Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[CH3:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[C:13]1[CH:18]=[C:17]([N:19]3[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]3)[N:16]=[C:15]([NH2:26])[N:14]=1)[CH2:9][NH:8][CH2:7][CH2:6]2.[CH:27]1([N:33]=[C:34]=[O:35])[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>>[NH2:26][C:15]1[N:14]=[C:13]([C:12]2[CH:11]=[C:10]3[C:5]([CH2:6][CH2:7][N:8]([C:34]([NH:33][CH:27]4[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]4)=[O:35])[CH2:9]3)=[CH:4][C:3]=2[CH3:2])[CH:18]=[C:17]([N:19]2[CH2:24][CH2:23][N:22]([CH3:25])[CH2:21][CH2:20]2)[N:16]=1
Reactant: Cc1cc2c(cc1-c1cc(N3CCN(C)CC3)nc(N)n1)CNCC2
Reactant: O=C=NC1CCCCC1
Agent: Cl
Product: Cc1cc2c(cc1-c1cc(N3CCN(C)CC3)nc(N)n1)CN(C(=O)NC1CCCCC1)CC2

Procedure:
This compound was prepared by using procedures analogous to those described for the synthesis of Example 77, Step 6 starting from 4-(6-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine HCl salt, and cyclohexylisocyanate. Analytic LCMS (M+H)+: m/z=464.2.
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:15]([CH2:16][CH3:17])[N:14]=[C:13]([C:18](=O)[CH3:19])[C:12]=2[OH:21])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[NH:22]([C:24]([NH:26][C:27]1[CH:35]=[CH:34][C:30]([C:31]([OH:33])=[O:32])=[CH:29][CH:28]=1)=[S:25])[NH2:23].CN(C)C=O>Cl.O>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:15]([CH2:16][CH3:17])[N:14]=[C:13]([C:18](=[N:23][NH:22][C:24]([NH:26][C:27]3[CH:35]=[CH:34][C:30]([C:31]([OH:33])=[O:32])=[CH:29][CH:28]=3)=[S:25])[CH3:19])[C:12]=2[OH:21])=[CH:7][CH:6]=1)([CH3:3])([CH3:2])[CH3:4]
Reactant: NNC(=S)Nc1ccc(C(=O)O)cc1
Reactant: CCn1nc(C(C)=O)c(O)c1-c1ccc(C(C)(C)C)cc1
Agent: Cl
Solvent: CN(C)C=O
Solvent: O
Product: CCn1nc(C(C)=NNC(=S)Nc2ccc(C(=O)O)cc2)c(O)c1-c1ccc(C(C)(C)C)cc1
Yield: 71.6 %

Procedure:
1-[5-(4-tert-Butylphenyl)-1-ethyl-4-hydroxy-1H-pyrazol-3-yl]ethanone (0.1718 mmol, 49.2 mg) and 4-hydrazinocarbonothioylaminobenzoic acid (0.1718 mmol, 36.3 mg) were stirred with dimethylformamide (3 mL) and two drops of concentrated hydrochloric acid at room temperature for 21 hours. After addition of water, the precipitated yellow solid was recovered by filtration, washed with water and dried by means of a vacuum pump. The resulting solid was stirred with chloroform/n-hexane for a while, then recovered by filtration and dried by means of a vacuum pump to give the desired product as a yellow solid (59 mg, yield 72%).
Reaction SMILES: [NH2:1][C:2]1[N:3]=[CH:4][N:5]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:6]=1[C:7]([NH2:9])=[O:8].[C:17]([O:21][C:22]([N:24]([CH2:26][CH2:27][CH2:28][C:29](O)=[O:30])[CH3:25])=[O:23])([CH3:20])([CH3:19])[CH3:18].Cl.N1C=CC=C(CC(O)=O)C=1>>[C:17]([O:21][C:22]([N:24]([CH2:26][CH2:27][CH2:28][C:29]([NH:1][C:2]1[N:3]=[CH:4][N:5]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:6]=1[C:7]([NH2:9])=[O:8])=[O:30])[CH3:25])=[O:23])([CH3:20])([CH3:19])[CH3:18]
Reactant: CN(CCCC(=O)O)C(=O)OC(C)(C)C
Reactant: NC(=O)c1c(N)ncn1Cc1ccccc1
Agent: Cl
Agent: O=C(O)Cc1cccnc1
Product: CN(CCCC(=O)Nc1ncn(Cc2ccccc2)c1C(N)=O)C(=O)OC(C)(C)C
Yield: 67 %

Procedure:
An amidation reaction and post-treatment were carried out under the same conditions as in Example 17, using 1.44 g (6.72 mmol) of 4-amino-1-benzyl-5-imidazolecarboxamide which was prepared in the same manner as in Reference Example 2 and 4-(N-t-butyloxycarbonyl-N-methylamino)butanoic acid, instead of 3-pyridylacetic acid hydrochloride, to obtain 1.86 g of 4-(4-(N-t-butyloxycarbonyl-N-methylamino)butanoylamino)-1-benzyl-5-imidazole carboxamide (yield 67%).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:11])[C:9]#[N:10])=[CH:4][CH:3]=1.[CH3:12][C:13](OC(C)=O)=[O:14]>N1C=CC=CC=1>[C:9]([CH:8]([CH3:11])[C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:13](=[O:14])[CH3:12])=[CH:7][CH:6]=1)#[N:10]
Reactant: CC(C#N)c1ccc(N)cc1
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)Nc1ccc(C(C)C#N)cc1
Temperature: 25 °C

Procedure:
A solution of 2-(4-Amino-phenyl)-propionitrile (10.2 g, 69.8 mmol) in pyridine (40 mL) was added Ac2O (7.49 g, 73.4 mmol) at room temperature. The reaction mixture was refluxed for 1 hrs then cooled to room temperature, and concentrated in vacuo.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:13][CH:14]([CH3:16])[CH3:15])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2[CH:28]=[CH:29][CH:30]=[N:31][C:26]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.N1CCCC1.CCN(CC)CC>C(Cl)Cl>[CH3:15][CH:14]([CH3:16])[CH2:13][C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])[C:10](=[O:12])[N:31]1[CH2:30][CH2:29][CH2:28][CH2:26]1
Reactant: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Reactant: CC(C)C[C@@H](NC(=O)OC(C)(C)C)C(=O)O
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: C1CCNC1
Product: CC(C)C[C@@H](NC(=O)OC(C)(C)C)C(=O)N1CCCC1
Temperature: 25 °C
Reaction time: 5 h
Yield: 95.2 %

Procedure:
To a mixture of (R)-2-(tert-butoxycarbonylamino)-4-methylpentanoic acid (1.0 g, 4.32 mmol), HATU (1.97 g, 5.19 mmol) and pyrrolidine (0.76 mL, 8.65 mmol) in DCM (30 mL) was added Et3N (1.2 mL, 8.65 mmol). The reaction mixture was stirred at room temperature for 5 h and then washed with saturated aqueous NaHCO3 and brine. The organics were dried over MgSO4 and concentrated. Purification by silica column chromatography (MeOH/DCM, 0-10%) afforded the title compound as a light yellow oil (1.17g, 95%).
Reaction SMILES: CN(C)[CH2:3][CH2:4][C:5]([C:7]1[CH:12]=[C:11]([O:13][CH3:14])[C:10]([O:15][CH3:16])=[C:9]([O:17][CH3:18])[CH:8]=1)=[O:6].[OH:20][C:21]1[C:28]([OH:29])=[C:27]([O:30][CH3:31])[CH:26]=[CH:25][C:22]=1C=O.[CH3:32]CN(CC)CC>[Br-].C([N+]1C(C)=C(CCO)SC=1)C>[CH3:18][O:17][C:9]1[CH:8]=[C:7]([CH:12]=[C:11]([O:13][CH3:14])[C:10]=1[O:15][CH3:16])[C:5]([C:4]1[CH2:31][O:30][C:27]2[C:26]([CH:3]=1)=[CH:25][CH:22]=[C:21]([O:20][CH3:32])[C:28]=2[OH:29])=[O:6]
Reactant: CCN(CC)CC
Reactant: COc1ccc(C=O)c(O)c1O
Reactant: COc1cc(C(=O)CCN(C)C)cc(OC)c1OC
Agent: CC[n+]1csc(CCO)c1C
Agent: [Br-]
Product: COc1ccc2c(c1O)OCC(C(=O)c1cc(OC)c(OC)c(OC)c1)=C2
Temperature: 115 °C
Yield: 11 %

Procedure:
A mixture of 2-(N,N-dimethylamino)ethyl-(3′,4′,5′-trimethoxyphenyl)ketone (4, 1.17 g, 4.37 mmol), 2,3-dihydroxy-4-methoxybenzaldehyde (2, 0.74 g, 4.37 mmol), 3-ethyl-5-(2-hydroxyethyl)-4-methylthiazolium bromide (0.12 g, 0.44 mmol) and Et3N (1 ml) was heated under reflux at 115° C. for 3.5 hours. After quenching with 1M HCl, the product was extracted with CH2Cl2. The combined extract was washed with water, rinsed with brine and dried over anhydrous magnesium sulfate. Purification was done by silica gel flash column chromatography (60:40, hexane-ethyl acetate) which afforded the pure yellow-colored phenol (0.179 g, 0.48 mmol) in 11% yield. The phenol had a melting point of 189-190° C.
Reaction SMILES: [NH:1]([CH2:6][C:7]([OH:9])=[O:8])[CH2:2][C:3]([OH:5])=[O:4].[OH-].[Na+].C([O:14][C:15](=[O:20])[C:16]([CH2:18][OH:19])=[CH2:17])C.Cl>O>[C:15]([CH:16]([CH2:18][OH:19])[CH2:17][N:1]([CH2:6][C:7]([OH:9])=[O:8])[CH2:2][C:3]([OH:5])=[O:4])([OH:20])=[O:14]
Reactant: O=C(O)CNCC(=O)O
Reactant: C=C(CO)C(=O)OCC
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=C(O)CN(CC(=O)O)CC(CO)C(=O)O
Temperature: 80 °C
Reaction time: 20 h
Yield: 45 %

Procedure:
(0.05 mole) of iminodiacetic acid were suspended in 25 ml of water and neutralized with sodium hydroxide to pH=10-12. 6.5 g. (0.05 mole) of ethyl--2--hydroxymethylacrylate was added dropwise to the solution and the temperature of the resulting mixture increased to 80°C. The pH was maintained at 10-12 by further addition of sodium hydroxide. The reaction mixture was stirred at 80°C for 20 hours and then cooled to room temperature and acidified to pH=1.5 with concentrated hydrochloric acid. The solvent was distilled under reduced pressure to half the weight of the solution and the product was allowed to crystallize. The white precipitate was filtered, washed with water and methanol and then dried in a vacuum to 5.3 g. of white powder. The yield was 45% of theoretical and the product had a melting point of 195 °C.
Reaction SMILES: [OH:1][C@H:2]1[CH2:11][CH2:10][CH2:9][C@@:8]2([CH3:12])[C@H:3]1[CH2:4][CH2:5][CH2:6][C:7]2=[O:13].N1C=CN=C1.[C:19]([Si:23](Cl)([CH3:25])[CH3:24])([CH3:22])([CH3:21])[CH3:20]>CN(C)C=O>[C:19]([Si:23]([CH3:25])([CH3:24])[O:1][C@H:2]1[CH2:11][CH2:10][CH2:9][C@@:8]2([CH3:12])[C@H:3]1[CH2:4][CH2:5][CH2:6][C:7]2=[O:13])([CH3:22])([CH3:21])[CH3:20]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: C[C@]12CCC[C@H](O)[C@@H]1CCCC2=O
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)O[C@H]1CCC[C@]2(C)C(=O)CCC[C@@H]12
Temperature: 100 °C
Reaction time: 8 h

Procedure:
To a solution of 2.3 g (12.6 mMol) of (4aR,5S,8aS)-5-Hydroxy-8a-methyl-octahydro-naphtalen-1-one in 63 ml of dimethylformamide are added under stirring and argon atmosphere 3.74 g (24.8 mMol) of tertio-butyl-dimethyl-silychloride and 1.94 g (28.5 mMol) of imidazole. The reaction mixture is heated to 100° C. for 4 hours, then additional 3.74 g of tert-butyl-dimethyl-silylchloride and 1.94 g of imidazole are added and the reaction mixture is kept overnight at 100° C. The reaction mixture is poured onto ice-water and extracted three times with diethylether. The combined organic extract is washed once with water and brine, dried over sodium sulfate and evaporated in vacuo. The residue is chromatographed over 250 g of silica gel with hexane/ethylacetate 9/1 to yield 3.17 g (85%) of low melting crystalline (4aR,5S,8aS)-5-(tert-Butyl-dimethyl-silanyloxy)-8a-methyl-octahydro-naphtalen-1-one.
Reaction SMILES: [H-].[Na+].[CH3:3][S:4][CH2:5][C:6]([O:8][CH3:9])=[O:7].[CH:10]([O:12][CH3:13])=[O:11].[C:14]1([CH3:24])[CH:19]=[CH:18][C:17]([S:20]([Cl:23])(=[O:22])=[O:21])=[CH:16][CH:15]=1>CN(C=O)C>[CH3:3][S:4][C:5](=[CH:13][O:12][S:20]([C:17]1[CH:18]=[CH:19][C:14]([CH3:24])=[CH:15][CH:16]=1)(=[O:22])=[O:21])[C:6]([O:8][CH3:9])=[O:7].[Cl:23][CH:6]=[C:5]([S:4][CH3:3])[C:10]([O:12][CH3:13])=[O:11]
Reactant: COC=O
Reactant: COC(=O)CSC
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)C(=CCl)SC
Product: COC(=O)C(=COS(=O)(=O)c1ccc(C)cc1)SC
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a suspension of 21.4 g (535 mmol) of sodium hydride (60% in oil) in 200 ml of DMF was added dropwise a mixture of 25.8 g (214 mmol) of methyl 2-(methylthio)acetate and 26.5 g (428 mmol) of methyl formate under ice cooling and stirred at room temperature overnight. To the reaction mixture was added portionwise 27.0 g (141 mmol) of p-toluenesulfonyl chloride under ice cooling and stirred at room temperature for 1 hour. After dilution with tert-butyl methyl ether, the solution was washed sequentially with water and saturated NaCl solution, dried over anhydrous MgSO4, and concentrated. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=5/1) to obtain 9.72 g of methyl 2-(methylthio)-3-(p-toluenesulfonyloxy)-2-propenoate and 1.88 g of methyl 3-chloro-2-(methylthio)-2-propenoate.
Reaction SMILES: C(N(CC)C(C)C)(C)C.[CH3:10][N:11]1[CH2:16][CH2:15][N:14]([C:17]2[S:18][CH:19]=[C:20]([C:22]3[CH:27]=[CH:26][C:25]([C:28]([NH:30][C:31]4([C:37]([NH:39][C@H:40]([CH2:45][OH:46])[CH2:41][CH2:42][S:43][CH3:44])=[O:38])[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]4)=[O:29])=[CH:24][CH:23]=3)[N:21]=2)[CH2:13][CH2:12]1>CS(C)=O.C(Cl)Cl>[CH3:10][N:11]1[CH2:16][CH2:15][N:14]([C:17]2[S:18][CH:19]=[C:20]([C:22]3[CH:23]=[CH:24][C:25]([C:28]([NH:30][C:31]4([C:37]([NH:39][C@H:40]([CH:45]=[O:46])[CH2:41][CH2:42][S:43][CH3:44])=[O:38])[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]4)=[O:29])=[CH:26][CH:27]=3)[N:21]=2)[CH2:13][CH2:12]1
Reactant: CSCC[C@@H](CO)NC(=O)C1(NC(=O)c2ccc(-c3csc(N4CCN(C)CC4)n3)cc2)CCCCC1
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CSCC[C@@H](C=O)NC(=O)C1(NC(=O)c2ccc(-c3csc(N4CCN(C)CC4)n3)cc2)CCCCC1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 64.4 %

Procedure:
Under an argon gas atmosphere, 453 mg (3.5 mmol) of N,N-diisopropylethylamine was added dropwise to a solution of 658 mg (3.5 mmol) of sulfur trioxide-pyridine complex in 10 ml of anhydrous dimethyl sulfoxide and 5 ml of anhydrous methylene chloride under ice-cooling, and the mixture was stirred for 15 minutes. Further, under ice-cooling, a solution of 319 mg (0.58 mmol) of N-[[1-[[[4-[2-(4-methyl-1-piperazinyl)-4-thiazolyl]phenyl]carbonyl]amino]cyclohexyl]carbonyl]-L-methioninol in 3 ml of anhydrous dimethyl sulfoxide was added to the reaction solution, and the mixture was stirred at the same temperature for 2 hours. The reaction solution was poured to ice-water and extracted with ethyl acetate twice. The organic layer was washed with a saturated aqueous sodium hydrogencarbonate solution and then saturated brine, and after it was dried with anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. 20 ml of diisopropyl ether was added to the residue, and the mixture was stirred at room temperature for 18 hours. The obtained crystal was collected by filtration to obtain 203 mg (64%) of the title compound.
Reaction SMILES: Br[C:2]1[O:3][C:4]2[C:24]([O:25]C(=O)C)=[C:23]([O:29][CH3:30])[CH:22]=[CH:21][C:5]=2[C:6]=1[C:7](=[O:20])[C:8]1[CH:13]=[C:12]([O:14][CH3:15])[C:11]([O:16][CH3:17])=[C:10]([O:18][CH3:19])[CH:9]=1.O.[NH2:32][NH2:33]>O1CCCC1>[NH:32]([C:2]1[O:3][C:4]2[C:24]([OH:25])=[C:23]([O:29][CH3:30])[CH:22]=[CH:21][C:5]=2[C:6]=1[C:7](=[O:20])[C:8]1[CH:13]=[C:12]([O:14][CH3:15])[C:11]([O:16][CH3:17])=[C:10]([O:18][CH3:19])[CH:9]=1)[NH2:33]
Reactant: NN
Reactant: COc1cc(C(=O)c2c(Br)oc3c(OC(C)=O)c(OC)ccc23)cc(OC)c1OC
Solvent: O
Solvent: C1CCOC1
Product: COc1cc(C(=O)c2c(NN)oc3c(O)c(OC)ccc23)cc(OC)c1OC
Temperature: 60 °C

Procedure:
To a solution of the 2-Bromo-7-acetoxy-3-(3,4,5-trimethoxybenzoyl)-6-methoxybenzofuran (30 mg, 0.062 mmol) in tetrahydrofuran (0.5 ml) was added hydrazine monohydrate (15 μL, 0.3 mmol). A yellow precipitate immediately formed and the heterogeneous mixture was heated to 60° C. for 1 hour during which time more solid separated from the reaction. After cooling, the solid product was collected by filtration, washed with ether and dried under vacuum (6 mg, 25%); 1H NMR (d6-DMSO) δ 9.70 (br s, 1H), 9.27 (br s, 1H), 6.85 (s, 2H), 6.68 (d, J=8.5 Hz, 1H), 6.21 (d, J=8.5 Hz, 1H), 5.00 (br s, 2H), 3.73 (s, 6H), 3.71 (s, 3H), 3.70 (s, 3H).
Reaction SMILES: CC[C@@H]1[C@@H]2C[C@H]([C@@H](OC3C4C(=CC=CC=4)C(O[C@@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3C=C([O:22]C)C=C4)N(CC2)C1.[OH2:59].[Br:60][C:61]1[C:70]([CH:71]=[CH2:72])=[C:69]([CH3:73])[CH:68]=[C:67]2[C:62]=1[CH:63]=[CH:64][CH:65]=[N:66]2>C(O)(C)(C)C.C(OCC)(=O)C>[Br:60][C:61]1[C:70]([C@@H:71]([OH:22])[CH2:72][OH:59])=[C:69]([CH3:73])[CH:68]=[C:67]2[C:62]=1[CH:63]=[CH:64][CH:65]=[N:66]2
Reactant: O
Reactant: C=Cc1c(C)cc2ncccc2c1Br
Reactant: CC[C@H]1CN2CC[C@H]1C[C@@H]2[C@@H](Oc1nnc(O[C@@H](c2ccnc3ccc(OC)cc23)[C@H]2C[C@@H]3CCN2C[C@@H]3CC)c2ccccc12)c1ccnc2ccc(OC)cc12
Solvent: CC(C)(C)O
Solvent: CCOC(C)=O
Product: Cc1cc2ncccc2c(Br)c1[C@@H](O)CO
Temperature: 0 °C
Reaction time: 48 h

Procedure:
A biphasic mixture of AD-mix-β (1.2 g, excess) in tert-butanol (4.5 mL)/H2O (4.5 mL) was cooled to 0° C. and 5-bromo-7-methyl-6-vinylquinoline (210 mg, 0.85 mmol) was added. The reaction mixture was stirred for 2 days at 0° C. The mixture was diluted with ethyl acetate, washed with water and brine, dried over Na2SO4, filtered and concentrated and purified by flash column chromatography (silica gel, 0 to 100% ethyl acetate/hexanes) to give (R)-1-(5-bromo-7-methylquinolin-6-yl)ethane-1,2-diol. 1H-NMR: 400 MHz, (CD3OD) δ 8.82 (d, J=4.4 Hz, 1H), 8.76 (d, J=8.8 Hz, 1H), 7.84 (s, 1H), 7.61-7.57 (m, 1H), 5.84 (dd, J=8.8, 4.8 Hz, 1H), 4.00 (dd, J=11.2, 8.8 Hz, 1H), 3.80 (dd, J=11.2, 4.4 Hz, 1H), 2.81 (s, 3 H).
Reaction SMILES: [OH-].[K+].[CH3:3][S:4][C:5]1[CH:10]=[CH:9][C:8]([SH:11])=[CH:7][CH:6]=1.I[C:13]1[CH:21]=[C:20]([O:22][CH3:23])[CH:19]=[CH:18][C:14]=1[C:15]([OH:17])=[O:16]>O.[Cu]>[CH3:23][O:22][C:20]1[CH:21]=[C:13]([S:11][C:8]2[CH:9]=[CH:10][C:5]([S:4][CH3:3])=[CH:6][CH:7]=2)[C:14]([C:15]([OH:17])=[O:16])=[CH:18][CH:19]=1
Reactant: CSc1ccc(S)cc1
Reactant: COc1ccc(C(=O)O)c(I)c1
Agent: [Cu]
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: COc1ccc(C(=O)O)c(Sc2ccc(SC)cc2)c1
Reaction time: 0.25 h

Procedure:
A solution of 170 g. of potassium hydroxide in 1.6 liters of water is treated under a nitrogen atmosphere at 50° C. with 102 g. of 4-methylthio-thiophenol. The resulting mixture is stirred for an additional 15 minutes. The mixture is then treated with 2.4 g. of copper powder and 180 g. of 2-iodo-4-methoxy-benzoic acid and heated under reflux for 7 hours. The mixture is filtered while hot, acidified with concentrated hydrochloric acid, cooled and filtered. The residue is washed with water, dried under reduced pressure, and there is obtained 4-methoxy-6-[(4-methylthio-phenyl)-thio]-benzoic acid having a melting point of 202°-203° C.
Reaction SMILES: Br[CH2:2][CH2:3][CH:4]1[O:8][C:7]([CH3:10])([CH3:9])[C:6]([CH3:12])([CH3:11])[O:5]1.[CH2:13]([NH2:19])[CH2:14][CH2:15][CH:16]=[CH:17][CH3:18].[OH-].[Na+]>O>[CH2:13]([NH:19][CH2:2][CH2:3][CH:4]1[O:8][C:7]([CH3:10])([CH3:9])[C:6]([CH3:12])([CH3:11])[O:5]1)[CH2:14][CH2:15][CH:16]=[CH:17][CH3:18]
Reactant: CC1(C)OC(CCBr)OC1(C)C
Reactant: CC=CCCCN
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC=CCCCNCCC1OC(C)(C)C(C)(C)O1
Temperature: 100 °C
Reaction time: 0.5 h

Procedure:
2-Bromoethyl-4,4,5,5-tetramethyl-1,3-dioxolane (20 grams) and 4-hexenylamine (100 ml) are charged into a glass reaction vessel equipped with a mechanical stirrer, thermometer and reflux condenser. The reaction mixture is heated at a temperature of about 100° C. for a period of about 3 hours. After this time sodium hydroxide (10 grams) dissolved in water (100 ml) is added and the resulting mixture is stirred for a period of about 30 minutes. The reaction mixture is then extracted with ether. The ether extract is dried over anhydrous magnesium sulfate, filtered and stripped of solvent to yield the desired product N-hex-4-enyl-N-(4,4,5,5-tetramethyl-1,3-dioxolan-2-ylethyl)amine.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][N:8]1[C:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:11]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:10]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[N:9]1.[SH:31][CH2:32][C:33]([O:35][CH3:36])=[O:34].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>CCCCCC.C(OCC)(=O)C.C(#N)C>[C:25]1([C:10]2[C:11]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)=[C:12]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)[N:8]([CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][S:31][CH2:32][C:33]([O:35][CH3:36])=[O:34])[N:9]=2)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: BrCCCCCCn1nc(-c2ccccc2)c(-c2ccccc2)c1-c1ccccc1
Reactant: COC(=O)CS
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC#N
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: COC(=O)CSCCCCCCn1nc(-c2ccccc2)c(-c2ccccc2)c1-c1ccccc1
Yield: 95.4 %

Procedure:
A mixture of 1-(6-bromohexyl)-3,4,5-triphenyl-lH-pyrazole (6.53 g, 14 mmol), methyl mercaptoacetate (1.66 g, 15 mmol), potassium carbonate (2.26 g, 16.5 mmol), potassium iodide (catalytic amount) and acetonitrile (150 mL) was heated at reflux for 4 hours. The mixture was cooled, filtered and concentrated in vacuo to give an oil. Chromatography on a column of silica gel using a mixture of hexane and ethyl acetate (4:1) as eluent furnished methyl [[6-(3,4,5-triphenyl-lH-pyrazol-1-yl)hexyl]thio]acetate (6.47 g, 91%) as an oil.
Reaction SMILES: [Br:1][C:2]1[C:3]([CH3:14])=[C:4]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[S:8][CH2:7][CH2:6][C:5]2=[O:13].C(Cl)Cl.CO.[BH4-].[Na+]>O>[Br:1][C:2]1[C:3]([CH3:14])=[C:4]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[S:8][CH2:7][CH2:6][CH:5]2[OH:13]
Reactant: Cc1cc(Br)c(C)c2c1SCCC2=O
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Solvent: CO
Product: Cc1cc(Br)c(C)c2c1SCCC2O
Temperature: 0 °C
Yield: 99.8 %

Procedure:
A 100 ml three-necked flask was charged with 5.9 g (0.022 mol) of 6-bromo-5,8-dimethylthiochroman-4-one, and then, 30 ml of methylene chloride and 10 ml of methanol were added and dissolved. The entire reaction system was cooled to 0° C. in an ice salt bath, and 0.42 g.(0.011 mol) of sodium borohydride was added by small portions. Thereafter, the mixture was allowed to react for 2 hours while it was cooled as above. The reaction mixture was poured into 100 ml of water, and the mixture was extracted with methylene chloride. The extract was dried over anhydrous sodium sulfate, and methylene chloride was distilled off under reduced pressure to give 6.0 g of 6-bromo-5,8-dimethyl-4-hydroxythiochroman as a solid. Then, 6.0 g of this 6-bromo-5,8-dimethyl-4-hydroxythiochroman was charged into a 100 ml eggplant-shaped flask, and 20 ml of ethanol was added to form a solution. Then, 10 drops of concentrated sulfuric acid was added, and the mixture was refluxed under heat for 1 hour. The reaction mixture was allowed to cool and poured into 100 ml of water, and the mixture was extracted with methylene chloride. The extract was dried over anhydrous sodium sulfate, and methylene chloride was distilled off under reduced pressure to give 5.8 g of 6-bromo-5,8-dimethyl-4-ethoxythiochroman as an oily substance.
Reaction SMILES: [CH2:1]([O:8][NH:9][C:10]1[CH:15]=[CH:14][N:13]=[C:12]([CH2:16][CH3:17])[C:11]=1[Cl:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(O[CH:30]1[CH2:35][CH2:34][C:33]2([CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]2)[CH2:32][CH2:31]1)(C1C=CC(C)=CC=1)(=O)=O>>[CH2:1]([O:8][N:9]([C:10]1[CH:15]=[CH:14][N:13]=[C:12]([CH2:16][CH3:17])[C:11]=1[Cl:18])[CH:38]1[CH2:39][CH2:40][C:33]2([CH2:34][CH2:35][CH2:30][CH2:31][CH2:32]2)[CH2:36][CH2:37]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCc1nccc(NOCc2ccccc2)c1Cl
Reactant: Cc1ccc(S(=O)(=O)OC2CCC3(CCCCC3)CC2)cc1
Product: CCc1nccc(N(OCc2ccccc2)C2CCC3(CCCCC3)CC2)c1Cl
Yield: 95 %

Procedure:
Was prepared analogously to Example 7 from 4-(O-benzylhydroxylamino)-3-chloro-2-ethylpyridine (Example 52) and 3-tosyloxyspiro[5.5]undecane. Yield: 95%