Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[C:7]([OH:8])=[CH:6][CH:5]=[C:4]([Br:9])[N:3]=1.[C:10]([O-])([O-])=O.[K+].[K+].CI.O>CS(C)=O>[Br:1][C:2]1[C:7]([O:8][CH3:10])=[CH:6][CH:5]=[C:4]([Br:9])[N:3]=1
Reactant: Oc1ccc(Br)nc1Br
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: CI
Solvent: O
Product: COc1ccc(Br)nc1Br
Temperature: 25 °C

Procedure:
To a solution of 52.5 g 2,6-dibromopyridin-3-ol (example E1) in 90 ml DMSO were added 26.2 g K2CO3 and 43.8 ml methyl iodide and the reaction mixture was stirred under reflux for one hour. The mixture was allowed to cool down to room temperature and poured into 1 l of water and stirred for 3 h at 80° C. After cooling to room temperature the resulting solid was filtered, the filter cake was washed with ice cold water and dried under vacuum to yield the title compound.
Reaction SMILES: Cl[C:2]1[S:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.[CH2:11]1[CH2:16][CH2:15][CH:14]([CH2:17][C@H:18]([NH2:22])[C:19]([OH:21])=O)[CH2:13][CH2:12]1.[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28]([NH:31][CH2:32][CH2:33][NH2:34])=[CH:27][CH:26]=1>>[S:3]1[C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=[C:2]1[NH:22][C@@H:18]([CH2:17][CH:14]1[CH2:13][CH2:12][CH2:11][CH2:16][CH2:15]1)[C:19]([NH:34][CH2:33][CH2:32][NH:31][C:28]1[CH:29]=[CH:30][C:25]([O:24][CH3:23])=[CH:26][CH:27]=1)=[O:21]
Reactant: Clc1nc2ccccc2s1
Reactant: COc1ccc(NCCN)cc1
Reactant: N[C@@H](CC1CCCCC1)C(=O)O
Product: COc1ccc(NCCNC(=O)[C@H](CC2CCCCC2)Nc2nc3ccccc3s2)cc1

Procedure:
The title compound was prepared from 2-chlorobenzothiazole, L-cyclohexylalanine and N1-(4-methoxy-phenyl)-ethane-1,2-diamine.-2HCl using the procedure analogous to that described in example 2. HPLC-MS calcd. for C25H32N4O2S (M+H+) 453.22, found 453.5.
Reaction SMILES: [O-]CC.[Na+].[OH:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:14][CH:13]=2)=[CH:8][CH:7]=1.C1C=CC=CC=1.Cl[CH:31]([C:37]([CH3:39])=O)[C:32]([O:34][CH2:35][CH3:36])=[O:33]>C(Cl)(Cl)(Cl)Cl>[CH2:35]([O:34][C:32]([C:31]1[O:5][C:6]2[CH:7]=[CH:8][C:9]([C:12]3[CH:17]=[CH:16][C:15]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])=[CH:14][CH:13]=3)=[CH:10][C:11]=2[C:37]=1[CH3:39])=[O:33])[CH3:36]
Reactant: CCOC(=O)Cc1ccc(-c2ccc(O)cc2)cc1
Reactant: CCOC(=O)C(Cl)C(C)=O
Agent: CC[O-]
Agent: [Na+]
Solvent: c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: CCOC(=O)Cc1ccc(-c2ccc3oc(C(=O)OCC)c(C)c3c2)cc1
Reaction time: 2 h

Procedure:
To a solution of 0.25 mole of sodium ethoxide is added 64 g. (0.25 mole) of ethyl 4-(4-hydroxyphenyl)phenylacetate. After stirring two hours the solution is evaporated, benzene is added, and the solution is further evaporated. The residue is dissolved in 800 ml. of benzene, 0.25 mole of ethyl α-chloroacetoacetate is added, and the mixture is stirred at room temperature, then heated at its reflux temperature for 16 hours and filtered hot. Evaporation provides a residue which is dissolved in carbon tetrachloride and filtered through silica gel. This intermediate is treated with concentrated sulfuric acid at 0° C. After stirring one hour, ice is added and the mixture is extracted with benzene. The benzene layer is dried, then evaporated. The residue is recrystallized from a dichloromethanehexane mixture, then carbon tetrachloride, to provide ethyl 4-(2-ethoxycarbonyl 3-methylbenzofuran-5-yl)phenylacetate, m.p. 110°-112° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:15]=[CH:14][CH:13]=[CH:12][C:4]=1[O:5][CH:6]([Cl:11])[CH:7]([OH:10])[CH2:8][CH3:9].[CH:16]([NH2:19])([CH3:18])[CH3:17]>C(O)CCC>[ClH:11].[CH:16]([NH:19][CH2:9][CH2:8][CH:7]([OH:10])[CH2:6][O:5][C:4]1[CH:12]=[CH:13][CH:14]=[CH:15][C:3]=1[O:2][CH3:1])([CH3:18])[CH3:17]
Reactant: CC(C)N
Reactant: CCC(O)C(Cl)Oc1ccccc1OC
Solvent: CCCCO
Product: COc1ccccc1OCC(O)CCNC(C)C
Product: Cl
Temperature: 120 °C

Procedure:
A mixture which contained 11.6 g. (0.05 mole) of 1-(2-methoxyphenoxy)-2-hydroxybutyl chloride, 50 ml. of isopropyl amine and 100 ml. of n-butanol was charged in a steel bomb and heated at 120° C. for 24 hr. The resulting reaction mixture was filtered. The filtrate was concentrated to dryness and mixed with 200 ml. of 3N hydrochloric acid, extracted with ether and the aqueous layer was made basic. The base insoluble oil was extracted into isopropyl ether, dried over sodium sulfate and concentrated to dryness. The residue was dissolved in isopropanol and mixed with 20 ml. ethereal hydrogen chloride. The gummy precipitate recrystallized using isopropyl ether and isopropanol. The hydrochloride (8.3 g.) melted at 83°-85° C.
Reaction SMILES: [C:1]([O:5][C@@H:6]1[CH2:10][C@H:9]([OH:11])[CH:8]=[CH:7]1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[C:19](OC=C)(=[O:21])[CH3:20].C(Cl)(Cl)Cl>COC(C)(C)C>[C:1]([O:5][C@@H:6]1[CH2:10][C@H:9]([O:11][C:19](=[O:21])[CH3:20])[CH:8]=[CH:7]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)O[C@H]1C=C[C@@H](O)C1
Reactant: C=COC(C)=O
Solvent: CCN(CC)CC
Solvent: COC(C)(C)C
Solvent: ClC(Cl)Cl
Product: CC(=O)O[C@@H]1C=C[C@H](OC(C)(C)C)C1
Temperature: 25 °C
Reaction time: 17 h
Yield: 50 %

Procedure:
Cis-4-tert-butyloxy-cyclopent-2-enol (485 mg, 3.1 mmol, prepared in example 9) is dissolved in tert-butyl methyl ether (8.6 mL, anhydrous). To the solution is added triethylamine (0.7 eq), pancreatin (3 wt eq, available from Sigma Chemical Company), and vinyl acetate (5 eq). The reaction is allowed to stir for 17 hours at room temperature. The reaction is then filtered through diatomaceous earth and the filtrate is concentrated under vacuum. The products are separated by chromatography on silica gel (10% to 20% ethyl acetate/hexane) to provide (-)-acetic acid cis-4-tert-butyloxy-cyclopent-2-enyl ester (B, 50% yield, 76% ee), [α]D =-10.90, (c=0.98, chloroform), 1H NMR (CDCl3) δ 5.94 (d, 1 H, J=5.5 Hz), 5.89 (d, 1 H, J=5.5 Hz), 5.46 (appt, 1 H, J=5.5 Hz), 4.52 (appt, 1 H, J=5.5 Hz), 2.8 (m, 1 H), 2.0 (s, 3 H), 1.6 (d appt, 1 H, J=4.8, 14 Hz), 1.22 (s, 9 H); 13C NMR (CDCl3) δ 171.2, 138.6, 131.6, 77.4, 77.2, 41, 28.7, 28.6, 21.4; IR (neat) νmax 2976, 1738, 1364, 1242, 1196, 1067, 1020 cm-1 ; CIMS m/e (% relative intensity) 199 (M+H+, 4), 139 (M+H+ --AcOH, 70), 83 (100), and (-)-cis-4-tert-butyloxy-cyclopent-2-enol (A, 194 mg, 40% yield, >98% ee), [α]D =-17.2°, (c=1.09, chloroform) as a yellow oil.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([C:7]2[C:15]3[C:10](=[CH:11][C:12]([OH:16])=[CH:13][CH:14]=3)[N:9]3[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:8]=23)=[CH:3][CH:2]=1.[CH2:22]([O:24][C:25](=[O:30])[C:26](Br)([CH3:28])[CH3:27])[CH3:23]>>[CH2:22]([O:24][C:25](=[O:30])[C:26]([O:16][C:12]1[CH:11]=[C:10]2[C:15]([C:7]([C:4]3[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=3)=[C:8]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][N:9]32)=[CH:14][CH:13]=1)([CH3:28])[CH3:27])[CH3:23]
Reactant: Oc1ccc2c(-c3ccncc3)c3n(c2c1)CCCCC3
Reactant: CCOC(=O)C(C)(C)Br
Product: CCOC(=O)C(C)(C)Oc1ccc2c(-c3ccncc3)c3n(c2c1)CCCCC3

Procedure:
The above compound was prepared from 7,8,9,10-tetrahydro-11-(4-pyridyl)-6H-azepino[1,2-a]indole-3-ol and 2-bromo-2-methyl-propanoic acid ethylester using a procedure analogous to that of Example 10.
Reaction SMILES: [O:1]([CH2:8][CH2:9][OH:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:11][C:12]1[C:13]([N:18]2[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][C@@H:19]2[CH3:31])=[N:14][CH:15]=[CH:16][N:17]=1>>[ClH:11].[CH3:31][C@H:19]1[CH2:20][NH:21][CH2:22][CH2:23][N:18]1[C:13]1[C:12]([O:10][CH2:9][CH2:8][O:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[N:17][CH:16]=[CH:15][N:14]=1
Reactant: C[C@H]1CN(C(=O)OC(C)(C)C)CCN1c1nccnc1Cl
Reactant: OCCOc1ccccc1
Product: C[C@H]1CNCCN1c1nccnc1OCCOc1ccccc1
Product: Cl
Yield: 68 %

Procedure:
The title compound was prepared starting from 2-phenoxy-1-ethanol and 3-chloro-2-[4-tert-butoxycarbonyl-(2S)-methyl-1-piperazinyl]pyrazine (prepared according to the procedure of Example 172, Step 2, with the exception that (2S)-methylpiperazine was to substituted for (2R)-methylpiperazine). MS m/z 315 (M+H)+. Yield 68%; mp 162-163° C. Anal. (C17H22N4O2.HCl) C, H, N.
Reaction SMILES: C(O[C:4]([C:6]1([CH2:19][CH2:20]OC)[CH2:11][CH2:10][N:9]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:8][CH2:7]1)=[O:5])C.[F:23][C:24]([F:34])([F:33])[O:25][C:26]1[CH:32]=[CH:31][C:29]([NH2:30])=[CH:28][CH:27]=1.[Cl-].C[Al+]C>C1(C)C=CC=CC=1>[CH2:12]([N:9]1[CH2:8][CH2:7][C:6]2([C:4](=[O:5])[N:30]([C:29]3[CH:31]=[CH:32][C:26]([O:25][C:24]([F:23])([F:33])[F:34])=[CH:27][CH:28]=3)[CH2:20][CH2:19]2)[CH2:11][CH2:10]1)[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: CCOC(=O)C1(CCOC)CCN(Cc2ccccc2)CC1
Reactant: Nc1ccc(OC(F)(F)F)cc1
Agent: C[Al+]C
Agent: [Cl-]
Solvent: Cc1ccccc1
Product: O=C1N(c2ccc(OC(F)(F)F)cc2)CCC12CCN(Cc1ccccc1)CC2
Temperature: 25 °C

Procedure:
To a solution of 1-benzyl-4-(2-methoxyethyl)-piperidine-4-carboxylic acid ethyl ester (5.2 g, 0.017 mol) and 4-(trifluormethoxy)aniline (4.57 ml, 0.034 mol) in toluene (200 ml) under an argon atmosphere at room temperature, was added dimethylaluminium chloride (0.9M solution in heptane, 37 ml, 0.034 mol) and the mixture was refluxed for 4 hours. The reaction mixture was cooled to room temperature and quenched was sat. Na2SO4 (aq) solution and the mixture was filtered through Celite® and evaporated under reduced pressure. The crude residue was purified by flash column chromatography (1:3 AcOEt/heptane) to give 8-benzyl-2-(4-trifluoromethoxy-phenyl)-2,8-diaza-spiro[4.5]decan-1-one as a white solid. MS (ESI): 405.4 (MH+).
Reaction SMILES: F[B-](F)(F)F.[N+:6]([C:9]1[CH:10]=[C:11]([N+]#N)[CH:12]=[CH:13][CH:14]=1)([O-:8])=[O:7].C([O-])(=O)C.[K+].[C:22]1([O:28][CH3:29])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>>[CH3:29][O:28][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:11]1[CH:12]=[CH:13][CH:14]=[C:9]([N+:6]([O-:8])=[O:7])[CH:10]=1
Reactant: COc1ccccc1
Reactant: N#[N+]c1cccc([N+](=O)[O-])c1
Agent: CC(=O)[O-]
Agent: F[B-](F)(F)F
Agent: [K+]
Product: COc1ccccc1-c1cccc([N+](=O)[O-])c1
Reaction time: 12 h

Procedure:
Anisole (400 mL) and 3-nitrobenzenediazonium tetrafluoroborate (54.5 g, 0.23 mol) were placed in a 1-L flask and stirred mechanically. Potassium acetate (49.0 g, 0.5 mol) was added in one portion. The mixture turned red and warmed slightly. Stirring was continued 12 h., then the solution was filtered and the anisole evaporated in vacuo. Column chromatography of the residue (alumina, 0-10% ether/hexane, first yellow band) and recrystallization (95% EtOH) provided pure 2-methoxy-3'-nitrobiphenyl: 18 g (35%); mp 68°-69° C.
Reaction SMILES: [NH2:1][C@H:2]([CH3:6])[C:3]([OH:5])=[O:4].CN(C)C(N(C)C)=N.C([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])(=O)C>CO>[F:21][C:20]([F:23])([F:22])[C:19]([NH:1][C@H:2]([CH3:6])[C:3]([OH:5])=[O:4])=[O:18]
Reactant: CC(=O)OCC(F)(F)F
Reactant: C[C@@H](N)C(=O)O
Agent: CN(C)C(=N)N(C)C
Solvent: CO
Product: C[C@@H](NC(=O)C(F)(F)F)C(=O)O
Reaction time: 5 h
Yield: 97.2 %

Procedure:
(R)-2-amino propionic acid (8.9 g, 0.1 mol) was dissolved in 100 ml of methanol, and 1,1,3,3-tetramethyl guanidine (15.6 g, 0.136 mol) was added. At room temperature, trifluoroethyl acetate (18.5 g, 0.13 mol) was added dropwise. After the completion of the addition, stirring is conducted to allow a reaction to proceed for 5 hours. Most solvent was removed by evaporation, and the residue was poured into 100 ml of water, acidified with 12 ml of concentrated hydrochloric acid, and extracted with ethyl acetate (3×60 ml). The organic phases were combined, washed with saturated brine, dried with anhydrous sodium sulfate, concentrated and crystallized, washed with 160 ml of hexane, filtered, and dried, obtaining 18.0 g of product. The yield was 97.3%. MS: m/z 185.1
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][CH3:10])=[CH:4][CH:3]=1.Cl.[NH2:13][OH:14].[OH-].[Na+].Cl>O.C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[N:13][OH:14])[CH2:9][CH3:10])=[CH:4][CH:3]=1
Reactant: NO
Reactant: CCC(=O)c1ccc(Cl)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CCC(=NO)c1ccc(Cl)cc1

Procedure:
33.6 g of p-chloropropiophenone was mixed with 200 ml of ethanol and 40 ml of water. 24 g of hydroxylamine hydrochloride was added. 44 g of solid sodium hydroxide was added over a 10-minute period to the stirred mixture at room temperature. The mixture was heated to 80°, then refluxed for 80 minutes. The mixture was cooled and poured into cold dilute hydrochloric acid. The resulting mixture was filtered. The solid product was dissolved in methylene chloride; the solution was dried (MgSO4) and stripped of solvent. Recrystallization of the solid product from hexane gave 1-(4-chlorophenyl)-1-propanone oxime (4A), m.p.: 56°-57.5°.
Reaction SMILES: [Na].ClC(Cl)(Cl)[C:4]([C:6]1[NH:7][CH:8]=[C:9]([I:11])[CH:10]=1)=[O:5].[CH3:14][OH:15]>>[CH3:14][O:15][C:4]([C:6]1[NH:7][CH:8]=[C:9]([I:11])[CH:10]=1)=[O:5]
Reactant: O=C(c1cc(I)c[nH]1)C(Cl)(Cl)Cl
Reactant: CO
Agent: [Na]
Product: COC(=O)c1cc(I)c[nH]1
Temperature: 0 °C
Reaction time: 2 h
Yield: 95 %

Procedure:
To a solution of 300 mL of dry methanol was added 0.52 gm (0.023 mol) of sodium and the solution was stirred until all sodium was reacted. The solution was cooled to 0° C. and 19.5 gm (0.057 mol) of 2,2,2-trichloro-1-(4-iodo-1H-pyrrol-2-yl)-ethanone was added as a solid over a 15 min period. After 15 min at 0° C. the solution was warmed to room temperature and stirred for an additional 2 h. The solvents were removed at reduced pressure and the residue dissolved in diethyl ether. The ether layer was washed with H2O, saturated brine, dried (Na2SO4) and the solvents removed at reduced pressure. The solid was recystallized from hot hexanes-trace EtOAc to yield 13.7 gm (95% yield) of a light brown solid. This was used without further purification.
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[OH:8].[F:9][C:10]([F:21])([F:20])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[CH2:17][CH2:18]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[I:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[O:8][CH2:18][CH2:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[C:10]([F:9])([F:20])[F:21]
Reactant: OCCc1ccccc1C(F)(F)F
Reactant: Oc1ccccc1I
Agent: CCOC(=O)/N=N/C(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: FC(F)(F)c1ccccc1CCOc1ccccc1I
Temperature: 25 °C
Yield: 56 %

Procedure:
To a stirred solution of the 2-iodophenol (220.0 mg, 1.0 mmol), the 2-(2-(trifluoromethyl)phenyl)ethanol (228.0 mg, 1.2 mmol), and triphenyl phosphine (314.0 mg, 1.2 mmol) in anhydrous THF (5 mL) at 0° C. was added DEAD (40% in toluene, 1.20 mmol, 0.35 mL) dropwise. The yellow solution was allowed to warm to room temperature and stirring was continued overnite. After evaporating the solvent under reduced pressure the crude residue was dissolved in DCM (15 mL). The organic layer was washed with 10% NaOH (2×10 mL), water and brine. The organic phase was dried (Na2SO4), filtered and evaporated under reduced pressure. The crude residue was purified by column chromatography on silica gel using hexanes/EtOAc as the eluent. The compound was isolated in 56% yield as a white solid. 1H NMR: 3.17 (t, 2H, J=6.8 Hz), 4.22 (t, 2H, J=6.8 Hz), 6.90-7.10 (m, 4H), 7.15-7.23 (m 1H), 7.30-7.45 (m, 2H), 7.74 (dd, 1H, J=7.6, 1.6 Hz).
Reaction SMILES: [O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[C:10]([C:11](=[O:13])[CH3:12])[C:5]=2[O:4][CH2:3][CH2:2]1.[H-].[Na+].[C:16](OCC)(=[O:18])[CH3:17]>>[O:1]1[C:6]2[CH:7]=[CH:8][CH:9]=[C:10]([C:11](=[O:13])[CH2:12][C:16](=[O:18])[CH3:17])[C:5]=2[O:4][CH2:3][CH2:2]1
Reactant: CC(=O)c1cccc2c1OCCO2
Reactant: CCOC(C)=O
Agent: [H-]
Agent: [Na+]
Product: CC(=O)CC(=O)c1cccc2c1OCCO2
Temperature: 80 °C

Procedure:
1-(2,3-Dihydro-1,4-benzodioxin-5-yl)-ethanone (1.2 g) was dissolved in 20 mL of ethyl acetate, and sodium hydride (0.33 g, 60% oil dispersion) was added. The reaction mixture was heated to 80° C. overnight, quenched with water, and neutralized with carbon dioxide to give an oily product of 1-(2,3-dihydro-1,4-benzodioxin-5-yl)butan-1,3-dione (0.37 g).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([N:7]2[CH2:12][CH2:11][CH:10]([C:13](Cl)=[O:14])[CH2:9][CH2:8]2)=[CH:3][CH:2]=1.Cl.[NH2:17][CH2:18][CH2:19][CH:20]([NH:29][C:30](=[O:46])[CH2:31][NH:32][S:33]([C:36]1[CH:45]=[CH:44][C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH:37]=1)(=[O:35])=[O:34])[C:21]([N:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1)=[O:22]>>[CH:37]1[C:38]2[C:43](=[CH:42][CH:41]=[CH:40][CH:39]=2)[CH:44]=[CH:45][C:36]=1[S:33]([NH:32][CH2:31][C:30]([NH:29][CH:20]([C:21]([N:23]1[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1)=[O:22])[CH2:19][CH2:18][NH:17][C:13]([CH:10]1[CH2:11][CH2:12][N:7]([C:4]2[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=2)[CH2:8][CH2:9]1)=[O:14])=[O:46])(=[O:35])=[O:34]
Reactant: O=C(Cl)C1CCN(c2ccncc2)CC1
Reactant: NCCC(NC(=O)CNS(=O)(=O)c1ccc2ccccc2c1)C(=O)N1CCCCC1
Agent: Cl
Product: O=C(CNS(=O)(=O)c1ccc2ccccc2c1)NC(CCNC(=O)C1CCN(c2ccncc2)CC1)C(=O)N1CCCCC1
Yield: 17 %

Procedure:
Using an analogous procedure to that described in Example 1, 1-(4-pyridyl)piperidine-4-carbonyl chloride was reacted with N-[3-amino-1-(piperidinocarbonyl)propyl]-2-(2-naphthalenesulphonamido)acetamide hydrochloride salt to give 2-(2-naphthalenesulphonamido)-N-{1-piperidinocarbonyl-3-[1-(4-pyridyl)piperidin-4-ylcarbonylamino]-propyl}acetamide in 17% yield;
Reaction SMILES: [CH3:1][NH:2][CH3:3].[CH2:4](O)[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]>[H][H].[Cr]([O-])([O-])=O.[Cu+2]>[CH2:4]([N:2]([CH3:3])[CH3:1])[CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH3:15]
Reactant: CNC
Reactant: [H][H]
Reactant: CCCCCCCCCCCCO
Agent: O=[Cr]([O-])[O-]
Agent: [Cu+2]
Product: CCCCCCCCCCCCN(C)C

Procedure:
In Example 1 of U.S. Pat. No. 4 138 437, dimethylamine is reacted with 1-dodecanol in the presence of hydrogen and copper chromite as catalyst. To work up the reaction product, it is filtered off from the catalyst and a dodecyldimethylamine is produced as crude product. The crude product is subjected to vacuum distillation to separate off high-boiling byproducts. The distilled C12 -alkyldimethylamine obtained after taking off a first runnings contains about 140 ppm of monomethylamine, 150 ppm of dimethylamine and about 64 ppm of trimethylamine and has a more or less unpleasant odor.
Reaction SMILES: [C:1]1(O)[C:10]2[CH:9]=[CH:8][CH:7]=[C:6]([OH:11])[C:5]=2[CH:4]=[CH:3][CH:2]=1.[C:13](=[O:16])([O-])[O-].[K+].[K+].S(OC)(O[CH3:23])(=O)=O.O>CC(C)=O>[CH3:23][O:11][C:6]1[C:5]2[C:10](=[C:1]([O:16][CH3:13])[CH:2]=[CH:3][CH:4]=2)[CH:9]=[CH:8][CH:7]=1
Reactant: Oc1cccc2c(O)cccc12
Reactant: O=C([O-])[O-]
Reactant: COS(=O)(=O)OC
Agent: [K+]
Solvent: CC(C)=O
Solvent: O
Product: COc1cccc2c(OC)cccc12
Temperature: 25 °C
Yield: 95.2 %

Procedure:
Naphthalene-1,5-diol (16.0 g, 100 mmol) and potassium carbonate (27.6 g, 200 mmol) were stirred in acetone (300 mL) and dimethyl sulfate (32 mL) was added using syringe. The mixture was then heated to reflux under nitrogen overnight. Water (300 mL) was added after the mixture was cooled to room temperature. The precipitate was collected by filtration and washed with water (4×50 mL), then methanol (3×50 mL). After drying under vacuum, the solid was heated at reflux in ethanol (300 mL) for 2 hours. After cooling to room temperature, the desired product was then collected by filtration to give a pale brown solid (17.9 g, 95.2%). 1H NMR (500 MHz, CDCl3): δ 7.45 (d, J=8.5 Hz, 2H), 7.33 (t, J=8.5 Hz, 2H), 6.83 (d, J=8.5 Hz, 2H), 4.00 (s, 6H).
Reaction SMILES: [CH2:1](Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[OH:15][C:16]1[CH:25]=[C:24]([NH:26][C:27](=[O:40])[CH:28]=[CH:29][C:30]2[CH:39]=[CH:38][C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH:31]=2)[CH:23]=[CH:22][C:17]=1[C:18]([O:20][CH3:21])=[O:19].C1CCN2C(=NCCC2)CC1.Cl.[N+:53]([CH3:56])([O-:55])=[O:54]>CN(C=O)C.O>[CH2:1]([O:15][C:16]1[CH:25]=[C:24]([NH:26][C:27](=[O:40])[CH2:28][CH:29]([C:30]2[CH:39]=[CH:38][C:37]3[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH:31]=2)[CH2:56][N+:53]([O-:55])=[O:54])[CH:23]=[CH:22][C:17]=1[C:18]([O:20][CH3:21])=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: BrCc1ccccc1
Reactant: COC(=O)c1ccc(NC(=O)C=Cc2ccc3ccccc3c2)cc1O
Reactant: C[N+](=O)[O-]
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Solvent: C1CCC2=NCCCN2CC1
Product: COC(=O)c1ccc(NC(=O)CC(C[N+](=O)[O-])c2ccc3ccccc3c2)cc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 72 %

Procedure:
Benzyl bromide (0.236 g, 1.38 mmol) and K2CO3 (0.190 g, 1.38 mmol) were added to a stirred solution of 43 (0.400 g, 1.15 mmol) in anhydrous DMF (7 ml) under Ar. The reaction mixture was stirred at room temperature overnight and the mixture was poured in water (15 ml). The product was extracted with ethyl acetate (2×15 ml), dried over Na2SO4 and the solvent removed under reduced pressure. The resultant product 44 was stirred in the microwave reactor in presence of DBU (0.192 g, 1.27 mmol), and nitromethane (7 ml) in the microwave), at 100° C. for 15 min. After cooling to room temperature, the reaction mixture was poured into HCl 1M (10 ml). The product was extracted with ethyl acetate (2×15 ml), dried over Na2SO4 and the solvent removed under reduced pressure. Chromatography on silica gel (60:40 hexanes/ethyl acetate) afforded 49 (0.413 g, 0.83 mmol, 72%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ 2.88 (1H, dd, J 6.8, 15.6 Hz), 2.96 (1H, dd, J 7.2, 15.2 Hz), 3.86 (3H, s), 4.26 (1H, quint, J 7.1 Hz), 4.83 (1H, dd, J 7.4, 12.6 Hz), 4.93 (1H, dd, J 6.8, 12.4 Hz), 5.10 (2H, s), 6.71 (1H, dd, J 2.0, 8.8 Hz), 7.13 (1H, bs), 7.28-7.32 (1H, m), 7.36-7.39 (3H, m), 7.47-7.52 (5H, m), 7.71 (1H, bs), 7.77-7.86 (4H, m). 13C NMR (400 MHz, CDCl3) δ 40.68, 40.81, 52.15, 70.70, 79.44, 101.39, 111.15, 115.91, 124.94, 126.67, 126.79, 126.89, 127.22, 127.93, 128.05, 128.79, 128.72, 129.39, 133.11, 133.60, 135.89, 136.54, 142.68, 159.61, 166.42, 168.57. MS (API-ES): m/z found 499 [M+H]+ (100%), HRMS (API-ES) m/z 499.1862 [M+H]+.
Reaction SMILES: Br[CH:2](Br)[C:3]1[C:4]([CH:9](Br)Br)=[CH:5][CH:6]=[CH:7][CH:8]=1.[C:13]1(=[O:20])[CH:18]=[CH:17][C:16](=[O:19])[CH:15]=[CH:14]1.[I-].[Na+]>CN(C=O)C>[CH:5]1[C:4]2[C:3](=[CH:2][C:18]3[C:13](=[O:20])[C:14]4[C:15]([C:16](=[O:19])[C:17]=3[CH:9]=2)=[CH:9][C:4]2[C:3](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH:2]=4)[CH:8]=[CH:7][CH:6]=1
Reactant: O=C1C=CC(=O)C=C1
Reactant: BrC(Br)c1ccccc1C(Br)Br
Agent: [I-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=C1c2cc3ccccc3cc2C(=O)c2cc3ccccc3cc21
Temperature: 120 °C
Reaction time: 8 h
Yield: 87.6 %

Procedure:
To a clear solution of α,α,α′,α′-tetrabromo-o-xylene (30.5 g, 0.073 mol) in DMF (100 mL) was added benzoquinone (3.125 g, 0.03 mol) and sodium iodide (27.25 g, 0.18 mol). The resulting brown suspension was heated and stirred at 120° C. overnight. After cooling to RT, the yellow solids were filtered via vacuum filtration. The yellow solids were washed with water, saturated sodium bisulfite solution and dried to yield the product (8.1 g, 91%). 1H NMR (500 MHz, CDCl3): δ 8.96 (s, 4H), 8.14 (m, 4H), 7.72 (m, 4H). 13C NMR (125.68 MHz, CDCl3): δ 183.2, 135.47, 130.80, 130.30, 129.98, 129.66. m/z: 308 [W].
Reaction SMILES: [N:1]([CH2:4][CH2:5][C:6]1[N:7]=[C:8]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:14][CH:13]=2)[O:9][C:10]=1[CH3:11])=[N+]=[N-].O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[CH2:19]([O:18][C:15]1[CH:16]=[CH:17][C:12]([C:8]2[O:9][C:10]([CH3:11])=[C:6]([CH2:5][CH2:4][NH2:1])[N:7]=2)=[CH:13][CH:14]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: Cc1oc(-c2ccc(OCc3ccccc3)cc2)nc1CCN=[N+]=[N-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Solvent: O
Product: Cc1oc(-c2ccc(OCc3ccccc3)cc2)nc1CCN
Temperature: 25 °C
Yield: 62.4 %

Procedure:
To a solution of 4-(2-azido-ethyl)-2-(4-benzyloxy-phenyl)-5-methyl-oxazole (660 mg) in THF (10 ml) were added water (0.3 ml) and triphenylphosphine (570 mg). The reaction mixture was stirred over night at RT. Then the solvent was removed and the residue was purified by chromatography (CH2Cl2/MeOH 4:1) yielding 2-[2-(4-benzyloxy-phenyl)-5-methyl-oxazol-4-yl]-ethylamine (380 mg) as a white solid.