Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([NH2:14])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:15]([C:17]1[CH2:34][CH2:33][C@@:32]2([CH3:35])[C:19](=[CH:20][CH2:21][C@@H:22]3[C@@H:31]2[CH2:30][CH2:29][C@@:27]2([CH3:28])[C@H:23]3[CH2:24][CH2:25][C@@H:26]2[C:36](O)=[O:37])[CH:18]=1)#[N:16].C(N(CC)CC)C.S(Cl)(C1C=CC(C)=CC=1)(=O)=O>CN(C)C1C=CN=CC=1.C(Cl)Cl>[C:2]1([CH:1]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[NH:14][C:36]([C@H:26]2[CH2:25][CH2:24][C@H:23]3[C@H:22]4[C@H:31]([CH2:30][CH2:29][C@:27]23[CH3:28])[C@:32]2([CH3:35])[C:19]([CH:18]=[C:17]([C:15]#[N:16])[CH2:34][CH2:33]2)=[CH:20][CH2:21]4)=[O:37])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NC(c1ccccc1)c1ccccc1
Reactant: C[C@]12CC[C@H]3[C@@H](CC=C4C=C(C#N)CC[C@@]43C)[C@@H]1CC[C@@H]2C(=O)O
Agent: CN(C)c1ccncc1
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C[C@]12CC[C@H]3[C@@H](CC=C4C=C(C#N)CC[C@@]43C)[C@@H]1CC[C@@H]2C(=O)NC(c1ccccc1)c1ccccc1
Yield: 92 %

Procedure:
0.106 ml of benzhydrylamine were added to a solution of 100 mg of 3-cyanoandrosta-3,5-diene-17β-carboxylic acid [prepared as described in Example 1(b)], a catalytic amount of 4-dimethylaminopyridine and 0.131 ml of triethylamine in 4 ml of methylene chloride. 88.0 mg of tosyl chloride were then divided into three portions and added to this reaction mixture at 30 minute intervals at room temperature, whilst stirring. One hour after finishing the addition of the tosyl chloride, the reaction mixture was diluted with methylene chloride, and washed with 1N aqueous hydrochloric acid, with water, with an aqueous solution of sodium hydrogencarbonate, and with a saturated aqueous solution of sodium chloride, in that order. It was then dried over anhydrous magnesium sulfate, and concentrated by evaporation under reduced pressure. The resulting residue was crystallized from acetone, to give 138 mg (yield 92%) of the title compound.
Reaction SMILES: [CH3:1][C@H:2]([OH:9])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N+:29]([C:32]1[CH:40]=[CH:39][C:35]([C:36](O)=[O:37])=[CH:34][CH:33]=1)([O-:31])=[O:30].C(OC(N=NC(OC(C)C)=O)=O)(C)C.C1(C)C=CC=CC=1>C1COCC1.O>[N+:29]([C:32]1[CH:33]=[CH:34][C:35]([C:36]([O:9][C@@H:2]([CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8])[CH3:1])=[O:37])=[CH:39][CH:40]=1)([O-:31])=[O:30].[CH3:1][C@H:2]([OH:9])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: O=C(O)c1ccc([N+](=O)[O-])cc1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: CCCCCC[C@H](C)O
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: Cc1ccccc1
Solvent: O
Product: CCCCCC[C@@H](C)OC(=O)c1ccc([N+](=O)[O-])cc1
Reaction time: 2 h

Procedure:
After (S)-2-octanol (300 mg, 2.30 mmol), triphenylphosphine (724 mg, 2.76 mmol), 4-nitrobenzoic acid (465 mg, 2.76 mmol), and THF (12 ml) were added to a 50 ml flask, a 40% azodicarboxylic acid diisopropyl ester-toluene solution (1.45 ml, 2.76 mmol) dissolved in THF (6 ml) was added dropwise thereto at 20° C., and the reaction was allowed to proceed for two hours. Water (0.5 mL) was added, and concentration was carried out. Then, water (10 ml) was added to the solution, and extraction was then carried out using diethyl ether (10 ml, ×2). Then, the organic layer was washed with water (10 mL) and saturated salt water (10 ml), and dehumidified with anhydrous magnesium sulfate. Subsequently, a crude product obtained by concentration was purified by column chromatography (silica gel, 5% ethyl acetate-hexane solution) to give (R)-2-(4-nitrobenzoyloxy)octane as a pale yellow liquid substance (616 mg, yield: 96%/(S)-2-octanol).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([CH3:8])[C:5](Br)=[CH:4][CH:3]=1.[Cu][C:11]#[N:12]>CN(C=O)C>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:11]#[N:12])=[C:6]([CH3:8])[N:7]=1
Reactant: N#C[Cu]
Reactant: Cc1nc(N)ccc1Br
Solvent: CN(C)C=O
Product: Cc1nc(N)ccc1C#N

Procedure:
A mixture of 6-amino-3-bromo-2-methylpyridine (20.0 g, 0.107 mol)(Maybridge) and copper (I) cyanide 11.0 g, 0.123 mol) in DMF (25 ml) was heated to reflux for 4 h. The DMF was evaporated in vacuo and the residue was partitioned between ethyl acetate and 10% sodium cyanide solution. The organic layer was washed with 10% sodium cyanide solution and brine, dried (Na2SO4) and evaporated in vacuo to a brown solid. This was dissolved in a minimum amount of ethyl acetate and the product was precipitated by adding hexanes. The mixture was filtered to give the title compound as a brown powder:
Reaction SMILES: [OH2:1].[C:2]1([CH3:12])[CH:7]=[CH:6][C:5]([S:8]([OH:11])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[S:13](Cl)(Cl)=[O:14]>C1CCCCC1>[C:2]1([CH3:12])[CH:3]=[CH:4][C:5]([S:8]([O:11][S:13]([C:5]2[CH:6]=[CH:7][C:2]([CH3:12])=[CH:3][CH:4]=2)(=[O:14])=[O:1])(=[O:9])=[O:10])=[CH:6][CH:7]=1
Reactant: O=S(Cl)Cl
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: O
Solvent: C1CCCCC1
Product: Cc1ccc(S(=O)(=O)OS(=O)(=O)c2ccc(C)cc2)cc1
Temperature: 50 °C
Yield: 54.8 %

Procedure:
150.0 g (789 mmol) of p-toluenesulphonic acid monohydrate were suspended in 360 g of cyclohexane and heated to 50° C. with stirring. 240.0 g (1997 mmol, 2.6 eq.) of thionyl chloride were then added dropwise over a period of 190 min at such a rate that moderate gas evolution was observed. After addition had ended, the mixture was stirred at 50° C. for a further 0.5 h. 80 g of excess thionyl chloride/cyclohexane were then distilled off at a bottom temperature of 71-76° C. The residue was cooled to 5° C. and stirred at this temperature for 1 h. The precipitated solid was filtered off and washed with 150 ml of cyclohexane. After drying under reduced pressure, 70.5 g (53% of theory) of p-toluenesulphonic anhydride were isolated.
Reaction SMILES: [O:1]=[C:2]1[CH2:9]C(C)(C)[CH2:5][C:4]([CH3:10])=[CH:3]1.[C:11]([OH:14])(=[O:13])[CH3:12].O=[O+][O-]>O>[O:1]=[C:2]([CH3:9])[CH2:3][C:4]([CH3:10])([CH3:5])[CH2:12][C:11]([OH:14])=[O:13]
Reactant: CC1=CC(=O)CC(C)(C)C1
Reactant: CC(=O)O
Agent: O=[O+][O-]
Solvent: O
Product: CC(=O)CC(C)(C)CC(=O)O
Reaction time: 6 h
Yield: 87 %

Procedure:
Isophorone was ozonized in the presence of 0.23% manganous acetate. For the reaction 43 grams isophorone, 120 grams acetic acid, 60 grams water and 100 milligrams Mn(OAc)2. 4H2O were charged to the reactor and ozonized in the usual manner at ambient temperature and pressure. The essentially colorless reaction mixture developed a slight greenish coloration after about three hours and after six hours was dark brown. Ozone addition was terminated at this point. The absence of active oxygen made any decomposition precautionary step unnecessary and the reaction mixture was directly treated under vacuum to strip off acetic acid and water. Vacuum distillation of the resulting crude product at 0.3 mm Hg gave an 87 percent yield of 96.5% pure 5-keto-3,3-dimethylhexanoic acid boiling in the range 95° C. to 100° C.
Reaction SMILES: CC([C@]1(O)[C@@]2(C)[C@]3(O)[C@]45O[C@@]2(O)C[C@@](C)([C@@]4(O)CCC([C@H]5[OH:19])=C)[C@]3(O)[C@@H]1OC(C1NC=CC=1)=O)C.IC1C=CC(C(NCCC(O)=O)=O)=CC=1.O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.[CH:65]1([N:71]=[C:72]=[N:73][CH:74]2[CH2:79][CH2:78][CH2:77][CH2:76][CH2:75]2)[CH2:70][CH2:69][CH2:68][CH2:67][CH2:66]1>CN(C1C=CN=CC=1)C.C(Cl)Cl.O1CCCC1.O>[C:72]([NH:71][CH:65]1[CH2:66][CH2:67][CH2:68][CH2:69][CH2:70]1)([NH:73][CH:74]1[CH2:79][CH2:78][CH2:77][CH2:76][CH2:75]1)=[O:19]
Reactant: C=C1CC[C@]2(O)[C@]3(C)C[C@]4(O)O[C@@]2([C@@H]1O)[C@]1(O)[C@@]3(O)[C@H](OC(=O)c2ccc[nH]2)[C@](O)(C(C)C)[C@@]14C
Reactant: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Agent: O=C(O)CCNC(=O)c1ccc(I)cc1
Agent: O=P12OP3(=O)OP(=O)(O1)OP(=O)(O2)O3
Solvent: ClCCl
Solvent: C1CCOC1
Solvent: O
Product: O=C(NC1CCCCC1)NC1CCCCC1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Dehydroryanodine (100 mg, 0.2 mmol), N-(p-iodobenzoyl)-β-alanine (50 mg, 0.22 mmol) and DMAP (2 mg, 0.02 mmol), all dried over P2O5, were dissolved in a solvent mixture of CH2Cl2 (10 ml) and tetrahydrofuran (0.1 ml) dried over Molecular Sieve. To the stirred solution, dicyclohexylcarbodiimide (DCC, 52 mg., 0.25 mmol) was added at once and the stirred reaction maintained at room temperature for 6 hours. Water (0.1 ml) was added to inactivate excess DCC and stirring was continued for 30 minutes. The crystals of dicyclohexylurea thus formed were filtered off and washed twice with CH2Cl2.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[CH3:9].C(N(CC)CC)C.[CH3:17][S:18](Cl)(=[O:20])=[O:19].CCOC(C)=O>ClCCl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][S:18]([CH3:17])(=[O:20])=[O:19])=[CH:4][C:3]=1[CH3:9]
Reactant: Cc1cc(O)ccc1Br
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: Cc1cc(OS(C)(=O)=O)ccc1Br
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 4-bromo-3-methylphenol (10.2 g, 54.5 mmol) in 100 mL of dichloromethane at 0° C. was added triethylamine (15.2 mL, 109 mmol), followed by methanesulfonyl chloride (6.33 mL, 81.8 mmol). The reaction was stirred overnight, allowing it to warm to room temperature. The solution was poured into EtOAc, washed with water, saturated NH4Cl solution, saturated aq. NaHCO3 and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The resulting product was isolated as a white solid which required no further purification.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[O:8])[S:5][CH:6]=1.[CH2:9](O)[CH2:10][OH:11].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[C:4]([CH:7]2[O:11][CH2:10][CH2:9][O:8]2)[S:5][CH:6]=1
Reactant: O=Cc1cc(Br)cs1
Reactant: OCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Product: Brc1csc(C2OCCO2)c1
Reaction time: 1.5 h

Procedure:
4-Bromo-thiophene-2-carbaldehyde (9.24 g, 48.4 mmol), ethane-1,2-diol (13.5 mL, 242 mmol), toluene-4-sulfonic acid monohydrate (416 mg, 2.42 mmol) were dissolved in toluene (100 mL), and the solution was stirred for 1.5 hours under reflux. An aqueous solution of saturated sodium bicarbonate was added to the reaction solution at 0° C., which was then extracted with ethyl acetate, the organic layer was washed with brine and dried over anhydrous magnesium sulfate. The solvent was evaporated in vacuo, the residue was purified by NH silica gel column chromatography (hexane:ethyl acetate=20:1), and the title compound (11.8 g, quantitatively) was obtained as a white solid.
Reaction SMILES: N[CH2:2][CH2:3][CH2:4][Si:5]([O:12][CH2:13][CH3:14])([O:9][CH2:10][CH3:11])[O:6][CH2:7][CH3:8].C([N:17](CC)CC)C.[C:22](Cl)(=[O:25])[CH:23]=[CH2:24]>C1COCC1>[CH2:7]([O:6][Si:5]([O:12][CH2:13][CH3:14])([O:9][CH2:10][CH3:11])[CH2:4][CH2:3][CH2:2][C:23](=[CH2:24])[C:22]([NH2:17])=[O:25])[CH3:8]
Reactant: C=CC(=O)Cl
Reactant: CCO[Si](CCCN)(OCC)OCC
Reactant: CCN(CC)CC
Solvent: C1CCOC1
Product: C=C(CCC[Si](OCC)(OCC)OCC)C(N)=O
Temperature: 0 °C
Reaction time: 10 h
Yield: 70.2 %

Procedure:
3-Aminopropyltriethoxysilane (1.5 g, 6.78 mmol) and triethylamine (1.03 g, 10.17 mmol) were dissolved in dry THF (7 mL) at 0° C. under nitrogen atmosphere. Acryloyl chloride (0.92 g, 10.17 mmol) in dry THF (7 mL) was slowly added to the mixture at 0° C. The resulting mixture was stirred at 0° C. for 10 h. The resulting mixture was filtered through a sintered glass filter and the filtrate was concentrated to give a product as a red oil (1.31 g, 70%). This compound was used without further purification.
Reaction SMILES: [NH2:1][C@H:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][C@H:3]1[O:15][CH2:16][CH3:17].[Cl:18][C:19]1[N:20]=[C:21]([C:26](O)=[O:27])[NH:22][C:23]=1[CH2:24][CH3:25].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>>[Cl:18][C:19]1[N:20]=[C:21]([C:26]([NH:1][C@H:2]2[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:12])([CH3:13])[CH3:14])=[O:9])[CH2:4][C@H:3]2[O:15][CH2:16][CH3:17])=[O:27])[NH:22][C:23]=1[CH2:24][CH3:25]
Reactant: CCc1[nH]c(C(=O)O)nc1Cl
Reactant: CCO[C@@H]1CN(C(=O)OC(C)(C)C)CC[C@@H]1N
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Product: CCO[C@@H]1CN(C(=O)OC(C)(C)C)CC[C@@H]1NC(=O)c1nc(Cl)c(CC)[nH]1

Procedure:
The same operation as in Example (1g) was performed using tert-butyl cis(±)-4-amino-3-ethoxypiperidine-1-carboxylate obtained by the method described in Example (112d) (0.48 g, 1.96 mmol), 4-chloro-5-ethyl-1H-imidazole-2-carboxylic acid obtained by the method described in Example (1d) (0.31 g, 1.51 mmol), WSC hydrochloride (0.88 g, 4.59 mmol) and HOBT (0.21 g, 1.51 mmol), to obtain 0.59 g of the title compound as a white foamy substance (91%).
Reaction SMILES: [CH3:1][Si:2]([CH3:5])(Cl)[Cl:3].[Al+3].[Cl-].[Cl-].[Cl-].[CH3:10][SiH:11]([CH3:13])[CH3:12].C[Mg][Cl:16].C[SiH](Cl)Cl.COC1C=CC=CC=1OC>C1(C)C=CC=CC=1>[CH3:1][SiH:2]([CH3:5])[Cl:3].[CH3:10][Si:11]([CH3:13])([CH3:12])[Cl:16]
Reactant: C[Si](C)(Cl)Cl
Reactant: C[SiH](C)C
Reactant: C[Mg]Cl
Agent: C[SiH](Cl)Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: COc1ccccc1OC
Solvent: Cc1ccccc1
Product: C[SiH](C)Cl
Product: C[Si](C)(C)Cl
Reaction time: 1 h

Procedure:
A four-necked flask equipped with a condenser, thermometer, gas feed tube, and stirrer was charged with 129.1 g (1.0 mol) of dimethyldichlorosilane, 100 ml of toluene, and 1.3 g (0.01 mol) of AlCl3, which were agitated with the stirrer. To the flask at room temperature, trimethylsilane which had been synthesized in a separate flask from methyl-magnesium chloride and 57.5 g (0.5 mol) of methyldichlorosilane was fed. Agitation was continued for one hour. 2.8 g (0.02 mol) of o-dimethoxybenzene was added to the reaction solution which was agitated for a further one hour. Dimethylchlorosilane and trimethylchlorosilane were isolated from the reaction solution by distillation. There were obtained 42.6 g of dimethylchlorosilane and 47.3 g of trimethylchlorosilane in a yield of 90% and 87%, respectively.
Reaction SMILES: [C:1]1(B(O)O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[Br:14][C:15]1[CH:16]=[C:17](I)[CH:18]=[CH:19][CH:20]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[Br:14][C:15]1[CH:20]=[C:19]([C:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:4]=[CH:3][CH:2]=2)[CH:18]=[CH:17][CH:16]=1
Reactant: Brc1cccc(I)c1
Reactant: OB(O)c1cccc2ccccc12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: Brc1cccc(-c2cccc3ccccc23)c1
Yield: 76 %

Procedure:
Under an argon gas atmosphere, 200.0 g (1.163 mol) of 1-naphthaleneboronic acid, 329.0 g (1.163 mol) of 3-bromoiodobenzene, 26.9 g (23.3 mmol) of tetrakis(triphenylphosphine)palladium(0), 3.7 L of toluene and 1.74 L of aqueous solution of 2M sodium carbonate were added together, and stirred while being refluxed for 24 hours. After the reaction was over, the mixture experienced filtration, through which aqueous phase thereof was eliminated. After organic phase thereof was washed by water and dried with magnesium sulfate, the toluene was distilled away under reduced pressure. Residue thereof was refined by silica-gel column chromatography, such that 250 g of 1-(3-bromophenyl)naphthalene was obtained at an yield of 76%.
Reaction SMILES: [N:1]12[CH2:8][CH2:7][C:4]([C:9]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[OH:10])([CH2:5][CH2:6]1)[CH2:3][CH2:2]2.CC#N.[C:26]1([O:32][CH2:33][CH2:34][Br:35])[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C(OCC)(=O)C.CCCCCC>[Br-:35].[OH:10][C:9]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:4]12[CH2:5][CH2:6][N+:1]([CH2:34][CH2:33][O:32][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)([CH2:2][CH2:3]1)[CH2:8][CH2:7]2
Reactant: OC(c1ccccc1)(c1ccccc1)C12CCN(CC1)CC2
Reactant: BrCCOc1ccccc1
Solvent: CCCCCC
Solvent: CCOC(C)=O
Solvent: CC#N
Product: OC(c1ccccc1)(c1ccccc1)C12CC[N+](CCOc3ccccc3)(CC1)CC2
Product: [Br-]
Temperature: 60 °C
Reaction time: 16 h
Yield: 68.1 %

Procedure:
To a solution of 1-azabicyclo[2.2.2]oct-4-yl(diphenyl)methanol (0.0550 g, 0.187 mmol) in 2 CH3CN/3 CHCl3 (2.5 mL) was added 2-bromoethyl phenyl ether (0.06 0 g, 0.29 mmol). The solution was stirred at 60° C. for 16 h. The reaction was cooled down to room temperature and then diluted with ethyl acetate and hexane causing a solid to crash out of solution. This solid was filtered off, and washed with hexane to give the title compound (0.063 g, 67.6%). EI-MS m/z 414 (M+) Rt (1.94 min).
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]2[C:6](=[O:10])[CH2:7][CH2:8][CH2:9][C:2]1=2.[Br:11]Br>CCOCC.C(Cl)(Cl)(Cl)Cl>[Br:11][CH:7]1[CH2:8][CH2:9][C:2]2[S:1][CH:5]=[CH:4][C:3]=2[C:6]1=[O:10]
Reactant: BrBr
Reactant: O=C1CCCc2sccc21
Solvent: ClC(Cl)(Cl)Cl
Solvent: CCOCC
Product: O=C1c2ccsc2CCC1Br
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 98.2 %

Procedure:
Into a solution of 6,7-dihydrobenzo[b]thiophen-4(5H)-one (15.3 g, 100 mmol) in ether (600 mL) at −10° C. is added Br2 (16.0 g, 100 mmol) in carbon tetrachloride (CCl4) (100 mL) dropwise over 50 minutes. After an additional 15 minutes at −10° C., the cold bath is removed and the mixture is allowed to warm to ambient temperature. After 1 hour, the mixture is diluted with hexane (300 mL) and washed with water (2×500 mL), aqueous sodium chloride (150 mL) and concentrated under reduced pressure to yield the crude 5-bromo-6,7-dihydrobenzo[b]thiophen-4(5H)-one (22.7 g, 98%) to which is added DMF (˜200 mL), Li2CO3 (14.8 g, 200 mmol) and LiBr (17.4 g, 200 mmol). The mixture is heated for 5 hours at 90° C. and cooled. The crude mixture is poured into water, filtered and the filtrate extracted with EtOAc (600 mL), acidified to pH=1 with concentrated HCl and extracted with EtOAc (600 mL). The combined organic layers are concentrated under reduced pressure to yield a dark oil. The crude material is subjected to chromatography on silica gel, eluting with dichloromethane in hexanes 30-100%, to provide the title compound as an off-white solid (7.62 g, 51% yield).
Reaction SMILES: [CH2:1]([O:19][CH:20]([CH2:23][O:24][C:25]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[CH2:21][OH:22])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[C:44]1([CH3:54])[CH:49]=[CH:48][C:47]([S:50](Cl)(=[O:52])=[O:51])=[CH:46][CH:45]=1.C(OCC)C>N1C=CC=CC=1>[C:44]1([CH3:54])[CH:49]=[CH:48][C:47]([S:50]([O:22][CH2:21][CH:20]([CH2:23][O:24][C:25]([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)([C:32]2[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=2)[C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[O:19][CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])(=[O:52])=[O:51])=[CH:46][CH:45]=1
Reactant: CCCCCCCCCCCCCCCCCCOC(CO)COC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Solvent: CCOCC
Product: CCCCCCCCCCCCCCCCCCOC(COC(c1ccccc1)(c1ccccc1)c1ccccc1)COS(=O)(=O)c1ccc(C)cc1
Reaction time: 48 h
Yield: 83.1 %

Procedure:
A solution of 2-O-octadecyl-3-O-trityl-glycerol (10 g, 17.04 mmol) in 52 mL anhydrous pyridine is added dropwise during 30 min. to a solution of p-toluenesulfonyl chloride (5.1 g, 26.75 mmol) in 39 mL anhydrous pyridine with stirring. After 2 days at room temperature, diethyl ether (162 mL) is added, and the precipitate formed is removed by filtration. The organic phase is washed successively with water (6×50 mL), 0.5N HCl (2×29 mL), 0.5N sodium carbonate (2×29 mL), and water (4×50 mL). Evaporation of the solvent in vacuo gives an oily product which becomes solid after drying in vacuo. The product, 1-O-p-toluenesulfonyl-2-O-octadecyl-3-O-trityl-glycerol (10.5 g, 85% yield), is used for the next step without purification.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([OH:9])[CH:5]=[N:6][C:7]=1[Cl:8].[C:10](=O)([O-])[O-].[K+].[K+].IC>C(#N)C.O>[Br:1][C:2]1[C:7]([Cl:8])=[N:6][CH:5]=[C:4]([O:9][CH3:10])[CH:3]=1
Reactant: O=C([O-])[O-]
Reactant: Oc1cnc(Cl)c(Br)c1
Agent: [K+]
Solvent: CI
Solvent: CC#N
Solvent: O
Product: COc1cnc(Cl)c(Br)c1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
To a stirred mixture of 5-bromo-6-chloropyridin-3-ol (2.95 g, 14.15 mmol) and potassium carbonate (1.28 mL, 21.23 mmol) in acetonitrile (45 mL) under a nitrogen atmosphere was added iodomethane (0.93 mL, 14.86 mmol). The reaction mixture was stirred at room temperature for 24 h. The reaction mixture was diluted with water and extracted with EtOAc (2×). The combined organic layers were washed with sat. sodium chloride, dried over magnesium sulfate, filtered, and concentrated. The resulting crude product was purified by silica gel chromatography to give 3-bromo-2-chloro-5-methoxypyridine. MS (ESI, pos. ion) m/z: 221.9 and 223.9 (M+1).
Reaction SMILES: C(O[C:5](=[O:7])C)(=O)C.[OH:8][NH:9][CH2:10][CH2:11][CH2:12][P:13](=[O:16])([OH:15])[OH:14]>C(O)=O>[CH:5]([N:9]([CH2:10][CH2:11][CH2:12][P:13](=[O:14])([OH:16])[OH:15])[OH:8])=[O:7]
Reactant: CC(=O)OC(C)=O
Reactant: O=P(O)(O)CCCNO
Solvent: O=CO
Product: O=CN(O)CCCP(=O)(O)O
Reaction time: 0.17 h

Procedure:
Formic acid (20 ml.) was added dropwise to acetic anhydride (40 ml.) at 0°-5° C. in the course of 15 minutes with stirring. After stirring was continued at the same temperature for 10 minutes and then at 45°-50° C. for 15 minutes, the mixture was cooled down to 0°-5° C. To this cooled mixture was added dropwise a solution of 3-(N-hydroxyamino)propylphosphonic acid (32.8 g.) in formic acid (60 ml.) at the same temperature in the course of 20 minutes, stirred for additional 45 minutes at ambient temperature, and then the resultant mixture was concentrated under reduced pressure. The residue was dissolved in ethanol (300 ml.), treated with activated charcoal (6 g.) and then filtered. The filtrate was diluted with ethanol (200 ml.) and treated with 28% aqueous ammonia (28 ml.) with stirring under ice-cooling to give an oily precipitate. The precipitate was separated by decantation and dissolved in water (120 ml.). The aqueous solution was treated with activated charcoal (4 g.), and filtered. To the aqueous filtrate was added ethanol (800 ml.) at 80° C. and allowed to stand overnight at ambient temperature to give crystalline monoammonium salt of 3-(N-formyl-N-hydroxyamino)propylphosphonic acid (30.55 g.), mp 158°-160.5° C. (dec.) The same monoammonium salt (4.35 g.) was recovered additionally from the mother liquor, by concentrating it to about 100 ml under reduced pressure mixing with ethanol (300 ml.) and allowing to stand at ambient temperature for 2 hours.