Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [ClH:1].[NH2:2][C:3]([NH2:5])=[NH:4].C[O-].[Na+].[C:9]1([C:19]2[CH:20]=[C:21]([CH:37]=[CH:38][CH:39]=2)[C:22](OCC(C)(NS(C(F)(F)F)(=O)=O)C)=[O:23])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:12][CH2:11][CH:10]=1.C(OCC)(=O)C>CN(C)C=O.O>[ClH:1].[C:9]1([C:19]2[CH:20]=[C:21]([CH:37]=[CH:38][CH:39]=2)[C:22]([NH:4][C:3]([NH2:5])=[NH:2])=[O:23])[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH2:12][CH2:11][CH:10]=1
Reactant: CC(C)(COC(=O)c1cccc(C2=CCCc3ccccc32)c1)NS(=O)(=O)C(F)(F)F
Reactant: N=C(N)N
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: N=C(N)NC(=O)c1cccc(C2=CCCc3ccccc32)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 58.6 %

Procedure:
To a solution of guanidine hydrochloride (0.87 g) in N,N-dimethylformamide (5 ml) was added sodium methoxide (1.6 ml, 28% in methanol) under nitrogen atmosphere. After being stirred for 30 minutes at room temperature, to the reaction mixture was added a solution of 2-methyl-2-trifluoromethylsulfonylaminopropyl 3-(3,4-dihydro-1-naphthyl)benzoate (0.59 g) in N,N-dimethylformamide (5 ml). After being stirred for 21 hours at room temperature, the reaction mixture was poured into a mixture of ethyl acetate and water. The organic layer was successively washed with brine and dried over magnesium sulfate. The solvent was evaporated in vacuo, and the residue was dissolved in ethyl acetate and crystallized from slight excess 4N-hydrogen chloride-ethyl acetate. The crystalline was triturated with diethyl ether to give [3-(3,4-dihydro-1-naphthyl)benzoyl]guanidine hydrochloride (0.25 g).
Reaction SMILES: C(OC([N:8](C(OC(C)(C)C)=O)[C:9]1[S:10][C:11]([C:14]2[CH:15]=[C:16]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:17]3[N:18]([CH:20]=[C:21]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[N:22]=3)[CH:19]=2)=[CH:12][N:13]=1)=O)(C)(C)C>C(O)(C(F)(F)F)=O>[NH2:8][C:9]1[S:10][C:11]([C:14]2[CH:15]=[C:16]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:17]3[N:18]([CH:20]=[C:21]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[N:22]=3)[CH:19]=2)=[CH:12][N:13]=1
Reactant: CCOC(=O)c1cn2cc(-c3cnc(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)s3)cc(-c3ccccc3)c2n1
Solvent: O=C(O)C(F)(F)F
Product: CCOC(=O)c1cn2cc(-c3cnc(N)s3)cc(-c3ccccc3)c2n1
Yield: 38.7 %

Procedure:
A solution of ethyl 6-(2-(bis(tert-butoxycarbonyl)amino)thiazol-5-yl)-8-phenyl-imidazo[1,2-a]pyridine-2-carboxylate (28 mg) in 3 ml of TFA was stirred at room temperature for 2 hours. The Solvent was evaporated and the residue made basic with NH4OH/MeOH/CH2Cl2 (1:9:90) solution, and then evaporated to dryness. The residue was purified by column chromatography on silica gel using ethyl acetate as eluent to give 7 mg of Ethyl 6-(2-aminothiazol-5-yl)-8-phenylimidazo[1,2-a]pyridine-2-carboxylate as a white solid. LCMS (Conditions C): 2.53 min (RT); (M+H)+=365.28 (100%). 1H NMR, 400 MHz, DMSO: δ 8.56 (m, 2 H), 8.11 (m, 2 H), 7.81 (s, 1H), 7.65 (s, 1H), 7.56-7.47 (m, 3 H), 7.32 (bs, 2 H), 4.33 (q, J=7.1 Hz, 2 H), 1.31 (t, J=7.0 Hz, 3 H).
Reaction SMILES: [H-].[Na+:2].NC1C=CC=CC=1.[CH3:10][C:11]1[C:12]([CH3:17])=[C:13]([CH3:16])[CH2:14][CH:15]=1>O1CCCC1>[CH3:10][C:11]1[CH:15]=[CH:14][C:13]([CH3:16])([Na:2])[C:12]=1[CH3:17]
Reactant: [Na+]
Reactant: CC1=CCC(C)=C1C
Agent: [H-]
Solvent: C1CCOC1
Solvent: Nc1ccccc1
Product: CC1=C(C)C(C)([Na])C=C1
Temperature: 50 °C
Reaction time: 3 h

Procedure:
Sodium hydride (containing mineral oil; the content of sodium hydride: 60%) (0.80 g) and aniline (0.046 g) were added to the solution of trimethylcyclopentadiene (1.08 g) dissolved in tetrahydrofuran (6.12 g), and stirred at 50° C. for 3 hours. Thus, trimethylcyclopentadienylsodium was obtained in the form of a solution in tetrahydrofuran.
Reaction SMILES: C([O:3][C:4](=[O:31])[C:5](=[O:30])[CH2:6][C:7]([C:9]1[CH:14]=[CH:13][C:12]([N:15]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:11][CH:10]=1)=[O:8])C.[Li+].[OH-]>C1COCC1>[CH2:23]([N:15]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:12]1[CH:13]=[CH:14][C:9]([C:7](=[O:8])[CH2:6][C:5](=[O:30])[C:4]([OH:31])=[O:3])=[CH:10][CH:11]=1)[C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: CCOC(=O)C(=O)CC(=O)c1ccc(N(Cc2ccccc2)Cc2ccccc2)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: O=C(O)C(=O)CC(=O)c1ccc(N(Cc2ccccc2)Cc2ccccc2)cc1

Procedure:
In a manner similar to example AI-2-1, 4-(4-dibenzylaminophenyl)-2,4-dioxobutanoic acid ethyl ester (0.29 g, 0.7 mmol) was hydrolyzed using 0.58 ml 1N LiOH in 5 ml THF to afford 0.237 g (87%) of AIV-3-1 as an orange solid. MP=161-162° C. 1H NMR (400 MHz, CDCl3) δ4.76 (s, 4H), 6.79 (d, 2H, J=9.34 Hz), 6.99 (s, 1H), 7.20 (d, 4H, J=6.78 Hz), 7.30 (t, 2H, J=7.14 Hz), 7.35 (t, 4H, J=7.33 Hz), 7.86 (d, 2H, J=9.15 Hz).
Reaction SMILES: N[C:2]1[CH:3]=[CH:4][C:5]([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)=[C:6]2[C:10]=1[C:9](=[O:11])[NH:8][CH2:7]2.[I-:17].[K+].II.N(OC(C)(C)C)=O>C(#N)C.[Cu](I)I>[I:17][C:2]1[CH:3]=[CH:4][C:5]([C:12]2[S:13][CH:14]=[CH:15][CH:16]=2)=[C:6]2[C:10]=1[C:9](=[O:11])[NH:8][CH2:7]2
Reactant: Nc1ccc(-c2cccs2)c2c1C(=O)NC2
Reactant: [I-]
Agent: I[Cu]I
Agent: CC(C)(C)ON=O
Agent: II
Solvent: CC#N
Product: O=C1NCc2c(-c3cccs3)ccc(I)c21
Yield: 44 %

Procedure:
In a similar manner to Step 4 of Example 140, 7-amino-4-(thiophen-2-yl)isoindolinone (212 mg, 0.920 mmol) was dissolved in acetonitrile (14.8 mL), and the solution was treated with potassium iodide (183 mg, 1.10 mmol), copper iodide (210 mg, 1.10 mmol), iodine (280 mg, 1.10 mmol) and tert-butyl nitrite (0.382 mL, 2.76 mmol), followed by purification by preparative thin-layer chromatography (chloroform/acetonitrile-6/1, chloroform/methanol=10/1) to obtain 7-iodo-4-(thiophen-2-yl)isoindolinone (138 mg, yield 44%).
Reaction SMILES: [CH:1]([CH:3]1[O:8][CH2:7][CH2:6][N:5]([C:9]([O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[O:10])[CH2:4]1)=O.C1(P(C2C=CC=CC=2)(C2C=CC=CC=2)=[CH:26][C:27]([O:29][CH3:30])=[O:28])C=CC=CC=1>C(Cl)Cl>[CH3:30][O:29][C:27](=[O:28])[CH:26]=[CH:1][CH:3]1[O:8][CH2:7][CH2:6][N:5]([C:9]([O:11][CH2:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[O:10])[CH2:4]1
Reactant: O=CC1CN(C(=O)OCc2ccccc2)CCO1
Reactant: COC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: ClCCl
Product: COC(=O)C=CC1CN(C(=O)OCc2ccccc2)CCO1
Temperature: 25 °C
Reaction time: 12 h
Yield: 48 %

Procedure:
A mixture of benzyl 2-formylmorpholine-4-carboxylate (1.5 g, 6 mmol) and methyl 2-(triphenylphosphoranylidene)acetate (2.01 g, 6 mmol) in DCM (30 mL) was stirred at 25° C. for 12 hours under N2. The mixture was concentrated in vacuo, and the residue was purified by a silica gel column chromatography (PETROLEUM ETHER/EtOAc (V/V)=3/1) to give the title compound as colorless oil (0.88 g, 48%). The compound was characterized by the following spectroscopic data:
Reaction SMILES: [Cl:1][C:2]1[C:18]([N+:19]([O-])=O)=[C:17]([F:22])[CH:16]=[CH:15][C:3]=1[C:4]([NH:6][S:7]([N:10]([CH:12]([CH3:14])[CH3:13])[CH3:11])(=[O:9])=[O:8])=[O:5].CO.[H][H]>C1(C)C=CC=CC=1.[Pt]>[Cl:1][C:2]1[C:18]([NH2:19])=[C:17]([F:22])[CH:16]=[CH:15][C:3]=1[C:4]([NH:6][S:7]([N:10]([CH:12]([CH3:14])[CH3:13])[CH3:11])(=[O:9])=[O:8])=[O:5]
Reactant: [H][H]
Reactant: CC(C)N(C)S(=O)(=O)NC(=O)c1ccc(F)c([N+](=O)[O-])c1Cl
Agent: [Pt]
Solvent: CO
Solvent: Cc1ccccc1
Product: CC(C)N(C)S(=O)(=O)NC(=O)c1ccc(F)c(N)c1Cl
Temperature: 70 °C
Reaction time: 12 h

Procedure:
8.00 g (23.0 mmol) of N-(2-chloro-4-fluoro-3-nitrobenzoyl)-N′-isopropyl-N′-methylsulfamide in 33 g of toluene and 8 g of methanol were admixed with 190 mg (0.055 mol %) of 3% Pt/C and hydrogenated with 5 bar of hydrogen with stirring at 70° C. After 12 h the solution was depressurized, the reaction mixture was filtered and the solvent was removed by distillation. This gave 4.7 g (64%) of the title compound in the form of a solid (m.p.: 147-149° C.).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[S:10][C:11]([NH:38]C(=O)OC(C)(C)C)=[C:12]([C:14](=[O:37])[NH:15][C:16]2[CH:17]=[N:18][N:19]([CH3:36])[C:20]=2[N:21]2[CH2:27][CH2:26][CH:25]([NH:28]C(=O)C(F)(F)F)[CH:24]([F:35])[CH2:23][CH2:22]2)[N:13]=1.Cl.O1CCOCC1>CO>[NH2:38][C:11]1[S:10][C:9]([C:3]2[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=2[F:8])=[N:13][C:12]=1[C:14]([NH:15][C:16]1[CH:17]=[N:18][N:19]([CH3:36])[C:20]=1[N:21]1[CH2:22][CH2:23][CH:24]([F:35])[CH:25]([NH2:28])[CH2:26][CH2:27]1)=[O:37]
Reactant: Cn1ncc(NC(=O)c2nc(-c3c(F)cccc3F)sc2NC(=O)OC(C)(C)C)c1N1CCC(F)C(NC(=O)C(F)(F)F)CC1
Agent: Cl
Solvent: CO
Solvent: C1COCCO1
Product: Cn1ncc(NC(=O)c2nc(-c3c(F)cccc3F)sc2N)c1N1CCC(N)C(F)CC1
Temperature: 60 °C

Procedure:
tert-Butyl 2-(2,6-difluorophenyl)-4-(5-(4-fluoro-5-(2,2,2-trifluoroacetamido)azepan-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate was suspended in MeOH (20 mL) in a pressure vessel and to this was added a solution of HCl in 1,4-dioxane (4 M, 20 mL, 80.0 mmol). The vessel was sealed and the mixture heated at 60° C. for 16 hr. The solvent was removed under reduced pressure and the residue was purified via silica gel column chromatography (0-10% 7 N ammonia in MeOH/DCM) to yield 5-amino-N-(5-(4-amino-5-fluoroazepan-1-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2,6-difluorophenyl)thiazole-4-carboxamide as a pale brown solid (653 mg, 70% over two steps). The 4-amino and the 5-fluoro groups are cis. 1H NMR (400 M Hz, CDCl3) δ 8.63 (s, 1H), 7.84 (s, 1H), 7.37-7.29 (m, 1H), 7.03 (t, J=8.7 Hz, 2H), 6.13 (s, 2H), 4.48 (dtd, J=47.9, 8.6, 3.6 Hz, 1H), 3.72 (s, 3H), 3.37-3.15 (m, 5H), 2.23-1.92 (m, 3H), 1.75-1.67 (m, 1H). Alkyl NH2 not observed. LCMS (ES+) m/z 466 (M+1). Chiral separation of the racemic mixture by SFC gave 147 as a single enantiomer. 1H NMR (400 MHz, DMSO) δ 9.04 (s, 1H), 7.59 (s, 1H), 7.56-7.43 (m, 3H), 7.26 (dd, J=14.5, 5.9 Hz, 2H), 4.82 (dd, J=47.0, 7.4 Hz, 1H), 3.63 (s, 3H), 3.29-3.15 (m, 4H), 3.08-2.91 (m, 2H), 2.24-2.06 (m, 1H), 1.91-1.76 (m, 2H), 1.74-1.59 (m, 1H). MS (ESI) m/z: 466.1 [M+H+].
Reaction SMILES: [F:1][CH:2]([C:21]1[O:22]CC(C)(C)N=1)[CH2:3][CH2:4][C:5]#[C:6][CH2:7][C:8]#[C:9][CH2:10][CH2:11][CH2:12][CH2:13][CH:14]=[CH:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].[OH2:28]>Cl>[F:1][CH:2]([CH2:3][CH2:4][C:5]#[C:6][CH2:7][C:8]#[C:9][CH2:10][CH2:11][CH2:12][CH2:13]/[CH:14]=[CH:15]\[CH2:16][CH2:17][CH2:18][CH2:19][CH3:20])[C:21]([OH:22])=[O:28]
Reactant: CCCCCC=CCCCCC#CCC#CCCC(F)C1=NC(C)(C)CO1
Reactant: O
Agent: Cl
Product: CCCCC/C=C\CCCCC#CCC#CCCC(F)C(=O)O
Temperature: 23 °C
Reaction time: 0.25 h
Yield: 66 %

Procedure:
A suspension of 2-(1-fluorononadec-13-en-4,7-diynyl)-4,5-dihydro-4,4-dimethyloxazole (86 mg) in 3 ml of 3N HCl was refluxed wih stirring under argon for 15 min. It was cooled to about 23° C., diluted with 3 ml of water, and extracted three times with ether. The ether extracts were combined, washed with brine, and dried over MgSO4. Concentration of ether at 35° C./35 mmHg gave the crude acid which was purified by flash chromatography on silica gel (8 g, 230-400 mesh). Elution with HOAc-CH3OH-CHCl3 under nitrogen afforded 49 mg (66% yield by weight) of (Z)-2-fluoro-14-eicosene-5,8-diynoic acid as a colorless oil.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([S:15]([NH2:18])(=[O:17])=[O:16])[C:5]2[O:10][S:9](=[O:12])(=[O:11])[C:8]([CH3:13])=[CH:7][C:6]=2[CH:14]=1.[H][H].C(N(CC)CC)C>O1CCCC1>[O:12]=[S:9]1(=[O:11])[C:8]([CH3:13])=[CH:7][C:6]2[CH:14]=[CH:2][CH:3]=[C:4]([S:15]([NH2:18])(=[O:16])=[O:17])[C:5]=2[O:10]1
Reactant: [H][H]
Reactant: CC1=Cc2cc(Br)cc(S(N)(=O)=O)c2OS1(=O)=O
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC1=Cc2cccc(S(N)(=O)=O)c2OS1(=O)=O
Temperature: 0 °C
Yield: 75.1 %

Procedure:
120 g of 6-bromo-2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonamide are dissolved in 2.4 liters of tetrahydrofuran and the solution is hydrogenated with hydrogen for 40 minutes, in the presence of 41.3 g of triethylamine and 12.0 g of 5% on carbon catalyst, under normal pressure and in the temperature range from 20° to 25° C. The mixture is filtered, the filtrate is concentrated, and the residue is taken up in 1300 ml of hot 90% aqueous ethanol. The insoluble constituents are separated and the solution is cooled to 0° C. The precipitate is separated and dried, affording 70 g of 2,2-dioxo-3-methyl-1,2-benzoxathiin-8-ylsulfonamide of m.p. 204°-205° C.
Reaction SMILES: [CH3:1][O:2][C:3]([CH:5]1[C:9](=O)[CH2:8][S:7][CH2:6]1)=[O:4].Cl.[NH2:12][OH:13].C(=O)([O-])[O-].[Ba+2]>CO>[CH3:1][O:2][C:3]([CH:5]1[C:9](=[N:12][OH:13])[CH2:8][S:7][CH2:6]1)=[O:4]
Reactant: NO
Reactant: COC(=O)C1CSCC1=O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Ba+2]
Solvent: CO
Product: COC(=O)C1CSCC1=NO
Yield: 98.5 %

Procedure:
A suspension of 4-oxo-tetrahydro-thiophene-3-carboxylic acid methyl ester (33) (16.96 g, 106 mmol), hydroxylamine hydrochloride (16.96 g, 244 mmol) and barium carbonate (48.16 g, 244 mmol) in methanol (800 mL) was refluxed overnight. The solution was cooled and filtered. The filtrate was concentrated in vacuo. The residue was suspended in water and extracted by ethyl acetate. The combined organic phase was dried over MgSO4 and concentrated to yield 18.30 g (98%) of an isomeric mixture of 4-hydroxyimino-tetrahydro-thiophene-3-carboxylic acid methyl ester as a viscous oil. 1H NMR (400 MHz, CDCl3) δ 3.14-4.11 (m, 7H), 8.17 (m, 1H) ppm. The isomeric mixture was used in the following step without further purification.
Reaction SMILES: P(N)([O-])[O-].[CH2:5]=[CH:6][CH2:7][CH2:8][CH2:9][CH3:10].[CH3:11][C@:12]12[CH2:29][CH2:28][C@H:27]3[C@@H:17]([CH2:18][CH2:19][C:20]4[C@:25]3([CH3:26])[CH:24]=[CH:23][C:22](=[O:30])[CH:21]=4)[C@@H:16]1[CH2:15][CH2:14][C:13]2=[O:31].C[Si](Cl)(C)C>CCOCC.C(Cl)Cl.[Cu].C1C=CC=CC=1>[CH2:5]([C@@H:24]1[C@@:25]2([CH3:26])[C:20]([CH2:19][CH2:18][C@@H:17]3[C@@H:27]2[CH2:28][CH2:29][C@@:12]2([CH3:11])[C@H:16]3[CH2:15][CH2:14][C:13]2=[O:31])=[CH:21][C:22](=[O:30])[CH2:23]1)[CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: C=CCCCC
Reactant: C[C@]12C=CC(=O)C=C1CC[C@@H]1[C@@H]2CC[C@]2(C)C(=O)CC[C@@H]12
Agent: [Cu]
Agent: C[Si](C)(C)Cl
Agent: NP([O-])[O-]
Solvent: c1ccccc1
Solvent: CCOCC
Solvent: ClCCl
Product: CCCCCC[C@H]1CC(=O)C=C2CC[C@@H]3[C@H](CC[C@]4(C)C(=O)CC[C@@H]34)[C@]21C
Temperature: 25 °C
Reaction time: 1 h
Yield: 16 %

Procedure:
(C6H6) (10.1 mg, 0.02 mmol, 0.05 eq.) and the phosphoramidite ligand (21.6 mg, 0.040 mmol, 0.10 eq.) were dissolved in Et2O (2.0 mL) under an argon atmosphere and allowed to stir for 1 h at room temperature. In another flask, Cp2ZrHCl (206.0 mg, 0.80 mmol, 2.0 eq.) was added to a stirred, room temperature, solution of 1-hexene (0.13 mL, 1.0 mmol, 2.5 eq.) in CH2Cl2 (0.40 mL) under an argon atmosphere. After stirring for 40 min, the resulting clear yellow solution was transferred via syringe over about 1 min to the stirred solution containing the copper and ligand under an argon atmosphere. The resulting dark mixture was allowed to stir for an additional 10 min before 1,4-androstadiene-3,17-dione (114.0 mg, 0.40 mmol, 1.0 eq.) and TMSCl (0.26 mL, 2.00 mmol, 5.0 eq.) were added sequentially dropwise via syringe. Stirring at room temperature was continued arbitrarily for 15 h before the reaction was quenched by the addition of Et2O (ca 3 mL) and NH4Cl (1 M aq., ca 1.5 mL). The mixture was partitioned between the aqueous and Et2O layers and the former phase was extracted with Et2O (3×10 mL). The combined organic phase was washed with NaHCO3 (sat. aq., ca 10 mL), dried (Na2SO4), filtered and concentrated in vacuo to give an oil. Flash column chromatography of the yellow residue (5:30:65 EtOAc/DCM/petrol; SiO2) gave major diastereomer (1) (+)-1α-hexyl-4-androstene-3,17-dione (75 mg, 0.20 mmol, 50%) and minor diastereomer (1a) (+)-1α-hexyl-4-androstene-3,17-dione (24 mg, 0.064 mmol, 16%). Diastereomeric ratio (3.6:1) was determined by integration of 1H NMR spectra.
Reaction SMILES: CI.[C:3](=O)([O-])[O-].[K+].[K+].[CH3:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=[O:15])=[CH:12][C:11]=1[C@H:19]1[C@H:24]([O:25][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C@@H:23]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C@H:22]([O:41][CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[C@@H:21]([CH2:49][O:50][CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[O:20]1>CN(C=O)C>[CH3:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]([O:16][CH3:3])=[O:15])=[CH:12][C:11]=1[C@H:19]1[C@H:24]([O:25][CH2:26][C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[C@@H:23]([O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[C@H:22]([O:41][CH2:42][C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)[C@@H:21]([CH2:49][O:50][CH2:51][C:52]2[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=2)[O:20]1
Reactant: Cc1ccc(C(=O)O)cc1[C@@H]1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: COC(=O)c1ccc(C)c([C@@H]2O[C@H](COCc3ccccc3)[C@@H](OCc3ccccc3)[C@H](OCc3ccccc3)[C@H]2OCc2ccccc2)c1
Reaction time: 3 h
Yield: 84.9 %

Procedure:
Methyl iodide (0.17 ml) and potassium carbonate (0.4 g) were added to a solution of 4-methyl-3-[(2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]-tetrahydro-2H-pyran-2-yl]benzoic acid (1.5 g) in DMF (10 ml) at room temperature and the mixture was stirred for three hours. The insoluble matter was separated by filtration and the filtrate was diluted with ethyl acetate. The diluted solution was washed with water and saturated brine in that order and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated. The residue was purified by silica gel column chromatography (n-hexane-ethyl acetate) to obtain methyl 4-methyl-3-[(2S,3S,4R,5R,6R)-3,4,5-tris(benzyloxy)-6-[(benzyloxy)methyl]-tetrahydro-2H-pyran-2-yl]benzoate (1.3 g).
Reaction SMILES: C(N(CC)CC)C.CC1C=CC(S([Cl:18])(=O)=O)=CC=1.[CH3:19][O:20][C:21]([C:23]1[O:24][C:25]([CH3:30])=[C:26]([CH2:28]O)[CH:27]=1)=[O:22]>ClCCl>[CH3:19][O:20][C:21]([C:23]1[O:24][C:25]([CH3:30])=[C:26]([CH2:28][Cl:18])[CH:27]=1)=[O:22]
Reactant: COC(=O)c1cc(CO)c(C)o1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)c1cc(CCl)c(C)o1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 33.8 %

Procedure:
Triethylamine (196 μl, 1.41 mmoles), followed by 4-methyl-benzenesulphonyl chloride (247 mg, 1.293 mmoles) were added to a stirred solution of 4-hydroxymethyl-5-methyl-furan-2-carboxylic acid methyl ester (16) (200 mg, 1.176 mmoles) in dry dichloromethane at 0° C. under an argon atmosphere. The reaction mixture was stirred at 0° C. for 15 minutes, then allowed to warm to room temperature and was stirred for a further 4 hours. The mixture was washed with saturated aqueous sodium bicarbonate (50 ml) and brine (50 ml), and dried (MgSO4). After removal of the solvent, the residue was purified by flash chromatography, using petrol/diethyl ether 19:1 v/v as eluent, to afford compound 159 (75 mg) as a white solid. LC/MS System D; Rt=6.34 mins, m/z (ES+)=189 (M+H for C8H9ClO3).
Reaction SMILES: [CH2:1]([O:8][CH:9]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH2:10][CH:11]=[CH2:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C12BC(CCC1)CCC2.[O:31]1CCCC1>>[CH2:1]([O:8][CH:9]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])[CH2:10][CH2:11][CH2:12][OH:31])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: C1CCOC1
Reactant: C=CCC(CCCCCCCCC)OCc1ccccc1
Agent: B1C2CCCC1CCC2
Product: CCCCCCCCCC(CCCO)OCc1ccccc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 80 %

Procedure:
A solution of 9.3 g of 4-benzyloxy-1-tridecene in 40 ml of tetrahydrofuran was added, dropwise, under nitrogen, to 70.4 ml of 9-borabicyclo[3.3.1]nonane (0.5M solution in hexane). The reaction mixture was stirred at room temperature for 3 hrs. and quenched by the sequential addition of 18 ml of ethanol, 6 ml of 6N sodium hydroxide, and 12 ml of 30% hydrogen peroxide. The reaction mixture was heated at 50° for 2 hrs. and then allowed to stand at ambient temperature overnight. Upon standing the mixture separated into aqueous and organic phases. The aqueous phase was saturated with potassium carbonate and the organic phase was separated, washed with 30 ml of a 10% aqueous solution of sodium sulfite and 30 ml of a saturated aqueous solution of sodium chloride, dried over anhydrous potassium carbonate, and concentrated. The residue was taken up in 20% diethyl ether/hexane, filtered, and concentrated to an oil. Flash chromatography of the oil on silica gel using hexane diethyl ether (2:1 by volume) as the eluent yielded 7.7 g (80%) of 4-benzyloxytridecan-1-ol as an oil.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:14](=[O:15])[CH2:13][C:12](=[O:16])[NH:11][C:10]3[C:17]4[C:22]([CH:23]=[CH:24][C:9]2=3)=[CH:21][CH:20]=[CH:19][CH:18]=4)=[CH:4][CH:3]=1.[I:25][C:26]1[CH:34]=[CH:33][C:29]([C:30](Cl)=[O:31])=[C:28]([O:35][CH3:36])[CH:27]=1.IC1C=CC=CC=1C(NCCN1C(=O)CC(=O)NC2C3C(C=CC1=2)=CC=CC=3)=O>>[I:25][C:26]1[CH:34]=[CH:33][C:29]([C:30]([NH:1][C:2]2[CH:7]=[CH:6][C:5]([N:8]3[C:14](=[O:15])[CH2:13][C:12](=[O:16])[NH:11][C:10]4[C:17]5[C:22]([CH:23]=[CH:24][C:9]3=4)=[CH:21][CH:20]=[CH:19][CH:18]=5)=[CH:4][CH:3]=2)=[O:31])=[C:28]([O:35][CH3:36])[CH:27]=1
Reactant: COc1cc(I)ccc1C(=O)Cl
Reactant: Nc1ccc(N2C(=O)CC(=O)Nc3c2ccc2ccccc32)cc1
Agent: O=C1CC(=O)N(CCNC(=O)c2ccccc2I)c2ccc3ccccc3c2N1
Product: COc1cc(I)ccc1C(=O)Nc1ccc(N2C(=O)CC(=O)Nc3c2ccc2ccccc32)cc1
Yield: 93 %

Procedure:
By using 5-(4-aminophenyl)-1H-naphtho[1,2-b][1,4]diazepine-2,4(3H,5H)-dione obtained in Example 1, (3), and 4-iodo-2-methoxybenzoyl chloride, the title compound (yield 93%) was obtained in the same manner as that of Example 1, (4).
Reaction SMILES: [Cl:1][S:2]([OH:5])(=O)=[O:3].[CH2:6]([Cl:13])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>>[Cl:13][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([S:2]([Cl:1])(=[O:5])=[O:3])=[CH:9][CH:8]=1
Reactant: ClCc1ccccc1
Reactant: O=S(=O)(O)Cl
Product: O=S(=O)(Cl)c1ccc(CCl)cc1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a 250 mL flask, fitted with addition funnel, reflux condenser and thermometer, is placed 50 g (0.43 mole) of chlorosulfonic acid. Benzyl chloride, (18 g, 0.14 mole) is added to the reaction mixture, slowly, with continuous stirring, over a period of two hours. The temperature of the reaction is kept near room temperature using a water bath. After the addition is complete, the stirring is continued for at least one hour. After analysis by thin layer chromatography shows that the reaction is complete, the reaction mixture is poured into 150 g of crushed ice. The solid is collected and washed with cold water several times. The crude product is further purified by recrystallization. The product is characterized using 1H NMR spectroscopy.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([O:12][CH2:13][C:14]#[C:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]([F:25])([F:24])[F:23])=[CH:18][CH:17]=2)=[C:6]([CH:11]=1)[C:7]([O:9]C)=[O:8].[OH-].[Li+]>CO.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:12][CH2:13][C:14]#[C:15][C:16]2[CH:17]=[CH:18][C:19]([C:22]([F:23])([F:24])[F:25])=[CH:20][CH:21]=2)=[C:6]([CH:11]=1)[C:7]([OH:9])=[O:8]
Reactant: COC(=O)c1cc(F)ccc1OCC#Cc1ccc(C(F)(F)F)cc1
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: O=C(O)c1cc(F)ccc1OCC#Cc1ccc(C(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
100 mg (0.28 mmol) of methyl 5-fluoro-2-[3-(4-trifluoromethylphenyl)prop-2-ynyloxy]benzoate are dissolved in 2 ml of methanol and 2 ml of water, and 20.3 mg (0.85 mmol) of lithium hydroxide are added. After stirring at room temperature for 12 h, the crystals which have separated out are filtered off with suction, washed with water, 1 N hydrochloric acid and petroleum ether and dried on a clay dish. 74.9 mg (0.20 mmol, 71% of theory) of the title compound are isolated.