Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[C:3](=[O:34])[C:4]2[C:9]([C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=1)=[CH:8][CH:7]=[C:6]([O:21][CH2:22][CH2:23][N:24]1[CH2:29][CH2:28][N:27]([S:30]([CH3:33])(=[O:32])=[O:31])[CH2:26][CH2:25]1)[CH:5]=2.O1CCN(CCOC2C=C3C(C(C4C=CC=CC=4)=C(Br)C3=O)=CC=2)CC1.[F:61][C:62]1[CH:63]=[C:64](B(O)O)[CH:65]=[CH:66][C:67]=1[F:68]>>[F:61][C:62]1[CH:63]=[C:64]([C:2]2[C:3](=[O:34])[C:4]3[C:9]([C:10]=2[C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:18])[F:19])=[CH:13][CH:12]=2)=[CH:8][CH:7]=[C:6]([O:21][CH2:22][CH2:23][N:24]2[CH2:29][CH2:28][N:27]([S:30]([CH3:33])(=[O:32])=[O:31])[CH2:26][CH2:25]2)[CH:5]=3)[CH:65]=[CH:66][C:67]=1[F:68]
Reactant: OB(O)c1ccc(F)c(F)c1
Reactant: CS(=O)(=O)N1CCN(CCOc2ccc3c(c2)C(=O)C(Br)=C3c2ccc(C(F)(F)F)cc2)CC1
Agent: O=C1C(Br)=C(c2ccccc2)c2ccc(OCCN3CCOCC3)cc21
Product: CS(=O)(=O)N1CCN(CCOc2ccc3c(c2)C(=O)C(c2ccc(F)c(F)c2)=C3c2ccc(C(F)(F)F)cc2)CC1
Yield: 49 %

Procedure:
The procedure of Step 7 of Example 1 was repeated except for using 2-bromo-6-[2-(4-(methylsulfonyl)piperazin-1-yl)ethoxy]-3-[4-(trifluoromethyl)phenyl]-1H-inden-1-one obtained in Step 1 of Example 47 as a starting material instead of 6-(2-morpholinoethoxy)-2-bromo-3-phenyl-1H-inden-1-one, and 3,4-difluorophenylboronic acid instead of 3-pyridinylboronic acid, and being purified by prep HPLC (CH3CN/H2O=7:3) to obtain the title compound (49%).
Reaction SMILES: [SH:1][C:2]1[N:7]2[CH:8]=[CH:9][N:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1.Br[CH2:12][CH2:13][CH2:14][Cl:15].C(N(CC)CC)C>C(O)C>[Cl:15][CH2:14][CH2:13][CH2:12][S:1][C:2]1[N:7]2[CH:8]=[CH:9][N:10]=[C:6]2[CH:5]=[CH:4][CH:3]=1
Reactant: ClCCCBr
Reactant: Sc1cccc2nccn12
Solvent: CCO
Solvent: CCN(CC)CC
Product: ClCCCSc1cccc2nccn12
Temperature: 25 °C
Reaction time: 17 h
Yield: 72.1 %

Procedure:
To a suspension of 5-mercaptoimidazo[1,2-a]pyridine (5.02 g, 33.4 mmoles) and 1-bromo-3-chloropropane (5.26 g, 33.4 mmoles) in ethanol (100 ml) was added triethylamine (4.66 ml, 33.4 mmoles) and the mixture was stirred at room temperature for 17 hours. After the solvent was distilled off, chloroform was added to the residue, which was washed with water and dried over anhydrous magnesium sulfate. After the solvent was distilled off, the residue was purified by column chromatography (eluent: ethyl acetate) to obtain 5.46 g of the desired product (72.0%, light brown oily product).
Reaction SMILES: [CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:3]=1[C:13](Cl)=[O:14].[CH3:16][O:17][C:18](=[O:27])[C:19]1[CH:24]=[CH:23][C:22]([CH2:25][NH2:26])=[N:21][CH:20]=1>>[N:21]1[CH:20]=[CH:19][CH:24]=[CH:23][C:22]=1[CH2:25][NH2:26].[CH3:16][O:17][C:18](=[O:27])[C:19]1[CH:24]=[CH:23][C:22]([CH2:25][NH:26][C:13]([C:3]2[C:4]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=3)=[N:5][O:6][C:2]=2[CH3:1])=[O:14])=[N:21][CH:20]=1
Reactant: COC(=O)c1ccc(CN)nc1
Reactant: Cc1onc(-c2ccccc2)c1C(=O)Cl
Product: COC(=O)c1ccc(CNC(=O)c2c(-c3ccccc3)noc2C)nc1
Product: NCc1ccccn1
Yield: 169.6 %

Procedure:
As described for example 1a, 5-methyl-3-phenyl-isoxazole-4-carboxylic acid chloride (0.5 g, 2.26 mmol) was converted, using 6-aminomethyl-nicotinic acid methyl ester (313 mg, 1.88 mmol) (J. Med. Chem. 2002, 45, 5005-5022), instead of 2-picolylamine, to the title compound (0.56 g, 85%) which was obtained as a white solid. MS: m/e: 352.0 [M+H]+.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([OH:10])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].Br[C:12]1[CH:17]=[CH:16][CH:15]=[C:14](Br)[N:13]=1.[C:19](=[O:22])([O-])[O-].[Na+].[Na+]>CN1CCCC1=O>[N+:1]([C:4]1[CH:5]=[C:6]([CH:7]=[CH:8][CH:9]=1)[O:10][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:22][C:19]2[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)[N:13]=1)([O-:3])=[O:2]
Reactant: Brc1cccc(Br)n1
Reactant: O=C([O-])[O-]
Reactant: O=[N+]([O-])c1cccc(O)c1
Agent: [Na+]
Solvent: CN1CCCC1=O
Product: O=[N+]([O-])c1cccc(Oc2cccc(Oc3cccc([N+](=O)[O-])c3)n2)c1
Yield: 93.4 %

Procedure:
A reaction vessel equipped with a stirrer was charged with 15.3 grams (0.11 mol) of 3-nitrophenol, 11.9 grams (0.05 mol) of 2,6-dibromopyridine, 8.5 grams (0.08 mol) of anhydrous sodium carbonate and 100 ml of 1-methyl-2-pyrrolidinone. The mixture was elevated its temperature with stirring under ventilation of nitrogen and reacted at 160°-175° C. for 15 hours. After ending the reaction, the resultant mixture was treated by the same procedure as in Example 11 to give 16.5 grams (93.4% yield) of 2,6-bis(3-nitrophenoxy)pyridine as the intermediate.
Reaction SMILES: [C:1]([O:7][CH2:8][C:9]1[CH:14]=[C:13]([C:15](=[O:17])[CH3:16])[CH:12]=[CH:11][C:10]=1[O:18][CH3:19])(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].CC(O[CH:25](N(C)C)[N:26]([CH3:28])[CH3:27])(C)C.O.CCCC(C)C>C(OC)(C)(C)C>[C:1]([O:7][CH2:8][C:9]1[CH:14]=[C:13]([C:15](=[O:17])/[CH:16]=[CH:25]/[N:26]([CH3:28])[CH3:27])[CH:12]=[CH:11][C:10]=1[O:18][CH3:19])(=[O:6])[C:2]([CH3:4])([CH3:3])[CH3:5]
Reactant: CN(C)C(OC(C)(C)C)N(C)C
Reactant: COc1ccc(C(C)=O)cc1COC(=O)C(C)(C)C
Solvent: COC(C)(C)C
Solvent: CCCC(C)C
Solvent: O
Product: COc1ccc(C(=O)/C=C/N(C)C)cc1COC(=O)C(C)(C)C
Temperature: 54 °C
Yield: 79.6 %

Procedure:
5-acetyl-2-methoxybenzyl pivalate (66.24 g, 251.7 mmol) was added to Bredereck's reagent (175.5 g, 1000.7 mmol) held under a nitrogen atmosphere. The resulting solution was heated at 54° C. for 240 minutes. Water (600 mL) was then added and the mixture allowed to stir for an hour. Methyl tert-butyl ether was then added (500 ml) and the mixture stirred and allowed to settle. The upper organic layer was separated off and retained. Further methyl-tert-butyl ether was then added (500 ml) and the mixture stirred and allowed to settle. The upper organic layer was separated off and combined with the original upper organic layer. The combined organic layers were washed twice with water (2×300 mL), discarding the two lower aqueous washes. Solvent (850 mL) is removed from the reaction by atmospheric distillation and iso-hexane (100 mL) added. The clear solution was allowed to cool to 20° C. whereby a white, crystalline solid was obtained. Further iso-hexane (50 mL) was added and the solid filtered off at around 20° C. The solid was washed twice with fresh iso-hexane (2×100 mL) and dried to constant weight to afford 64 g of the desired 5-[(2E)-3-(dimethylamino)prop-2-enoyl]-2-methoxybenzyl pivalate (2).
Reaction SMILES: C(C[O:5][C:6](=[O:14])[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[OH:13])(O)=O.C(N([CH2:20][CH3:21])CC)C.[OH2:22]>CC(C)=O>[CH3:21][C:20]([O:13][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[C:6]([OH:5])=[O:14])=[O:22]
Reactant: O=C(O)COC(=O)c1ccccc1O
Reactant: CCN(CC)CC
Reactant: O
Solvent: CC(C)=O
Product: CC(=O)Oc1ccccc1C(=O)O
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a mixture of 2-hydroxy-benzoic acid carboxymethyl ester (22.8 grams) and triethylamine (22.6 ml) in acetone (200 ml) was added dichloro linker (10 grams). The reaction mixture was stirred at room temperature for 1 hour and then refluxed for 18 hours. The reaction mixture was poured onto cold water and crude product was extracted into ethyl acetate. It was washed with 5% sodium bicarbonate solution and water, followed by drying over sodium sulphate. The solvent was distilled off and precipitated with diisopropyl alcohol to give 8 grams of pure Aspirin dimer diol as a white powder with a melting point of 99-102° C. The product was characterized by 1H NMR (DMSO-d6) δ 4.40 (s, 2H, CH2), 4.90 (s, 2H, CH2), 5.15 (s, 2H, CH2), 7.05 (m, 2H, Ar), 7.62 (t, 1H, Ar), 7.90 (d, 1H, Ar), 10.30 (s, 1H, ArOH).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([OH:16])=[N:6][C:7]=1[NH:8][CH:9]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.[CH:17]1([NH:24]C2N=C(O)C=CC=2[N+]([O-])=O)CCCCCC1.N#CBr>C(O)C>[NH2:24][C:17]1[N:8]([CH:9]2[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]2)[C:7]2=[N:6][C:5]([OH:16])=[CH:4][CH:3]=[C:2]2[N:1]=1
Reactant: O=[N+]([O-])c1ccc(O)nc1NC1CCCCCC1
Reactant: Nc1ccc(O)nc1NC1CCCCCC1
Agent: N#CBr
Solvent: CCO
Product: Nc1nc2ccc(O)nc2n1C1CCCCCC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
5-Amino-6-(cycloheptylamino)pyridin-2-ol, prepared in a similar manner as the one described in Example 1.3 from 6-(cycloheptylamino)-5-nitropyridin-2-ol (0.225 g, 0.895 mmol), was taken up in ethanol (20 mL). Cyanogen bromide (0.153 g, 1.34 mmol) was then added. The resulting solution was stirred at room temperature overnight. The solvent was removed under reduced pressure. The residue was purified by preparative HPLC to give the title compound (0.004 g). LCMS m/z=247.0 [M+H]+; 1H NMR (400 MHz, acetonitrile-d3) δ ppm 1.50-1.80 (m, 6H), 1.80-2.05 (m, 4H), 2.45-2.55 (m, 2H), 4.25-4.35 (m, 1H), 6.55 (d, J=8.5 Hz, 1H), 7.59 (d, J=8.5 Hz, 1H).
Reaction SMILES: [H-].[Na+].[N:3]1([CH2:8][CH2:9][CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)[CH:7]=[CH:6][N:5]=[N:4]1.Cl[CH2:20][C:21]1[C:22]([CH3:37])=[N:23][C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=2)=[CH:25][CH:26]=1.O>CN(C)C=O>[CH3:37][C:22]1[C:21]([CH2:20][O:18][C:15]2[CH:14]=[CH:13][C:12]([CH2:11][CH2:10][CH2:9][CH2:8][N:3]3[CH:7]=[CH:6][N:5]=[N:4]3)=[CH:17][CH:16]=2)=[CH:26][CH:25]=[C:24]([C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:35])([F:36])[F:34])[CH:28]=2)[N:23]=1
Reactant: Oc1ccc(CCCCn2ccnn2)cc1
Reactant: Cc1nc(-c2cccc(C(F)(F)F)c2)ccc1CCl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1nc(-c2cccc(C(F)(F)F)c2)ccc1COc1ccc(CCCCn2ccnn2)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 88.2 %

Procedure:
29 mg (0.73 mmol) of 60% sodium hydride were added to at 0° C. to a solution of 152 mg (0.70 mmol) 4-(4-[1,2,3]triazol-1-yl-butyl)-phenol in 8.0 ml N,N-dimethylformamide and stirred for 30 min. at 0° C. 200 mg (0.70 mmol) 3-chloromethyl-2-methyl-6-(3-trifluoromethyl-phenyl)-pyridine (WO 2005/049573) were given to the reaction mixture and stirring continued at room temperature (r.t.) overnight. After addition of 16 ml water the mixture was stirred for 1 h, the formed precipitate isolated by filtration, washed with water, water/methanol 1:1, n-heptane, and ether. The residue was dried at 40° C. in vacuum to give 288 mg (88%) of the title compound as beige powder.
Reaction SMILES: [CH3:1][O:2][CH2:3][C@H:4]1[N:8]([C:9]([O:11][C:12]([CH3:15])(C)C)=[O:10])[CH2:7][C@@H:6]([C:16](O)=O)[CH2:5]1.[CH2:19](Br)[C:20]1C=C[CH:23]=[CH:22][CH:21]=1.C[N:28](C=O)C>>[CH3:1][O:2][CH2:3][C@H:4]1[N:8]([C:9]([O:11][CH2:12][C:15]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:10])[CH2:7][C@@H:6]([C:16]#[N:28])[CH2:5]1
Reactant: CN(C)C=O
Reactant: BrCc1ccccc1
Reactant: COC[C@@H]1C[C@H](C(=O)O)CN1C(=O)OC(C)(C)C
Product: COC[C@@H]1C[C@H](C#N)CN1C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 85 %

Procedure:
cis-5-Methoxymethyl-Boc-3-Pyrrolidine Benzyl Ester Acid {cis-Boc-(5-MOM)-PCA-OBn} 4.8. cis-5-Methoxymethyl-Boc-3-pyrrolidine carboxylic acid (1.4 g, 5.3 mmol) was dissolved in DMF (26.5 mL). CS2CO3 (1.73 g, 5.3 mmol) and benzyl bromide (0.76 mL, 6.4 mmol) were added, and the reaction mixture was stirred 24 h at room temperature. The reaction mixture was concentrated, and the residue was dissolved in H2O. The aqueous solution was extracted with ethyl acetate. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by column chromatography eluting with ethyl acetate/hexanes (1/1, v/v) to afford 1.88 g (85% yield) of the desired product as an oil.
Reaction SMILES: [N+:1]([CH:4]=[C:5]1[NH:10][CH2:9][CH2:8][CH2:7][S:6]1)([O-:3])=[O:2].C(N(CC)CC)C.Cl[C:19]([O:21][CH2:22][CH2:23][Br:24])=[O:20]>ClCCl>[Br:24][CH2:23][CH2:22][O:21][C:19]([N:10]1[CH2:9][CH2:8][CH2:7][S:6][C:5]1=[CH:4][N+:1]([O-:3])=[O:2])=[O:20]
Reactant: O=[N+]([O-])C=C1NCCCS1
Reactant: O=C(Cl)OCCBr
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(OCCBr)N1CCCSC1=C[N+](=O)[O-]
Temperature: 0 °C
Yield: 79.2 %

Procedure:
To a mixture of 12.8 g 2-nitromethylene-tetrahydro-2H-1,3-thiazine, 21 ml triethylamine and 120 ml dichloro methane was added dropwise over 75 minutes, at -30° C. under nitrogen, a solution of 18 g 2-bromoethyl chloroformate in 100 ml dichloro methane. The reaction mixture was allowed to warm to 0° C., over 30 minutes, with stirring, and then washed with 2% hydrochloric acid. The organic phase was separated off and dried (MgSO4), and the solvent was evaporated off. The solid material (27.2 g) was purified on a silica gel column using a 199:1 mixture (vol/vol) of dichloro methane and methanol, to yield 19.7 g of crystals, having a melting point of 79°-81° C.
Reaction SMILES: [CH2:1]([C@@H:8]1[CH2:12]OC(=O)[N:9]1[C:14](=[O:36])[CH:15]([CH2:19][C:20]1[C:25]([Cl:26])=[CH:24][C:23]([O:27]CC2C=CC=CC=2)=[CH:22][C:21]=1[Cl:35])[CH2:16][CH:17]=O)[C:2]1C=CC=CC=1.NC1CC[O:41][CH2:40]C1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[Cl:26][C:25]1[CH:24]=[C:23]([OH:27])[CH:22]=[C:21]([Cl:35])[C:20]=1[CH2:19][C@@H:15]1[CH2:16][CH2:17][N:9]([CH:8]2[CH2:1][CH2:2][O:41][CH2:40][CH2:12]2)[C:14]1=[O:36]
Reactant: NC1CCOCC1
Reactant: O=CCC(Cc1c(Cl)cc(OCc2ccccc2)cc1Cl)C(=O)N1C(=O)OC[C@H]1Cc1ccccc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCl
Product: O=C1[C@H](Cc2c(Cl)cc(O)cc2Cl)CCN1C1CCOCC1
Yield: 71.6 %

Procedure:
Treat a solution of 4-(4-(R)-benzyl-2-oxo-oxazolidin-3-yl)-3-(4-benzyloxy-2,6-dichloro-benzyl)-4-oxo-butyraldehyde (Preparation 27) (10.4 g, 20 mmol) and 4-aminotetrahydropyran (2 g, 20 mmol) in dichloromethane (100 mL) with acetic acid (1 mL, 20 mmol). Stir the reaction 1 hr at room temperature then add sodium triacetoxyborohydride (12.6 g, 60 mmol) and stir for an additional 4 hr at room temperature. Quench with water and separate the organic layer. Wash with brine, dry over magnesium sulfate, filter, and remove the solvent under vacuum. Purify by silica gel column chromatography using hexanes:ethyl acetate to afford 4.93 g (57%) of desired product: MS (m/z): 434 (M+).
Reaction SMILES: [Br:1]Br.[CH3:3][O:4][N:5]=[C:6]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[CH3:17])[C:7]([O:9][CH3:10])=[O:8]>ClC(Cl)(Cl)Cl.C(OCC)(=O)C.O>[CH3:3][O:4][N:5]=[C:6]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[CH2:17][Br:1])[C:7]([O:9][CH3:10])=[O:8]
Reactant: CON=C(C(=O)OC)c1ccccc1C
Reactant: BrBr
Solvent: ClC(Cl)(Cl)Cl
Solvent: CCOC(C)=O
Solvent: O
Product: CON=C(C(=O)OC)c1ccccc1CBr
Yield: 45.7 %

Procedure:
21.4 g (0.133 mole) of bromine are added to 27.5 g (0.133 mole) of 2-methylphenylglyoxylic acid methyl ester O-methyloxime dissolved in 400 ml of tetrachloromethane, while stirring. Thereafter, the mixture is refluxed for four hours with exposure to a 300 W Hg vapor lamp. It is thenevaporated down, the residue is taken up in ethyl acetate/water and the solution is washed with H2O, dried with sodium sulfate and evaporated down. The crude product is purified by chromatography over silica gel using 9:1 cyclohexane/ethyl acetate. 17.4 g (46%) of the abovementioned compound is obtained as an oil.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([O:17][CH2:18][C:19]([F:22])([F:21])[F:20])=[N:10][CH:11]=[C:12]([CH:16]=2)[C:13](O)=[O:14])=[CH:4][C:3]=1[CH3:23].[F:24][C:25]([F:34])([F:33])[C:26]1[N:30]=[C:29]([CH2:31][NH2:32])[O:28][N:27]=1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([O:17][CH2:18][C:19]([F:22])([F:20])[F:21])=[N:10][CH:11]=[C:12]([CH:16]=2)[C:13]([NH:32][CH2:31][C:29]2[O:28][N:27]=[C:26]([C:25]([F:24])([F:33])[F:34])[N:30]=2)=[O:14])=[CH:4][C:3]=1[CH3:23]
Reactant: NCc1nc(C(F)(F)F)no1
Reactant: Cc1cc(-c2cc(C(=O)O)cnc2OCC(F)(F)F)ccc1Cl
Product: Cc1cc(-c2cc(C(=O)NCc3nc(C(F)(F)F)no3)cnc2OCC(F)(F)F)ccc1Cl

Procedure:
The title compound was synthesized in analogy to Example 1 using 5-(4-chloro-3-methylphenyl)-6-(2,2,2-trifluoroethoxy)nicotinic acid (example BJ) and 3-trifluoromethyl-[1,2,4]oxadiazol-5-methanamine (example AK) as starting materials; LC-MS (UV peak area/ESI) 100%, 493.0523 (M+H)+.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]=1[CH:12]=[O:13].[H-].[Na+].Br[CH2:17][CH2:18][CH:19]([CH3:21])[CH3:20]>C1COCC1>[CH2:17]([O:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]=1[CH:12]=[O:13])[CH2:18][CH:19]([CH3:21])[CH3:20]
Reactant: O=Cc1c(O)ccc2ccccc12
Reactant: CC(C)CCBr
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)CCOc1ccc2ccccc2c1C=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
2-Hydroxy-1-naphthaldehyde (1.72 g, 10.0 mmol) and THF (50 ml) were combined in a flask. NaH (312 mg, 13 mmol) was added, followed by 1-bromo-3-methylbutane (1.20 mL, 10.0 mmol). The solution was stirred at room temperature overnight, the solvent was removed in vacuo, and the residue was purified by chromatography (5–10% ethyl acetate/hexane): 1H NMR (400 MHz, CDCl3) δ 10.9 (s, 1H), 9.28 (dd, 1H, J=0.7 Hz, 8.6 Hz), 8.02 (d, 1H, J=9.1 Hz), 7.75 (d, 1H, J=8.1 Hz), 7.63–7.59 (m, 1H), 7.43–7.39 (m, 1H), 7.27 (d, 1H, J=9.2 Hz), 4.25 (t, 2H, J=6.5 Hz), 1.98–1.84 (m, 1H), 1.80–1.75 (m, 2H), 0.99 (d, 6H, J=6.6 Hz); ESMS m/e: 242.8 (M+H)+.
Reaction SMILES: [C:1]1(P([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)C2C=CC=CC=2)[CH:6]=CC=[CH:3][CH:2]=1.[C:20]1(C)C=CC=C[CH:21]=1>C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Rh]>[CH2:6]=[CH:1][CH:2]=[CH2:3].[CH2:20]=[CH:21][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: Cc1ccccc1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Agent: [Rh]
Agent: [Cl-]
Product: C=CC=C
Product: C=Cc1ccccc1
Temperature: 100 °C

Procedure:
The multiblock copolymer prepared as described above (30 grams) in toluene (200 milliliters) was combined with triphenylphosphine (6 grams) and tris(triphenylphosphine)rhodium chloride (1 gram) in toluene (50 milliliters) in a 500 milliliter Parr pressure reaction vessel. The mixture was purged with hydrogen, sealed, charged to 200 psi with hydrogen, and then heated with stirring to 100° C. The hydrogen pressure was increased to 800 psi. The hydrogen pressure was maintained above 600 psi for 24 hours at 100° C. with stirring. The reaction mixture was added to methanol. The precipitate was washed with water, acidic methanol, and then methanol. The precipitate was collected by filtration, and vacuum dried to yield 30 grams of brown powder. The copolymer was reprecipitated from methylene chloride (10 weight percent solids) into methanol (1 gallon) and then vacuum dried. The polymer was about 78 percent hydrogenated; 95 percent of the 1,2-vinyl groups and 54 percent of the 1,4-conformers were hydrogenated. The glass transition temperature measured using DSC was broad and centered near 54° C. The polymer was formulated into toner by melt extrusion, 92 weight percent, with 6 percent of REGAL 330® and 2 percent of TP-302™ (Nachem) followed by micronization. The minimum fix temperature of the toner was 230° F. and the hot offset temperature was between 280° and 300° F.
Reaction SMILES: [CH2:1]([S:4][C:5]1[C:6](=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:7]([OH:9])=[O:8])[CH:2]=[CH2:3].[SH:14]C(O)C.[CH2:18]([C:22](C)=[O:23])C(C)C>>[OH:23][CH2:22][CH2:18][S:14][CH2:3][CH2:2][CH2:1][S:4][C:5]1[C:6](=[CH:10][CH:11]=[CH:12][CH:13]=1)[C:7]([OH:9])=[O:8]
Reactant: C=CCSc1ccccc1C(=O)O
Reactant: CC(=O)CC(C)C
Reactant: CC(O)S
Product: O=C(O)c1ccccc1SCCCSCCO
Temperature: 80 °C

Procedure:
The allylthiosalicylic acid (194 parts) was dissolved in 427 parts of methyl isobutyl ketone. To the solution was added 78 parts of mercaptoethanol, and the mixture was heated at 80° C. for 8 hours with stirring and with introduction of nitrogen gas to obtain a hydroxyethylthiopropylthiosalicylic acid solution containing about 39% of solids. To the solution (699 parts) thereafter cooled to 50° C. were added the following compounds, and the mixture was heated at 50° C. for 7 hours in a nitrogen gas atmosphere to obtain a monomer C solution.
Reaction SMILES: O1CCCC1.[CH:6]([O:9][C:10](=[O:33])[C@H:11]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([N+:30]([O-])=O)=[CH:26][CH:25]=1)[NH:12][C:13](=[O:22])[C:14]1[C:19]([Cl:20])=[CH:18][CH:17]=[CH:16][C:15]=1[Cl:21])([CH3:8])[CH3:7].[S].[H][H]>[Pt].CC(O)C>[CH:6]([O:9][C:10](=[O:33])[C@H:11]([CH2:23][C:24]1[CH:25]=[CH:26][C:27]([NH2:30])=[CH:28][CH:29]=1)[NH:12][C:13](=[O:22])[C:14]1[C:15]([Cl:21])=[CH:16][CH:17]=[CH:18][C:19]=1[Cl:20])([CH3:8])[CH3:7]
Reactant: [H][H]
Reactant: CC(C)OC(=O)[C@H](Cc1ccc([N+](=O)[O-])cc1)NC(=O)c1c(Cl)cccc1Cl
Agent: [Pt]
Agent: [S]
Solvent: CC(C)O
Solvent: C1CCOC1
Product: CC(C)OC(=O)[C@H](Cc1ccc(N)cc1)NC(=O)c1c(Cl)cccc1Cl
Temperature: 10 °C

Procedure:
To 80 mL of tetrahydrofuran, there was added 31.3 g (content: about 50 wt %) of the wet crystals of Nα-(2,6-dichlorobenzoyl)-4-nitro-L-phenylalanine isopropyl ester at room temperature in a nitrogen gas atmosphere and the mixture was then stirred. To the mixture, there were added 80 mL of 2-propanol and 0.86 g of 3% Pt—S/C (wet product, obtained by applying platinum onto carbon and then poisoning the same with sulfur), hydrogen gas was then introduced into the reaction system and the reaction system was stirred at ordinary pressure. The reaction system was stirred at room temperature overnight as it was, and then the catalyst was removed from the reaction solution by filtration through Celite after the confirmation of the progress of the reaction according to HPLC. The resulting filtrate (initial amount of 178 g) was concentrated by distilling the solvent off under reduced pressure till the amount of the filtrate reached 91 g and 40 mL of 2-propanol was added to the concentrate to thus adjust the concentration of the condensate. To this liquid whose concentration had been adjusted, there was dropwise added 150 mL of water at room temperature to thus separate out a crystalline solid and the resulting suspension was maintained at a temperature of not higher than 10° C. overnight. The resulting crystals were filtered off, washed with 100 mL of water and the resulting wet crystals were dried at 60° C. under reduced pressure to thus give 13.16 g of the title compound as a white crystalline solid (overall yield of these two steps: 86%).
Reaction SMILES: C([O:3][C:4](=O)[CH2:5][CH2:6][CH2:7][N:8]1[CH2:13][CH2:12][CH:11]([O:14][CH:15]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:10][CH2:9]1)C.[H-].[H-].[H-].[H-].[Li+].[Al+3].O>CCOCC>[CH:15]([O:14][CH:11]1[CH2:12][CH2:13][N:8]([CH2:7][CH2:6][CH2:5][CH2:4][OH:3])[CH2:9][CH2:10]1)([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: CCOC(=O)CCCN1CCC(OC(c2ccccc2)c2ccccc2)CC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Solvent: O
Product: OCCCCN1CCC(OC(c2ccccc2)c2ccccc2)CC1
Yield: 43 %

Procedure:
The compound obtained from step 1 (0.4 g) was dissolved in ether, and cooled in an ice bath. LiAlH4 (0.1 g) was added slowly to the solution. The resulting mixture was reacted at room temperature for 1 hr. before adding water to end the reaction. The resulting solution was then extracted by using water and ester. An organic solution layer was dehydrated over magnesium sulfate, filtered, and concentrated under reduced pressure. The column chromatography was performed thereon, thereby obtaining crude yellowish liquid product (0.15, 43% yield) of the title.