Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[CH2:10]([C:14]1[CH:21]=[CH:20][C:17]([CH:18]=O)=[CH:16][CH:15]=1)[CH2:11][CH2:12][CH3:13].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1C=CC=CC=1>[CH2:10]([C:14]1[CH:15]=[CH:16][C:17]([CH:18]=[N:1][C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=2)=[CH:20][CH:21]=1)[CH2:11][CH2:12][CH3:13]
Reactant: N#Cc1ccc(N)cc1
Reactant: CCCCc1ccc(C=O)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: c1ccccc1
Product: CCCCc1ccc(C=Nc2ccc(C#N)cc2)cc1

Procedure:
A mixture of 11.8 g. of p-aminobenzonitrile and 16.2 g. of p-n-butylbenzaldehyde in 200 ml. of benzene is treated with 300 mg. of p-toluenesulfonic acid and reacted as described in Example 1. After the addition of 3 g. of solid potassium carbonate, the mixture is filtered and evaporated, whereby there are obtained 27.0 g. of a yellow oil which crystallizes with cooling. Purification is carried out by several recrystallizations from isopropanol as described in Example 1. The p-[(p-n-butylbenzyliden)amino]benzonitrile which is obtained has a melting point of 38.1°-38.7° C. and a clearing point of 62.6° C. UV (ethanol): ε280 = 24900 (shoulder at 314 nm). The nuclear magnetic resonance, mass spectrum, infrared and microanalysis data confirm the structure.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[C:9]([C:17]1[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][C:18]=1[F:24])=[CH:10][C:11]1[N:15]([CH3:16])[N:14]=[N:13][N:12]=1.C([Li])CCC.[CH:30](OCC)=[O:31]>O1CCCC1>[F:24][C:18]1[CH:19]=[C:20]([CH3:23])[CH:21]=[CH:22][C:17]=1[C:9]([C:3]1[CH:4]=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=1[F:1])=[C:10]([C:11]1[N:15]([CH3:16])[N:14]=[N:13][N:12]=1)[CH:30]=[O:31]
Reactant: CCOC=O
Reactant: Cc1ccc(C(=Cc2nnnn2C)c2ccc(C)cc2F)c(F)c1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: Cc1ccc(C(=C(C=O)c2nnnn2C)c2ccc(C)cc2F)c(F)c1
Reaction time: 0.25 h
Yield: 37.3 %

Procedure:
To a solution of 1,1-bis(2-fluoro-4-methylphenyl)-2-(1-methyl-1H-tetrazol-5-yl)ethene (1.6 g, 5.0 mmoles) in tetrahydrofuran (20 mL) at -78° C. was added butyl lithium (2.3 mL of a 2.2M solution, 5 mmoles). After stirring for 15 minutes, ethyl formate (0.44 g, 6.0 mmoles) was added and the solution stirred with cooling for 2 hours. The reaction was quenched with 1N hydrochloric acid and the mixture extracted with diethyl ether. The extracts were dried (MgSO4) and evaporated. The residue was crystallized from isopropyl acetate to give 0.66 g of the title compound; m.p.=154°-155° C.
Reaction SMILES: [CH3:1][CH:2]([S:5][C:6]1[CH:11]=[CH:10][C:9]([SH:12])=[CH:8][CH:7]=1)[CH2:3][CH3:4].C(=O)([O-])[O-].[K+].[K+].Br[CH2:20][CH2:21][N:22]1[C:26](=[O:27])[C:25]2=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]2[C:23]1=[O:32].O>CN(C=O)C>[CH3:1][CH:2]([S:5][C:6]1[CH:7]=[CH:8][C:9]([S:12][CH2:20][CH2:21][N:22]2[C:26](=[O:27])[C:25]3=[CH:28][CH:29]=[CH:30][CH:31]=[C:24]3[C:23]2=[O:32])=[CH:10][CH:11]=1)[CH2:3][CH3:4]
Reactant: CCC(C)Sc1ccc(S)cc1
Reactant: O=C1c2ccccc2C(=O)N1CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCC(C)Sc1ccc(SCCN2C(=O)c3ccccc3C2=O)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To 4-(1-methylpropylthio)benzenethiol (8.79 g, 44.3 mmol) in 25 ml of DMF is added, under N2, potassium carbonate (7.05 g, 51.0 mmol) followed by dropwise addition of N-(bromoethyl)phthalimide (12.94 g, 51.0 mmol) in 30 ml of DMF. The mixture is stirred at RT overnight. Water is then added and the aqueous phase is extracted with ether. The combined organic layers are washed with 5% sodium hydroxide, with water and with brine, dried and the solvent removed to give N-{2-[4-(1-methylpropylthio)phenylthio]ethyl)phthalimide. Following the procedures of Example 13, the above phthalimide (2.12 g, 5.7 mmol) is reacted with hydrazine hydrate (0.28 ml, 5.7 mmol) to give 2-[4-(1-methylpropylthio)phenylthio]ethylamine.
Reaction SMILES: [C:1]([C:3]1[CH:33]=[CH:32][C:6]([O:7][C:8]2[CH:9]=[C:10]([NH:23][C:24]([CH:26]3[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]3)=[O:25])[CH:11]=[C:12]([O:14][C:15]3[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[CH:17][CH:16]=3)[CH:13]=2)=[CH:5][CH:4]=1)#[N:2].Br[CH2:35][CH:36]1[CH2:38][CH2:37]1>>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([O:7][C:8]2[CH:9]=[C:10]([NH:23][C:24]([CH:26]3[CH2:27][CH2:28][N:29]([CH2:35][CH:36]4[CH2:38][CH2:37]4)[CH2:30][CH2:31]3)=[O:25])[CH:11]=[C:12]([O:14][C:15]3[CH:16]=[CH:17][C:18]([C:21]#[N:22])=[CH:19][CH:20]=3)[CH:13]=2)=[CH:32][CH:33]=1)#[N:2]
Reactant: N#Cc1ccc(Oc2cc(NC(=O)C3CCNCC3)cc(Oc3ccc(C#N)cc3)c2)cc1
Reactant: BrCC1CC1
Product: N#Cc1ccc(Oc2cc(NC(=O)C3CCN(CC4CC4)CC3)cc(Oc3ccc(C#N)cc3)c2)cc1
Yield: 59.4 %

Procedure:
Following the procedure of Example 11(e) 4-[3,5-bis-(4-cyano-phenoxy)-phenyl-carbamoyl]-piperidine 1.5 g (3.42 mmol) and bromomethylcyclopropane (0.647 g, 4.79 mmol) were used to afford 1.0 g of the required product. Percentage purity (LCMS): 73.1%, (M+1)=492.1+1.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH:3]([CH2:7][N:8]2[CH2:17][CH2:16][C:15]3[C:10](=[CH:11][C:12]([O:20][CH3:21])=[C:13]([O:18][CH3:19])[CH:14]=3)[C:9]2=[O:22])[CH2:2]1.[Cl:23][CH2:24][CH2:25][CH2:26][O:27][C:28]1[CH:33]=[C:32]([O:34][CH3:35])[CH:31]=[C:30]([O:36][CH3:37])[CH:29]=1>>[ClH:23].[CH3:35][O:34][C:32]1[CH:33]=[C:28]([CH:29]=[C:30]([O:36][CH3:37])[CH:31]=1)[O:27][CH2:26][CH2:25][CH2:24][N:1]1[CH2:6][CH2:5][CH2:4][CH:3]([CH2:7][N:8]2[CH2:17][CH2:16][C:15]3[C:10](=[CH:11][C:12]([O:20][CH3:21])=[C:13]([O:18][CH3:19])[CH:14]=3)[C:9]2=[O:22])[CH2:2]1
Reactant: COc1cc(OC)cc(OCCCCl)c1
Reactant: COc1cc2c(cc1OC)C(=O)N(CC1CCCNC1)CC2
Product: COc1cc(OC)cc(OCCCN2CCCC(CN3CCc4cc(OC)c(OC)cc4C3=O)C2)c1
Product: Cl

Procedure:
Prepared from 2-[(piperidin-3-yl)-methyl]-6,7-dimethoxy-1-oxo-1,2,3,4-tetrahydro-isoquinoline and 1-chloro-3-(3,5-dimethoxy-phenoxy)-propane analogously to Example 1.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]([C:11]1[CH:16]=[CH:15][N:14]=[C:13]([CH3:17])[CH:12]=1)=[O:10].[F:18][C:19]([F:32])([F:31])[O:20][C:21]1[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1>>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][S:27]([C:24]2[CH:23]=[CH:22][C:21]([O:20][C:19]([F:18])([F:31])[F:32])=[CH:26][CH:25]=2)(=[O:29])=[O:28])=[C:3]([C:9]([C:11]2[CH:16]=[CH:15][N:14]=[C:13]([CH3:17])[CH:12]=2)=[O:10])[CH:4]=1
Reactant: O=S(=O)(Cl)c1ccc(OC(F)(F)F)cc1
Reactant: Cc1cc(C(=O)c2cc(Cl)ccc2N)ccn1
Product: Cc1cc(C(=O)c2cc(Cl)ccc2NS(=O)(=O)c2ccc(OC(F)(F)F)cc2)ccn1

Procedure:
The title compound was prepared according to the general procedure for the synthesis of N-Aryl-benzenesulfonamides previously described using (2-Amino-5-chloro-phenyl)-(2-methyl-pyridin-4-yl)-methanone and 4-trifluoromethoxy-benzenesulfonyl chloride and purified by HPLC. 1H NMR (CDCl3) δ 10.17(s, 1H) 8.63 (d, J=4 Hz, 1H) 7.78 (m, 3H) 7.51 (s, 1H) 7.30 (s, 1H) 7.17 (s, 1H) 7.09 (s, 1H) 6.97 (d, J=4 Hz, 2H) 2.64 (s, 3H). MS (ES) m/z=471.0 (M++1).
Reaction SMILES: [C:1]1([C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4])[OH:2].C(=O)([O-])[O-].[K+].[K+].Cl[C:16]1[N:21]=[CH:20][C:19]([Cl:22])=[CH:18][N:17]=1.O>CN(C)C=O>[Cl:22][C:19]1[CH:18]=[N:17][C:16]([O:2][C:1]2[CH:8]=[CH:7][CH:6]=[CH:5][C:3]=2[OH:4])=[N:21][CH:20]=1
Reactant: Oc1ccccc1O
Reactant: Clc1cnc(Cl)nc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: Oc1ccccc1Oc1ncc(Cl)cn1
Temperature: 25 °C
Reaction time: 8 h
Yield: 57.4 %

Procedure:
To a mixture of 6.0 grams (0.055 mole) catechol and 7.0 grams of potassium carbonate stirring in 45 ml of dimethylformamide, 7.0 grams of 2,5-dichloropyrimidine was added and the mixture stirred at room temperature overnight followed by heating at 80° for 4 hours. Excess water was added to the reaction mixture, and the aqueous mixture extracted with 300 ml of ethyl ether. The ether extract was washed with H2O (2X), brine, dried (magnesium sulfate), filtered, and the solvent removed to yield a yellow oil which slowly crystallized. From a 1-chlorobutane/cyclohexane mixture, the crude solid was recrystallized to give 6.0 grams of product, m.p. 131°-139°; ir (Nujol): 2.90-3.30 (OH), 12.80, 13.30 microns.
Reaction SMILES: [CH3:1][CH:2]([C:8]([O:10][CH2:11][CH3:12])=[O:9])[C:3]([O:5][CH2:6][CH3:7])=[O:4].[H-].[Na+].[Br:15][C:16]1[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[CH:19]=[CH:18][C:17]=1F>CN(C=O)C>[Br:15][C:16]1[CH:21]=[C:20]([N+:22]([O-:24])=[O:23])[CH:19]=[CH:18][C:17]=1[C:2]([CH3:1])([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:8]([O:10][CH2:11][CH3:12])=[O:9]
Reactant: CCOC(=O)C(C)C(=O)OCC
Reactant: O=[N+]([O-])c1ccc(F)c(Br)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)C(C)(C(=O)OCC)c1ccc([N+](=O)[O-])cc1Br
Temperature: 0 °C
Reaction time: 0.05 h
Yield: 98.9 %

Procedure:
Diethyl 2-methylmalonate (4.31 mL, 25.0 mmol) was dissolved in 25 mL of anhydrous DMF. This solution was cooled to 0° C. under an atmosphere of nitrogen. Sodium hydride (1.04 g, 26 mmol, 60% by weight in mineral oil) was slowly added to the solution. The resulting mixture was allowed to stir for 3 minutes at 0° C., and then at room temperature for 10 minutes. 2-Bromo-1-fluoro-4-nitrobenzene (5.00 g, 22.7 mmol) was quickly added and the mixture turned bright red. After stirring for 10 minutes at room temperature, the crude mixture was evaporated to dryness and then partitioned between dichloromethane and a saturated aqueous solution of sodium chloride. The layers were separated and the organic phase was washed twice with a saturated aqueous solution of sodium chloride. The organics were concentrated to yield diethyl 2-(2-bromo-4-nitrophenyl)-2-methylmalonate (8.4 g, 99%) as a pale yellow oil which was used without further purification. Retention time 1.86 min.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[C:12]([NH:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([CH:25]([CH3:27])[CH3:26])=[CH:21][C:20]=3[OH:28])=[N:13][CH:14]=[CH:15][CH:16]=2)=[O:10])=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:48]([NH:55][CH2:56][CH2:57]O)([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49].N(C(OCC)=O)=NC(OCC)=O>O1CCCC1>[C:48]([NH:55][CH2:56][CH2:57][O:28][C:20]1[CH:21]=[C:22]([CH:25]([CH3:26])[CH3:27])[CH:23]=[CH:24][C:19]=1[CH2:18][NH:17][C:12]1[C:11]([C:9]([NH:8][C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[O:10])=[CH:16][CH:15]=[CH:14][N:13]=1)([O:50][C:51]([CH3:54])([CH3:53])[CH3:52])=[O:49]
Reactant: CC(C)(C)OC(=O)NCCO
Reactant: CC(C)c1ccc(CNc2ncccc2C(=O)Nc2ccc(Cl)cc2)c(O)c1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CC(C)c1ccc(CNc2ncccc2C(=O)Nc2ccc(Cl)cc2)c(OCCNC(=O)OC(C)(C)C)c1
Temperature: 25 °C
Reaction time: 72 h
Yield: 33.7 %

Procedure:
To a solution of N-(4-chlorophenyl)-2-[2-hydroxy-4-isopropylbenzylamino]pyridine-3-carboxamide (0.050 g, 0.13 mmol), triphenylphosphine (0.033 g, 0.13 mmol) and N-Boc-ethanolamine (0.018 mg, 0.11 mmol) in 0.3 mL tetrahydrofuran at −10° C. was added a solution of diethyl azodicarboxylate (0.02 mL, 0.13 mmol) in 0.3 mL tetrahydrofuran. The reaction was stirred at room temperature for 3 days. The solvent was removed in vacuo; and the crude material was purified by chromatography over silica, using an eluent gradient of 20-30% ethyl acetate in hexanes, to afford the named product (0.02 g, 30%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]([C:14]3[CH:19]=[CH:18][C:17]([N+:20]([O-])=[O:21])=[CH:16][CH:15]=3)=[CH:12][CH:11]=[N:10]2)=[CH:5][CH:4]=1.[F:23][C:24]1[CH:29]=[CH:28][C:27]([CH2:30]C#N)=[CH:26][CH:25]=1>>[F:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[O:21][N:20]=[C:17]3[CH:18]=[CH:19][C:14]([C:13]4[N:9]([C:6]5[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=5)[N:10]=[CH:11][CH:12]=4)=[CH:15][C:16]=23)=[CH:26][CH:25]=1
Reactant: COc1ccc(-n2nccc2-c2ccc([N+](=O)[O-])cc2)cc1
Reactant: N#CCc1ccc(F)cc1
Product: COc1ccc(-n2nccc2-c2ccc3noc(-c4ccc(F)cc4)c3c2)cc1

Procedure:
The title compound, light green solid (51 mg, 39%), MS (ISP) m/z=386.2 [(M+H)+], mp 179° C., was prepared in accordance with the general method of example 1 from 1-(4-methoxy-phenyl)-5-(4-nitro-phenyl)-1H-pyrazole (intermediate G) (100 mg, 353 μmol) and commercially available 2-(4-fluoro-phenyl)-acetonitrile.
Reaction SMILES: [OH:1][CH2:2][C@@H:3]([NH:14]C(=O)C)[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([N+:11]([O-:13])=[O:12])[CH:6]=1.[ClH:18]>C(OCC)C>[ClH:18].[NH2:14][C@@H:3]([CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([N+:11]([O-:13])=[O:12])[CH:6]=1)[CH2:2][OH:1]
Reactant: CC(=O)N[C@H](CO)Cc1cccc([N+](=O)[O-])c1
Agent: Cl
Solvent: CCOCC
Product: N[C@H](CO)Cc1cccc([N+](=O)[O-])c1

Procedure:
The process is performed as in Example 2, starting with 5.8 g of N-[(1S)-2-hydroxy-1-(3-nitrobenzyl)ethyl]acetamide in 60 cm3 of aqueous 6N hydrochloric acid, for 10 hours at a temperature in the region of 100° C. After cooling the medium, the precipitate is filtered off and then washed with 30 cm3 of acetone and 3 times 50 cm3 of ether, and dried in an oven under reduced pressure (10 Pa) at a temperature in the region of 60° C. The filtrate is concentrated under reduced pressure (5 kPa) at about 5° C. The residue obtained is taken up in 30 cm3 of diethyl ether and the crystals are filtered off, washed with twice 30 cm3 of ether and dried in an oven under the same conditions as above. The 2 crops crystallized are combined. 5.65 g of (2S)-2-amino-3-(3-nitrophenyl)-1-propanol hydrochloride are obtained in the form of a beige-colored solid melting at 188° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:11]2[CH2:15][CH2:14][CH2:13][CH:12]2[CH2:16][C:17]([O-:19])=[O:18])[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.CO.[OH-].[Na+]>O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([N:11]2[CH2:15][CH2:14][CH2:13][CH:12]2[CH2:16][C:17]([OH:19])=[O:18])[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1
Reactant: COc1cc(OC)cc(N2CCCC2CC(=O)[O-])c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: COc1cc(OC)cc(N2CCCC2CC(=O)O)c1

Procedure:
A mixture of 53.6 g. (0.192 mole) methyl dl-2-[1-(3,5-dimethoxyphenyl)pyrrolidin-2-yl]acetate, 250 ml. methanol and 22.8 g. (0.57 mole) sodium hydroxide in 200 ml. water was stirred at room temperature for 2.5 hours. The methanol was evaporated and the aqueous residue cooled in ice. To this was added dropwise 48 ml. concentrated hydrochloric acid, the mixture extracted with 4×150 ml. methylene chloride, the extract washed with water, dried (MgSO4) and the solvent evaporated to afford 48.9 g. (96%) of product. 1H-NMR (CDCl3) ppm (delta): 3.80 (s, 6H, OCH3), 4.10 (m, 1H, N-CH), 5.82 (s, 3H, aromatic), 11.0 (s, 1H, COOH). Mass spectrum (m/e): 206 (base peak), 265 (M+).
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][S:5](Cl)(=[O:7])=[O:6].[NH2:9][C:10]([CH3:14])([CH3:13])[C:11]#[N:12].C(N(CC)CC)C>C(Cl)Cl>[CH3:13][C:10]([NH:9][S:5]([CH2:4][CH2:3][CH2:2][Cl:1])(=[O:7])=[O:6])([CH3:14])[C:11]#[N:12]
Reactant: CC(C)(N)C#N
Reactant: O=S(=O)(Cl)CCCCl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C#N)NS(=O)(=O)CCCCl
Reaction time: 8 h
Yield: 88.1 %

Procedure:
To a stirred mixture of 9.90 g (0.05 mole) 3-chloropropane sulfonyl chloride and 4.71 g (0.056 mole) 2-amino-2-methyl-propionitrile in 100 ml methylene chloride at 0° C., 5.66 g (0.056 mole) triethylamine as a 10% solution in methylene chloride was added very slowly. The reaction mixture was allowed to stir overnight in the gradually melting ice bath. The reaction mixture was washed three times with 50 ml water. The organic layer was dried over calcium sulfate and evaporated to give 9.90 g of the above-identified product as a brown oil.
Reaction SMILES: [CH3:1][CH:2]([CH2:4][CH2:5][CH2:6][C@H:7]([CH2:9][CH2:10][CH2:11][C@H:12]([CH2:14][CH2:15][CH2:16]/[C:17](=[CH:19]/[CH2:20][OH:21])/[CH3:18])[CH3:13])[CH3:8])[CH3:3].[H][H]>C(O)C.[Ni]>[CH2:20]([OH:21])[CH2:19][CH:17]([CH2:16][CH2:15][CH2:14][CH:12]([CH2:11][CH2:10][CH2:9][CH:7]([CH2:6][CH2:5][CH2:4][CH:2]([CH3:3])[CH3:1])[CH3:8])[CH3:13])[CH3:18]
Reactant: C/C(=C\CO)CCC[C@H](C)CCC[C@H](C)CCCC(C)C
Reactant: [H][H]
Agent: [Ni]
Solvent: CCO
Product: CC(C)CCCC(C)CCCC(C)CCCC(C)CCO
Yield: 99.5 %

Procedure:
A solution of phytol (49.3 g, 166 mmol) in ethanol (250 ml) was reduced with hydrogen gas at atmospheric pressure over Raney nickel for 3 days. The catalyst was removed by filtration through Celite® and the filtrate concentrated under reduced pressure to give phytanol (49.3 g, 100%). 1H-n.m.r. (CDCl3) δ0.8-0.95 (m, 15H), 1.0-1.75 (m, 24H), 3.65-3.75 (m, 2H). 13C-n.m.r. (CDCl3) δ19.67 (3×Me), 22.60 (Me), 22.69 (Me), 24.36 (CH2), 24.45 (CH2), 24.78 (CH2), 27.95 (CH), 29.50 (CH), 32.76 (2×CH), 37.28-37.43 (m, 5×CH2), 39.35 (CH2), 39.73 and 40.05 (together CH2), 61.18 (CH2).
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][NH2:11].O=C1CCC(=O)N1[O:19][C:20](=O)[C:21]1[CH:26]=[CH:25][C:24]([O:27][C:28](=[O:37])[N:29]([CH3:36])[C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[CH:23][CH:22]=1>>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][NH:11][C:20]([C:21]1[CH:26]=[CH:25][C:24]([O:27][C:28](=[O:37])[N:29]([CH3:36])[C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)=[CH:23][CH:22]=1)=[O:19]
Reactant: NCc1nc2ccccc2[nH]1
Reactant: CN(C(=O)Oc1ccc(C(=O)ON2C(=O)CCC2=O)cc1)c1ccccc1
Product: CN(C(=O)Oc1ccc(C(=O)NCc2nc3ccccc3[nH]2)cc1)c1ccccc1

Procedure:
The title product was prepared from C-(1H-benzimidazol-2-yl)-methylamine and 4-(methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo-pyrrolidin-1-yl ester. The crude product was subjected to preparative HPLC (method C) (8%, off-white crystals). HPLC-MS m/z=401.1 (M+1), Rt: 2.56 min.
Reaction SMILES: [O:1]=[S:2]1(=[O:23])[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][NH:10][S:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[N+:20]([O-:22])=[O:21])(=[O:13])=[O:12])[CH2:4][CH2:3]1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:31][CH2:32][O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35].C(OCC)(=O)C>CN(C=O)C.O>[Si:34]([O:33][CH2:32][CH2:31][N:10]([CH2:9][CH2:8][N:5]1[CH2:6][CH2:7][S:2](=[O:1])(=[O:23])[CH2:3][CH2:4]1)[S:11]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[N+:20]([O-:22])=[O:21])(=[O:12])=[O:13])([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35]
Reactant: CC(C)(C)[Si](C)(C)OCCBr
Reactant: O=[N+]([O-])c1ccccc1S(=O)(=O)NCCN1CCS(=O)(=O)CC1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OCCN(CCN1CCS(=O)(=O)CC1)S(=O)(=O)c1ccccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 97.6 %

Procedure:
N-(2-(1,1-dioxido-4-thiomorpholinyl)ethyl)-2-nitrobenzenesulfonamide (0.400 g, 1.10 mmol) was combined with cesium carbonate (0.538 g, 1.65 mmol) in DMF (5 mL). The slurry was stirred at rt for 30 min, then to it was added (2-bromoethoxy)(tert-butyl)dimethylsilane (0.527 g, 2.20 mmol). The resulting mixture was stirred at rt for 18 h. Dilution with ethyl acetate (60 mL) and water (40 mL) followed by shaking gave a separation of phases. The organic phase was isolated, washed with water (2×30 mL) and brine (25 mL), dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to a residue. Purification by silica gel chromatography (gradient 100% DCM to 100:1 DCM:MeOH) gave the title compound as a yellow solid (0.560 g, 98% yield). LCMS: m/z 522 (M+H+), retention time 2.22 min (method 11). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 0.01 (s, 6H) 0.86 (s, 9H) 2.75 (t, J=5.95 Hz, 2H) 3.05 (s, 8H) 3.44 (t, J=5.49 Hz, 2H) 3.57 (t, J=6.41 Hz, 2H) 3.70 (t, J=5.49 Hz, 2H) 7.63-7.78 (m, 3H) 8.02-8.11 (m, 1H).
Reaction SMILES: [O:1]=[C:2]1[CH2:7][CH2:6][CH2:5][O:4][C@@H:3]1[C@H:8]1[N:11]([Si](C)(C)C)[C:10](=[O:16])[C@@H:9]1[C@H:17]([O:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[CH3:18].[CH2:24]([O:27][C:28]([N:30]1[CH2:34][CH:33]([S:35]S(C2C=CC=CC=2)(=O)=O)[CH2:32][N:31]1[C:45]([O:47][CH2:48][CH:49]=[CH2:50])=[O:46])=[O:29])[CH:25]=[CH2:26].C1(S(=O)(SC)=O)C=CC=CC=1>>[CH2:24]([O:27][C:28]([N:30]1[CH2:34][CH:33]([S:35][CH:7]2[CH2:6][CH2:5][O:4][C@H:3]([C@H:8]3[NH:11][C:10](=[O:16])[C@@H:9]3[C@H:17]([O:19][Si:20]([CH3:23])([CH3:22])[CH3:21])[CH3:18])[C:2]2=[O:1])[CH2:32][N:31]1[C:45]([O:47][CH2:48][CH:49]=[CH2:50])=[O:46])=[O:29])[CH:25]=[CH2:26]
Reactant: C=CCOC(=O)N1CC(SS(=O)(=O)c2ccccc2)CN1C(=O)OCC=C
Reactant: C[C@@H](O[Si](C)(C)C)[C@H]1C(=O)N([Si](C)(C)C)[C@@H]1[C@H]1OCCCC1=O
Agent: CSS(=O)(=O)c1ccccc1
Product: C=CCOC(=O)N1CC(SC2CCO[C@H]([C@H]3NC(=O)[C@@H]3[C@@H](C)O[Si](C)(C)C)C2=O)CN1C(=O)OCC=C

Procedure:
(3S,4S)-4-[(2R)-3-Oxotetrahydropyran-2-yl]-1-(trimethylsilyl) -3-[(R)-1-(trimethylsilyloxy)ethyl]azetidin-2-one was reacted as in Reference Example 38 except that 1,2-bis(allyloxycarbonyl)-4-phenylsulfonylthiopyrazolidine was used in lieu of S-methyl benzenethiosulfonate to give (3S,4S)-4-[(2R)-4-[[1,2-bis(allyloxycarbonyl)pyrazolidin-4-yl]thio]-3-oxotetrahydropyran-2-yl]-3-[(R)-1-(trimethylsilyloxy)ethyl]azetidin-2-one.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]([O:10][C:11](=[O:34])[NH:12][C:13]1[C:14]([CH3:33])=[N:15][O:16][C:17]=1[C:18]1[CH:23]=[CH:22][C:21](B2OC(C)(C)C(C)(C)O2)=[CH:20][CH:19]=1)[CH3:9].[CH2:35]([O:37][C:38](=[O:48])[CH2:39][C:40]1[CH:45]=[C:44](Br)[CH:43]=[CH:42][C:41]=1[F:47])[CH3:36]>Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[CH2:35]([O:37][C:38](=[O:48])[CH2:39][C:40]1[CH:45]=[C:44]([C:21]2[CH:20]=[CH:19][C:18]([C:17]3[O:16][N:15]=[C:14]([CH3:33])[C:13]=3[NH:12][C:11]([O:10][CH:8]([C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])[CH3:9])=[O:34])=[CH:23][CH:22]=2)[CH:43]=[CH:42][C:41]=1[F:47])[CH3:36]
Reactant: Cc1noc(-c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)c1NC(=O)OC(C)c1ccccc1Cl
Reactant: CCOC(=O)Cc1cc(Br)ccc1F
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Product: CCOC(=O)Cc1cc(-c2ccc(-c3onc(C)c3NC(=O)OC(C)c3ccccc3Cl)cc2)ccc1F

Procedure:
Following the procedure described in Example 17, Step 2, {3-methyl-5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-isoxazol-4-yl}-carbamic acid 1-(2-chloro-phenyl)-ethyl ester, (5-bromo-2-fluoro-phenyl)-acetic acid ethyl ester, and (1,1′-bis(diphenylphosphino)ferrocene)-dichloropalladium(II) were reacted to provide (4′-{-4-[1-(2-chloro-phenyl)-ethoxycarbonylamino]-3-methyl-isoxazol-5-yl}-4-fluoro-biphenyl-3-yl)-acetic acid ethyl ester, which was hydrolyzed to the acid as described in Example 17, Step 3.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:12])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([OH:11])[CH:6]=1.Br[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O.CN(C=O)C>[CH3:1][O:2][C:3](=[O:12])[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH3:14])[CH:6]=1
Reactant: CCCCCCCCCCCCCCCCCCBr
Reactant: COC(=O)Cc1cccc(O)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCCCCCCCOc1cccc(CC(=O)OC)c1
Yield: 79.6 %

Procedure:
A mixture of 1.0 g (6 mmol) of 3-hydroxyphenylacetic acid methyl ester, 2.2 g (6.6 mmol) of 1-bromooctadecane and 3.7 g (27 mmol) of anhydrous potassium carbonate in 80 ml of anhydrous acetone and 15 ml of DMF was stirred at reflux for 67 hours. The solvent was removed at reduced pressure, water was added to the residue and the product was extracted with ethyl acetate. The dried extract was concentrated to a solid which was purified by chromatography on 150 g of silica gel using 10% ethyl acetate-hexane to give 2.0 g (80% yield, mp 43°-45°) of 3-(octadecyloxy) phenylacetic acid methyl ester. The mass and nmr spectra were consistent with the structure.
Reaction SMILES: [CH3:1][N:2]1[C:6]([S:7][CH2:8][CH2:9][Cl:10])=[N:5][N:4]=[N:3]1.C(OC(C1C=C(C(OCC)=O)NN=1)=O)C.Br[CH2:27][CH2:28][Cl:29].BrCCBr>>[CH3:1][N:2]1[C:6]([CH2:27][CH2:28][Cl:29])([S:7][CH2:8][CH2:9][Cl:10])[N:5]=[N:4][NH:3]1.[CH3:1][N:2]1[C:6]([S:7][CH2:8][CH2:9][Cl:10])=[N:5][N:4]=[N:3]1
Reactant: ClCCBr
Agent: CCOC(=O)c1cc(C(=O)OCC)[nH]n1
Agent: Cn1nnnc1SCCCl
Solvent: BrCCBr
Product: CN1NN=NC1(CCCl)SCCCl

Procedure:
When an equivalent amount of 1-methyl-5-(2-chloroethylthio)-1H-tetrazole is substituted for 3,5-diethoxycarbonyl-1H-pyrazole and an equivalent amount of 2-bromochloroethane is substituted for 1,2-dibromoethane in the procedure of Example 4, 2-(1-methyl-5-(2-chloroethylthio)-1H-tetrazol-5-yl)ethyl chloride is isolated after column chromatography 1-methyl-5-(2-chloroethylthio)-1H-tetrazole, Aldrich, 59%, A).