trifluoromethanesulfonate (1.439 g).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][CH:11]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[O:19][Si](C(C)C)(C(C)C)C(C)C)[N:10]([C:30]([C:32]3[C:37]([F:38])=[CH:36][C:35]([F:39])=[CH:34][C:33]=3[F:40])=[O:31])[N:9]=2)=[CH:4][CH:3]=1.FC1C=CC(C2SC(C3C=CC=C(OC)C=3O[Si](C(C)C)(C(C)C)C(C)C)N(C(C3C(F)=CC(F)=CC=3F)=O)N=2)=CC=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.Br[CH2:102][C:103]1[O:104][CH:105]=[CH:106][C:107]=1[C:108]([O:110][CH3:111])=[O:109]>>[CH3:111][O:110][C:108]([C:107]1[CH:106]=[CH:105][O:104][C:103]=1[CH2:102][O:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[CH:11]1[N:10]([C:30](=[O:31])[C:32]2[C:37]([F:38])=[CH:36][C:35]([F:39])=[CH:34][C:33]=2[F:40])[N:9]=[C:8]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=2)[S:12]1)=[O:109]
Reactant: CC(C)[Si](Oc1ccccc1C1SC(c2ccc(F)cc2)=NN1C(=O)c1c(F)cc(F)cc1F)(C(C)C)C(C)C
Reactant: COC(=O)c1ccoc1CBr
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: COc1cccc(C2SC(c3ccc(F)cc3)=NN2C(=O)c2c(F)cc(F)cc2F)c1O[Si](C(C)C)(C(C)C)C(C)C
Agent: [F-]
Product: COC(=O)c1ccoc1COc1ccccc1C1SC(c2ccc(F)cc2)=NN1C(=O)c1c(F)cc(F)cc1F
Reaction time: 0.25 h

Procedure:
[5-(4-Fluoro-phenyl)-2-(2-triisopropylsilanyloxy-phenyl)-[1,3,4]thiadiazol-3-yl]-(2,4,6-trifluoro-phenyl)-methanone (0.67 mmol), prepared as described for [5-(4-fluoro-phenyl)-2-(3-methoxy-2-triisopropylsilanyloxy-phenyl)-[1,3,4]thiadiazol-3-yl]-(2,4,6-trifluoro-phenyl)-methanone in example 3, is treated with tetrabutylammonium fluoride (1.0 M in THF) (1.3 mmol) at room temperature. After 15 minutes, methyl 2-(bromomethyl)-3-furoate (0.74 mmol) is added and the mixture is stirred for an additional 12 hours. The solvent is removed in vacuo and the residue is purified on silica to yield 2-{2-[5(4-fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-phenoxymethyl}-furan-3-carboxylic acid methyl ester as a yellow solid: LC/MS (ES+): 571.1 (M+1)+.
Reaction SMILES: [Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][N:8]([C@H:11]3[C@:15]([C:17]#[CH:18])([OH:16])[C@H:14]([O:19]C(=O)C4C=CC(C)=CC=4)[C@@H:13]([CH2:29][O:30]C(=O)C4C=CC(C)=CC=4)[O:12]3)[C:4]=2[N:5]=[CH:6][N:7]=1.C[O-].[Na+].Cl>CO.C(Cl)Cl>[Cl:1][C:2]1[C:3]2[CH:10]=[CH:9][N:8]([C@H:11]3[C@:15]([C:17]#[CH:18])([OH:16])[C@H:14]([OH:19])[C@@H:13]([CH2:29][OH:30])[O:12]3)[C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: C#C[C@@]1(O)[C@H](OC(=O)c2ccc(C)cc2)[C@@H](COC(=O)c2ccc(C)cc2)O[C@H]1n1ccc2c(Cl)ncnc21
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: C#C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1n1ccc2c(Cl)ncnc21
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
Crude intermediate (2R,3R,4R,5R)-2-(4-Chloro-pyrrolo[2,3-d]pyrimidin-7-yl)-4-(4-methylbenzoyloxy)-5-(4-methylbenzoyloxymethyl)-3-ethynyl-tetrahydro-furan-3-ol (434 mg, 0.74 mmol) is dissolved in MeOH (5 ml) and CH2Cl2 (5 ml). 30% sodium methoxide in methanol solution (1.38 ml, 7.4 mmol, 10 equiv.) is added and the mixture is stirred at room temperature for 15 mins. The mixture is neutralized to pH 7.0 by addition of 1N HCl solution and evaporated under vacuum to dry, purified by flash chromatography (CH2Cl2:MeOH=92:8) to yield (2R,3R,4R,5R)-2-(4-Chloro-pyrrolo[2,3-d]pyrimidin-7-yl)-3-ethynyl-5-hydroxymethyl-tetrahydrofuran-3,4-diol. 1H-NMR (CDCl3): δ 8.58 (s, 1H), 8.00 (d, 1H, J=3.9 Hz), 6.68 (d, 1H, J=3.9 Hz), 6.49 (s, 1H), 4.51 (d, 1H, J=9.0 Hz), 4.20-3.75 (m, 3H), 2.51 (s, 1H). ESI-MS: calcd. for C13H12ClN3O4 (309.05). found: 310.3.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([C:11]([OH:13])=O)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:14]([O:21][CH2:22][CH2:23][CH2:24][NH:25][CH2:26][CH2:27][OH:28])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.C(N(CC)C(C)C)(C)C.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([C:11](=[O:13])[N:25]([CH2:24][CH2:23][CH2:22][O:21][CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)[CH2:26][CH2:27][OH:28])[CH3:10])([CH3:2])([CH3:3])[CH3:4]
Reactant: C[C@H](NC(=O)OC(C)(C)C)C(=O)O
Reactant: OCCNCCCOCc1ccccc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: C[C@H](NC(=O)OC(C)(C)C)C(=O)N(CCO)CCCOCc1ccccc1
Yield: 66.6 %

Procedure:
A solution of N-(tert-butoxycarbonyl)-L-alanine (90 mg, 0.48 mmol), 2-(3-benzyloxy-propylamino)-ethanol (100 mg, 0.48 mg), N,N-diisopropylethylamine (185 mg, 1.43 mmol), 1-hydroxybenzotriazole (71 mg, 0.52 mmol), and N-ethyl-N′-(3-dimethylaminopropyl)carbodiimide hydrochloride (101 mg, 0.52 mmol) in N,N-dimethylformamide (2 ml) was stirred at room temperature for 18 h, then partitioned between 1 M aq. hydrochloric acid solution and ethyl acetate. The organic layer was dried (MgSO4), filtered, and evaporated. Chromatography (SiO2; heptane-ethyl acetate gradient) produced the title compound (121 mg, 67%). Colorless oil, MS (ISP)=381.4 (M+H)+.
Reaction SMILES: C([O:8][CH2:9][CH2:10][C:11]([CH:13]([CH2:23][CH2:24][CH2:25][CH:26]([O:32]CC1C=CC=CC=1)[CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20]([OH:22])=[O:21])=[O:12])C1C=CC=CC=1.[H][H]>C(O)C.[Pd]>[OH:8][CH2:9][CH2:10][C:11]([CH:13]([CH2:23][CH2:24][CH2:25][CH:26]([OH:32])[CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20]([OH:22])=[O:21])=[O:12]
Reactant: CCCCCC(CCCC(CCCCCCC(=O)O)C(=O)CCOCc1ccccc1)OCc1ccccc1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: CCCCCC(O)CCCC(CCCCCCC(=O)O)C(=O)CCO
Yield: 97 %

Procedure:
A magnetically stirred solution of 8-(3-benzyloxypropionyl)-12-benzyloxyheptadecanoic acid (2.37 g., 4.4 millimole) in ethanol (50 ml.) is subjected to hydrogenation at atmospheric pressure at 23° C. in the presence of a 10% palladium on charcoal catalyst (0.3 g.) for one hour. The hydrogen uptake is 2.4 ml. (100% theory). The catalyst is removed by filtration and the solvent is removed by evaporation in vacuo to give 8-(3-hydroxypropionyl)-12-hydroxyheptadecanoic acid . 1/3 chloroformate as a viscous, colorless liquid (1.55 g., 97% yield); pmr (CDCl3) δ 0.88 (3H, t), 2.03 (H,m), 2.32 (2H,t), 2.68 (2H,t, J=5.5 cps.), 3.65 (H, b.s.), 3.86 (2H,t, J=5.5 cps.), 5.50 (3H, exchangeable s) and 7.32 (1/3H,s).
Reaction SMILES: Cl.[N+:2]([C:5]1[CH:6]=[C:7]([NH:11][NH2:12])[CH:8]=[CH:9][CH:10]=1)([O-:4])=[O:3].[N:13]1[CH:18]=NC=N[CH:14]=1.C(=O)(O)[O-].[Na+]>C(O)C>[N+:2]([C:5]1[CH:6]=[C:7]([N:11]2[CH:18]=[N:13][CH:14]=[N:12]2)[CH:8]=[CH:9][CH:10]=1)([O-:4])=[O:3]
Reactant: NNc1cccc([N+](=O)[O-])c1
Reactant: c1ncncn1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Product: O=[N+]([O-])c1cccc(-n2cncn2)c1
Yield: 49.3 %

Procedure:
A mixture of 3-nitrophenylhydrazine hydrochloride (8.77 g) and 1,3,5-triazine (2.50 g) in ethanol (40 ml) was stirred under reflux for 4 hours. Then the mixture was poured into aqueous sodium bicarbonate and extracted with ethyl acetate twice. The combined organic phase was washed with aqueous sodium bicarbonate and brine, dried over magnesium sulfate and concentrated. The residue was chromatographed on silica gel column (hexane-ethyl acetate, 3:7) to give 1-(3-nitrophenyl)-1H-1,2,4-triazole (2.89 g) as a solid.