Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([C:3]1([OH:17])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH:4]1[CH:15]=[CH2:16])=[CH2:2].[BH4-].[Na+]>C(Cl)Cl.[OH-].[Na+]>[C:3]1(=[O:17])[CH2:1][CH2:2][CH2:16][CH2:15][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]=[CH:11][CH2:12][CH2:13][CH2:14]1
Reactant: C=CC1CCCCCCCCCCC1(O)C=C
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: O=C1CCCC=CCCCCCCCCCC1
Yield: 70 %

Procedure:
A mixture of 1,2-divinylcyclododecan-1-ol (0.125 g, 5.10-4 mol) and mercuric trifluoroacetate (0.215 g) in methylene chloride (4 cc) is kept at a temperature of the order of 20° C. After a reaction time of 1 hour 30 minutes, a solution of sodium borohydride (0.005 g) in 3 N sodium hydroxide solution (0.33 cc) is added to the reaction mixture. The reaction mixture is extracted with methylene chloride (3×10 cc). The organic extracts are dried over magnesium sulphate. After filtration and concentration of the solvent under reduced pressure (20 mm Hg; 2.7 kPa), cyclohexadec-5-en-1-one (0.087 g) is obtained with a yield of 70%.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](O)=[O:7])=[CH:4][CH:3]=1.S(Cl)([Cl:13])=O>C(Cl)(Cl)(Cl)Cl>[Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([Cl:13])=[O:7])=[CH:4][CH:3]=1
Reactant: O=C(O)c1ccc(Br)cc1
Reactant: O=S(Cl)Cl
Solvent: ClC(Cl)(Cl)Cl
Product: O=C(Cl)c1ccc(Br)cc1

Procedure:
A solution of 4-bromobenzoic acid (0.113 moles) and thionyl chloride (45 ml) in carbon tetrachloride (100 ml) was heated at reflux for 3.5 hours. Solvent and excess thionyl chloride were removed under reduced pressure and the crude 4-bromobenzoyl chloride was used in subsequent reactions without further purification. ##STR5##
Reaction SMILES: [C:1]1([C:11](=[O:14])[CH2:12][CH3:13])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[Br-:15].[Br-].[Br-].C1([N+](C)(C)C)C=CC=CC=1.C1([N+](C)(C)C)C=CC=CC=1.C1([N+](C)(C)C)C=CC=CC=1>O1CCCC1>[Br:15][CH:12]([CH3:13])[C:11]([C:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1)=[O:14]
Reactant: CCC(=O)c1cccc2ccccc12
Reactant: [Br-]
Agent: C[N+](C)(C)c1ccccc1
Solvent: C1CCOC1
Product: CC(Br)C(=O)c1cccc2ccccc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 175.6 %

Procedure:
To a solution of 1-(naphth-1-yl)-1-propanone (4.0 g) in anhydrous tetrahydrofuran (50 ml) was added phenyltrimethylammonium tribromide (8.0 g). The resulting mixture was stirred overnight at room temperature then partitioned between petroleum ether and aqueous sodium carbonate solution. The organic layer was separated, washed with water, brine, dried with sodium sulphate, filtered and evaporated in vacuo to yield crude 2-bromo-1-(naphth-1-yl)-1-propanone (5.7 g).
Reaction SMILES: [C:1]([O:5][C:6](=[O:58])[CH2:7][N:8]1[CH:12]=[CH:11][N:10]=[C:9]1[CH2:13][N:14]([CH2:44][C:45]1[N:46]([CH2:50][C:51](=[O:57])[O:52][C:53]([CH3:56])([CH3:55])[CH3:54])[CH:47]=[CH:48][N:49]=1)[CH2:15][CH2:16][CH2:17][CH2:18][C@H:19]([NH:27][C:28](=[O:43])[NH:29][C@H:30]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:31][CH2:32][C:33](O)=[O:34])[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])([CH3:4])([CH3:3])[CH3:2].[NH2:59][CH2:60][CH2:61][C:62]1[CH:67]=[CH:66][C:65]([S:68]([NH2:71])(=[O:70])=[O:69])=[CH:64][CH:63]=1.CCN(C(C)C)C(C)C>CN(C=O)C>[C:53]([O:52][C:51](=[O:57])[CH2:50][N:46]1[CH:47]=[CH:48][N:49]=[C:45]1[CH2:44][N:14]([CH2:13][C:9]1[N:8]([CH2:7][C:6](=[O:58])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH:12]=[CH:11][N:10]=1)[CH2:15][CH2:16][CH2:17][CH2:18][C@H:19]([NH:27][C:28]([NH:29][C@@H:30]([CH2:31][CH2:32][C:33](=[O:34])[NH:59][CH2:60][CH2:61][C:62]1[CH:63]=[CH:64][C:65]([S:68](=[O:69])(=[O:70])[NH2:71])=[CH:66][CH:67]=1)[C:36]([O:38][C:39]([CH3:40])([CH3:41])[CH3:42])=[O:37])=[O:43])[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])([CH3:54])([CH3:55])[CH3:56]
Reactant: NCCc1ccc(S(N)(=O)=O)cc1
Reactant: CC(C)(C)OC(=O)Cn1ccnc1CN(CCCC[C@H](NC(=O)N[C@@H](CCC(=O)O)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)Cc1nccn1CC(=O)OC(C)(C)C
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)Cn1ccnc1CN(CCCC[C@H](NC(=O)N[C@@H](CCC(=O)NCCc1ccc(S(N)(=O)=O)cc1)C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)Cc1nccn1CC(=O)OC(C)(C)C
Yield: 101.8 %

Procedure:
A solution of (S)-4-(3-((S)-6-(bis((1-(2-tert-butoxy-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)-1-tert-butoxy-1-oxohexan-2-yl)ureido)-5-tert-butoxy-5-oxopentanoic acid (80 mg, 0.098 mmol), 4-(2-aminoethyl)benzenesulfonamide (30 mg, 0.15 mmol), 2-(1-H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl uronium hexafluorophosphate methanaminium (HATU, 50 mg, 0.17 mmol), and DIPEA (0.50 mL) in DMF (5 mL) was stirred at 40° C. overnight. The solvents were evaporated under reduced pressure to give a residue, which was purified by Biotage SP4 using a gradient of 0-20% MeOH in DCM to give (S)-tert-butyl 6-(bis((1-(2-tert-butoxy-2-oxoethyl)-1H-imidazol-2-yl)methyl)amino)-2-(3-((S)-1-tert-butoxy-1,5-dioxo-5-(4-sulfamoylphenethylamino)pentan-2-yl)ureido)hexanoate (100 mg, 100%). ESMS m/z: 501.9 (M/2+H)+.
Reaction SMILES: [C:1]1([NH:7][C:8]2[CH:13]=[CH:12][C:11]([N:14]=O)=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(O)CCCCC.[OH-].[Na+]>>[C:1]1([NH:7][C:8]2[CH:13]=[CH:12][C:11]([NH2:14])=[CH:10][CH:9]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: O=Nc1ccc(Nc2ccccc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCCCCCO
Product: Nc1ccc(Nc2ccccc2)cc1
Temperature: 100 °C
Reaction time: 0.25 h

Procedure:
To a 1-liter three-necked round bottom flask fitted with a stirrer, a condenser and a thermometer were added 99.0 (0.5 mole) N-phenyl-4-nitrosoaniline, 254 g n-hexanol and 40 g (0.5 mole) aqueous NaOH (50% by weight). The dark reddish brown solution was stirred, heated to 100° C., at which point an exotherm developed, and heating was discontinued. A temperature rise to 120° C. was observed within 15 minutes. After another 15 minutes, the temperature returned to 100° C. Stirring was continued for one hour while maintaining the reaction mixture at 100°-105° C. Thereafter, a sample of the reaction mixture was analyzed by HPLC; no nitroso starting material was detected.
Reaction SMILES: [CH:1]1([CH:4]([C:23]2[CH:28]=[CH:27][C:26](B3OC(C)(C)C(C)(C)O3)=[CH:25][CH:24]=2)[N:5]2[CH2:10][CH2:9][C:8]([CH2:17][C:18]([OH:21])([CH3:20])[CH3:19])([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[O:7][C:6]2=[O:22])[CH2:3][CH2:2]1.Br[C:39]1[CH:44]=[CH:43][N:42]([CH3:45])[C:41](=[O:46])[CH:40]=1>>[CH:1]1([CH:4]([C:23]2[CH:28]=[CH:27][C:26]([C:39]3[CH:44]=[CH:43][N:42]([CH3:45])[C:41](=[O:46])[CH:40]=3)=[CH:25][CH:24]=2)[N:5]2[CH2:10][CH2:9][C:8]([CH2:17][C:18]([OH:21])([CH3:20])[CH3:19])([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[O:7][C:6]2=[O:22])[CH2:2][CH2:3]1
Reactant: Cn1ccc(Br)cc1=O
Reactant: CC(C)(O)CC1(c2ccccc2)CCN(C(c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)C2CC2)C(=O)O1
Product: Cn1ccc(-c2ccc(C(C3CC3)N3CCC(CC(C)(C)O)(c4ccccc4)OC3=O)cc2)cc1=O

Procedure:
The title compound was prepared from 3-{cyclopropyl-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]methyl}-6-(2-hydroxy-2-methyl-propyl)-6-phenyl-[1,3]oxazinan-2-one (for preparation see below) and 4-bromo-1-methyl-1H-pyridin-2-one following a procedure analogous to that described in Example 3. LC-MS (Method 1): tR=3.57 min; Mass spectrum (ESI+): m/z=487 [M+H]+.
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:3]=1[NH2:4].[C:12]1(=O)[O:17][C:15](=[O:16])[C:14]2[CH2:18][CH2:19][CH2:20][CH2:21][C:13]1=2>C(O)(=O)C.O>[F:1][C:2]1[CH:8]=[CH:7][C:6]([N+:9]([O-:11])=[O:10])=[CH:5][C:3]=1[N:4]1[C:15](=[O:16])[C:14]2[CH2:18][CH2:19][CH2:20][CH2:21][C:13]=2[C:12]1=[O:17]
Reactant: O=C1OC(=O)C2=C1CCCC2
Reactant: Nc1cc([N+](=O)[O-])ccc1F
Solvent: O
Solvent: CC(=O)O
Product: O=C1C2=C(CCCC2)C(=O)N1c1cc([N+](=O)[O-])ccc1F
Yield: 77.5 %

Procedure:
2-Fluoro-5-nitroaniline (IV) (50 g) and 3,4,5,6-tetrahydrophthalic anhydride (49 g) were dissolved in acetic acid (200 ml), and the resultant solution was heated under reflux for 4 hours. After cooling, the reaction mixture was diluted with water and extracted with ethyl acetate. The extract was concentrated, and the precipitated crystals were collected by filtration to give 72 g of N-(2-fluoro-5-nitrophenyl)-3,4,5,6-tetrahydrophthalimide (VII). M.P., 154.9° C.
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.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.O.[CH3:54][N:55](C=O)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[NH:7]1[C:8]2[C:4](=[CH:3][C:2]([C:54]#[N:55])=[CH:10][CH:9]=2)[CH:5]=[N:6]1
Reactant: CN(C)C=O
Reactant: Brc1ccc2[nH]ncc2c1
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: O
Product: N#Cc1ccc2[nH]ncc2c1
Temperature: 150 °C
Yield: 24 %

Procedure:
To a suspension of 5-bromo-indazole (2.0 g, 10.2 mmol), Zn(CN)2 (1.4 g, 12.2 mmol), and Xantphos (0.9 g, 1.5 mmol), in DMF (10 mL) and water (0.1 mL) was added Pd2(dba)3 (417 mg, 0.51 mmol) under N2 at rt. The suspension was heated at 150° C. for 1.5 h in the microwave. The solution was filtered and concentrated, and the residue was purified by silica gel chromatography (10-20% MeOH/DCM) to give 350 mg (24%) of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 7.62 (2H, s), 8.20 (2H, d, J=8.0 Hz), 10.56 (1H, br s).
Reaction SMILES: C(O)[C@H]1O[C@H](O[C@]2(CO)O[C@H](CO)[C@@H](O)[C@@H]2O)[C@H](O)[C@@H](O)[C@@H]1O.C(=O)([O-])[O-].[Ca+2].[O:29]=[C:30]([CH:34]=[CH:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:31]([O-:33])=[O:32].[K+].S(=O)(=O)(O)O>O>[OH:29][C@H:30]([CH:34]=[CH:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[C:31]([OH:33])=[O:32]
Reactant: O=C([O-])C(=O)C=Cc1ccccc1
Agent: O=C([O-])[O-]
Agent: O=S(=O)(O)O
Agent: OC[C@H]1O[C@@](CO)(O[C@H]2O[C@H](CO)[C@@H](O)[C@H](O)[C@H]2O)[C@@H](O)[C@@H]1O
Solvent: O
Product: O=C(O)[C@H](O)C=Cc1ccccc1
Temperature: 30 °C
Reaction time: 48 h

Procedure:
A medium comprising 2% glucose, 1% yeast extract, 1% peptone, 10 ppm MnSO4 and 1% calcium carbonate was used for lactic acid bacteria. A medium comprising 1% glucose, 0.5% yeast extract, 0.5% peptone, 0.5% meat extract and 0.5% NaCl (pH 7) was used for other bacteria. A medium comprising 2% glucose, 0.3% yeast extract, 0.5% peptone and 0.3% malt extract (pH 6) was used for yeasts. 100 ml of each medium was introduced into a 500-ml Erlenmeyer flask and sterilized. Then one platinum loopful of each strain listed in Table 1 was inoculated into the corresponding medium and subjected to rotary shaking culture for 48 hours. After completion of the culture, the cells were separated by centrifuging and washed with a physiological saline solution once to thereby give viable cells. 50 ml of distilled water was introduced into a 500-ml Erlenmeyer flask and the above-mentioned viable cells were suspended therein. After adding 5 g of sucrose and 0.5 g of calcium carbonate thereto, the mixture was shaken at 30° C. for 10 minutes. Then 0.5 g of potassium 2-keto-4-phenyl-3-butenoate was added thereto and the mixture was allowed to react under shaking at 30° C. for 40 hours. After the completion of the reaction, the pH value of the reaction mixture was adjusted to 1 or below with sulfuric acid. Then it was extracted with 100 mi of ethyl acetate and the solvent was removed from the extract. Then the amount and optical purity of the (R)-2-hydroxy-4-phenyl-3-butenoic acid thus formed were determined by high-performance liquid chromatography.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][C:3]=1[F:9].CC(C)([O-])C.[K+].Cl[C:17]1[CH:22]=[CH:21][N:20]=[C:19]([C:23]([NH:25][CH3:26])=[O:24])[CH:18]=1>CN(C)C(=O)C.C(OCC)C>[CH3:26][NH:25][C:23]([C:19]1[CH:18]=[C:17]([O:8][C:5]2[CH:6]=[CH:7][C:2]([NH2:1])=[C:3]([F:9])[CH:4]=2)[CH:22]=[CH:21][N:20]=1)=[O:24]
Reactant: CNC(=O)c1cc(Cl)ccn1
Reactant: Nc1ccc(O)cc1F
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CCOCC
Solvent: CC(=O)N(C)C
Product: CNC(=O)c1cc(Oc2ccc(N)c(F)c2)ccn1
Temperature: 0 °C
Reaction time: 0.42 h
Yield: 121.2 %

Procedure:
A solution of 4-amino-3-fluorophenol (500 mg, 3.9 mmol) in N,N-dimethylacetamide (6 mL) cooled to 0° C. was treated with potassium tert-butoxide (441 mg, 3.9 mmol), and the brown solution was allowed to stir at 0° C. for 25 min. To the mixture was added 4-chloro-N-methyl-2-pyridinecarboxamide (516 mg, 3.0 mmol) as a solution in dimethylacetamide (4 mL). The reaction was heated at 100° C. for 16 h. The mixture was cooled to room temperature, quenched with H2O (20 mL), and extracted with ehtylacetate (4×40 mL). The combined organics were washed with H2O (2×30 mL), dried (MgSO4), and evaporated to afford a red-brown oil. 1H-NMR indicated the presence of residual dimethylacetamide, thus the oil was taken up in diethylether (50 mL) and was further washed with brine (5×30 mL). The organic layer was dried (MgSO4) and concentrated to give 950 mg of the desired product as a red-brown solid, which was used in the next step without purification.
Reaction SMILES: [C:1]1([CH3:8])[C:6]([OH:7])=[CH:5][CH:4]=[CH:3][CH:2]=1.N1C(C)=CC=CC=1C.Cl[Sn](Cl)(Cl)Cl.[CH2:22]=[O:23]>C1(C)C=CC=CC=1>[OH:23][C:22]1[C:1]([CH3:8])=[CH:2][CH:3]=[CH:4][C:5]=1[CH:6]=[O:7]
Reactant: Cc1ccccc1O
Reactant: C=O
Agent: Cl[Sn](Cl)(Cl)Cl
Solvent: Cc1ccccc1
Solvent: Cc1cccc(C)n1
Product: Cc1cccc(C=O)c1O
Temperature: 20 °C
Reaction time: 0.5 h
Yield: 98.9 %

Procedure:
o-Cresol 20.0 g (185 mmol) was dissolved in toluene 400 ml and thereto was added 2,6-lutidine 18.4 g (171 mmol). SnCl4 4.8 g (18 mmol) was added to the mixture and the mixture was stirred for 30 min. at 20° C. Thereto was added paraformaldehyde (purity: 95 weight %) 12.9 g (409 mmol) and the mixture was stirred at 80° C. for 5 hours to the conversion of 78%. And the reaction was kept for 10 hours at 100° C. to confirm the disappearance of the raw material, o-cresol. The reaction solution was cooled to room temperature, extracted with water-toluene in a separatory funnel and the organic layer was dried over anhydrous magnesium sulfate and dried in vacuo to give 2-hydroxy-3-methylbenzaldehyde 24.9 g (yield: 99%, selectivity: 99%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH3:9].[Cl:10]Cl>N(C(C)(C)C#N)=NC(C)(C)C#N.C(#N)C>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[CH2:9][Cl:10]
Reactant: ClCl
Reactant: Cc1ccc(Cl)cc1Cl
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: CC#N
Product: ClCc1ccc(Cl)cc1Cl
Reaction time: 0.5 h

Procedure:
1 Mol of 2,4-dichloro-methylbenzene and 322 g of acetonitrile are heated to reflux. 0.8 g of azobisisobutyronitrile is added and this addition is repeated every half hour. Chlorine gas is simultaneously introduced in a slight excess. 0.75 Mol of product is obtained after 2 hours.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([C:11]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][N:22]4[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]4)=[CH:15][CH:14]=3)=[O:12])=[C:9]([CH:28]3[CH2:33][CH2:32][C:31](=[O:34])[CH2:30][CH2:29]3)[S:8][C:7]=2[CH:35]=1.C1COCC1.[BH4-].[Na+].O>CO.C(Cl)(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[C:10]([C:11]([C:13]3[CH:18]=[CH:17][C:16]([O:19][CH2:20][CH2:21][N:22]4[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]4)=[CH:15][CH:14]=3)=[O:12])=[C:9]([CH:28]3[CH2:29][CH2:30][CH:31]([OH:34])[CH2:32][CH2:33]3)[S:8][C:7]=2[CH:35]=1
Reactant: COc1ccc2c(C(=O)c3ccc(OCCN4CCCCC4)cc3)c(C3CCC(=O)CC3)sc2c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Solvent: O
Product: COc1ccc2c(C(=O)c3ccc(OCCN4CCCCC4)cc3)c(C3CCC(O)CC3)sc2c1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 63.7 %

Procedure:
50 mg of (6-methoxy-2-(4-oxocyclohexyl)benzo[b]thien-3-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone is dissolved in 4 mL of methanol and 0.5 mL of THF and cooled with ice. 6 mg of sodium borohydride is added, and this mixture is agitated at 0° C. for 15 minutes. Water is added to the reaction mixture, and the organic layer is extracted with ethyl acetate, then washed with water and dried with anhydrous sodium sulfate, after which the solvent is distilled off. The crude product thus obtained is refined by TLC (developing solvent was chloroform:methanol=19:1), which gives 32 mg of [6-methoxy-2-(4-hydroxycyclohexyl)benzo[b]thien-3-yl)[4-[2-(1-piperidinyl)ethoxy]phenyl]methanone.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:11]=[C:12]([S:14]([F:19])([F:18])([F:17])([F:16])[F:15])[CH:13]=1)[C:5]([N:7]([O:9][CH3:10])[CH3:8])=[O:6].[C:20](OC(=O)C)(=[O:22])[CH3:21].FC(F)(F)C(OC(=O)C(F)(F)F)=O>>[C:20]([NH:1][C:2]1[CH:3]=[C:4]([CH:11]=[C:12]([S:14]([F:19])([F:15])([F:16])([F:17])[F:18])[CH:13]=1)[C:5]([N:7]([O:9][CH3:10])[CH3:8])=[O:6])(=[O:22])[CH3:21]
Reactant: CON(C)C(=O)c1cc(N)cc(S(F)(F)(F)(F)F)c1
Reactant: CC(=O)OC(C)=O
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Product: CON(C)C(=O)c1cc(NC(C)=O)cc(S(F)(F)(F)(F)F)c1

Procedure:
3-Amino-N-methoxy-N-methyl-5-pentafluorosulfanylbenzamide (1.2 g, example 4b) was reacted analogously to example 4c) with acetic anhydride instead of with trifluoroacetic anhydride. 1.3 g of the desired compound were isolated.
Reaction SMILES: N([O:3][C:4](C)(C)[CH3:5])=O.ClC1C=C2C(=O)N(O)C(=O)C2=CC=1.C1(=NO)CCCCC1.[N+](C1CCCCC1)([O-])=O.[C:38]1(=[O:44])[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1>C(O)(=O)C.C1CCCCC1>[C:4]([O:44][CH:38]1[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]1)(=[O:3])[CH3:5]
Reactant: O=C1CCCCC1
Reactant: CC(C)(C)ON=O
Agent: O=C1c2ccc(Cl)cc2C(=O)N1O
Agent: O=[N+]([O-])C1CCCCC1
Agent: ON=C1CCCCC1
Solvent: C1CCCCC1
Solvent: CC(=O)O
Product: CC(=O)OC1CCCCC1
Temperature: 80 °C
Reaction time: 20 h

Procedure:
Cyclohexane (1 ml), t-butyl nitrite (1 mmol), 4-chloro-N-hydroxyphthalimide (0.2 mmol), and acetic acid (1 ml) were placed in a flask and were stirred at 80° C. in an atmosphere of argon gas (1 atm=0.101 MPa) for 20 hours. The resulting reaction mixture was analyzed to find that cyclohexanone oxime, nitrocyclohexane, cyclohexanone, and cyclohexyl acetate were formed in yields of 13%, 9%, 2%, and 2%, respectively.
Reaction SMILES: [Li+].[OH-].C[O:4][C:5](=[O:25])[C:6]1[CH:11]=[CH:10][C:9]([CH:12]([C:14]2[NH:18][C:17]3[CH:19]=[CH:20][C:21]([O:23][CH3:24])=[CH:22][C:16]=3[N:15]=2)[SH:13])=[CH:8][CH:7]=1.Cl>O.C1COCC1>[CH3:24][O:23][C:21]1[CH:20]=[CH:19][C:17]2[NH:18][C:14]([CH:12]([SH:13])[C:9]3[CH:10]=[CH:11][C:6]([C:5]([OH:25])=[O:4])=[CH:7][CH:8]=3)=[N:15][C:16]=2[CH:22]=1
Reactant: COC(=O)c1ccc(C(S)c2nc3cc(OC)ccc3[nH]2)cc1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: COc1ccc2[nH]c(C(S)c3ccc(C(=O)O)cc3)nc2c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A solution of LiOH.H20 (1.02 g, 24.4 mmol) in water (15 ml) was added to a suspension of 376a (3.99 g, 9.75 mmol of in THF (10 ml). The reaction mixture was stirred 16 h at room temperature. The reaction mixture was acidified with a solution of HCl 1 M to pH 4. The desired product was triturated 20 min. at 0° C. and then filtered and dried. Compound 376b was obtained as a white powder (100% yield, 3.05 g). 1H NMR: (DMSO) δ (ppm): 12.85 (bs, 1H), 7.86 (d, J=8.1 Hz, 2H), 7.53 (d, J=8.1 Hz, 2H), 7.35 (d, J=8.1 Hz, 1H), 6.97 (d, J=2.2 Hz, 1H), 6.76 (dd, J=8.8, 2.2 Hz, 1H), 4.60 (s, 2H), 3.82 (s, 3H). MS: (calc.) 314.1, (obt.), 315.1 (MH)+.
Reaction SMILES: FC(F)(F)C(O[CH2:6][N:7]([N+:9]([O-:11])=[O:10])[CH3:8])=O.[F:14][C:15]([N+:21]([O-:23])=[O:22])([N+:18]([O-:20])=[O:19])[CH2:16][OH:17]>>[F:14][C:15]([N+:21]([O-:23])=[O:22])([N+:18]([O-:20])=[O:19])[CH2:16][O:17][CH2:6][N:7]([N+:9]([O-:11])=[O:10])[CH3:8]
Reactant: CN(COC(=O)C(F)(F)F)[N+](=O)[O-]
Reactant: O=[N+]([O-])C(F)(CO)[N+](=O)[O-]
Product: CN(COCC(F)([N+](=O)[O-])[N+](=O)[O-])[N+](=O)[O-]

Procedure:
reacting one mole of 2-nitro-2-azapropyl trifluoroacetate with one mole of 2-fluoro-2,2-dinitroethanol in a polar solvent at a temperature of from 0° C. to 40° C. to form 1-fluoro-1,1,5-trinitro-3-oxa-5azahexane, wherein the reaction is run under vacuum to remove trifluoroacetic acid generated by the reaction; and
Reaction SMILES: [C:1]([Si:5]([CH3:17])([CH3:16])[O:6][C:7]1[CH:15]=[C:14]2[C:10]([CH:11]=[CH:12][NH:13]2)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].[C:18]([O:22][C:23](=[O:26])[CH2:24]Br)([CH3:21])([CH3:20])[CH3:19].C(=O)([O-])[O-].[Cs+].[Cs+]>>[C:18]([O:22][C:23](=[O:26])[CH2:24][N:13]1[C:14]2[C:10](=[CH:9][CH:8]=[C:7]([O:6][Si:5]([C:1]([CH3:4])([CH3:3])[CH3:2])([CH3:17])[CH3:16])[CH:15]=2)[CH:11]=[CH:12]1)([CH3:21])([CH3:20])[CH3:19]
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc2cc[nH]c2c1
Reactant: CC(C)(C)OC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Product: CC(C)(C)OC(=O)Cn1ccc2ccc(O[Si](C)(C)C(C)(C)C)cc21

Procedure:
In analogy to the procedure described in example 1 b], 6-(tert-butyl-dimethyl-silanyloxy)-1H-indole was reacted with bromo-acetic acid tert-butyl ester in the presence of cesium carbonate to obtain [6-(tert-butyl-dimethyl-silanyloxy)-indol-1-yl]-acetic acid tert-butyl ester as colorless liquid.
Reaction SMILES: [NH:1]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:2]([C:5]([OH:7])=[O:6])[CH2:3][OH:4].C[O-].[Na+].[CH2:18](I)[CH3:19]>C1COCC1.CO>[NH:1]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:2]([C:5]([OH:7])=[O:6])[CH2:3][O:4][CH2:18][CH3:19]
Reactant: CC(C)(C)OC(=O)N[C@@H](CO)C(=O)O
Reactant: CCI
Agent: C[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: CCOC[C@H](NC(=O)OC(C)(C)C)C(=O)O
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
To a solution of 0.94 g BocSer in 66 mL THF was added a solution of 1.47 g NaOMe in 2.6 mL MeOH, followed by 11.7 g EtI. After 15 minutes, more NaOMe (0.49 g) and EtI (2 mL) were added and the reaction was stirred at RT overnight. More NaOMe and EtI were added and the reaction was stirred for an additional 6 hours. The mixture was concentrated in vacuo, dissolved in 25 mL H2O and washed 2×25 mL ether. The aqueous phase was acidified with concentrated HCl and extracted 4×25 mL CH2Cl2. The combined extracts were dried over MgSO4, filtered and concentrated in vacuo to 0.34 g crude product which carried on. NMR (300 MHz, CDCl3), delta 1.19 (t, J=7 Hz, 3H), 1.46 (s, 9H), 3.53 (q, J=7 Hz, 2H), 4.43 (m, 1H).
Reaction SMILES: [OH:1][C:2]1([C:6]2[C:7]([O:15][C@@H:16]([CH3:21])[C:17]([F:20])([F:19])[F:18])=[CH:8][C:9]([C:12]([OH:14])=O)=[N:10][CH:11]=2)[CH2:5][CH2:4][CH2:3]1.[CH3:22][S:23]([CH2:26][C:27]([NH2:35])([CH3:34])[C:28]1[N:32]=[C:31]([CH3:33])[O:30][N:29]=1)(=[O:25])=[O:24]>>[OH:1][C:2]1([C:6]2[C:7]([O:15][C@@H:16]([CH3:21])[C:17]([F:19])([F:20])[F:18])=[CH:8][C:9]([C:12]([NH:35][C:27]([C:28]3[N:32]=[C:31]([CH3:33])[O:30][N:29]=3)([CH3:34])[CH2:26][S:23]([CH3:22])(=[O:25])=[O:24])=[O:14])=[N:10][CH:11]=2)[CH2:5][CH2:4][CH2:3]1
Reactant: C[C@H](Oc1cc(C(=O)O)ncc1C1(O)CCC1)C(F)(F)F
Reactant: Cc1nc(C(C)(N)CS(C)(=O)=O)no1
Product: Cc1nc(C(C)(CS(C)(=O)=O)NC(=O)c2cc(O[C@@H](C)C(F)(F)F)c(C3(O)CCC3)cn2)no1

Procedure:
The title compound was synthesized in analogy to Example 112e, using 5-(1-hydroxycyclobutyl)-4-[(1S)-2,2,2-trifluoro-1-methyl-ethoxy]pyridine-2-carboxylic acid (Example 126d) and 2-Methanesulfonyl-1-methyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethylamine (example 109d) as starting materials and isolated (28 mg, 42%); MS (ESI, m/z): 507.5 (M+H+).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH:7]=[CH:8][C:9]([OH:11])=[O:10])[CH:2]=1.CO>[Pd].C(O)C>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][CH2:8][C:9]([OH:11])=[O:10])[CH:2]=1
Reactant: O=C(O)C=Cc1cccnc1
Agent: [Pd]
Solvent: CCO
Solvent: CO
Product: O=C(O)CCc1cccnc1
Reaction time: 8 h
Yield: 100.7 %

Procedure:
A mixture of 3-(pyridin-3-yl)propenoic acid (10.0 g, 67 mmol), 10% palladium-activated carbon (1 g), methanol (100 mL) and ethanol (100 mL) was stirred overnight under hydrogen atmosphere. The resultant reaction mixture was filtered, evaporated, and dried to give 3-(pyridin-3-yl)propionic acid (10.2 g, quantitative).