Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:4][C@H:5]1[CH2:10][CH2:9][C@H:8]2[C@H:11]3[C@H:20]([CH2:21][CH2:22][C@:6]12[CH3:7])[C@@H:19]1[C:14](=[CH:15][C:16](=[O:23])[CH2:17][CH2:18]1)[CH2:13][C@H:12]3[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][O:29][Si](C(C)(C)C)(C)C)(=[O:3])[CH3:2].S(=O)(=O)(O)O>CO.C(OCC)C>[C:1]([O:4][C@H:5]1[CH2:10][CH2:9][C@H:8]2[C@H:11]3[C@H:20]([CH2:21][CH2:22][C@:6]12[CH3:7])[C@@H:19]1[C:14](=[CH:15][C:16](=[O:23])[CH2:17][CH2:18]1)[CH2:13][C@H:12]3[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][OH:29])(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@H]1CC[C@H]2[C@@H]3[C@H](CCCCCO[Si](C)(C)C(C)(C)C)CC4=CC(=O)CC[C@@H]4[C@H]3CC[C@]12C
Agent: O=S(=O)(O)O
Solvent: CO
Solvent: CCOCC
Product: CC(=O)O[C@H]1CC[C@H]2[C@@H]3[C@H](CCCCCO)CC4=CC(=O)CC[C@@H]4[C@H]3CC[C@]12C
Yield: 100.8 %

Procedure:
A solution of 48 g of 17β-acetoxy-7α-(5-tert-butyl-dimethylsilyloxypentyl)-estr-4-en-3-one in 350 ml of methanol is allowed to stand with 35 ml of 8 vol % sulfuric acid for 30 minutes at room temperature. The solution is diluted with diethyl ether, washed neutral with water, and dried. After the concentration by evaporation, 37.7 g of 17β-acetoxy-7α-(5-hydroxypentyl)-estr-4-en-3-one is obtained as an oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][CH2:12][NH:13][C:14](=[O:28])[C:15]([NH:17][C@H:18]([CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:19][OH:20])=O.CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>C1COCC1>[CH2:21]([C@@H:18]1[CH2:19][O:20][C:15]([C:14]([NH:13][CH2:12][CH2:11][C:5]2[C:4]3[C:8](=[CH:9][CH:10]=[C:2]([Cl:1])[CH:3]=3)[NH:7][CH:6]=2)=[O:28])=[N:17]1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: O=C(NCCc1c[nH]c2ccc(Cl)cc12)C(=O)N[C@@H](CO)Cc1ccccc1
Agent: CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC
Solvent: C1CCOC1
Product: O=C(NCCc1c[nH]c2ccc(Cl)cc12)C1=N[C@H](Cc2ccccc2)CO1
Temperature: 80 °C
Reaction time: 20 h
Yield: 3 %

Procedure:
A sealed tube containing (R)—N1-(2-(5-chloro-1H-indol-3-yl)ethyl)-N2-(1-hydroxy-3-phenylpropan-2-yl)oxalamide (0.104 g, 0.260 mmol) and Burgess reagent [(methoxycarbonylsulfamoyl)triethylammonium hydroxide inner salt (0.102 g; 0.416 mmol)] in dry THF (6 mL) was stirred at 80° C. for 20 hours. The solution was evaporated and the resulting residue was purified by flash chromatography on silica gel (eluent 7 to 60% ethyl acetate in dichloromethane) to give 0.003 g (3%) of (R)-4-benzyl-N-(2-(5-chloro-1H-indol-3-yl)ethyl)-4,5-dihydrooxazole-2-carboxamide as a white solid.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([C:8]2[S:9][CH:10]=[CH:11][CH:12]=2)[CH:5]=[CH:4][C:3]=1[NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17].[C:21](Cl)(=[O:25])[CH:22]([CH3:24])[CH3:23]>ClCCl.O>[C:21]([NH:1][C:2]1[CH:7]=[C:6]([C:8]2[S:9][CH:10]=[CH:11][CH:12]=2)[CH:5]=[CH:4][C:3]=1[NH:13][C:14](=[O:20])[O:15][C:16]([CH3:17])([CH3:19])[CH3:18])(=[O:25])[CH:22]([CH3:24])[CH3:23]
Reactant: CC(C)(C)OC(=O)Nc1ccc(-c2cccs2)cc1N
Reactant: CC(C)C(=O)Cl
Solvent: ClCCl
Solvent: O
Product: CC(C)C(=O)Nc1cc(-c2cccs2)ccc1NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 16 h
Yield: 80.5 %

Procedure:
To a solution of tert-butyl (2-amino-4-(thiophen-2-yl)phenyl)carbamate (200 mg, 0.689 mmol) in dichloromethane (4 mL) was added isobutyryl chloride (0.08 mL, 0.76 mmol, 1 equiv.) and TEA (0.23 mL, 1.72 mmol, 2.5 equiv.) at 0° C. The reaction was warmed to room temperature and stirred for 16 h. The reaction was then diluted with dichloromethane and water. The organic layers were washed with water and brine, dried over Na2SO4 and concentrated. The crude material was purified by column chromatography (silica gel, EtOAc/hexanes) to afford tert-butyl (2-isobutyramido-4-(thiophen-2-yl)phenyl)carbamate (0.2 g, 81% yield).
Reaction SMILES: C(OC(O[CH2:8][CH3:9])CBr)C.Br.C(=O)(O)[O-].[Na+].[NH2:16][C:17]1[N:18]=[N:19][C:20]([Cl:23])=[CH:21][CH:22]=1>C(O)(C)C>[Cl:23][C:20]1[CH:21]=[CH:22][C:17]2[N:18]([CH:8]=[CH:9][N:16]=2)[N:19]=1
Reactant: CCOC(CBr)OCC
Reactant: Nc1ccc(Cl)nn1
Agent: Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)O
Product: Clc1ccc2nccn2n1
Temperature: 25 °C
Reaction time: 0.05 h
Yield: 86 %

Procedure:
Bromoacetaldehyde diethylacetal (13.7 g, 69.5 mmol, 1.8 equiv) was added to hydrobromic acid (4.0 mL) and heated to reflux for 1.5 h. The reaction mixture was cooled to rt then poured into a reaction flask containing excess sodium bicarbonate in isopropanol. The solution was stirred for 3 min and then filtered. To the mother liquor was added 3-amino-6-chloropyridazine (5.0 g, 38.6 mmol, 1.0 equiv) and heated to reflux for 2 h. The reaction mixture was quenched with water and extracted with ethyl acetate. Purification using column chromatography gave 5.1 g of the brown solid, 86%: 1H NMR (400 MHz, CDCl3) δ 7.89 (s, 1H), 7.88 (d, J=9.3 Hz, 1H), 7.74 (s, 1H), 7.01 (d, J=9.3 Hz, 1H).
Reaction SMILES: [CH3:1][O:2][C:3]1[N:4](C2CCCCO2)[C:5]2[C:10]([N:11]=1)=[C:9]([NH2:12])[N:8]=[C:7]([O:13][CH2:14][CH:15]1[CH2:19][CH2:18][CH2:17][O:16]1)[N:6]=2.[F:26][C:27]([F:32])([F:31])[C:28]([OH:30])=[O:29]>CO>[F:26][C:27]([F:32])([F:31])[C:28]([OH:30])=[O:29].[CH3:1][O:2][C:3]1[NH:4][C:5]2[C:10]([N:11]=1)=[C:9]([NH2:12])[N:8]=[C:7]([O:13][CH2:14][CH:15]1[CH2:19][CH2:18][CH2:17][O:16]1)[N:6]=2
Reactant: COc1nc2c(N)nc(OCC3CCCO3)nc2n1C1CCCCO1
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Product: COc1nc2c(N)nc(OCC3CCCO3)nc2[nH]1
Reaction time: 24 h

Procedure:
8-(Methoxy)-2-[(tetrahydro-2-furanyl methyl)oxy]-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (1.1614 g) was dissolved in methanol (20 mL) and treated with neat trifluoroacetic acid (2 mL). The reaction mixture was stirred for 24 hours to give a white suspension. The reaction mixture was then evaporated to dryness under reduced pressure. The resultant white solid was suspended using ethyl acetate (10 mL) and then isolated by filtration, washing with ethyl acetate (2 mL). The solid was air-dried under suction and then dried further under vacuo at 50° C. This gave the title compound as a white solid (1.0602 g).
Reaction SMILES: [Br:1][C:2]1[S:3][C:4]([C:7]2([CH2:10][O:11][C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=3)[CH2:9][O:8]2)=[CH:5][CH:6]=1.[NH:19]1[CH:23]=[N:22][CH:21]=[N:20]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[Br:1][C:2]1[S:3][C:4]([C:7]([OH:8])([CH2:9][N:19]2[CH:23]=[N:22][CH:21]=[N:20]2)[CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)=[CH:5][CH:6]=1
Reactant: Clc1ccc(OCC2(c3ccc(Br)s3)CO2)cc1
Reactant: c1nc[nH]n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: OC(COc1ccc(Cl)cc1)(Cn1cncn1)c1ccc(Br)s1
Yield: 54.7 %

Procedure:
16 g of crude 2-(2-bromo-thien-5-yl)-2-(4-chlorophenoxymethyl)-oxirane in 200 ml of acetonitrile are heated under reflux with 11 g (0.157 mol) of 1,2,4-triazole and 5 g of potassium carbonate for 4 hours. Thereafter, the reaction mixture is poured onto water, and extracted with methylene chloride. The methylene chloride phase is dried over sodium sulphate and evaporated down in vacuo. The residue is chromatographed over silica gel using the chloroform/ethyl acetate (1:1) system. 10.5 g (55% of theory) of 2-(2-bromo-thien-5-yl)-1-(4-chlorophenoxy)-3-(1,2,4-triazol-1-yl)-propan-2-ol are obtained in the form of a yellow resin which crystallizes after standing for a long time. Melting point 108°-112° C.
Reaction SMILES: [Na].Cl[C:3]1[NH:8][C:7](=[O:9])[C:6]([F:10])=[CH:5][N:4]=1.[CH2:11]([OH:15])[CH2:12][CH2:13][CH3:14]>>[CH2:11]([O:15][C:3]1[NH:8][C:7](=[O:9])[C:6]([F:10])=[CH:5][N:4]=1)[CH2:12][CH2:13][CH3:14]
Reactant: CCCCO
Reactant: O=c1[nH]c(Cl)ncc1F
Agent: [Na]
Product: CCCCOc1ncc(F)c(=O)[nH]1
Yield: 91.9 %

Procedure:
A 5.8 g quantity of metal sodium is dissolved in 300 ml of absolute n-butanol, 14.9 g of 2-chloro-5-fluoropyrimidin-4-one is added to the solution and the mixture is heated in a sealed tube at 140° to 150° C for 5 hours for reaction. The solvent is distilled off from the reaction mixture, 50 ml of water is added to the residue and the pH of the mixture is adjusted to 4-5 to separate out crystals, which are recrystallized from ethanol to give 17.1 g of white crystalline 2-n-butoxy-5-fluoropyrimidin-4-one in a yield of 91.9 %, m.p. 127°-129° C.
Reaction SMILES: [Cl:1][C:2]1[CH:19]=[C:18](F)[C:17]([N+:21]([O-:23])=[O:22])=[CH:16][C:3]=1[C:4]([NH:6][C:7]1[CH:15]=[C:14]2[C:10]([CH:11]=[N:12][NH:13]2)=[CH:9][CH:8]=1)=[O:5].[NH4+].[OH-].[NH2:26]C1C=C(F)C([N+]([O-])=O)=CC=1C(NC1C=C2C(C=NN2)=CC=1)=O>O1CCOCC1.O>[NH2:26][C:18]1[C:17]([N+:21]([O-:23])=[O:22])=[CH:16][C:3]([C:4]([NH:6][C:7]2[CH:15]=[C:14]3[C:10]([CH:11]=[N:12][NH:13]3)=[CH:9][CH:8]=2)=[O:5])=[C:2]([Cl:1])[CH:19]=1
Reactant: Nc1cc(F)c([N+](=O)[O-])cc1C(=O)Nc1ccc2cn[nH]c2c1
Reactant: O=C(Nc1ccc2cn[nH]c2c1)c1cc([N+](=O)[O-])c(F)cc1Cl
Agent: [NH4+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Product: Nc1cc(Cl)c(C(=O)Nc2ccc3cn[nH]c3c2)cc1[N+](=O)[O-]

Procedure:
A solution of 2-chloro-4-fluoro-N-(1H-indazol-6-yl)-5-nitrobenzamide (2 mmol) in dioxane (4 mL) was reacted with aqueous NH4OH using the conditions described in Example 115. After the formation of 2-amino-4-fluoro-N-(1H-indazol-6-yl)-5-nitrobenzamide was complete, the volatiles were removed in vacuo. The residue obtained was suspended in cold water with stirring. The solid formed was collected by filtration, washed with water, and dried in vacuo to provide the product, 4-amino-2-chloro-N-(1H-indazol-6-yl)-5-nitrobenzamide as a yellow solid.
Reaction SMILES: [Br:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[N+:12]([O-])=O)[C:5]([Cl:15])=[N:4][CH:3]=1.O1CCCC1>C(O)C.[Pt].[S]>[NH2:12][C:10]1[CH:9]=[CH:8][CH:7]=[C:6]2[C:11]=1[C:2]([Br:1])=[CH:3][N:4]=[C:5]2[Cl:15]
Reactant: O=[N+]([O-])c1cccc2c(Cl)ncc(Br)c12
Agent: [Pt]
Agent: [S]
Solvent: CCO
Solvent: C1CCOC1
Product: Nc1cccc2c(Cl)ncc(Br)c12
Temperature: 25 °C
Reaction time: 15 h
Yield: 102.1 %

Procedure:
A solution of 4-bromo-1-chloro-5-nitroisoquinoline (14.0 g) prepared according to the method described in a known literature (Nair et al., Indian J. Chem., 1967, 5, 403) in ethanol (75 ml) and tetrahydrofuran (75 ml) was added with 3% platinum-sulfur/activated carbon (3% Pt-S/C, NE Chemcat, CM011, 14.0 g), and the mixture was stirred at room temperature for 15 hours under a hydrogen gas atmosphere. The atmosphere was replaced with nitrogen gas, and then the insoluble matters were removed by filtration through Celite, and the solvent was evaporated under reduced pressure to obtain the title compound (12.8 g).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9](=[O:31])[C:10]2[CH:15]=[CH:14][C:13]([C:16]([O:18]C)=[O:17])=[CH:12][C:11]=2[NH:20][CH2:21][CH:22]2[CH2:27][CH2:26][N:25]([CH:28]([CH3:30])[CH3:29])[CH2:24][CH2:23]2)=[N:6][CH:7]=1.O1CCCC1.[OH-].[Li+].Cl>O>[ClH:1].[C:16]([C:13]1[CH:14]=[CH:15][C:10]([C:9]([NH:8][C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][N:6]=2)=[O:31])=[C:11]([NH:20][CH2:21][CH:22]2[CH2:27][CH2:26][N:25]([CH:28]([CH3:30])[CH3:29])[CH2:24][CH2:23]2)[CH:12]=1)([OH:18])=[O:17]
Reactant: COC(=O)c1ccc(C(=O)Nc2ccc(Cl)cn2)c(NCC2CCN(C(C)C)CC2)c1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)N1CCC(CNc2cc(C(=O)O)ccc2C(=O)Nc2ccc(Cl)cn2)CC1
Reaction time: 17 h
Yield: 60.9 %

Procedure:
A solution of N-(5-chloropyridin-2-yl)-2-(1-isopropylpiperidin-4-ylmethylamino)-4-methoxycarbonylbenzamide (100 mg, 0.225 mmol) in 4:1 tetrahydrofuran:water (2.5 mL) was treated with lithium hydroxide (20 mg, 0.90 mmol). After 17 h, the pH of the mixture was adjusted to 2–3 by addition of 1 N HCl. The mixture was then concentrated and the residue purified by RPHPLC affording 32 mg (30%) of the title compound as a hydrochloride salt.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:10][C:9](=[O:11])O[C:7](=[O:12])[C:6]=2[CH:13]=1.[CH3:14][O:15][C:16]1[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[CH:24][C:17]=1[CH2:18][NH:19][CH2:20]C(O)=O>CC1C=CC(C)=CC=1>[CH3:14][O:15][C:16]1[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[CH:24][C:17]=1[CH2:18][N:19]1[C:7](=[O:12])[C:6]2[CH:13]=[C:2]([CH3:1])[CH:3]=[CH:4][C:5]=2[NH:10][C:9](=[O:11])[CH2:20]1
Reactant: Cc1ccc2[nH]c(=O)oc(=O)c2c1
Reactant: COc1ccc(CNCC(=O)O)c(OC)c1
Solvent: Cc1ccc(C)cc1
Product: COc1ccc(CN2CC(=O)Nc3ccc(C)cc3C2=O)c(OC)c1
Temperature: 150 °C

Procedure:
A suspension of 6-methyl-2H-3,1-bezoxazine-2,4(1H)-dione (18.3 g, 103 mmol) containing (2,4-dimethoxy-benzylamino)-acetic acid (25.6 g, 114 mmol) in p-xylene (125 mL) was heated under reflux (150° C.) for 2.5 h. After cooling to room temperature the precipitate was filtered off and washed with p-xylene (2×20 ml). Yield: 34.1 g (97%). m/z 341 (MH+).
Reaction SMILES: Cl.Cl.Cl.[O:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[C:12]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([NH2:27])[CH2:23][CH2:22]4)[CH2:15][CH2:14]3)[C:7]=2[O:6][CH2:5]1.[Cl:28][CH:29]1[CH2:32][CH:31]([C:33](O)=[O:34])[CH2:30]1>>[O:4]1[C:8]2[CH:9]=[CH:10][CH:11]=[C:12]([N:13]3[CH2:18][CH2:17][N:16]([CH2:19][CH2:20][C@H:21]4[CH2:26][CH2:25][C@H:24]([NH:27][C:33]([CH:31]5[CH2:32][CH:29]([Cl:28])[CH2:30]5)=[O:34])[CH2:23][CH2:22]4)[CH2:15][CH2:14]3)[C:7]=2[O:6][CH2:5]1
Reactant: N[C@H]1CC[C@H](CCN2CCN(c3cccc4c3OCO4)CC2)CC1
Reactant: O=C(O)C1CC(Cl)C1
Agent: Cl
Product: O=C(N[C@H]1CC[C@H](CCN2CCN(c3cccc4c3OCO4)CC2)CC1)C1CC(Cl)C1

Procedure:
The title compound, white solid (13 mg, 35.6%), MS (ISP) m/z=448.2 [(M+H)+], was prepared in accordance with the general method of example 1 from Trans-4-[2-(4-Benzo[1,3]dioxol-4-yl-piperazin-1-yl)-ethyl]-cyclohexylamine hydrochloride (Intermediate A) (30 mg, 81.5 mmol) and 3-chlorocyclobutanecarboxylic acid.
Reaction SMILES: Br[CH:2]([CH2:8][CH2:9]Br)[C:3]([O:5][CH2:6][CH3:7])=[O:4].C(N(CC)CC)C.[CH2:18]([NH2:25])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>O>[CH2:18]([N:25]1[CH2:9][CH2:8][CH:2]1[C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1
Reactant: NCc1ccccc1
Reactant: CCOC(=O)C(Br)CCBr
Solvent: O
Solvent: CCN(CC)CC
Product: CCOC(=O)C1CCN1Cc1ccccc1
Yield: 52.4 %

Procedure:
(Wasserman, H. H. et al. J Org. Chem. 1981, 46(15), 2991-2999). A mixture of (±)ethyl 2,4-dibromobutanoate (39) (15 g, 54.8 mmol), triethylamine (16.6 g, 164 mmol) and benzylamine (5.87 g, 54.8 mmol) was heated to reflux for 3 hours then concentrated under reduced pressure to give a solid suspension. Water (150 ml) was then added and the mixture extracted with ether (2×100 ml). The organic phase was dried and then concentrated under reduced pressure and the residue purified by dry flash chromatography on silica (hexanes then 1:3 ethyl acetate/hexanes) to give 40 as a pale yellow oil (6.3 g, 53%); 1H NMR (300 MHz, CDCl3) δ 7.37-7.27 (m, 5H), 4.16-4.03 (m, 2H), 3.82 (d, J=12.6 Hz, 1H), 3.73 (dd, J=8.4, 8.4 Hz, 1H), 3.61 (d, J=12.8 Hz, 1H), 3.34 (ddd, J=7.4, 7.4, 2.0 Hz, 1H), 2.95 (ddd, J=7.4, 7.4, 7.4 Hz, 1H), 2.44-2.31 (m, 1H), 2.27-2.16 (m, 1H), 1.20 (t, J=7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 172.5, 137.1, 129.0, 128.7, 128.2, 127.1, 64.5, 62.4, 60.5, 50.8, 21.5, 14.0.
Reaction SMILES: [OH:1][CH:2]([CH2:53][N:54]1[C:77]([CH3:79])([CH3:78])[CH2:76][C:57]2([NH:61][C:60](=[O:62])[N:59]([CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH3:74])[C:58]2=[O:75])[CH2:56][C:55]1([CH3:81])[CH3:80])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH:22]([OH:52])[CH2:23][N:24]3[C:47]([CH3:49])([CH3:48])[CH2:46][C:27]4([NH:31][C:30](=[O:32])[N:29]([CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH3:44])[C:28]4=[O:45])[CH2:26][C:25]3([CH3:51])[CH3:50])=[CH:16][CH:15]=2)([CH3:13])[CH3:12])=[CH:7][CH:6]=1.C(O[C:86](=[O:88])[CH3:87])(=O)C>C(OCC)(=O)C>[C:2]([O:52][CH:22]([CH2:23][N:24]1[C:25]([CH3:50])([CH3:51])[CH2:26][C:27]2([N:31]([C:86](=[O:88])[CH3:87])[C:30](=[O:32])[N:29]([CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH3:44])[C:28]2=[O:45])[CH2:46][C:47]1([CH3:48])[CH3:49])[CH2:21][O:20][C:17]1[CH:16]=[CH:15][C:14]([C:11]([C:8]2[CH:7]=[CH:6][C:5]([O:4][CH2:3][CH:2]([O:1][C:17](=[O:20])[CH3:16])[CH2:53][N:54]3[C:55]([CH3:80])([CH3:81])[CH2:56][C:57]4([N:61]([C:5](=[O:4])[CH3:6])[C:60](=[O:62])[N:59]([CH2:63][CH2:64][CH2:65][CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH3:74])[C:58]4=[O:75])[CH2:76][C:77]3([CH3:79])[CH3:78])=[CH:10][CH:9]=2)([CH3:13])[CH3:12])=[CH:19][CH:18]=1)(=[O:1])[CH3:3]
Reactant: CCCCCCCCCCCCN1C(=O)NC2(CC(C)(C)N(CC(O)COc3ccc(C(C)(C)c4ccc(OCC(O)CN5C(C)(C)CC6(CC5(C)C)NC(=O)N(CCCCCCCCCCCC)C6=O)cc4)cc3)C(C)(C)C2)C1=O
Reactant: CC(=O)OC(C)=O
Solvent: CCOC(C)=O
Product: CCCCCCCCCCCCN1C(=O)N(C(C)=O)C2(CC(C)(C)N(CC(COc3ccc(C(C)(C)c4ccc(OCC(CN5C(C)(C)CC6(CC5(C)C)C(=O)N(CCCCCCCCCCCC)C(=O)N6C(C)=O)OC(C)=O)cc4)cc3)OC(C)=O)C(C)(C)C2)C1=O

Procedure:
A mixture of 1.1 g of 2,2-bis{4-[2-hydroxy-3-(3-dodecyl-7,7,9,9-tetramethyl-2,4-dioxo-1,3,8-triazaspiro[4.5]dec-8-yl)propoxy]phenyl}propane and 10 g of acetic anhydride was refluxed for 48 hours. After completion of the reaction, the reaction mixture was dissolved in ethyl acetate and treated with an aqueous alkali. The solution was then dried and condensed by evaporation under reduced pressure, affording a viscous product which was purified by column chromatography through silica gel eluted with a 1:1 by volume mixture of ethyl acetate and n-hexane, giving the desired Compound No. 259 in the form of a white powder melting at 52°-55° C.
Reaction SMILES: [Cl:1][C:2]1[CH:20]=[CH:19][C:5]([O:6][C:7]2[CH:12]=[C:11]([CH:13]([CH3:18])[C:14]([O:16][CH3:17])=[O:15])[CH:10]=[CH:9][N:8]=2)=[CH:4][CH:3]=1.[CH3:21]I.[H-].[Na+]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:6][C:7]2[CH:12]=[C:11]([C:13]([CH3:21])([CH3:18])[C:14]([O:16][CH3:17])=[O:15])[CH:10]=[CH:9][N:8]=2)=[CH:19][CH:20]=1
Reactant: CI
Reactant: COC(=O)C(C)c1ccnc(Oc2ccc(Cl)cc2)c1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COC(=O)C(C)(C)c1ccnc(Oc2ccc(Cl)cc2)c1
Reaction time: 0.5 h

Procedure:
Methyl 2-(2-p-chlorophenoxy-4-pyridyl)propionate (3.13 g) is treated with methyl iodide in the presence of 50 % sodium hydride in anhydrous tetrahydrofuran in a nitrogen atmosphere at room temperature for 1 hour and then at 40° C for 30 minutes, whereby methyl 2-(2-p-chlorophenoxy-4-pyridyl)isobutyrate (2.59 g) is obtained as crystals melting at 92° to 92.5° C. Then, this substance is treated with a mixture of 20 % aqueous potassium hydroxide and 95 % ethanol with refluxing for 10 minutes, whereby 2-(2-p-chlorophenoxy-4-pyridyl)isobutyric acid (2.35 g) is obtained as crystals melting at 135° to 136° C.
Reaction SMILES: C(O[C:5](=[O:7])[CH3:6])(=O)C.[NH2:8][C:9]1[CH:14]=[CH:13][C:12]([S:15]([F:20])([F:19])([F:18])([F:17])[F:16])=[CH:11][CH:10]=1.O>C(O)(=O)C>[C:5]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([S:15]([F:20])([F:16])([F:17])([F:18])[F:19])=[CH:11][CH:10]=1)(=[O:7])[CH3:6]
Reactant: Nc1ccc(S(F)(F)(F)(F)F)cc1
Reactant: CC(=O)OC(C)=O
Solvent: O
Solvent: CC(=O)O
Product: CC(=O)Nc1ccc(S(F)(F)(F)(F)F)cc1
Temperature: 65 °C
Reaction time: 1 h

Procedure:
Acetic-anhydride was added during 5 minutes to a stirred solution of 4-aminophenylsulphur pentafluoride (30.2 g) in acetic acid at 40° C. and then heated at 65° C. for 0.5 hour. The cooled mixture was added to water, stirred for 1 hour and filtered. The solid was washed with water, sodium bicarbonate solution and water, dried and purified by stirring with hexane to give 4-acetamidophenylsulphur pentafluoride (27.0 g), m.p.131-132° C.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([O:17][C:18]([CH3:23])([CH3:22])[C:19]([OH:21])=O)[CH:15]=3)[N:10]([CH3:24])[C:9]=2[CH3:25])=[CH:4][CH:3]=1.[CH2:26]([NH:29][CH2:30][CH2:31][CH3:32])[CH2:27][CH3:28]>>[CH2:26]([N:29]([CH2:30][CH2:31][CH3:32])[C:19](=[O:21])[C:18]([O:17][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][CH:13]=1)[N:10]([CH3:24])[C:9]([CH3:25])=[C:8]2[C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1)([CH3:22])[CH3:23])[CH2:27][CH3:28]
Reactant: CCCNCCC
Reactant: Cc1c(-c2ccc(Cl)cc2)c2cc(OC(C)(C)C(=O)O)ccc2n1C
Product: CCCN(CCC)C(=O)C(C)(C)Oc1ccc2c(c1)c(-c1ccc(Cl)cc1)c(C)n2C

Procedure:
The compound was prepared from 2-[3-(4-chlorophenyl)-1,2-dimethyl-1H-indole-5-yloxy]-2-methyl-propanoic acid and dipropylamine using a procedure analogous to that of Example 130.
Reaction SMILES: [Br:1][C:2]1[C:3]([C:11]([OH:13])=[O:12])=[C:4]2[NH:10][CH:9]=[N:8][C:5]2=[N:6][CH:7]=1.OS(O)(=O)=O.[CH3:19]O>>[Br:1][C:2]1[C:3]([C:11]([O:13][CH3:19])=[O:12])=[C:4]2[NH:10][CH:9]=[N:8][C:5]2=[N:6][CH:7]=1
Reactant: CO
Reactant: O=C(O)c1c(Br)cnc2nc[nH]c12
Agent: O=S(=O)(O)O
Product: COC(=O)c1c(Br)cnc2nc[nH]c12
Reaction time: 10 h
Yield: 70 %

Procedure:
Absolute methanol (30 ml) is added to 6-bromo-1H-imidazo[4,5-b]pyridine-7-carboxylic acid x208 (Zerenex; 2.2 g, 9.1 mmol). Concentrated H2SO4 (4 ml) is added to the obtained suspension at 0° C. The reaction mixture is refluxed under protection from the air moisture and vigorous stirring for 10 h. The reaction mixture is then evaporated to half-volume in the vacuum of a rotary evaporator and neutralized under cooling with ice with aqueous ammonia to pH 8-9. The formed precipitate is quickly separated by filtration, washed with ice-cold water (2×30 ml), and dried over P2O5 at 1 mmHg overnight to afford methyl 6-bromo-1H-imidazo[4,5-b]pyridine-7-carboxylate x209 (1.63 g).
Reaction SMILES: [C:1]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][N:10]1[C:11]([NH:13][C:14](/[C:16]/1=[CH:17]\[CH2:18][C:19](=[O:25])[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])=[O:15])=[O:12])([OH:3])=[O:2].C>CCO.CCOCC>[C:1]([CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][N:10]1[CH:16]([CH2:17][CH2:18][C:19](=[O:25])[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[C:14](=[O:15])[NH:13][C:11]1=[O:12])([OH:3])=[O:2]
Reactant: CCCCCC(=O)C/C=C1\C(=O)NC(=O)N1CCCCCCC(=O)O
Solvent: CCOCC
Solvent: CCO
Product: CCCCCC(=O)CCC1C(=O)NC(=O)N1CCCCCCC(=O)O

Procedure:
A solution of 1-(6-carboxyhexyl-5-((E)-3-oxooctylidene)hydantoin (3.06 g) in EtOH (60 ml) was stirred with 10% palladised charcoal (200 mg) under hydrogen at room temperature and pressure, absorption of 1 molecular equivalent of hydrogen occurring in 2 hours. The catalyst was filtered, the filtrate was evaporated in vacuo, and the residual gum was set aside to give a mass of colourless crystals. The crystals were suspended in ether (4 ml) and collected, affording pure 1-(6-carboxyhexyl)-5-(3-oxo-octyl)hydantoin, m.p. 84.5°-86°. A stirred suspension of 0.5 g of this compound in water (15 ml) at 0° C. was treated with NaHCO3 (0.36 g) and then, during 3 minutes, with sodium borohydride (54 mg). After 45 minutes, more sodium borohydride (54 mg) was added and, after a further 11/2 hours, the clear solution was set aside at room temperature for 11/2 hours. The solution was then acidified to Congo Red with hydrochloric acid, the liberated carboxylic acid was extracted into chloroform, and the chloroform solution was washed and dried over magnesium sulphate. Evaporation of the solvent afforded 1-(6-carboxyhexyl)-5-(3-hydroxyoctyl) hydantoin as a mixture of diastereomers which was subjected to HPLC (SiO2, CHCl3 /MeOH/HOAc 97.75:1.25:1.0), affording the individual diastereomers as colourless gums, Rf. 0.44 and 0.40 (relative to 0.64 for a marker of the starting oxo-compound) on SiO2 in CHCl3 /MeOH/HOAc 90:5:5.