Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[NH2:2][N:3]=[CH:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12](=[O:18])[CH2:13][CH2:14][C:15]([OH:17])=O)=[C:7]([CH2:19][CH3:20])[CH:6]=1.Cl.NN=CC1C=CC(NC(=O)CCC(O)=O)=CC=1.[NH2:39][CH:40]([CH:47]=[CH2:48])[CH2:41][C:42]([O:44][CH2:45][CH3:46])=[O:43]>>[NH2:2][N:3]=[CH:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12](=[O:18])[CH2:13][CH2:14][C:15]([NH:39][CH:40]([CH:47]=[CH2:48])[CH2:41][C:42]([O:44][CH2:45][CH3:46])=[O:43])=[O:17])=[C:7]([CH2:19][CH3:20])[CH:6]=1
Reactant: CCc1cc(C=NN)ccc1NC(=O)CCC(=O)O
Reactant: C=CC(N)CC(=O)OCC
Agent: Cl
Agent: NN=Cc1ccc(NC(=O)CCC(=O)O)cc1
Product: C=CC(CC(=O)OCC)NC(=O)CCC(=O)Nc1ccc(C=NN)cc1CC

Procedure:
The title compound was prepared in the manner of Example 1 substituting 4-[[4-(aminoiminomethyl)-2-ethylphenyl]amino]-4-oxobutanoic acid hydrochloride for 4-[[4-(aminoiminomethyl)phenyl]amino]-4-oxobutanoic acid hydrochloride and using ethyl 3-amino-4-pentenoate. The product was purified by reverse phase HPLC using the conditions of Example 1 to afford the title compound. The product was verified by 13C NMR (CD3OD) δ 12.8, 13.1, 23.7, 30.5, 31.3, 38.9, 48.4, 60.4, 114.5, 124.6, 125.2, 125.6, 128.1, 136.8, 138.0, 140.9, 166.8, 171.0, 171.1, 172.5; Chemical Ionization Mass Spectrometry (MH+)=389.
Reaction SMILES: [CH:1]([CH:3]1[CH2:8][CH2:7][CH:6]2[O:9][CH:5]2[CH2:4]1)=[CH2:2].[CH3:10][O:11][SiH:12]([O:15][CH3:16])[O:13][CH3:14]>[H+].[H+].Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl>[O:9]1[CH:6]2[CH:5]1[CH2:4][CH:3]([CH2:1][CH2:2][Si:12]([O:15][CH3:16])([O:13][CH3:14])[O:11][CH3:10])[CH2:8][CH2:7]2
Reactant: CO[SiH](OC)OC
Reactant: C=CC1CCC2OC2C1
Agent: Cl[Pt-2](Cl)(Cl)(Cl)(Cl)Cl
Agent: [H+]
Product: CO[Si](CCC1CCC2OC2C1)(OC)OC
Temperature: 89 °C
Reaction time: 0.3 h
Yield: 90 %

Procedure:
The apparatus of Example B was charged with 148.8 g (1.2 mol) of 1-vinyl-3,4-epoxycyclohexane, 1.3 g of a carboxylic acid promoter, and 0.15 ml Of 10% chloroplatinic acid catalyst solution. The flask contents were heated to 89° C. and dropwise addition of 122.8 g (1.0 mol) of trimethoxysilane was begun. The reaction temperature was controlled at 90°-95° C. with an ice bath. Reaction was maintained at that temperature for half an hour after completion of addition, which took 18 minutes. Analysis by gas chromatography showed a yield of 90% of 2-(3,4-epoxycyclohexyl)ethyltrimethoxysilane. This example demonstrates a standard preparation of 2-(3,4-epoxycyclohexylethyltrimethoxysilane using commercial chloroplatinic acid.
Reaction SMILES: CS(OCC([N:9]1[C:22]2[CH:21]=[C:20]([C:23]#[N:24])[CH:19]=[CH:18][C:17]=2[S:16][C:15]2[C:10]1=[CH:11][CH:12]=[CH:13][CH:14]=2)C)(=O)=O.N1CCCC1>C1(C)C=CC=CC=1>[CH:21]1[C:22]2[NH:9][C:10]3[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=3)[S:16][C:17]=2[CH:18]=[CH:19][C:20]=1[C:23]#[N:24]
Reactant: CC(COS(C)(=O)=O)N1c2ccccc2Sc2ccc(C#N)cc21
Solvent: Cc1ccccc1
Solvent: C1CCNC1
Product: N#Cc1ccc2c(c1)Nc1ccccc1S2
Reaction time: 24 h
Yield: 87.6 %

Procedure:
A mixture of (2RS)-2-(2-cyano-10-phenothiazinyl)-1-propyl methanesulphonate (10 g) and pyrrolidine (11.6 cc) in toluene (50 cc) is brought to 90° C. with stirring for 24 hours. After cooling, the mixture is concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. and the residue is taken up with ethyl ether (200 cc) and 4N aqueous sodium hydroxide solution (15 cc). After stirring for 10 minutes, settling is allowed to take place and the organic phase is washed with saturated aqueous sodium chloride solution (3×25 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 20° C. The residual oil (11.3 g) is dissolved in 0.5N aqueous hydrochloric acid solution (60 cc). This solution is washed with ethyl ether (100 cc), then alkalinized with an excess of N aqueous sodium hydroxide solution and extracted with ethyl ether (100 cc). The organic phase is washed with saturated aqueous sodium chloride solution (50 cc), dried over magnesium sulphate, filtered and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 20° C. The residual yellow oil (9.5 g) is purified on a column (height: 30 cm; diameter: 5.8 cm) on silica gel (0.04-0.063 mm) under a slight excess pressure of nitrogen (40 kPa), eluting with a mixture (95:5 by volume) (one litre) of methylene chloride and methanol and collecting 100-cc fractions. Fractions 3 to 10 are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 40° C. 10-[2RS]-1-(1-Pyrrolidinyl)-2-propyl]-2-phenothiazinecarbonitrile (5.45 g) is thereby obtained in the form of a yellow oil.
Reaction SMILES: [C:1]1([C:7]2[C:8]([NH2:12])=[N:9][O:10][N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:13]([O:18]CC)(=[O:17])[C:14]([CH3:16])=O.[Li+].[OH-]>O1CCOCC1>[C:1]1([C:7]2[C:8]([NH:12][CH:14]([C:13]([OH:18])=[O:17])[CH3:16])=[N:9][O:10][N:11]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: Nc1nonc1-c1ccccc1
Reactant: CCOC(=O)C(C)=O
Agent: [Li+]
Agent: [OH-]
Solvent: C1COCCO1
Product: CC(Nc1nonc1-c1ccccc1)C(=O)O

Procedure:
Following General Procedure II-D and using 4-phenyl-furazan-3-ylamine (Maybridge) and ethyl pyruvate (Aldrich), the ethyl ester was prepared. Following General Procedure II-A, Method B (LiOH/H20/dioxane) and using the ethyl ester, the title compound was prepared.
Reaction SMILES: [C:1]1([CH2:11][NH:12][C:13]([CH:15]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:16](O)=[O:17])=[O:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C(N1C=CN=C1)(N1C=CN=C1)=O.ClCCl.[NH2:41][C@H:42]([C:49]([NH:51][C@H:52]([CH:57]=[N:58][NH:59][C:60]([NH2:62])=[O:61])[CH2:53][CH:54]([CH3:56])[CH3:55])=[O:50])[CH2:43][C:44]1[N:48]=[CH:47][NH:46][CH:45]=1>CN(C)C=O.C(N(CC)CC)C>[C:1]1([CH2:11][NH:12][C:13]([CH:15]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:16]([NH:41][C@H:42]([C:49]([NH:51][C@H:52]([CH:57]=[N:58][NH:59][C:60]([NH2:62])=[O:61])[CH2:53][CH:54]([CH3:56])[CH3:55])=[O:50])[CH2:43][C:44]2[N:48]=[CH:47][NH:46][CH:45]=2)=[O:17])=[O:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: CC(C)C[C@@H](C=NNC(N)=O)NC(=O)[C@@H](N)Cc1c[nH]cn1
Reactant: O=C(O)C(Cc1ccccc1)C(=O)NCc1cccc2ccccc12
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CC(C)C[C@@H](C=NNC(N)=O)NC(=O)[C@H](Cc1c[nH]cn1)NC(=O)C(Cc1ccccc1)C(=O)NCc1cccc2ccccc12
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 12.6 %

Procedure:
A mixture of 102 mg of (±)-2-(1-naphthylmethylcarbamoyl)-3-phenylpropionic acid and 50 mg of 1,1'-carbonyldiimidazole was added to 5 ml of dichloromethane, and the mixture was stirred for 40 minutes at room temperature. The reaction mixture was added to a solution of 202 mg of L-histidyl-L-leucinal semicarbazone.2p-toluenesulfonic acid salt and 0.09 ml of triethylamine in 3 ml of N,N-dimethylformamide, and the mixture was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure, and a 5% aqueous sodium bicarbonate solution was added to the residue. The mixture was extracted with ethyl acetate, dried and concentrated under reduced pressure. The residue was purified by preparative silica gel thin layer chromatography (developing solvent: lower layer of chloroform/methanol/water=8/3/1 by volume) to obtain 24 mg of N-[(±)-2-(1-naphthylmethylcarbamoyl)-3-phenylpropionyl]-L-histidyl-L-leucinal semicarbazone as a white powder.
Reaction SMILES: [NH2:1][C:2]1[C:3]([F:12])=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6].N1C=CC=CC=1.[F:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=1[S:27](Cl)(=[O:29])=[O:28]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[F:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=1[S:27]([NH:1][C:2]1[C:3]([F:12])=[C:4]([CH:9]=[CH:10][CH:11]=1)[C:5]([O:7][CH3:8])=[O:6])(=[O:29])=[O:28]
Reactant: O=S(=O)(Cl)c1cc(F)ccc1F
Reactant: COC(=O)c1cccc(N)c1F
Agent: CN(C)c1ccncc1
Solvent: c1ccncc1
Solvent: ClCCl
Product: COC(=O)c1cccc(NS(=O)(=O)c2cc(F)ccc2F)c1F
Temperature: 0 °C
Reaction time: 8 h

Procedure:
To a solution of methyl 3-amino-2-fluorobenzoate (21.8 g, 129 mmol) in DCM (300 mL) were added pyridine (30.6 g, 387.6 mmol) and a catalytic amount of DMAP. The mixture was cooled to 0° C. 2,5-Difluorobenzene-1-sulfonyl chloride (28.8 g, 136 mmol) in DCM (20 mL) was added dropwise to the mixture. The reaction was stirred at rt overnight. The reaction mixture was washed with water (300 mL), and extracted with DCM (2×200 mL). The organic layer was washed with brine, dried over anhydrous NaSO4, filtered and concentrated under reduced pressure to give the crude product, which was washed with petroleum ether to afford the title compound of Step A. (16 g, 35.9%). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.71-10.91 (br, 1H), 7.65-7.73 (m, 1H), 7.48-7.62 (m, 4H), 7.20-7.28 (m, 1H), 3.77 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[I:9].[F:10][C:11]([F:23])([F:22])[C:12]1[N:17]=[C:16]([CH3:18])[C:15]([C:19](Cl)=[O:20])=[CH:14][CH:13]=1>>[Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH:6][C:19]([C:15]2[C:16]([CH3:18])=[N:17][C:12]([C:11]([F:23])([F:10])[F:22])=[CH:13][CH:14]=2)=[O:20])=[CH:4][C:3]=1[I:9]
Reactant: Cc1nc(C(F)(F)F)ccc1C(=O)Cl
Reactant: Nc1ccc(Cl)c(I)c1
Product: Cc1nc(C(F)(F)F)ccc1C(=O)Nc1ccc(Cl)c(I)c1

Procedure:
Procedure D was performed with 4-chloro-3-iodoaniline (225 mg, 0.889 mmol) and 6-(trifluoromethyl)-2-methylpyridine-3-carbonyl chloride (237 mg, 0/93 mmol, 1.05 eq) at 0° C. for 30 minutes. The crude residue was purified by silica gel chromatography (2-50% ethyl acetate/hexanes) to yield N-(4-chloro-3-iodophenyl)-6-(trifluoromethyl)-2-methylpyridine-3-carboxamide as a white solid.
Reaction SMILES: [N:1]1([C:6]2[CH:14]=[CH:13][C:9]([C:10]([OH:12])=O)=[CH:8][CH:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:15][CH2:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][OH:24])=[CH:19][CH:18]=1.ON1C2C=CC=CC=2N=N1.C(Cl)CCl>CN(C1C=CN=CC=1)C.N1C=CC=CC=1>[OH:24][CH2:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][NH:15][C:10](=[O:12])[C:9]2[CH:8]=[CH:7][C:6]([N:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)=[CH:14][CH:13]=2)=[CH:18][CH:19]=1
Reactant: O=C(O)c1ccc(N2CCCC2)cc1
Reactant: NCc1ccc(CO)cc1
Agent: CN(C)c1ccncc1
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: c1ccncc1
Product: O=C(NCc1ccc(CO)cc1)c1ccc(N2CCCC2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 78.5 %

Procedure:
To a mixture of 4-pyrrolidin-1-ylbenzoic acid (2.0 g, 10.5 mmol), (4-aminomethylphenyl)methanol (4.3 g, 31.4 mmol), 1-hydroxybenzotriazole (1.7 g, 12.6 mmol), and DMAP (256 mg, 2.1 mmol) in pyridine (50 mL) was added EDC (3.0 g, 15.7 mmol), and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and an aqueous NaHCO3 solution (50 mL) was added. The mixture was extracted with 5% MeOH in CHCl3 (150 mL×2), and the organic layer was dried (MgSO4) and evaporated under reduced pressure. The crude product was purified by MPLC on silica gel (3% MeOH in CHCl3) to afford the titled compound (2.56 g, 79%) as a white solid.
Reaction SMILES: C([O:8][C:9]([CH:11]1[CH2:15][CH:14]([CH2:16][CH:17]=[CH:18][CH2:19][CH3:20])[CH2:13][N:12]1[CH2:21][C:22]1[N:23]([CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[CH:24]=[CH:25][N:26]=1)=[O:10])C1C=CC=CC=1.C1COCC1.O.O.[OH-].[Li+]>O>[CH2:27]([N:23]1[CH:24]=[CH:25][N:26]=[C:22]1[CH2:21][N:12]1[CH2:13][CH:14]([CH2:16][CH:17]=[CH:18][CH2:19][CH3:20])[CH2:15][CH:11]1[C:9]([OH:10])=[O:8])[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1
Reactant: CCC=CCC1CC(C(=O)OCc2ccccc2)N(Cc2nccn2Cc2ccccc2)C1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CCC=CCC1CC(C(=O)O)N(Cc2nccn2Cc2ccccc2)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 95.2 %

Procedure:
To a stirred solution of 1-(1-benzyl-1H-imidazol-2-ylmethyl)-4-pent-2-enyl-pyrrolidine-2-carboxylic acid benzyl ester (257.2 mg, 0.6 mmol, 1 equiv) in a 4:1 THF/H2O (8 mL), at room temperature, was added lithium hydroxide monohydrate (250 mg, 5.96 mmol, 10 equiv). The resulting reaction mixture was stirred at room temperature overnight, and evaporated to dryness. The residue obtained was dissolved in water (10 mL), and the pH of the resulting solution was adjusted to between 3 and 4, and extracted with EtOAc (3×100 mL). The combined organic extracts were washed with brine, dried over Na2SO4, filtered, and evaporated to dryness, affording the acid product 1-(1-Benzyl-1H-imidazol-2-ylmethyl)-4-pent-2-enyl-pyrrolidine-2-carboxylic acid (202 mg, 98%): Rf=0.4 (7:2:1 CH2Cl2/hexanes/MeOH), KMnO4 visualization stain; MS (ESPOS): 355 [M+H]+; MS (ESNEG): 352 [M−H]−.
Reaction SMILES: Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[CH3:13][C:14]1[CH:26]=[CH:25][C:24]([NH2:27])=[CH:23][C:15]=1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17].[C:28]([C:32]([CH2:34][N:35]1[C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=2[N:39]([CH:46]2[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]2)[CH2:38][CH:37]([NH2:52])[C:36]1=[O:53])=[O:33])([CH3:31])([CH3:30])[CH3:29]>O1CCCC1.C(N(CC)CC)C>[C:28]([C:32]([CH2:34][N:35]1[C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][C:40]=2[N:39]([CH:46]2[CH2:51][CH2:50][CH2:49][CH2:48][CH2:47]2)[CH2:38][CH:37]([NH:52][C:2]([NH:27][C:24]2[CH:25]=[CH:26][C:14]([CH3:13])=[C:15]([C:16]([O:18][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:17])[CH:23]=2)=[O:4])[C:36]1=[O:53])=[O:33])([CH3:31])([CH3:29])[CH3:30]
Reactant: CC(C)(C)C(=O)CN1C(=O)C(N)CN(C2CCCCC2)c2ccccc21
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: Cc1ccc(N)cc1C(=O)OC(C)(C)C
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: Cc1ccc(NC(=O)NC2CN(C3CCCCC3)c3ccccc3N(CC(=O)C(C)(C)C)C2=O)cc1C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 235.2 %

Procedure:
Under ice-cooling, triphosgene (205 mg) was added to a solution of tert-butyl 2-methyl-5-aminobenzoate (383 mg) in anhydrous tetrahydrofuran (40 ml), triethylamine (825 μl) was added thereto five times over 15 minutes after divided into five portions. After the mixture was stirred at room temperature for 5 minutes, a solution of 1-tert-butylcarbonylmethyl-2-oxo-3-amino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (600 mg) in anhydrous tetrahydrofuran (10 ml) was added under ice-cooling. The resultant mixture was stirred at room temperature for one hour, the reaction mixture was poured into ice-water, extracted with ethyl acetate, and the organic layer was washed with saturated brine. After dried over anhydrous sodium sulfate, the solvent was evaporated under reduced pressure, diisopropyl ether was added to the residue for crystallization, and collected by filtration, to thereby obtain 960 mg of the title compound (Yield: 97%).
Reaction SMILES: [C:1]([O:4][C@H:5]1[CH2:22][C@@:20]2([CH3:21])[C@@H:16]([CH2:17][CH:18]=[C:19]2[S:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C@H:15]2[C@@:6]1([F:32])[C@:7]1([CH3:31])[C:12]([CH2:13][CH2:14]2)=[CH:11][C:10](=[O:30])[CH:9]=[CH:8]1)(=[O:3])[CH3:2].[CH2:33]([SH:35])[CH3:34].B(F)(F)F.CCOCC>ClCCl.C(Cl)(Cl)Cl>[C:1]([O:4][C@H:5]1[CH2:22][C@@:20]2([CH3:21])[C@@H:16]([CH2:17][CH2:18][C:19]2([S:35][CH2:33][CH3:34])[S:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[C@H:15]2[C@@:6]1([F:32])[C@:7]1([CH3:31])[C:12]([CH2:13][CH2:14]2)=[CH:11][C:10](=[O:30])[CH:9]=[CH:8]1)(=[O:3])[CH3:2]
Reactant: CCS
Reactant: CC(=O)O[C@H]1C[C@]2(C)C(Sc3ccccc3)=CC[C@H]2[C@@H]2CCC3=CC(=O)C=C[C@]3(C)[C@@]12F
Agent: FB(F)F
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Solvent: CCOCC
Product: CCSC1(Sc2ccccc2)CC[C@H]2[C@@H]3CCC4=CC(=O)C=C[C@]4(C)[C@@]3(F)[C@@H](OC(C)=O)C[C@@]21C
Temperature: -10 °C
Reaction time: 2.5 h

Procedure:
A solution of 1.0 g of 11β-acetyloxy-9-fluoro-17-(phenylthio)androsta-1,4,16-trien-3-one, 12 ml of dry dichloromethane and 0.5 ml of ethanethiol is cooled to -10° C. under nitrogen. Boron trifluoride etherate is then added. The solution is stirred at -10° C. under nitrogen for 2.5 hours. The resulting solution is diluted with dichloromethane, washed with saturated sodium bicarbonate and water, dried over anhydrous Na2SO4 and evaporated in vacuo to give a foamy solid. This is dissolved in chloroform and chromatographed on two precoated silica gel TLC plates (E. Merck, 20 cm×20 cm×2 mm, 1:4 ethyl acetate-chloroform for development) to give 800 mg of slightly impure title compound. This is crystallized from ethyl acetate-hexane to give 500 mg of title compound, melting point 145°-148° C., with consistent spectral data.
Reaction SMILES: CC1(C)[O:6][C@H:5]([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([CH2:15][CH2:16][CH2:17][CH:18]([NH:27]S(C(C)(C)C)=O)/[CH:19]=[N:20]/S(C(C)(C)C)=O)=[CH:11][CH:10]=2)[CH2:4][O:3]1.[CH2:35]([Mg]Cl)[CH2:36][CH3:37].C([Mg])CC>C1COCC1.C(OCC)C>[NH2:27][CH:18]([CH:19]([NH2:20])[CH2:35][CH2:36][CH3:37])[CH2:17][CH2:16][CH2:15][C:12]1[CH:11]=[CH:10][C:9]([O:8][CH2:7][C@@H:5]([OH:6])[CH2:4][OH:3])=[CH:14][CH:13]=1
Reactant: CCC[Mg]Cl
Reactant: CC1(C)OC[C@@H](COc2ccc(CCCC(/C=N/S(=O)C(C)(C)C)NS(=O)C(C)(C)C)cc2)O1
Agent: CCC[Mg]
Solvent: CCOCC
Solvent: C1CCOC1
Product: CCCC(N)C(N)CCCc1ccc(OC[C@@H](O)CO)cc1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a solution of 2-methyl-propane-2-sulfinic acid (4-[4-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-phenyl]-1-{[(E)-2-methyl-propane-2-sulfinylimino]-methyl}-butyl)-amide (907 mg, 1.7 mmol) in THF (20 ml) at 0° C. n-propylmagnesium chloride (1.76 ml of a 2M solution in diethyl ether, 3.52 mmol). The solution is stirred at 0° C. for 30 minutes then at room temperature for 3 hours. A further portion of n-propylmagnesium (1.76 ml of a 2M solution in diethyl ether, 3.52 mmol) is added and the mixture is stirred at room temperature overnight. The resulting mixture is quenched with sat. aq. NH4Cl solution (50 ml) and extracted with EtOAc (2×50 ml). The organic phase is dried (MgSO4) and concentrated in vacuo. The residue is dissolved in EtOAc (10 ml) and treated with 4M HCl/dioxan (10 ml). After 10 minutes, the solution is concentrated in vacuo and the residue diluted with DCM (100 ml). This is treated with sat. aq. NaHCO3 solution (100 ml) and the organic phase is removed and dried (MgSO4). The DCM solution is applied to a SCX-2 cartridge (10 g) and this is eluted with DCM and MeOH. The product is released with 2M NH3 in MeOH, and the methanolic ammonia fraction concentrated to give (S)-3-[4-(4,5-Diamino-octyl)-phenoxy]-propane-1,2-diol as a mixture of diastereomers as a gum; [M+H]+ 515.38
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][N:3]=1.[Cl:9][CH2:10][C:11]([CH2:13]Cl)=O.COCCOC>C(O)C>[Cl:9][CH2:10][C:11]1[N:1]=[C:2]2[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][N:3]2[CH:13]=1
Reactant: O=C(CCl)CCl
Reactant: Cc1ccnc(N)c1
Solvent: CCO
Solvent: COCCOC
Product: Cc1ccn2cc(CCl)nc2c1
Reaction time: 2.5 h
Yield: 1.8 %

Procedure:
A mixture of 2-amino-4-picoline (Aldrich; 500 g), 1,3-dichloroacetone (Aldrich; 5.89 g), and 1,2-dimethoxyethane (Aldrich; 44 mL) is stirred for 25 min at 53° C., at which time ethanol (47.5 mL) is added. After stirring for 2.5 h at reflux, the mixture is concentrated under reduced pressure and the residue is partitioned between dichloromethane and saturated sodium bicarbonate and brine. The organic layers are dried over MgSO4 and concentrated under reduced pressure. The crude material is chromatographed on silica gel using methanol/dichloromethane (1/99 to 2/98) to give, after crystallization from dichloromethane/hexane, 3.06 g of product. A portion of this material is dissolved in dichloromethane and refluxed with activated charcoal for 30 min. The activated charcoal is removed by filtration through a pad of diatomaceous earth and the filtrate is atmospherically concentrated, at which time hexane is added. The resulting solids are filtered, washed with hexane, and vacuum dried to give 0.15 g of 2-(chloromethyl)-7-methylimidazo[1,2-a]pyridine; mp 250° C. (decomp); ms m/z 180, 182; IR (mineral oil) 774, 1649, 1504, 1252, 701 cm-1 ; 1H NMR (CDCl3) δ 2.39, 4.75, 6.63, 7.32, 7.53, 7.95.
Reaction SMILES: C(O[C:5]1[CH:10]=[CH:9][C:8]([N:11]([C:16]([O:18][CH2:19][CH:20]=[CH2:21])=[O:17])[CH2:12][C:13]([OH:15])=O)=[C:7](N=C=O)[CH:6]=1)C=C.[CH2:25]([O:28][C:29](=[O:65])[C:30]([N:50]1[C@H:53]([SH:54])[C@@H:52]([C@H:55]([O:57][C:58]([O:60][CH2:61][CH:62]=[CH2:63])=[O:59])[CH3:56])[C:51]1=[O:64])=[P:31]([C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)([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)[CH:26]=[CH2:27]>[Ag]>[CH2:25]([O:28][C:29](=[O:65])[C:30]([N:50]1[C@H:53]([S:54][C:13](=[O:15])[CH2:12][N:11]([C:8]2[CH:7]=[CH:6][C:5]([NH:11][C:16]([O:18][CH2:19][CH:20]=[CH2:21])=[O:17])=[CH:10][CH:9]=2)[C:16]([O:18][CH2:19][CH:20]=[CH2:21])=[O:17])[C@@H:52]([C@H:55]([O:57][C:58]([O:60][CH2:61][CH:62]=[CH2:63])=[O:59])[CH3:56])[C:51]1=[O:64])=[P:31]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)([C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH:26]=[CH2:27]
Reactant: C=CCOC(=O)N(CC(=O)O)c1ccc(OCC=C)cc1N=C=O
Reactant: C=CCOC(=O)O[C@H](C)[C@H]1C(=O)N(C(C(=O)OCC=C)=P(c2ccccc2)(c2ccccc2)c2ccccc2)[C@@H]1S
Agent: [Ag]
Product: C=CCOC(=O)Nc1ccc(N(CC(=O)S[C@@H]2[C@@H]([C@@H](C)OC(=O)OCC=C)C(=O)N2C(C(=O)OCC=C)=P(c2ccccc2)(c2ccccc2)c2ccccc2)C(=O)OCC=C)cc1

Procedure:
Analogously to Example 1, 2.67 g of N-(4-allyloxy-carbonylaminophenyl)-N-(allyloxycarbonyl)-glycine are converted with 3.5 g of the silver salt of 2-[(3S,4R)-3-[(1R)-1-allyloxycarbonyloxyethyl]-4-mercapto-2-oxo-azetidin-1-yl]-2-triphenylphosphoranylideneacetic acid allyl ester into the title compound.
Reaction SMILES: [NH2:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[N:8]1[CH:17]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=2[Cl:25])[CH:16]([C:26]([OH:28])=[O:27])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:29].[CH2:30](O)[CH3:31].S(=O)(=O)(O)O.C(OCC)(=O)C>O>[NH2:1][CH:2]1[CH2:7][CH2:6][CH2:5][CH2:4][CH:3]1[N:8]1[CH:17]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=2[Cl:25])[CH:16]([C:26]([O:28][CH2:30][CH3:31])=[O:27])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]1=[O:29]
Reactant: CCO
Reactant: NC1CCCCC1N1C(=O)c2ccccc2C(C(=O)O)C1c1ccc(Cl)cc1Cl
Agent: O=S(=O)(O)O
Solvent: CCOC(C)=O
Solvent: O
Product: CCOC(=O)C1c2ccccc2C(=O)N(C2CCCCC2N)C1c1ccc(Cl)cc1Cl

Procedure:
To 4.33 g of (3RS,4RS)-2-[(1SR,2SR)-2-aminocyclohexyl]-3-(2,4-dichlorophenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic acid were added 50 ml of ethanol and 2 ml of concentrated sulfuric acid, followed by heating under reflux overnight. Ethyl acetate and water were added thereto to carry out a liquid separation operation, and the organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate and then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate) to obtain 2.3 g of ethyl(3RS,4RS)-2-[(1SR,2SR)-2-aminocyclohexyl]-3-(2,4-dichlorophenyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate as a yellow foam.
Reaction SMILES: [CH:1]1([N:11]2[C:15]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][N:13]=[C:12]2S)[CH:10]2[CH:5]([CH2:6][CH2:7][CH2:8][CH2:9]2)[CH2:4][CH2:3][CH2:2]1.[N+:21]([O-:24])([OH:23])=[O:22].N([O-])=O.[Na+].[OH-].[Na+]>O>[N+:21]([O-:24])([OH:23])=[O:22].[CH:1]1([N:11]2[C:15]([C:16]([O:18][CH3:19])=[O:17])=[CH:14][N:13]=[CH:12]2)[CH:10]2[CH:5]([CH2:6][CH2:7][CH2:8][CH2:9]2)[CH2:4][CH2:3][CH2:2]1
Reactant: COC(=O)c1cnc(S)n1C1CCCC2CCCCC21
Agent: O=N[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: O=[N+]([O-])O
Solvent: O
Product: COC(=O)c1cncn1C1CCCC2CCCCC21
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 39.4 %

Procedure:
A mixture of 77.7 parts of methyl 1-(decahydro-1-naphthalenyl)-2-mercapto-1H-imidazole-5-carboxylate, 157 parts of nitric acid, 300 parts of water and 0.2 parts of sodium nitrite was stirred for 1.5 hours at room temperature. The reaction mixture was poured into crushed ice and treated with a sodium hydroxide solution. The product was extracted with dichloromethane. The extract was dried, filtered and evaporated. The residue was converted into the nitrate salt in 1,1'-oxybisethane. The salt was filtered off and dried, yielding 33.9 parts (39.4%) of methyl 1-(decahydro-1-napthalenyl)-1H-imidazole-5-carboxylate mononitrate; mp. 148.6° C. (compound 1.03).