Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH:12]2[OH:24])=[CH:7][CH:6]=1)[CH:2]=[CH2:3].[CH3:25][S:26][C:27]1[CH:34]=[CH:33][C:30]([CH2:31]Cl)=[CH:29][CH:28]=1>>[CH2:1]([O:4][C:5]1[CH:6]=[CH:7][C:8]([CH:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH:12]2[O:24][CH2:31][C:30]2[CH:33]=[CH:34][C:27]([S:26][CH3:25])=[CH:28][CH:29]=2)=[CH:9][CH:10]=1)[CH:2]=[CH2:3]
Reactant: CSc1ccc(CCl)cc1
Reactant: C=CCOc1ccc(C2CCN(C(=O)OC(C)(C)C)CC2O)cc1
Product: C=CCOc1ccc(C2CCN(C(=O)OC(C)(C)C)CC2OCc2ccc(SC)cc2)cc1

Procedure:
In an analogous manner to that described in Example 1 (g), by alkylating tert-butyl (3RS,4RS)-4-(4-allyloxy-phenyl)-3-hydroxy-piperidine-1-carboxylate [Example 86 (b)] with 4-methylthio-benzyl chloride [J.Org.Chem. (1988), 53(3), 561-569] there was obtained tert-butyl (3RS,4RS)-4-(4-allyloxy-phenyl)-3-(4-methylsulphanyl-benzyloxy)-piperidine-1-carboxylate, from which by cleavage of the allyl group by means of bis-(triphenylphosphine)-palladium(II) diacetate analogously to Example 152 (e) there was obtained tert-butyl (3RS,4RS)-4-(4-hydroxy-phenyl)-3-(4-methylsulphanyl-benzyloxy)-piperidine-1-carboxylate. Subsequent alkylation with 5-bromomethyl-3-(2-methoxy-phenyl)-[1,2,4]oxadiazole analogously to Example 44 (e) gave tert-butyl (3RS,4RS)-4-{4-[3-(2-methoxy-phenyl)-[1,2,4]oxadiazol-5-ylmethoxy]-phenyl}-3-(4-methylsulphanyl-benzyloxy)-piperidine-1-carboxylate as a pale yellow, viscous oil; MS: 618 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][N:10]=1)[NH:7][C:6](=[O:11])[CH:5]2[C:12](=[O:18])[C:13]1[S:17][CH:16]=[CH:15][CH:14]=1.[C:19](=[O:25])=[N:20]S(Cl)(=O)=O.C(#N)C.ClS(NC=O)(=O)=O>CS(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][N:10]=1)[N:7]([C:19]([NH2:20])=[O:25])[C:6](=[O:11])[CH:5]2[C:12](=[O:18])[C:13]1[S:17][CH:16]=[CH:15][CH:14]=1
Reactant: O=C1Nc2cnc(Cl)cc2C1C(=O)c1cccs1
Reactant: O=C=NS(=O)(=O)Cl
Agent: O=CNS(=O)(=O)Cl
Solvent: CS(C)=O
Solvent: CC#N
Product: NC(=O)N1C(=O)C(C(=O)c2cccs2)c2cc(Cl)ncc21

Procedure:
The title compound was prepared from 5-chloro-3-(2-thenoyl)-6-azaoxindole (Example 3C) according to the procedure of Example 2C, using 5-chloro-3-(2-thenoyl)-6-azaoxindole (140 mg, 0.5 mmol), N-chlorosulfonyl isocyanate (65 L, 0.75 mmol), and acetonitrile (5 mL). The crude N-chlorosulfonyl carboxamide was hydrolysed by stirring in DMSO for 2 hours in a flask open to the air. The product was precipitated by addition of water and was collected by filtration. The solid was recrystallized from methanol. Yield: 27 mg (17%).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]#[C:9][CH:10]=[C:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[N:3]=1.Cl[C:18]1[N:19]=[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][N:21]2[C:26]=1[N+:27]([O-:29])=[O:28].C(N(CC)CC)C>>[CH3:1][C:2]1[N:3]=[C:4]([C:8]#[C:9][CH:10]=[C:11]2[CH2:12][CH2:13][N:14]([C:18]3[N:19]=[C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][N:21]4[C:26]=3[N+:27]([O-:29])=[O:28])[CH2:15][CH2:16]2)[CH:5]=[CH:6][CH:7]=1
Reactant: Cc1cccc(C#CC=C2CCNCC2)n1
Reactant: O=[N+]([O-])c1c(Cl)nc2ccccn12
Solvent: CCN(CC)CC
Product: Cc1cccc(C#CC=C2CCN(c3nc4ccccn4c3[N+](=O)[O-])CC2)n1
Yield: 55.1 %

Procedure:
A well homogenised mixture of the Compound of Example 3 (150 mg, 0.71 mmol), 2-chloro-3-nitroimidazo[1,2-a]pyridine (154 mg, 0.778 mmol) and triethylamine (0.152 mL, 1.06 mmol) was stirred at 25° C. for 24 h. The reaction crude was purified by flash chromatography (EtOAc—Petroleum Ether 1:1) affording the title product (146 mg).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.[I-:11].[Na+].CN[C@@H]1CCCC[C@H]1NC>O1CCOCC1.[Cu](I)I>[I:11][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2
Reactant: Brc1ccc2[nH]ncc2c1
Reactant: [I-]
Agent: I[Cu]I
Agent: CN[C@@H]1CCCC[C@H]1NC
Agent: [Na+]
Solvent: C1COCCO1
Product: Ic1ccc2[nH]ncc2c1
Yield: 98.1 %

Procedure:
5-Bromo-1H-indazole (2.0 g, 10.15 mmol) was dissolved in dioxane (50 ml) and stirred under N2 atmosphere. Copper iodide (97 mg, 0.51 mmol), sodium iodide (3.04 g, 20.3 mmol) and trans-1,2-bis-(methylamino)-cyclohexane (147 mg, 1.02 mmol) was added and the reaction mixture was stirred for 68 hours at 110° C. The cooled solution was filtered and the filtrate concentrated under reduced pressure. The residue was dissolved in DCM (20 mL) and extracted with aqueous ammonia (1M, 5×10 mL). The organic phase was then washed three times with an aqueous Na2S2O3 solution, dried over MgSO4, filtered and concentrated under reduced pressure to give the product as a white solid (2.43 g, 100%).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([N+:28]([O-])=O)=[CH:24][CH:23]=2)[C:8]2[C:13]([C:14]=1[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:5])[CH3:2].C(O)(C(F)(F)F)=O>>[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[CH:10][CH:9]=2)=[O:5])[CH3:2].[NH2:28][C:25]1[CH:24]=[CH:23][C:22]([CH2:21][N:7]2[C:8]3[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:14]([C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)=[CH:6]2)=[CH:27][CH:26]=1
Reactant: CCOC(=O)c1c(-c2ccccc2)c2ccccc2n1Cc1ccc([N+](=O)[O-])cc1
Solvent: O=C(O)C(F)(F)F
Product: CCOC(=O)c1cc2ccccc2[nH]1
Product: Nc1ccc(Cn2cc(-c3ccccc3)c3ccccc32)cc1

Procedure:
1-(4-Amino-benzyl)-3-phenyl-1H-indole indolecarboxylic acid ethyl ester was prepared from 1-(4-nitro-benzyl)-3-phenyl-1H-indolecarboxylic acid ethyl ester followed the procedure of Example 1 Step 1 as a yellow syrup: 1H NMR (DMSO-d6) δ 0.98 (t, J=7.2 Hz, 3H), 4.11 (q, J=7.2 Hz, 2H), 4.99 (br s, 2H), 5.59 (s, 2H), 6.44 (d, J=8.41 Hz, 2H), 6.85 (d, J=8.4 Hz, 2H), 7.13 (td, J=7.1, 0.8 Hz, 1H), 7.34 (td, J=7.1, 0.8 Hz, 1H), 7.38-7.41 (m, 3H), 7.44-7.49 (m, 3H), 7.69 (d, J=8.4 Hz, 1H); MS (ESI) Hz 371 (MH+); 369 ([M−H]−); Anal. calcd for C24H22N2O2.0.04 TFA C, 71.12; H, 5.92; N, 7.47. Found: C, 71.03; H, 5.87; N, 7.36.
Reaction SMILES: [CH:1]([C:3]1[CH:19]=[CH:18][CH:17]=[C:16]([CH:20]=[O:21])[C:4]=1[CH2:5][O:6][C:7]1[C:8]([N+:13]([O-:15])=[O:14])=[N:9][CH:10]=[CH:11][CH:12]=1)=[O:2].C(C1C=CC=C(C)C=1COC1C([N+]([O-])=O)=NC=CC=1)=O.[BH4-].[Na+]>C(O)C>[OH:2][CH2:1][C:3]1[CH:19]=[CH:18][CH:17]=[C:16]([CH3:20])[C:4]=1[CH2:5][O:6][C:7]1[C:8]([N+:13]([O-:15])=[O:14])=[N:9][CH:10]=[CH:11][CH:12]=1.[OH:21][CH2:20][C:16]1[CH:17]=[CH:18][CH:19]=[C:3]([CH2:1][OH:2])[C:4]=1[CH2:5][O:6][C:7]1[C:8]([N+:13]([O-:15])=[O:14])=[N:9][CH:10]=[CH:11][CH:12]=1
Reactant: O=Cc1cccc(C=O)c1COc1cccnc1[N+](=O)[O-]
Agent: Cc1cccc(C=O)c1COc1cccnc1[N+](=O)[O-]
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Product: Cc1cccc(CO)c1COc1cccnc1[N+](=O)[O-]
Product: O=[N+]([O-])c1ncccc1OCc1c(CO)cccc1CO
Temperature: 0 °C
Reaction time: 3 h

Procedure:
To a solution of a mixture (1.29 g) of 3-(2,6-diformylbenzyloxy)-2-nitropyridine and 3-(2-formyl-6-methylbenzyloxy)-2-nitropyridine in ethyl alcohol (30 ml) was added portionwise sodium borohydride (390 mg) with ice-cooling. After being stirred for 3 hours with ice-cooling, the reaction mixture was poured into ice-water and the resulting precipitates were filtrated off. The precipitates were subjected to column chromatography on silica gel (40 g), eluting with a mixture of chloroform and methanol (20:1) to give 3-(2-hydroxymethyl-6-methylbenzyloxy)-2-nitropyridine (330 mg) and 3-[2,6-bis(hydroxymethyl)benzyloxy]-2-nitropyridine (700 mg).
Reaction SMILES: [C:1]1([NH:7][CH2:8][C:9]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([S:18](=[O:21])(=[O:20])[NH2:19])=[CH:14][C:13]=2[Cl:22])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C=O.[CH:25]1C=CC=CC=1.CO>CN(C)C=O.O>[C:1]1([N:7]2[CH2:8][C:9](=[O:10])[N:11]([C:12]3[CH:17]=[CH:16][C:15]([S:18](=[O:21])(=[O:20])[NH2:19])=[CH:14][C:13]=3[Cl:22])[CH2:25]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: c1ccccc1
Reactant: NS(=O)(=O)c1ccc(NC(=O)CNc2ccccc2)c(Cl)c1
Agent: C=O
Solvent: CO
Solvent: O
Solvent: CN(C)C=O
Product: NS(=O)(=O)c1ccc(N2CN(c3ccccc3)CC2=O)c(Cl)c1
Reaction time: 24 h

Procedure:
2-Phenylamino-N-(2-chloro-4-sulphamoylphenyl)-acetamide (0.8g) was dissolved in dimethylformamide (20ml) and paraformaldehyde (100 g) in water (5 ml) added thereto. The mixture was kept at 80° for 24 hours and then the DMF was evaporated. The residue was recrystallised from ethanol to yield the product (500 mg.), m.p. 204°; mixed melting point with the product of Example 3(c) 206°. The product was found identical with the product of Example 3(c) on thin layer chromatography (Kieselgel F254, Merck; benzene; methanol 16:1) and on IR spectroscopy.
Reaction SMILES: [N+:1]([C:4]1[CH:8]=[CH:7][NH:6][N:5]=1)([O-:3])=[O:2].C(=O)([O-])[O-].[K+].[K+].[CH3:15][CH:16]1[CH2:18][O:17]1>CN(C)C=O.O>[N+:1]([C:4]1[CH:8]=[CH:7][N:6]([CH2:15][CH:16]([OH:17])[CH3:18])[N:5]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1cc[nH]n1
Reactant: CC1CO1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(O)Cn1ccc([N+](=O)[O-])n1
Temperature: 100 °C
Yield: 54.8 %

Procedure:
A solution of 3-nitro-1H-pyrazole (prepared in Example 3, 400 mg, 3.54 mmol) in N,N-dimethylformamide (5 mL) was treated with solid potassium carbonate (734 mg, 5.31 mmol) and 2-methyl-oxirane (500 μL, 3.54 mmol) and placed in a sealed tube and heated at 100° C. for 1 h in an oil bath. After this time the reaction was cooled to 25° C. and diluted with water (30 mL) and extracted with ethyl acetate (3×20 mL). The organic layers were then combined and washed with saturated aqueous brine solution (2×20 mL) and then dried over sodium sulfate, filtered and concentrated in vacuo with silica gel (2 g) and purified by Biotage Flash Chromatography (40S column, Silica gel, 60% ethyl acetate/hexanes) to afford 1-(3-nitro-pyrazol-1-yl)-propan-2-ol (332 mg, 55%) as a clear colorless oil: ES-HRMS m/e calcd for C6H9N3O3 (M+H)+ 172.0717, observed 172.0716; 36730-255 1H NMR (300 MHz, CDCl3) δ ppm 1.28 (d, J=6.3 Hz, 3H, CH3), 2.15 (br. s., 1H, OH), 4.03-4.13 (m, 1H, CH of CH2), 4.23-4.38 (m, 2H, OCH and CH of CH2), 6.91 (d, J=2.4 Hz, 1H, Ar), 7.56 (d, J=2.4 Hz, 1H, Ar).
Reaction SMILES: [Cl:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([CH:16]=[C:17]4[S:21][C:20](SC)=[N:19][C:18]4=[O:24])=[CH:13][CH:14]=3)[CH:9]=[N:8]2)=[C:4]([C:27]([F:30])([F:29])[F:28])[CH:3]=1.[F:31][CH:32]1[CH2:35][NH:34][CH2:33]1>>[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][C:12]([CH:16]=[C:17]4[S:21][C:20]([N:34]5[CH2:35][CH:32]([F:31])[CH2:33]5)=[N:19][C:18]4=[O:24])=[CH:13][CH:14]=3)[CH:9]=[N:8]2)=[C:4]([C:27]([F:28])([F:30])[F:29])[CH:3]=1
Reactant: CSC1=NC(=O)C(=Cc2ccc3c(cnn3Cc3ccc(Cl)cc3C(F)(F)F)c2)S1
Reactant: FC1CNC1
Product: O=C1N=C(N2CC(F)C2)SC1=Cc1ccc2c(cnn2Cc2ccc(Cl)cc2C(F)(F)F)c1

Procedure:
5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-(3-fluoro-azetidin-1-yl)-thiazol-4-one was prepared from 5-[1-(4-Chloro-2-trifluoromethyl-benzyl)-1H-indazol-5-ylmethylene]-2-methylsulfanyl-thiazol-4-one and 3-fluoro-azetidine following General Procedure B.
Reaction SMILES: [C:1]([C:3]1[C:11]2[C:6](=[CH:7][N:8]=[C:9]([CH3:12])[CH:10]=2)[N:5]([CH2:13][C:14]([O:16]C(C)(C)C)=[O:15])[N:4]=1)#[N:2].C(O)(C(F)(F)F)=[O:22]>>[C:1]([C:3]1[C:11]2[C:6](=[CH:7][N:8]=[C:9]([CH3:12])[CH:10]=2)[N:5]([CH2:13][C:14]([OH:16])=[O:15])[N:4]=1)(=[O:22])[NH2:2]
Reactant: O=C(O)C(F)(F)F
Reactant: Cc1cc2c(C#N)nn(CC(=O)OC(C)(C)C)c2cn1
Product: Cc1cc2c(C(N)=O)nn(CC(=O)O)c2cn1

Procedure:
A solution of tert-butyl 2-(3-cyano-5-methyl-1H-pyrazolo[3,4-c]pyridin-1-yl)acetate (250 mg, 0.92 mmol) in TFA (4 mL) was subjected to microwave irradiation at 140° C. for 90 min. The reaction mixture was concentrated in vacuo, the residual solid was suspended in methanol and concentrated again in vacuo. MS: 235.0 [M+H]+; tR (HPLC conditions k): 0.24 min.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([OH:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=2)[N:12]=[C:11]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=2)[N:10]=1.Br[C:32]1[CH:33]=[C:34](OC)[CH:35]=[CH:36][CH:37]=1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].BrCCCCCC>C(OCCO)C>[OH:1][C:2]1[CH:7]=[C:6]([O:8][CH2:34][CH2:33][CH2:32][CH2:37][CH2:36][CH3:35])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH3:22])[CH:16]=2)[N:12]=[C:11]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([O:29][CH3:30])[CH:24]=2)[N:10]=1
Reactant: COc1cccc(Br)c1
Reactant: COc1cccc(-c2nc(-c3cccc(OC)c3)nc(-c3ccc(O)cc3O)n2)c1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CCCCCCBr
Solvent: CCOCCO
Product: CCCCCCOc1ccc(-c2nc(-c3cccc(OC)c3)nc(-c3cccc(OC)c3)n2)c(O)c1
Reaction time: 1 h

Procedure:
10 g (0.025 mol) of 2-(2,4-dihydroxyphenyl)-4,6-bis(3-methoxyphenyl)-1,3,5-triazine (prepared by the method of Example 8 starting from 3-bromoanisole), 3.8 g of potassium carbonate and 30 mg of potassium iodide are heated in 25 ml of 2-ethoxyethanol at 110 C. for one hour, followed by dropwise addition of 6.7 g (0.041 mol) of 1-bromohexane and stirring at 110 C. for a further 32 hours. After cooling, the mixture is filtered, the solid material is washed neutral with water and then washed with methanol and dried. The crude product is purified by column chromatography (250 g SiO2 35-70 μm; eluent toluene/petroleum ether 1:1). This gives the compound of formula ##STR24##
Reaction SMILES: [Cl:1][C:2]1[C:7]2[CH2:8][NH:9][C:10](=[O:13])[CH2:11][S:12][C:6]=2[CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH3:16]I.O>CS(C)=O>[Cl:1][C:2]1[C:7]2[CH2:8][N:9]([CH3:16])[C:10](=[O:13])[CH2:11][S:12][C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: CI
Reactant: O=C1CSc2cccc(Cl)c2CN1
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CN1Cc2c(Cl)cccc2SCC1=O
Reaction time: 0.5 h

Procedure:
A solution of 6-chloro-4,5-dihydro-1,4-benzothiazepin-3(2H)-one (5.33 g, prepared in a similar manner to example 11 of international patent application WO 92/21668) in dry dimethylsulphoxide (60 ml) was added slowly at room temperature to a stirred suspension of sodium hydride (0.6 g) in dimethylsulphoxide (20 ml). After the addition was completed, the mixture was stirred for 30 minutes before adding methyl iodide (6 ml) dropwise. The reaction mixture was stirred at room temperature for one hour, water (160 ml) was added and the mixture was extracted with diethyl ether. The organic layer was washed with water and the solvent was removed by evaporation. Purification of the residue by flash chromatography using dichloromethane/ethyl acetate (9.8:0.2) as eluent gave 6-chloro-4-methyl-4,5-dihydro-1,4-benzothiazepin-3(2H)-one. Yield 3.8 g (m.p. 122°-125° C.).
Reaction SMILES: [OH:1][C:2]1[C:7]2[C:8](=[O:17])[CH2:9][C:10]3([S:16][C:6]=2[CH:5]=[C:4]([OH:18])[CH:3]=1)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]3.Br[CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22].C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[OH:1][C:2]1[C:7]2[C:8](=[O:17])[CH2:9][C:10]3([S:16][C:6]=2[CH:5]=[C:4]([O:18][CH2:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:3]=1)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]3
Reactant: CCOC(=O)CBr
Reactant: O=C1CC2(CCCCC2)Sc2cc(O)cc(O)c21
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCOC(=O)COc1cc(O)c2c(c1)SC1(CCCCC1)CC2=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 91.4 %

Procedure:
A mixture of 5,7-dihydroxy-spiro [2H-1-benzothiine-2,1'-cyclohexan]-4(3H)-one (prepared in Preparation 79) (0.47 g, 1.78 mmol ), ethyl bromoacetate (0.297 g, 1.78 mmol), anhydrous potassium carbonate (0.368 g, 2.67 mmol), and dry acetonitrile (5 ml) is stirred overnight at room temperature. The mixture is stirred at 35° C. for additional 5 hours. The reaction mixture is filtered to remove inorganic materials. The solvent is removed by distillation from the filtrate. The residue is placed on a silica gel column and eluted with a mixture of dichloromethane and ethyl acetate (9:1) to obtain ethyl 2-{(5-hydroxy-3,4-dihydro-4-oxospiro[2H-1-benzothiine-2,1'-cyclohexan]-7-yl)oxy}acetate as a crystalline solid (0.57 g, 91.5%). Recrystallization from diethyl ether gives a product having a melting point of 87°-88° C.
Reaction SMILES: Cl[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)=[C:6]([Cl:15])[N:5]=[CH:4][N:3]=1.C(N(C(C)C)CC)(C)C.[K].[CH2:26]([NH:33][S:34](=[O:37])(=[O:36])[NH2:35])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CS(C)=O.CO>[Cl:15][C:6]1[N:5]=[CH:4][N:3]=[C:2]([NH:35][S:34](=[O:36])(=[O:37])[NH:33][CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=1
Reactant: NS(=O)(=O)NCc1ccccc1
Reactant: Clc1ccc(-c2c(Cl)ncnc2Cl)cc1
Agent: [K]
Solvent: CS(C)=O
Solvent: CCN(C(C)C)C(C)C
Solvent: CO
Product: O=S(=O)(NCc1ccccc1)Nc1ncnc(Cl)c1-c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 44.1 %

Procedure:
To 4,6-dichloro-5-(4-chloro-phenyl)-pyrimidine (Referential Example 9) (2.59 g) dissolved in DMSO (14 ml) was added di-isopropyl-ethyl-amine (1.8 ml) followed by the addition of benzyl sulfamic acid amide potassium salt (2.25 g) [prepared from the product described in Referential Example 22 and potassium tert.-butylate in methanol followed by the evaporation of the solvent]. The mixture was stirred for 24 h at rt then poured onto water (300 ml) and diethylether (120 ml) was added and the solution was stirred for 30 min. The layers were separated and the water layer was acidified with solid citric acid (pH=3) and cooled to 0° C. for 1 h. The precipitated product was filtered off, washed with water and recrystallized from methanol to give benzyl sulfamic acid-[6-chloro-5-(p-chloro-phenyl)-4-pyrimidinyl]-amide (1.8 g). tR=4.94 min (LC); [M+H]+410.90 (ES+);
Reaction SMILES: [C:1]1([C:7]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[SH:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:21]([C:23]1[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=1)#[CH:22].CC(C)([O-])C.[K+]>O1CCCC1>[C:7]([S:8]/[CH:22]=[CH:21]\[C:23]1[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=1)([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)([C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: SC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: C#Cc1cccnc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: C(=C\c1cccnc1)\SC(c1ccccc1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Yield: 60.3 %

Procedure:
To a solution of triphenylmethanethiol (1.41 g) and 3-ethynylpyridine (0.5 g) in anhydrous tetrahydrofuran (10 ml) was added potassium t-butoxide (571 mg) at ambient temperature. The mixture was refluxed for 2 hours. After the reaction mixture was cooled to ambient temperature, the reaction mixture was poured into ice-water. The mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride, dried over magnesium sulfate and concentrated in vacuo to give a crystal. The crystal was washed with ethanol and dried to give 3-[(Z)-2-(tritylthio)vinyl]pyridine (1.11 g).
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[CH3:11].[C:12](OC(=O)C)(=[O:14])[CH3:13]>N1C=CC=CC=1>[C:12]([O:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[CH3:11])(=[O:14])[CH3:13]
Reactant: CC(=O)OC(C)=O
Reactant: Cc1cc(C(=O)O)ccc1O
Solvent: c1ccncc1
Product: CC(=O)Oc1ccc(C(=O)O)cc1C
Temperature: 25 °C
Reaction time: 8 h
Yield: 52.7 %

Procedure:
A solution of 5.42 g (35.6 mmol) of the 4-hydroxy-3-methylbenzoic acid in 50 ml of pyridine was added to 16.8 ml (178 mmol) of acetic anhydride. The resulting mixture was stirred overnight at room temperature, and the reaction mixture was distilled off under reduced pressure. The residue was dissolved in ethyl acetate. The resulting solution was washed with 2N hydrochloric acid and a saturated aqueous solution of sodium chloride and was then dried over Na2SO4. The solvent was distilled off under reduced pressure. The residue was recrystallized from ethyl acetate-hexane, whereby 3.64 g of 4-acetoxy-3-methylbenzoic acid were obtained as white powder (yield: 52.6%).
Reaction SMILES: [CH3:1][CH:2]([CH3:19])[CH2:3][C:4]1[NH:5][C:6]2[C:11]([CH:12]=1)=[C:10]([C:13]([F:16])([F:15])[F:14])[C:9]([C:17]#[N:18])=[CH:8][CH:7]=2.[Br:20][C:21]1[CH:22]=[N:23][CH:24]=[C:25]([C:27]2[O:28][C:29]([CH2:32]Cl)=[N:30][N:31]=2)[CH:26]=1>>[Br:20][C:21]1[CH:26]=[C:25]([C:27]2[O:28][C:29]([CH2:32][N:5]3[C:6]4[C:11](=[C:10]([C:13]([F:16])([F:14])[F:15])[C:9]([C:17]#[N:18])=[CH:8][CH:7]=4)[CH:12]=[C:4]3[CH2:3][CH:2]([CH3:19])[CH3:1])=[N:30][N:31]=2)[CH:24]=[N:23][CH:22]=1
Reactant: ClCc1nnc(-c2cncc(Br)c2)o1
Reactant: CC(C)Cc1cc2c(C(F)(F)F)c(C#N)ccc2[nH]1
Product: CC(C)Cc1cc2c(C(F)(F)F)c(C#N)ccc2n1Cc1nnc(-c2cncc(Br)c2)o1

Procedure:
Synthesized as described in Example 4 using 2-(2-methylpropyl)-4-(trifluoromethyl)-1H-indole-5-carbonitrile and 3-bromo-5-[5-(chloromethyl)-1,3,4-oxadiazol-2-yl]pyridine: 1H NMR (400 MHz, CDCl3) δ 9.04 (d, J=1.4 Hz, 1H), 8.84 (d, J=2.0 Hz, 1H), 8.43 (m, 1H), 7.68 (d, J=8.4 Hz, 1H), 7.59 (d, J=8.4 Hz, 1H), 6.67 (s, 1H), 5.63 (s, 2H), 2.82 (d, J=7.1 Hz, 2H), 2.13 (m, 1H), 1.08 (d, J=6.6 Hz, 6H); MS (ES) m/z 504 (M+1, isotope for Br) and 506 (M+1, isotope for Br).
Reaction SMILES: [N+](=[CH:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])=[N-].[N+](=C)=[N-].[OH:16][CH:17]([CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])[CH2:18][CH2:19][CH2:20][N:21]([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31]([OH:33])=[O:32])[C:22]([NH2:24])=[O:23].OC(CCCCC)CCCN(CCCCCCC(O)=O)C(N)=S>CCOCC>[OH:16][CH:17]([CH2:34][CH2:35][CH2:36][CH2:37][CH3:38])[CH2:18][CH2:19][CH2:20][N:21]([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][C:31]([O:33][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12])=[O:32])[C:22]([NH2:24])=[O:23]
Reactant: CCCCCCCCCC=[N+]=[N-]
Reactant: CCCCCC(O)CCCN(CCCCCCC(=O)O)C(N)=O
Agent: C=[N+]=[N-]
Agent: CCCCCC(O)CCCN(CCCCCCC(=O)O)C(N)=S
Solvent: CCOCC
Product: CCCCCCCCCCOC(=O)CCCCCCN(CCCC(O)CCCCC)C(N)=O

Procedure:
Using the method of Example 23 but substituting an ether solution of 1-diazodecane for the ether solution of diazomethane and 7-[1-(4-hydroxynonyl)ureido]heptanoic acid for 7-[1-(4-hydroxynonyl)thioureido]heptanoic acid, there is obtained decyl 7-[1-(4-hydroxynonyl)ureido]-heptanoate as a viscous oil.
Reaction SMILES: N1CCC[CH2:3][CH2:2]1.[Cl:7][CH2:8][C:9](=[O:16])[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12].C(=O)C>C(OCC)(=O)C>[CH:2](=[C:10]([C:9](=[O:16])[CH2:8][Cl:7])[C:11]([O:13][CH2:14][CH3:15])=[O:12])[CH3:3]
Reactant: CCOC(=O)CC(=O)CCl
Reactant: C1CCNCC1
Agent: CC=O
Solvent: CCOC(C)=O
Product: CC=C(C(=O)CCl)C(=O)OCC
Temperature: 0 °C
Reaction time: 5.5 h

Procedure:
0.25 part by weight of piperidine is added dropwise to a mixture of 32.9 parts by weight of ethyl 4-chloroacetoacetate and 9.6 parts by weight of acetaldehyde at -20° C. The mixture is left to stand at -20° C. for 5 to 6 hours and ice-cold 1N hydrochloric acid and ethyl acetate are then added. The ethyl acetate phase is separated off, extracted twice more with 1N hydrochloric acid and then once with water, dried over magnesium sulphate and concentrated. 35.6 parts by weight of a yellow oil are obtained, and are distilled using a bulb tube (oven temperature 80° to 110° C. under 0.07 mm). 15.5 parts by weight of product are obtained.