Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C@H:9]1[C@H:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@H:14]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@H:13]([CH3:32])[O:12][CH:10]1[OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1C[O:36][CH2:35][CH2:34]1>ClCCCl.C(OC(=O)C)(=O)C.N1C=CC=CC=1.C(OCC)(=O)C>[C:35]([O:11][CH:10]1[O:12][C@@H:13]([CH3:32])[C@@H:14]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@@H:15]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[C@@H:9]1[O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)(=[O:36])[CH3:34]
Reactant: C[C@@H]1OC(O)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@@H]1OCc1ccccc1
Reactant: C1CCOC1
Solvent: c1ccncc1
Solvent: ClCCCl
Solvent: CC(=O)OC(C)=O
Product: CC(=O)OC1O[C@@H](C)[C@@H](OCc2ccccc2)[C@@H](OCc2ccccc2)[C@@H]1OCc1ccccc1
Temperature: 25 °C
Reaction time: 22 h
Yield: 99 %

Procedure:
To a stirred solution of 500 g of 2,3,4-tri-O-benzyl-L-fucopyranose (1.15 mole) (Pfanstiehl, Inc.) in 500 ml 1,2-dichloroethane or 550 ml THF, 240 ml acetic anhydride, 135 ml pyridine was added, and the mixture stirred at room temperature for 22 hours. Subsequently, the reaction was diluted with ethyl acetate, washed with water, saturated with sodium bicarbonate and again with water. The solvents were moved in vacuo and azeotroped with toluene. The white solid was placed on a vacuum line, which afforded 542 g (99%) of 1-O-Acetyl-2,3,4-tri-O-benzyl-L-fucopyranose as a colorless crystalline solid in a mixture of anomeric acetates, mp=86°-87.5° C. 564.35 g 1-O-Acetyl-2,3,4-tri-O-benzyl-L-fucopyranose (1.19 moles, 1.00 eq.) and 214.6 ml 2-chloromethyl-3-trimethylsilyl-1-propene (1.19 mole, 1.00 eq.) were dissolved in 1.2 l acetonitrile (HPLC grade) and cooled to approximately 0° C. using an ice-water bath. Subsequently, 11.46 ml trimethylsilyltrifluoromethane sulfonate (59.28 mmoles, 0.05 eq.) was carefully added, the ice-water bath was allowed to melt and the reaction slowly warmed to room temperature (18 hours). Completion of the transformation from starting material to product was indicated by TLC. The reaction was terminated by pouring the reaction contents onto 1 l of ice-water, followed by adjustment to room temperature. The resulting mixture was extracted with 1 l ethyl acetate and the organic phase then washed with 1.0N aqueous sodium hydroxide and brine. The organic phase was dried over anhdyrous magnesium sulfate, filtered, and the solvent was removed in vacuo, which afforded 600.5 g of 2-Chloromethyl-3-(tri-O-benzyl-α-L--C-fucopyranoside)-1-propene (1) as light yellow solid. The product was purified either by crystallization in methanol at 0° C., or by column chromatography using Baker grade flash silica gel (47-61 mm) (ratio of 20 to 1), followed by elution with 5 to 10% ethyl acetate in hexanes giving a white solid (98%), mp 47°-49° C. In low scale reactions, the α- to β- ratios of the C-glycosidation reaction, was >10:1 in favor of the α-fucose derivative (Cha, et al., 1982, J. Am. Chem. Soc. 104:4976). The higher the reaction scale, the less β isomer could be observed; at scales in the multi-gram levels, sometimes only trace amounts.
Reaction SMILES: [BH4-].[Na+].[CH:3]([O:6][C:7]([N:9]1[CH2:14][CH2:13][CH:12]([O:15][N:16]=[C:17]2[CH2:22][CH2:21][N:20]([C:23]3[CH:28]=[C:27]([F:29])[C:26]([C:30](=[O:32])[CH3:31])=[CH:25][C:24]=3[F:33])[CH2:19][CH2:18]2)[CH2:11][CH2:10]1)=[O:8])([CH3:5])[CH3:4].C(OCC)(=O)C>CO.C([O-])(O)=O.[Na+]>[CH:3]([O:6][C:7]([N:9]1[CH2:14][CH2:13][CH:12]([O:15][N:16]=[C:17]2[CH2:18][CH2:19][N:20]([C:23]3[CH:28]=[C:27]([F:29])[C:26]([CH:30]([OH:32])[CH3:31])=[CH:25][C:24]=3[F:33])[CH2:21][CH2:22]2)[CH2:11][CH2:10]1)=[O:8])([CH3:5])[CH3:4]
Reactant: CC(=O)c1cc(F)c(N2CCC(=NOC3CCN(C(=O)OC(C)C)CC3)CC2)cc1F
Agent: O=C([O-])O
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: CCOC(C)=O
Product: CC(C)OC(=O)N1CCC(ON=C2CCN(c3cc(F)c(C(C)O)cc3F)CC2)CC1
Reaction time: 1 h

Procedure:
NaBH4 (0.15 g, 3.9 mmol) was added at 0° C. to a stirred solution of 50a (0.15 g, 0.34 mmol) in 5 mL of methanol. After 1 h, the mixture was diluted with 10 mL of saturated NaHCO3 and stirred for 20 minutes. The mixture was poured into ethyl acetate (25 mL), washed twice with brine (25 mL), dried and concentrated under vacuum. The residue was purified on an AS-H column (elution with 5% EtOH+0.1% triethylamine in hexane) to afford the 2 enantiomers of 4-{1-[2,5-difluoro-4-(1-hydroxy-ethyl)-phenyl]-piperidin-4-ylideneaminooxy}-piperidine-1-carboxylic acid isopropyl ester 50-1, LC-MS 422.2 (MFE-18), tR=6.45 (Method 2). EC50: 48 nM. 78 mg of the first enantiomer and 46 mg of the second enantiomer were obtained.
Reaction SMILES: C[O:2][C:3](=[O:22])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([NH:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([OH:20])[CH:15]=2)=[O:11])=[CH:6][C:5]=1[CH3:21].C1(P(=O)(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O.[OH-].[Li+]>O1CCCC1.CO.O>[OH:20][C:16]1[CH:15]=[C:14]([CH:19]=[CH:18][CH:17]=1)[CH2:13][NH:12][C:10]([C:7]1[CH:8]=[CH:9][C:4]([C:3]([OH:22])=[O:2])=[C:5]([CH3:21])[CH:6]=1)=[O:11]
Reactant: COC(=O)c1ccc(C(=O)NCc2cccc(O)c2)cc1C
Agent: O=P(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: Cc1cc(C(=O)NCc2cccc(O)c2)ccc1C(=O)O
Temperature: 25 °C
Reaction time: 4 h
Yield: 34 %

Procedure:
A solution of 4-(methoxycarbonyl)-3-methylbenzoic acid (Example 89; 4.83 g, 24.9 mmol) and triphenylphosphine (7.37 g, 28.1 mmol) in dichloromethane (100 mL) was cooled to ˜0° C. and N-chlorosuccinimide (3.75 g, 28.1 mmol) was added portionwise. The solution was allowed to warm to room temperature and stirred for 30 min. 3-Hydroxybenzylamine (Example 69; 4.00 g, 33.0 mmol) and diisopropylethylamine (4.00 g, 30.9 mmol) were added and the solution was allowed to stir at room temperature for 72 h. The solution was washed with 1N hydrochloric acid solution, water and brine (200 mL each), dried (MgSO4), filtered and evaporated to give a colorless solid (13.34 g) which contained 4-[[(3-hydroxybenzyl)amino]carbonyl]-2-methylbenzoic acid methyl ester and triphenylphosphine oxide. The solid was taken up in tetrahydrofuran/methanol (3:1; 200 mL) and a solution of lithium hydroxide monohydrate (4.00 g, 95.3 mmol) in water (50 mL) was added. The solution was stirred at room temperature for 4 h and then the solvent was evaporated under reduced pressure. The residual material was taken up in a mixture of 1N sodium hydroxide and diethyl ether (200 mL each) and the mixture was filtered to remove undissolved solids. The diethyl ether layer was discarded and the aqueous basic layer of the filtrate was acidified with conc. hydrochloric acid solution to ˜pH 1. The mixture was extracted with ethyl acetate (2×100 mL) and the combined organic layers were washed with brine (200 mL), dried (MgSO4), filtered and evaporated to give 4-[[(3-hydroxybenzyl)amino]carbonyl]-2-methylbenzoic acid as a colorless solid (2.40 g, 34% yield).
Reaction SMILES: [N:1]1[NH:2][N:3]=[N:4][C:5]=1[C:6]1[CH:17]=[CH:16][C:9]([O:10][CH2:11][C:12](OC)=[O:13])=[CH:8][CH:7]=1.O.[NH2:19][NH2:20]>CO>[NH:4]1[C:5]([C:6]2[CH:17]=[CH:16][C:9]([O:10][CH2:11][C:12]([NH:19][NH2:20])=[O:13])=[CH:8][CH:7]=2)=[N:1][N:2]=[N:3]1
Reactant: COC(=O)COc1ccc(-c2nn[nH]n2)cc1
Reactant: NN
Solvent: CO
Solvent: O
Product: NNC(=O)COc1ccc(-c2nnn[nH]2)cc1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 78 %

Procedure:
To a suspension of methyl [4-(2H-tetrazol-5-yl)phenoxy]acetate (1.10 g, 4.06 mmol) in MeOH (30 mL) was added hydrazine hydrate (2.0 mL). After stirring for 90 min at rt, the reaction mixture was evaporated off. The residue was taken up with MeOH (10 mL) and a white solid precipitated out. Filtration, washing with MeOH (2×3 mL) and drying under vacuo at 70° C. for 16 hrs gave 741 mg of the title compound (78%) as a white solid in 99.9% purity by HPLC (MaxPlot detection between 230 and 400 nm).
Reaction SMILES: C(N(CC)CC)C.[NH2:8][CH2:9][CH2:10][C:11]1[N:12]([CH3:25])[N:13]=[C:14]2[C:23]=1[C:22]1[CH2:21][CH2:20][CH2:19][CH2:18][C:17]=1[N:16]=[C:15]2[NH2:24].[CH:26]([N:29]=[C:30]=[O:31])([CH3:28])[CH3:27]>ClCCl.C(Cl)(Cl)Cl>[NH2:24][C:15]1[C:14]2=[N:13][N:12]([CH3:25])[C:11]([CH2:10][CH2:9][NH:8][C:30]([NH:29][CH:26]([CH3:28])[CH3:27])=[O:31])=[C:23]2[C:22]2[CH2:21][CH2:20][CH2:19][CH2:18][C:17]=2[N:16]=1
Reactant: Cn1nc2c(N)nc3c(c2c1CCN)CCCC3
Reactant: CC(C)N=C=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: CC(C)NC(=O)NCCc1c2c3c(nc(N)c2nn1C)CCCC3
Temperature: 4 °C

Procedure:
Triethylamine (2.84 mL, 20.4 mmol) was added to a suspension of 1-(2-aminoethyl)-2-methyl-6,7,8,9-tetrahydro-2H-pyrazolo[3,4-c]quinolin-4-amine (prepared as described in Example 50) (1.0 g, 4.08 mmol) in dichloromethane (50 mL) and cooled to 4° C. Isopropyl isocyanate (0.44 mL, 4.48 mmol) was added dropwise to the reaction mixture and maintained at ambient temperature for 16 hours. The reaction mixture was diluted with chloroform (50 mL) and the precipitate was collected by filtration, washed with water, and dried under reduced pressure to afford N-[2-(4-amino-2-methyl-6,7,8,9-tetrahydro-2H-pyrazolo[3,4-c]quinolin-1-yl)ethyl]-N′-isopropylurea as tan needles, mp 237-238° C.
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][CH:10]=1)[CH:6]=O.C1(P(=[CH:32][CH:33]=[O:34])(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1>[F:1][C:2]([F:12])([F:11])[C:3]1[CH:4]=[C:5](/[CH:6]=[CH:32]/[CH:33]=[O:34])[CH:8]=[CH:9][CH:10]=1
Reactant: O=CC=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: O=Cc1cccc(C(F)(F)F)c1
Solvent: Cc1ccccc1
Product: O=C/C=C/c1cccc(C(F)(F)F)c1
Yield: 51.1 %

Procedure:
3-(Trifluoromethyl)benzaldehyde (0.70 g) was dissolved in toluene (16 mL), and (triphenylphosphoranylidene)acetoaldehyde (1.22 g) was added. The reaction mixture was heated under reflux for 40 hr and concentrated, and the residue was purified by column chromatography (carrier: silica gel, eluent: hexane-ethyl acetate) to give the title compound (0.41 g) as an oil.
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[CH:8][NH:9]2)=[CH:5][CH:4]=1.[CH3:14][N:15]1[CH2:20][CH2:19][C:18](=O)[CH2:17][CH2:16]1>>[F:13][C:2]([F:1])([F:12])[C:3]1[CH:11]=[C:10]2[C:6]([C:7]([C:18]3[CH2:19][CH2:20][N:15]([CH3:14])[CH2:16][CH:17]=3)=[CH:8][NH:9]2)=[CH:5][CH:4]=1
Reactant: FC(F)(F)c1ccc2cc[nH]c2c1
Reactant: CN1CCC(=O)CC1
Product: CN1CC=C(c2c[nH]c3cc(C(F)(F)F)ccc23)CC1
Yield: 88.5 %

Procedure:
Beginning with 1.00 gm (5.4 mMol) 6-trifluoromethyl-1H-indole and 1.33 mL (11.0 mMol) 1-methyl-4-piperidone, 1.34 gm (89%) of the title compound were recovered as colorless crystals.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][S:6](Cl)(=[O:8])=[O:7].[CH2:10]([N:12](CC)CC)C.CN.C1COCC1>ClCCl>[Cl:1][CH2:2][CH2:3][CH2:4][CH2:5][S:6]([NH:12][CH3:10])(=[O:8])=[O:7]
Reactant: CCN(CC)CC
Reactant: O=S(=O)(Cl)CCCCCl
Agent: CN
Solvent: ClCCl
Solvent: C1CCOC1
Product: CNS(=O)(=O)CCCCCl
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 4-chlorobutane-1-sulfonyl chloride (117 mmol) and triethyl amine (117 mmol) in dichloro methane (250 ml) at 0° C. was added a 2M solution of methyl amine in THF (117 mmol) dropwise. The mixture was allowed to warm to room temperature with stirring overnight. The organic solution was washed with H2O and extracted with CH2Cl2, dried over MgSO4 and filtered. The solution was concentrated. The product was used without further purification.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:13])[C:8](Br)=[N:9][C:10]=1[CH3:11])=[O:5])[CH3:2].[C:14]([C:16]1[CH:21]=[CH:20][C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:18][CH:17]=1)#[CH:15]>>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH3:13])[C:8]([C:15]#[C:14][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[CH:18][CH:17]=2)=[N:9][C:10]=1[CH3:11])=[O:5])[CH3:2]
Reactant: C#Cc1ccc(-c2ccccc2)cc1
Reactant: CCOC(=O)c1c(C)nc(Br)n1C
Product: CCOC(=O)c1c(C)nc(C#Cc2ccc(-c3ccccc3)cc2)n1C

Procedure:
The title compound, MS: m/e=345.4 (M+H+) was prepared in accordance with the general method of example 1b from 2-bromo-3,5-dimethyl-3H-imidazole-4-carboxylic acid ethyl ester and 4-ethynylbiphenyl.
Reaction SMILES: O1CCCCC1[O:7][C@@H:8]1[C@@:39]2([CH3:40])[C:12](=[CH:13][CH2:14][C@@H:15]3[C@@H:38]2[CH2:37][CH2:36][C@@:35]2([CH3:41])[C@H:16]3[CH2:17][CH2:18][C@@H:19]2[C@H:20]([CH3:34])[CH2:21][C:22]#[C:23][C:24]([O:27]C2CCCCO2)([CH3:26])[CH3:25])[CH2:11][C@@H:10]([O:42]C2CCCCO2)[CH2:9]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.O>CO>[OH:7][C@@H:8]1[C@@:39]2([CH3:40])[C:12](=[CH:13][CH2:14][C@@H:15]3[C@@H:38]2[CH2:37][CH2:36][C@@:35]2([CH3:41])[C@H:16]3[CH2:17][CH2:18][C@@H:19]2[C@H:20]([CH3:34])[CH2:21][C:22]#[C:23][C:24]([OH:27])([CH3:25])[CH3:26])[CH2:11][C@@H:10]([OH:42])[CH2:9]1
Reactant: C[C@H](CC#CC(C)(C)OC1CCCCO1)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](OC5CCCCO5)C[C@H](OC5CCCCO5)[C@]4(C)[C@H]3CC[C@]12C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: CO
Product: C[C@H](CC#CC(C)(C)O)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](O)C[C@H](O)[C@]4(C)[C@H]3CC[C@]12C
Reaction time: 1 h
Yield: 78.8 %

Procedure:
A solution of 1.0 g (1.5 mmol) of 1α,3β,25-tris[(tetrahydro-2H-pyran-2-yl)oxyl]-cholest-5-en-23-yne in 14 ml of methanol was treated with 50 mg of p-toluenesulphonic acid monohydrate, and the mixture was left at room temperature for 1 hour. 16 ml of water was added dropwise while stirring. The separated material was filtered off under suction and dried. After chromatography on 60 g of silica gel with hexane/ether (1:1) and ethyl acetate, there was obtained 0.49 g (79%) of crystalline 1α,3β,25-trihydroxy-cholest-5-en-23yne of melting point 204°-206° C. Recrystallization of a sample from acetone gave crystals of melting point 205°-206° C.; [α]D25 =-12.6° (c=0.5 in methanol).
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:25]/[O:26][CH3:27])/[C:8]([NH:10][C@@H:11]2[C:23](=[O:24])[N:13]3[C:14]([C:20]([OH:22])=[O:21])=[C:15]([CH2:18]O)[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1.[CH:28]1[N:29]=[CH:30][N:31]2[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=12.C(#N)C.P(OCC)(OCC)OCC>C(N)=O>[NH2:1][C:2]1[S:3][CH:4]=[C:5](/[C:7](=[N:25]/[O:26][CH3:27])/[C:8]([NH:10][C@@H:11]2[C:23](=[O:24])[N:13]3[C:14]([C:20]([O-:22])=[O:21])=[C:15]([CH2:18][N+:29]4[CH:28]=[C:32]5[CH:33]=[CH:34][CH:35]=[CH:36][N:31]5[CH:30]=4)[CH2:16][S:17][C@H:12]23)=[O:9])[N:6]=1
Reactant: c1ccn2cncc2c1
Reactant: CO/N=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)O)=C(CO)CS[C@H]12)c1csc(N)n1
Agent: CCOP(OCC)OCC
Solvent: NC=O
Solvent: CC#N
Product: CO/N=C(\C(=O)N[C@@H]1C(=O)N2C(C(=O)[O-])=C(C[n+]3cc4ccccn4c3)CS[C@H]12)c1csc(N)n1
Temperature: 22.5 °C
Reaction time: 10 h

Procedure:
In 1 ml of formamide were dissolved 413 mg of 7β-[2-(2-aminothiazole-4-yl)-2-(Z)-methoxyiminoacetamido]-3-hydroxymethyl-3-cephem-4 -carboxylic acid and 354 mg of imidazo[1.5-a]pyridine. To the solution were added 1 ml of acetonitrile and 0.86 ml of triethyl phosphite, and the mixture was stirred at 20 to 25° C. for 10 hours. The resultant product was treated by the manner of Example 32 to give 7β-[2-(2-aminothiazol-4-yl)-2-(Z)-methoxyiminoacetamido]-3-(imidazo [1,5-a]pyridinium-2-yl)methyl-3-cephem-4-carboxylate.
Reaction SMILES: C(O)(=O)C.[CH2:5]([NH:12][C:13]1[CH:18]=[CH:17][C:16](/[CH:19]=[CH:20]/[N+:21]([O-:23])=[O:22])=[CH:15][CH:14]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[BH4-].[Na+]>CS(C)=O>[CH2:5]([NH:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][CH2:20][N+:21]([O-:23])=[O:22])=[CH:15][CH:14]=1)[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1
Reactant: O=[N+]([O-])/C=C/c1ccc(NCc2ccccc2)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: CC(=O)O
Product: O=[N+]([O-])CCc1ccc(NCc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 47.5 %

Procedure:
To an acetic acid (5.8 mL) and dimethyl sulfoxide (100 mL) solution of benzyl-(4-((E)-2-nitro-vinyl)-phenyl)-amine (5.82 g, 22.9 mmol) described in Manufacturing Example 68-1-2 was added sodium borohydride (1.39 g, 36.6 mmol) at room temperature while cooling appropriately. This mixture was stirred for 1 hour at room temperature. The mixture was partitioned into ethyl acetate and water. The organic layer was separated, washed with water, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=4:1-2:1) to obtain the title compound (2.79 g, 48%).
Reaction SMILES: C([N+](CCCC)(CCCC)CCCC)CCC.[O:18]=[C:19]1[C@@H:22]([NH:23][C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])[C@H:21]([CH3:34])[N:20]1[S:35]([O-:38])(=[O:37])=[O:36].[OH:39][C:40]1[CH:41]=[CH:42][CH:43]=[C:44]2[C:49]=1[N:48]=[CH:47][CH:46]=[CH:45]2>O.C(#N)C>[OH:39][C:40]1[CH:41]=[CH:42][CH:43]=[C:44]2[C:49]=1[NH+:48]=[CH:47][CH:46]=[CH:45]2.[O:18]=[C:19]1[C@@H:22]([NH:23][C:24]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:25])[C@H:21]([CH3:34])[N:20]1[S:35]([O-:38])(=[O:36])=[O:37]
Reactant: Oc1cccc2cccnc12
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: C[C@H]1[C@H](NC(=O)OCc2ccccc2)C(=O)N1S(=O)(=O)[O-]
Solvent: O
Solvent: CC#N
Product: Oc1cccc2ccc[nH+]c12

Procedure:
(3S-trans)-2-Oxo-3-[[(phenylmethoxy)carbonyl]amino]-4-methyl-1-azetidinesulfonic acid, tetrabutylammonium salt (500 mg, 0.9 mmol) was dissolved in a mixture of water and acetonitrile. The solution was passed through an AGMP-50 ion-exchange resin column (H⊕ form, 7 ml, 1.7 meq/ml) eluting with water. The eluate was run into a flask containing 8-hydroxyquinoline (131 mg, 0.9 mmol). Acetonitrile was removed from the resulting solution under reduced pressure at <35° C. and the remaining aqueous solution was lyophilized yielding a solid. Trituration with ether and drying in vacuo afforded the desired product as a yellow powder (398 mg), melting point 61°-68° C.
Reaction SMILES: [C:1]([NH:4][CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([O:13][CH3:14])[CH:8]=1)(=O)[CH3:2].P(Cl)(Cl)(Cl)=O>C1(C)C=CC=CC=1>[CH3:14][O:13][C:9]1[CH:8]=[C:7]2[C:12](=[CH:11][CH:10]=1)[C:1]([CH3:2])=[N:4][CH2:5][CH2:6]2
Reactant: COc1cccc(CCNC(C)=O)c1
Solvent: O=P(Cl)(Cl)Cl
Solvent: Cc1ccccc1
Product: COc1ccc2c(c1)CCN=C2C
Temperature: 25 °C
Reaction time: 8 h
Yield: 64.2 %

Procedure:
To a stirred solution of N-acetyl-3-methoxyphenethylamine (96.0 g, 0.497 m) in toluene (600 ml) at 15°-20° C. phosphorus oxychloride (190.5 g, 1.24 m) was added dropwise over 2 hours. The reaction was stirred overnight at room temperature, then poured into 1 liter of ice water. The organic layer was washed with dilute HCl (2×300 ml), and the aqueous layers were combined, basified, and extracted with CHCl3 (2×500 ml). The dried chloroform layer (MgSO4) was concentrated to an oil. The oil was dissolved in ether and acidified with HCl gas to yield 55.9 g of the product, 3,4-dihydro-6-methoxy-1-methylisoquinoline, m.p. 206°-207°.
Reaction SMILES: [CH:1]1[CH:2]=[CH:3][C:4]2[C:15](=[O:16])[C:14]3[C:9](=[C:10](O)[CH:11]=[CH:12][C:13]=3O)[C:7](=[O:8])[C:5]=2[CH:6]=1.[NH2:19][CH2:20][CH2:21][N:22]1[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1>O>[N:22]1([CH2:21][CH2:20][NH:19][C:13]2[C:14]3[C:15](=[O:16])[C:4]4[C:5](=[CH:6][CH:1]=[CH:2][CH:3]=4)[C:7](=[O:8])[C:9]=3[C:10]([NH:19][CH2:20][CH2:21][N:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)=[CH:11][CH:12]=2)[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]1
Reactant: O=C1c2ccccc2C(=O)c2c(O)ccc(O)c21
Reactant: NCCN1CCCCC1
Solvent: O
Product: O=C1c2ccccc2C(=O)c2c(NCCN3CCCCC3)ccc(NCCN3CCCCC3)c21
Reaction time: 8 h

Procedure:
A mixture of 4.07 g. or quinizarin, 21.74 g. of N-(2-aminoethyl)piperidine and 26 ml. of water is stirred under reflux for 2 hours and then allowed to stand overnight. The gummy solid is collected and washed with water by centrifugation, giving 1.99 g. of blue-black solid. This solid is dissolved in 15 ml. of chloroform and chromatographed by an abbreviated wet-column procedure on 100 g. of alumina, eluting with chloroform. A total of 180 ml. of eluate is collected in eight separate cuts from the time the eluate turns blue until a black band nears the bottom of the column. Cuts 1-6 are combined and evaporated giving 1.42 g. of blue-black crystals which are recrystallized from ethanol giving 1.35 g. of the desired product as blue-black needles, mp. 140°-141° C. Product dried in vacuo at 78° C. melted at 156°-157° C.
Reaction SMILES: [H-].[Na+].[C:3]([C:7]1[S:11][C:10]([NH:12][N:13]=[CH:14][CH3:15])=[N:9][N:8]=1)([CH3:6])([CH3:5])[CH3:4].[CH3:16][NH:17][C:18](ON=C(C1C=CC=CC=1)C#N)=[O:19].O>C1(C)C=CC=CC=1>[CH3:16][NH:17][C:18](=[O:19])[N:12]([C:10]1[S:11][C:7]([C:3]([CH3:6])([CH3:4])[CH3:5])=[N:8][N:9]=1)[N:13]=[CH:14][CH3:15]
Reactant: CC=NNc1nnc(C(C)(C)C)s1
Reactant: CNC(=O)ON=C(C#N)c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: O
Product: CC=NN(C(=O)NC)c1nnc(C(C)(C)C)s1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 47.3 %

Procedure:
Sodium hydride (0.12 g) was added to a stirred solution of acetaldehyde 5-t-butyl-1,3,4-thiadiazolyl hydrazone (0.99 g) in dry toluene (25 ml), and the mixture was stirred at room temperature for 15 minutes. 2-Methylaminocarbonyloxyimino-2-phenylacetonitrile (1.01 g) was added and the mixture was stirred for a further 2 hours and poured into water (20 ml). The organic phase was separated and dried over magnesium sulphate. The drying agent was filtered off and the toluene evaporated to give a yellow oil, purified by chromatography to give acetaldehyde 4-methyl-2-(5-t-butyl-1,3,4-thiadiazol-2-yl)semicarbazone (0.6 g, 47%) as a pale yellow oil.
Reaction SMILES: [CH3:1][C:2]1[C:7]([NH2:8])=[C:6]([N+:9]([O-:11])=[O:10])[CH:5]=[C:4]([N+:12]([O-:14])=[O:13])[CH:3]=1.C1(C)C=CC=CC=1.ClS([N:26]=[C:27]=[O:28])(=O)=O.ClS(NC(N)=O)(=O)=O>O>[CH3:1][C:2]1[C:7]([NH:8][C:27]([NH2:26])=[O:28])=[C:6]([N+:9]([O-:11])=[O:10])[CH:5]=[C:4]([N+:12]([O-:14])=[O:13])[CH:3]=1
Reactant: Cc1cc([N+](=O)[O-])cc([N+](=O)[O-])c1N
Reactant: O=C=NS(=O)(=O)Cl
Agent: NC(=O)NS(=O)(=O)Cl
Solvent: O
Solvent: Cc1ccccc1
Product: Cc1cc([N+](=O)[O-])cc([N+](=O)[O-])c1NC(N)=O

Procedure:
40 of 6-methyl-2,4-dinitroaniline are stirred for 4 hours at 80° C. in 500 parts of toluene with 34 parts of chlorosulfonyl isocyanate. The suspension of the chlorosulfonyl urea obtained is mixed at 25° C. with 40 parts of water and saponified at 60° C. to give 6-methyl-2,4-dinitrophenyl urea.
Reaction SMILES: [CH:1]1([CH2:9][OH:10])[CH2:6][CH2:5][CH:4]([CH2:7][OH:8])[CH2:3][CH2:2]1.[C:11]([Si:15]([CH3:18])([CH3:17])Cl)([CH3:14])([CH3:13])[CH3:12].N1C=CN=C1.[Br-].[Li+]>CN(C)C=O>[Si:15]([O:8][CH2:7][CH:4]1[CH2:5][CH2:6][CH:1]([CH2:9][OH:10])[CH2:2][CH2:3]1)([C:11]([CH3:14])([CH3:13])[CH3:12])([CH3:18])[CH3:17]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: OCC1CCC(CO)CC1
Agent: [Br-]
Agent: [Li+]
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OCC1CCC(CO)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 57 %

Procedure:
To a solution of cyclohexane-1,4-dimethanol (10.0 g) in N,N-dimethylformamide (100 mL) were added successively tert-butyldimethylchlorosilane (8.9 g) and imidazole (9.5 g), followed by stirring the reaction mixture at room temperature for 16 hours. To the reaction mixture were added ice and saturated aqueous lithium bromide solution, followed by extraction with diethyl ether. The organic layer was washed with saturated aqueous lithium bromide solution and saturated brine, dried and concentrated. The residue was purified by column chromatography on silica gel (ethyl acetate:hexane (volume ratio)=1:9 to 2:3) to give [4-(tert-butyldimethylsilanyloxymethyl)-cyclohexyl]-methano 1 (8.7 g).