Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11](C(OCC[Si](C)(C)C)=O)[CH2:10][CH:9]2[O:23][CH2:24][C:25]2[CH:34]=[C:33]([OH:35])[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH:26]=2)=[CH:4][CH:3]=1>[F-].C([N+](CCCC)(CCCC)CCCC)CCC>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH:9]2[O:23][CH2:24][C:25]2[CH:34]=[C:33]([OH:35])[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH:26]=2)=[CH:6][CH:7]=1
Reactant: C[Si](C)(C)CCOC(=O)N1CCC(c2ccc(F)cc2)C(OCc2cc(O)c3ccccc3c2)C1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Product: Oc1cc(COC2CNCCC2c2ccc(F)cc2)cc2ccccc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 82.7 %

Procedure:
70 mg (0.141 mmol) of β-trimethylsilylethyl (3RS,4RS)-4-(4-fluorophenyl)-3-(4-hydroxy-naphthalen-2-ylmethoxy)-piperidine-1-carboxylate were dissolved in 1.0 ml of tetrabutylammonium fluoride solution (1M in tetrahydrofuran) and stirred at room temperature for one hour. Subsequently, the mixture was partitioned between methylene chloride and aqueous 5% sodium hydrogen carbonate solution, then the organic phase was dried over magnesium sulphate and finally the solvent was distilled off under reduced pressure. The crude product (72 mg) was purified by chromatography on silica gel with a 10:1:0.1 mixture of methylene chloride, methanol and ammonia as the eluent. There were obtained 41 mg (83% of theory) of (3RS,4RS)-4-(4-fluorophenyl)-3-(4-hydroxy-naphthalen-2-ylmethoxy)-piperidine as a colourless solid. MS: 352 (M+H)+.
Reaction SMILES: C1(=O)[O:6][C:4](=[O:5])[CH:3]=[CH:2]1.[OH-].[Na+].[C:10]([O-:17])(=[O:16])/[CH:11]=[CH:12]\[C:13]([O-:15])=[O:14].[Na+].[Na+].C(O)(=O)C=C.S(OOS([O-])(=O)=O)([O-])(=O)=O.[NH4+].[NH4+].OO>O>[C:4]([OH:6])(=[O:5])[CH:3]=[CH2:2].[C:10]([OH:17])(=[O:16])/[CH:11]=[CH:12]\[C:13]([OH:15])=[O:14]
Reactant: O=C1C=CC(=O)O1
Reactant: O=C([O-])/C=C\C(=O)[O-]
Agent: C=CC(=O)O
Agent: O=S(=O)([O-])OOS(=O)(=O)[O-]
Agent: OO
Solvent: O
Product: O=C(O)/C=C\C(=O)O
Reaction time: 1 h

Procedure:
58.8 g (0.6 mole) of maleic anhydride, 200 g of water, 48 g (1.2 moles) of sodium hydroxide were charged in a flask equipped with a thermometer and a Dimroth condenser. Maleic anhydride was neutralized while performing agitation to prepare an aqueous solution of 30% disodium maleate. After that, the heating was performed to a reflux temperature under the normal pressure. Subsequently, 72 g (0.4 mole) of an aqueous solution of 40% acrylic acid, 50 g of an aqueous solution of 10% ammonium persulfate as an polymerization initiator, and 50 g of an aqueous solution of 14% hydrogen peroxide were gradually added dropwise separately over 4 hours respectively to perform the copolymerization reaction. After the completion of the dropwise addition, the agitation was continued for further 1 hour to complete the copolymerization reaction. After that, the neutralization was performed with 28 g (0.35 mole) of an aqueous solution of 49% sodium hydroxide to obtain an objective substance.
Reaction SMILES: C([O:8][C:9]1[C:14](=[O:15])[N:13]2[CH:16]=[CH:17][N:18]([CH3:19])[C:12]2=[N:11][C:10]=1[C:20]1[S:21][C:22]([CH2:25][C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)=[CH:23][N:24]=1)C1C=CC=CC=1>C(Cl)Cl>[Cl:32][C:29]1[CH:30]=[CH:31][C:26]([CH2:25][C:22]2[S:21][C:20]([C:10]3[N:11]=[C:12]4[N:18]([CH3:19])[CH:17]=[CH:16][N:13]4[C:14](=[O:15])[C:9]=3[OH:8])=[N:24][CH:23]=2)=[CH:27][CH:28]=1
Reactant: Cn1ccn2c(=O)c(OCc3ccccc3)c(-c3ncc(Cc4ccc(Cl)cc4)s3)nc12
Solvent: ClCCl
Product: Cn1ccn2c(=O)c(O)c(-c3ncc(Cc4ccc(Cl)cc4)s3)nc12
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of the product of example 11 (0.135 mmol) in CH2Cl2 (4 ml) was added FeCl3 (66 mg, 0.402 mmol) at room temperature. The mixture was stirred at room temperature for 2 hours, after which CH2Cl2 was evaporated under reduced pressure and ethyl acetate (30 ml) was added. Then the mixture was washed by 1N HCl (10 ml), H2O (10 ml) and brine (10 ml) successively, dried over Na2SO4 and concentrated into about 1 ml. The resulting solids were collected by filtration and washed with cold ethyl acetate (2-3 ml) to give the desired product.
Reaction SMILES: Cl[CH2:2][CH:3]([C:5]1[N:6]([CH3:10])[CH:7]=[CH:8][CH:9]=1)[OH:4].[CH3:11][NH2:12].[BH4-].[Na+]>CO.O>[CH3:11][NH:12][CH2:2][CH:3]([C:5]1[N:6]([CH3:10])[CH:7]=[CH:8][CH:9]=1)[OH:4]
Reactant: CN
Reactant: Cn1cccc1C(O)CCl
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: CNCC(O)c1cccn1C
Temperature: 0 °C
Reaction time: 1 h

Procedure:
2-chloro-1-(1-methyl-1H-pyrrol-2-yl)ethanol (Croce, P. D.; Ferraccioli, R.; Ritieni, A. Synthesis, 1990, 212-213) (2.05 g) is dissolved in methanol (40 mL) and added dropwise to a 2.0 M solution of methylamine in methanol (65 mL) at 0° C. The reaction mixture is stirred at 0° C. for 1 h and then allowed to warm to room temperature. The reaction mixture is stirred at room temperature for 18 h and then cooled to 0° C. Sodium borohydride (0.738 g) in H2O (40 mL) is added dropwise. The reaction mixture is stirred at 0° C. for 30 min and then allowed to warm to room temperature. The reaction mixture is stirred at room temperature for 18 h. An additional 0.738 g (19.5 mmol) of sodium borohydride is added and the reaction mixture is stirred at room temperature for 18 h. The reaction is quenched with a 1 N HCl solution and then concentrated in vacuo to remove methanol. The aqueous layer is adjusted to pH 12 with a 2 N NaOH solution and extracted with CH2Cl2 (4×100 mL). The combined organic layers are dried (MgSO4), filtered, and concentrated in vacuo. The resulting yellow oil is crystallized from ethyl acetate to yield 0.772 g of the title compound as a white solid.
Reaction SMILES: [OH-].[Na+].C1COCC1.[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:31][NH:32][C:33]2[CH:38]=[CH:37][C:36]([C:39]3[CH:44]=[CH:43][C:42]([Cl:45])=[CH:41][CH:40]=3)=[CH:35][CH:34]=2)=[C:13]([C:15]2[CH:16]=[CH:17][C:18]([C:21]([NH:23][CH2:24][CH2:25][C:26]([O:28]CC)=[O:27])=[O:22])=[N:19][CH:20]=2)[CH:14]=1>CO>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([CH2:31][NH:32][C:33]2[CH:38]=[CH:37][C:36]([C:39]3[CH:40]=[CH:41][C:42]([Cl:45])=[CH:43][CH:44]=3)=[CH:35][CH:34]=2)=[C:13]([C:15]2[CH:16]=[CH:17][C:18]([C:21]([NH:23][CH2:24][CH2:25][C:26]([OH:28])=[O:27])=[O:22])=[N:19][CH:20]=2)[CH:14]=1
Reactant: CCOC(=O)CCNC(=O)c1ccc(-c2cc(Cl)ccc2CNc2ccc(-c3ccc(Cl)cc3)cc2)cn1
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CO
Product: O=C(O)CCNC(=O)c1ccc(-c2cc(Cl)ccc2CNc2ccc(-c3ccc(Cl)cc3)cc2)cn1
Temperature: 25 °C

Procedure:
A 3M aqueous solution of NaOH (0.17 mL, 0.52 mmol) was added to a THF (1 mL) and MeOH (0.5 mL) solution of ethyl 3-(5-(5-chloro-2-(((4′-chloro-[1,1′-biphenyl]-4-yl)amino)methyl)phenyl)picolinamido)propanoate (95 mg, 0.17 mmol) and the resulting homogeneous mixture was stirred at room temperature. After 16 h the resulting mixture was concentrated in vacuo, suspended in water, and acidified with 2 M HCl. The resulting precipitate was filtered off and dried in vacuo to yield the title compound.
Reaction SMILES: Br[C:2]1[S:3][C:4]2[C:10]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)=[C:9]([C@H:18]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[C:19]([O:21]CC)=[O:20])[C:8]([CH3:29])=[CH:7][C:5]=2[N:6]=1.C([O-])([O-])=O.[K+].[K+].[CH3:36][N:37]1[C:45]2[C:40](=[CH:41][CH:42]=[C:43](B3OC(C)(C)C(C)(C)O3)[CH:44]=2)[C:39]([N:55]2[CH2:60][CH2:59][N:58]([CH3:61])[CH2:57][CH2:56]2)=[N:38]1.[OH-].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCO.O1CCOCC1.O>[C:25]([O:24][C@@H:18]([C:9]1[C:8]([CH3:29])=[CH:7][C:5]2[N:6]=[C:2]([C:43]3[CH:44]=[C:45]4[C:40]([C:39]([N:55]5[CH2:60][CH2:59][N:58]([CH3:61])[CH2:57][CH2:56]5)=[N:38][N:37]4[CH3:36])=[CH:41][CH:42]=3)[S:3][C:4]=2[C:10]=1[C:11]1[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=1)[C:19]([OH:21])=[O:20])([CH3:28])([CH3:26])[CH3:27]
Reactant: CN1CCN(c2nn(C)c3cc(B4OC(C)(C)C(C)(C)O4)ccc23)CC1
Reactant: CCOC(=O)[C@@H](OC(C)(C)C)c1c(C)cc2nc(Br)sc2c1-c1ccc(Cl)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCO
Solvent: C1COCCO1
Product: Cc1cc2nc(-c3ccc4c(N5CCN(C)CC5)nn(C)c4c3)sc2c(-c2ccc(Cl)cc2)c1[C@H](OC(C)(C)C)C(=O)O
Temperature: 100 °C
Reaction time: 3 h

Procedure:
A vial was charged with (S)-ethyl 2-(2-bromo-7-(4-chlorophenyl)-5-methylbenzo[d]thiazol-6-yl)-2-tert-butoxyacetate (75 mg, 0.151 mmol), KHCO3 (15.2 mg, 0.151 mmol), K2CO3 (41.7 mg, 0.302 mmol), 1-methyl-3-(4-methylpiperazin-1-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (55 mg, 0.154 mmol), Pd(PPh3)4 (17 mg, 15 μmol), H2O (400 μL), and dioxane (1.6 mL). The vessel was sealed and heated to 100° C. for 2 h. Then EtOH (absolute, 800 μL) and 2 M aq NaOH (400 μL) were added. Heating was continued at 100° C. for 3 h. The reaction was cooled to 23° C., and filtered (0.45 micron teflon syringe filter). The filtrate was purified by reverse phase HPLC, eluting by 5-100% acetonitrile in H2O with 0.1% TFA to give the desired product. LCMS-ESI+: calc'd for C33H36ClN5O3S: 618.2, 620.2 (M+H+); Found: 618.3, 620.2 (M+H+). 1H NMR (400 MHz, CD3OD): δ 8.10 (s, 1H), 7.93-7.83 (m, 2H), 7.79-7.65 (m, 2H), 7.64-7.55 (m, 3H), 5.16 (s, 2H), 4.09 (d, J=12.9 Hz, 1H), 3.97 (s, 3H), 3.63 (d, J=8.7 Hz, 2H), 3.39 (d, J=11.5 Hz, 2H), 3.36-3.22 (m, 2H), 3.00 (s, 3H), 2.62 (s, 3H), 0.98 (s, 9H).
Reaction SMILES: [NH2:1][C:2]1[C:3]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([CH2:17][CH2:18][OH:19])=[CH:13][CH:12]=2)=[N:4][C:5]([CH3:9])=[CH:6][C:7]=1[CH3:8].[C:20]([CH2:24][C:25](Cl)=[O:26])([CH3:23])([CH3:22])[CH3:21]>>[CH3:21][C:20]([CH3:23])([CH3:22])[CH2:24][C:25]([O:19][CH2:18][CH2:17][C:14]1[CH:15]=[CH:16][C:11]([N:10]2[C:3]3=[N:4][C:5]([CH3:9])=[CH:6][C:7]([CH3:8])=[C:2]3[N:1]=[C:25]2[CH2:24][C:20]([CH3:23])([CH3:22])[CH3:21])=[CH:12][CH:13]=1)=[O:26]
Reactant: Cc1cc(C)c(N)c(Nc2ccc(CCO)cc2)n1
Reactant: CC(C)(C)CC(=O)Cl
Product: Cc1cc(C)c2nc(CC(C)(C)C)n(-c3ccc(CCOC(=O)CC(C)(C)C)cc3)c2n1

Procedure:
The title compound was prepared according to the procedure described in step 5 of Example 1 from 2-{4-[(3-amino-4,6-dimethyl-2-pyridinyl)amino]phenyl}ethanol (step 4 of Example 1) and tert-butylacetyl chloride.
Reaction SMILES: [CH2:1]([CH2:3][NH2:4])[OH:2].Cl[C:6]1[N:7]=[N:8][CH:9]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH:11]=1.C(OCC)(=O)C.O>O1CCOCC1>[F:18][C:15]1[CH:14]=[CH:13][C:12]([C:10]2[CH:11]=[C:6]([NH:4][CH2:3][CH2:1][OH:2])[N:7]=[N:8][CH:9]=2)=[CH:17][CH:16]=1
Reactant: NCCO
Reactant: Fc1ccc(-c2cnnc(Cl)c2)cc1
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Solvent: O
Product: OCCNc1cc(-c2ccc(F)cc2)cnn1
Temperature: 120 °C

Procedure:
Ethanolamine (4.82 mL, 80 mmol) was added to a stirred mixture of 3-chloro-5-(4-fluorophenyl)pyridazine (2.08 g, 9.97 mmol) in Dioxane (40 mL) in a sealed tube. The mixture was heated to 120° C. overnight, treated with additional ethanolamine (1.2 mL, 20 mmol), and heated to 150° C. for 2 h. The mixture was cooled and poured into ethyl acetate (100 mL) and water (100 mL). The precipitate was filtered and dried to afford the title compound. 1H NMR (500 MHz, CD3SOCD3) δ 8.76 (d, 1H); 7.78 (dd, 2H); 7.36 (t, 2H); 7.02 (d, 1H); 6.85 (t, 1H); 4.78 (t, 1H); 3.58 (q, 2H); 3.45 (q, 2H). LRMS (APCI) calc'd for (C12H13FN3O) [M+H]+, 234.1. found 234.1.
Reaction SMILES: [O:1]([CH2:8][CH2:9][CH2:10]Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:12]([O-:15])(=[S:14])[CH3:13].[K+]>>[O:1]([CH2:8][CH2:9][CH2:10][S:14][C:12](=[O:15])[CH3:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC([O-])=S
Reactant: BrCCCOc1ccccc1
Agent: [K+]
Product: CC(=O)SCCCOc1ccccc1

Procedure:
Prepared in the same manner as Intermediate 3 from 3-phenoxypropyl bromide (8 ml) and potassium thioacetate (7.01 g) to give the title compound (10.35 g) as an orange oil.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:13]=1[C:12](=NO)[CH:11]=[CH:10][C:9]2=[O:16])([O-:3])=[O:2].Cl.[OH2:18]>O.O.O.O.[Fe](Cl)Cl>[N+:1]([C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:13]=1[C:12](=[O:18])[CH:11]=[CH:10][C:9]2=[O:16])([O-:3])=[O:2]
Reactant: O
Reactant: O=C1C=CC(=NO)c2c1cccc2[N+](=O)[O-]
Agent: Cl[Fe]Cl
Agent: Cl
Product: O=C1C=CC(=O)c2c1cccc2[N+](=O)[O-]
Temperature: 40 °C

Procedure:
42 g (0.21 mol) of iron (II) chloride tetrahydrate and 11 g (0.05 mol) of 8-nitro-1,4-naphthoquinone-1-oxime are introduced into 120 ml quantities of the solvents indicated in Table I below. While gaseous hydrogen chloride is slowly passed through them, the mixtures are left to react with continuous stirring at the temperatures indicated in Table I below until the respective reactions are complete. The increases in weight indicated in Table I below are obtained. After the reaction times specified in Table I, the mixtures are poured onto 500 ml of water heated to approximately 40°C, followed by stirring for 30 minutes. The 5-nitro-1,4-naphthoquinone formed is filtered off under suction, washed off under suction, washed with water until neutral and dried at 50°C. The yields of 5-nitro-1,4-naphthoquinone specified in Table I below in g and percent of the theoretical yield are obtained.
Reaction SMILES: [O:1]=[C:2]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C:3]([OH:5])=[O:4].[CH2:12]([Mg]Br)[CH3:13]>O1CCCC1>[OH:1][C:2]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)([CH2:12][CH3:13])[C:3]([OH:5])=[O:4]
Reactant: O=C(O)C(=O)c1ccccc1
Reactant: CC[Mg]Br
Solvent: C1CCOC1
Product: CCC(O)(C(=O)O)c1ccccc1
Reaction time: 5 h

Procedure:
A solution of 2-oxo-2-phenylacetic acid (10 g, 66.6 mmol) (Acros Organics B.V.B.A., Belgium) in tetrahydrofuran (THF, 200 mL) was treated at room temperature with ethylmagnesium bromide (2.5 M, 80 mL, 200 mmol). The reaction mixture was stirred for 5 h, partitioned between ethyl acetate and 1N—HCl. The organic layer was separated, dried (MgSO4) and concentrated in vacuo to afford 2-hydroxy-2-phenylbutanoic acid. A solution of 2-hydroxy-2-phenylbutanoic acid (100 mg, 0.55 mmol) and diisopropylethylamine (188 uL, 1.11 mmol) in N,N-dimethylformamide (2 mL) was treated at room temperature with benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (PyBop, 290 mg, 0.55 mmol). After 15 min, (3-fluoro-5-(trifluoromethyl)phenyl)methanamine (107 mg, 0.55 mmol) was added. The reaction mixture was stirred for 3 h, partitioned between dichloromethane and 0.5N—NaOH. The aqueous layer was removed and the organic layer was washed with 0.5N—HCl. The aqueous layer was removed by filtering through a plastic fit. The organic layer was evaporated in vacuo to give the racemic mixture of the amide which was resolved using the chiral column (CiralPak AD) to give the desired product (2-1); HRMS (M+H−H2O)=338.1167; 1H NMR (500 MHz, CDCl3) δ 7.59 (d, 1H, J=7.5 Hz), 7.51 (m, 1H), 7.42 (d, 1H, J=5.0 Hz), 7.37 (t, 1H, J=7.5 Hz), 7.32 (d, 1H, J=7.0 Hz), 7.13 (t, 1H, J=9.0 Hz), 7.01 (bs, 1H), 4.52 (dq, 2H, J=15.6, 6.4 Hz), 2.83 (s, 1H), 2.36 (m, 1H), 2.12 (m, 1H), 0.94 (t, 3H, J=7.2 Hz).
Reaction SMILES: Br[C:2]1[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=1.[CH:10]#[C:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20].C(N(CC)CC)C>O1CCCC1.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[Pd]Cl.[Cu]I>[C:10]([C:2]1[N:7]=[C:6]([CH:8]=[O:9])[CH:5]=[CH:4][CH:3]=1)#[C:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH3:20]
Reactant: C#CCCCCCCCCC
Reactant: O=Cc1cccc(Br)n1
Agent: Cl[Pd]Cl
Agent: [Cu]I
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CCCCCCCCCC#Cc1cccc(C=O)n1
Yield: 84.3 %

Procedure:
A solution of 6-bromopyridine-2-caboxaldehyde (15.0 g), 1-undecyne (12.9 g), triethylamine (24.5 g), bis(triphenylphosphine)palladium(II)chloride (1.1 g, 2%), and copper(I)iodide (0.15g, 1%) in dry tetrahydrofuran (60 ml) was heated under nitorgen at 55° C. for 10 hrs. The reaction mixture was filtered, the filter cake was washed with ethyl acetate, and the filtrate was evaporated. The residue was dissolved in ethyl acetate, and the solution was washed with half-saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and the filtrate was concentrated. The residue was flash chromatographed on silica gel, eluting with 0%-2%-ethyl acetate:hexane. The appropriate fractions were collected and evaporated to yield 17.5 g (84.0%) of product.
Reaction SMILES: [F:1][S:2]([F:13])([F:12])([F:11])([F:10])[C:3]1[CH:8]=[CH:7][C:6]([SH:9])=[CH:5][CH:4]=1.Br[C:15]1[C:24]([S:25]([CH3:28])(=[O:27])=[O:26])=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[C:17]([CH3:29])[CH:16]=1.C([O-])([O-])=O.[K+].[K+].O>CN(C=O)C>[CH3:28][S:25]([C:24]1[C:15]([S:9][C:6]2[CH:7]=[CH:8][C:3]([S:2]([F:10])([F:11])([F:12])([F:13])[F:1])=[CH:4][CH:5]=2)=[CH:16][C:17]([CH3:29])=[C:18]([CH:23]=1)[C:19]([O:21][CH3:22])=[O:20])(=[O:26])=[O:27]
Reactant: COC(=O)c1cc(S(C)(=O)=O)c(Br)cc1C
Reactant: FS(F)(F)(F)(F)c1ccc(S)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)c1cc(S(C)(=O)=O)c(Sc2ccc(S(F)(F)(F)(F)F)cc2)cc1C
Temperature: 110 °C
Reaction time: 2 h
Yield: 59 %

Procedure:
0.28 g of 4-pentafluorosulfanylthiophenol, 0.36 g of methyl 4-bromo-5-methanesulfonyl-2-methylbenzoate and 0.33 g of K2CO3 were dissolved in 8 ml of anhydrous DMF and stirred at 110° C. for 2 h. The reaction mixture was then poured into 100 ml of water and extracted twice with 100 ml of EA each time. The EA phase was then washed twice with 30 ml of water each time. The residue after drying over MgSO4 and removal of the solvent in vacuo was chromatographed on silica gel with CH2Cl2/DIP 1:2. 320 mg of a colorless foam were obtained.
Reaction SMILES: [OH:1][CH:2]1[CH2:6][CH2:5][CH:4]([CH:7]=[CH:8][CH:9]([OH:15])[CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])[CH:3]1[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([O:24]C)=O.O.[NH2:27][NH2:28]>CO>[OH:1][CH:2]1[CH2:6][CH2:5][CH:4]([CH:7]=[CH:8][CH:9]([OH:15])[CH2:10][CH2:11][CH2:12][CH2:13][CH3:14])[CH:3]1[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]([NH:27][NH2:28])=[O:24]
Reactant: CCCCCC(O)C=CC1CCC(O)C1CCCCCCC(=O)OC
Reactant: NN
Solvent: O
Solvent: CO
Product: CCCCCC(O)C=CC1CCC(O)C1CCCCCCC(=O)NN
Yield: 62.5 %

Procedure:
A solution of methyl 7-[2-hydroxy-5-(3-hydroxy-1-octenyl)cyclopentyl]heptanoate (0.4 g.), [prepared as described in Example 5], 100% hydrazine hydrate (0.8 ml.) and methanol (10 ml.) was refluxed for 24 hours. After 12 hours reflux a further amount of hydrazine hydrate (0.8 ml.) was added. The methanol was removed in vacuo and the residue diluted with water. The resulting solution was extracted twice with diethyl ether. The combined ether extracts were dried over magnesium sulphate to give 7-[2-hydroxy-5-(3-hydroxy-1-octenyl)-cyclopentyl]heptanohydrazide (0.25 g., 62.5%). (Found: C, 67.4; H, 10.6; N, 7.9. C20H38N2O3 requires C, 67.8; H,10.72; N, 7.9%) νmax 3300 cm-1, 1650 cm-1 (shoulder 1630 cm-1), 980 cm-1 (liquid film).
Reaction SMILES: [C:1]1([CH:7]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[N:8]2[CH2:13][CH2:12][CH:11]([C:14]([NH2:16])=O)[CH2:10][CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3].O.[OH-].[Na+]>C1COCC1>[NH2:16][CH2:14][CH:11]1[CH2:12][CH2:13][N:8]([CH:7]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:9][CH2:10]1
Reactant: NC(=O)C1CCN(C(c2ccccc2)c2ccccc2)CC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: NCC1CCN(C(c2ccccc2)c2ccccc2)CC1
Temperature: 70 °C
Yield: 57 %

Procedure:
Step 2): 1-Diphenylmethylpiperidine-4-carboxamide (1.5 g, 5.1 mmol) was added dropwise to a suspension of LiAlH4 (0.4 g, 10.5 mmol) in THF (30 ml). The mixture was heated at 70° C. for 3 hours and then cooled. To the mixture, water (0.4 ml), 15% NaOH solution (0.4 ml) and water (1.2 ml) were added dropwise in order, and insoluble materials were filtered off. The filtrate was concentrated. The residue was purified by column chromatography on silica gel (10% methanol in dichloromethane) to give 4-aminomethyl-1-diphenylmethylpiperidine (57.0%) as colorless crystals: mp 80° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4](B2OC(C)(C)C(C)(C)O2)[CH:5]=[C:6]([Cl:9])[C:7]=1[F:8].Br[C:20]([C:22]([F:25])([F:24])[F:23])=[CH2:21].C([O-])([O-])=O.[Cs+].[Cs+]>C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:9][C:6]1[CH:5]=[C:4]([C:20]([C:22]([F:25])([F:24])[F:23])=[CH2:21])[CH:3]=[C:2]([Cl:1])[C:7]=1[F:8]
Reactant: C=C(Br)C(F)(F)F
Reactant: CC1(C)OB(c2cc(Cl)c(F)c(Cl)c2)OC1(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: C1CCOC1
Product: C=C(c1cc(Cl)c(F)c(Cl)c1)C(F)(F)F
Temperature: 70 °C
Yield: 56.8 %

Procedure:
A mixture of 2-(3,5-dichloro-4-fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2.56 g, 8.83 mmol), 2-bromo-3,3,3-trifluoroprop-1-ene (1.85 g, 10.6 mmol), Cs2CO3 (11.5 mL, 2M, 17.7 mmol) and Pd(PPh3)2Cl2 (200 mg) in THF (30 mL) was heated at 70° C. in a sealed tube for 4 h. The mixture was cooled to rt and partitioned between ether and H2O. The aqueous layer was extracted with EA and the combined organic layers were dried over Na2SO4. The solvent was removed under reduced pressure and the crude product was purified by column chromatography on silica gel eluted with hexanes to give 1,3-dichloro-2-fluoro-5-(3,3,3-trifluoroprop-1-en-2-yl)benzene (1.3 g; yield 56%) as colorless oil. 1H NMR (500 MHz, CDCl3): δ 7.412 (d, J=6.5 Hz, 2 H), 6.057 (s, 1 H), 5.806 (s, 1 H) ppm.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:20])[C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([OH:16])[C:11]=2[N+:17]([O-])=O)=[N:6][CH:7]=1.[Cl-].[NH4+]>C(O)C.O>[NH2:17][C:11]1[C:12]([OH:16])=[CH:13][CH:14]=[CH:15][C:10]=1[C:9]([NH:8][C:5]1[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][N:6]=1)=[O:20]
Reactant: O=C(Nc1ccc(Br)cn1)c1cccc(O)c1[N+](=O)[O-]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: O
Product: Nc1c(O)cccc1C(=O)Nc1ccc(Br)cn1
Temperature: 25 °C
Yield: 6 %

Procedure:
N-(5-Bromo-2-pyridyl)-3-hydroxy-2-nitrobenzamide (7.71 g) was suspended in 50 ml of ethanol and 22 ml of distilled water, then 12.7 g of reduced iron and 2.45 g of ammonium chloride were added thereto and the mixture was heated to reflux for 6 hours. After it was cooled down to room temperature, insoluble matter was filtered and washed with chloroform. The filtrate was concentrated in vacuo, a saturated aqueous solution of sodium hydrogen carbonate was added thereto, the mixture was extracted with chloroform and the extract was washed with a saturated saline solution. The organic layer was dried over anhydrous magnesium sulfate and the solvent was evaporated in vacuo to give 0.42 g of 2-amino-N-(5-bromo-2-pyridyl)-3-hydroxybenzamide. Then N,N-dimethylformamide was added to the insoluble matter obtained by filtration of the reaction solution, the mixture was filtered and the filtrate was concentrated in vacuo. Water was added to the resulting residue and the resulting precipitate was collected by filtration and dried in vacuo to give additional 3.28 g of the above compound. Although this contained impurities therein, it was not purified but used for the next reaction as it was.