Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C@@H:2]([CH2:7][CH2:8][CH:9]=[C:10]([CH3:12])[CH3:11])[CH2:3][CH2:4][CH2:5]O.[CH3:13][S:14](Cl)(=[O:16])=[O:15].C(N(CC)CC)C.O>ClCCl>[CH3:13][S:14]([CH2:5][CH2:4][CH2:3][C@@H:2]([CH3:1])[CH2:7][CH2:8][CH:9]=[C:10]([CH3:12])[CH3:11])(=[O:16])=[O:15]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)=CCC[C@H](C)CCCO
Solvent: ClCCl
Solvent: O
Solvent: CCN(CC)CC
Product: CC(C)=CCC[C@H](C)CCCS(C)(=O)=O
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
To a solution of 4-(S)-methyl-8-methylnon-7-enyl alcohol (3.25 g, 19.1 mmol) in dichloromethane (50 mL) at 0° C. is added methanesulfonyl chloride (2.29 g, 20.0 mmol) followed by triethylamine (3.04 g, 30.0 mmol). After stirring for 10 minutes at 0° C., the reaction was allowed to warm to 25° C. and stirred for 3 hours. The reaction was poured into water (50 mL), separated and washed with dichloromethane (50 mL). The organic portions were combined, dried using magnesium sulfate, and evaporated to give the 1-methanesulfonyl-4-(S)-methyl-8-methylnon-7-ene as a yellow oil which is used without further purification.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8][C:9]#[N:10].[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.C([O-])(=O)C.[K+].[Cl-].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([C:2]2[C:3]([CH2:8][C:9]#[N:10])=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:15][CH:14]=1
Reactant: N#CCc1ccccc1Br
Reactant: COc1ccc(B(O)O)cc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Solvent: O
Product: COc1ccc(-c2ccccc2CC#N)cc1
Temperature: 70 °C
Reaction time: 2 h
Yield: 76.8 %

Procedure:
A mixture composed of 392 mg of 2-bromophenylacetonitrile, 334 mg of 4-methoxyphenylboronic acid, 0.9 mg of palladium acetate, 691 mg of potassium acetate, 645 mg of tetrabutylammonium bromide, and 2.2 ml of distilled water was stirred at 70° C. for 2 hours under an atmosphere of nitrogen. After the reaction mixture was poured into a saturated aqueous solution of sodium chloride, the product was extracted with ethyl acetate The organic layer was washed with water and dried over anhydrous magnesium sulfate. After the solvent was distilled off, the resulting crude product was purified by silica gel column chromatography (using a 3:1 mixture of hexane and ethyl acetate as the eluent) to obtain 343 mg of 4′-methoxy-2-biphenylaceto-nitrile.
Reaction SMILES: [ClH:1].O1CCOCC1.OC(C(F)(F)F)=O.OC(C(F)(F)F)=O.[CH3:22][C:23]1[S:24][C:25]2[CH:31]=[CH:30][C:29]([NH:32][C:33]([N:35]3[CH2:40][CH2:39][N:38](C(OC(C)(C)C)=O)[CH2:37][CH:36]3[CH2:48][O:49][C:50]3[CH:51]=[N:52][CH:53]=[CH:54][CH:55]=3)=[O:34])=[CH:28][C:26]=2[N:27]=1>CO>[ClH:1].[CH3:22][C:23]1[S:24][C:25]2[CH:31]=[CH:30][C:29]([NH:32][C:33]([N:35]3[CH2:40][CH2:39][NH:38][CH2:37][CH:36]3[CH2:48][O:49][C:50]3[CH:51]=[N:52][CH:53]=[CH:54][CH:55]=3)=[O:34])=[CH:28][C:26]=2[N:27]=1
Reactant: Cc1nc2cc(NC(=O)N3CCN(C(=O)OC(C)(C)C)CC3COc3cccnc3)ccc2s1
Agent: Cl
Solvent: O=C(O)C(F)(F)F
Solvent: C1COCCO1
Solvent: CO
Product: Cc1nc2cc(NC(=O)N3CCNCC3COc3cccnc3)ccc2s1
Reaction time: 1 h
Yield: 58 %

Procedure:
4 M HCl in 1,4-dioxane (6 mL, 24 mmol) was added to a solution of tert-butyl 4-(2-methylbenzo[d]thiazol-5-ylcarbamoyl)-3-((pyridin-3-yloxy)methyl)piperazine-1-carboxylate di-TFA salt (129.9 mg, 0.183 mmol) in MeOH (1 mL). After 1 h, the reaction mixture was concentrated under reduced pressure and purified by HPLC (5 to 50% MeCN/0.1% TFA in H2O/0.1% TFA gradient). The fractions containing the desired product were combined and brought to pH 12 with 1 N NaOH and were extracted with EtOAc (3×). The combined organics were dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was dissolved in MeOH (1 mL) and 4 M HCl in 1,4-dioxane (1 equiv. HCl, 0.028 mL) was added. The mixture was concentrated under reduced pressure to give 44.6 mg (58%) of the title compound as the hydrochloride salt. LC-MS: RT=4.22 min, [M+H]+=384.1.
Reaction SMILES: [CH2:1]([O:8][C@H:9]1[C@H:14]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C@@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@:12]([C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]3[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH2:49][O:50][CH:51]4[CH2:53][CH2:52]4)=[CH:43][CH:42]=3)[CH:34]=2)([O:31][CH3:32])[O:11][C@@H:10]1[CH:54]=[O:55])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:56]=[O:57].[OH-].[Na+].[BH4-].[Na+]>O1CCOCC1.O>[CH2:1]([O:8][C@H:9]1[C@H:14]([O:15][CH2:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C@@H:13]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C@@:12]([C:33]2[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]3[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH2:49][O:50][CH:51]4[CH2:52][CH2:53]4)=[CH:43][CH:42]=3)[CH:34]=2)([O:31][CH3:32])[O:11][C:10]1([CH2:56][OH:57])[CH2:54][OH:55])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CO[C@@]1(c2ccc(Cl)c(Cc3ccc(OCCOC4CC4)cc3)c2)O[C@H](C=O)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Reactant: C=O
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1COCCO1
Product: CO[C@@]1(c2ccc(Cl)c(Cc3ccc(OCCOC4CC4)cc3)c2)OC(CO)(CO)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Temperature: 70 °C
Reaction time: 4 h
Yield: 23.7 %

Procedure:
Crude (2S,3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-[2-(cyclopropoxy)ethoxy]phenyl]methyl]phenyl]-6-methoxy-tetrahydropyran-2-carbaldehyde 1e (1.3 g, 1.7 mmol) was dissolved in 15 mL 1,4-dioxane, followed by addition of 37% formaldehyde solution (2.6 mL, 34 mmol) and a solution of sodium hydroxide (204 mg, 5.1 mmol) in 5.1 mL water into the reaction mixture. The reaction mixture was stirred for 4 hours at 70° C., then cooled to 50° C. and stirred for 16 hours. The reaction mixture was extracted with ethyl acetate (20 mL×3) after 20 mL saturated sodium chloride solution were added. The organic extract was washed with saturated sodium bicarbonate solution (20 mL), saturated sodium chloride solution (20 mL), combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure. Then 20 mL of mixed solution (THF and MeOH, v:v=1:1) were added into the residue, before sodium borohydride (130 mg, 3.4 mmol) was added. The reaction mixture was stirred for 30 minutes and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (50 mL) and partitioned. The organic extract was washed with saturated sodium chloride solution (10 mL×2), combined, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated under reduced pressure, then the resulting residue was purified by silica gel chromatography with elution system B to obtain the title compound [(3S,4S,5R,6S)-3,4,5-tribenzyloxy-6-[4-chloro-3-[[4-[2-(cyclopropoxy)ethoxy]phenyl]methyl]phenyl]-2-(hydroxymethyl)-6-methoxy-tetrahydropyran-2-yl]methanol 1f (320 mg, colorless oil), yield: 23.7%.
Reaction SMILES: C([O-])([O-])=O.[Na+].[Na+].[CH:7]([C:9]1[S:13][CH:12]=[C:11](B(O)O)[CH:10]=1)=[O:8].Br[C:18]1[N:23]=[CH:22][CH:21]=[CH:20][N:19]=1>O.COCCOC.ClCCl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:19]1[CH:20]=[CH:21][CH:22]=[N:23][C:18]=1[C:11]1[CH:10]=[C:9]([CH:7]=[O:8])[S:13][CH:12]=1
Reactant: Brc1ncccn1
Reactant: O=Cc1cc(B(O)O)cs1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Solvent: ClCCl
Solvent: O
Product: O=Cc1cc(-c2ncccn2)cs1

Procedure:
A mixture of Na2CO3 (3.16 g) and 5-formyl-3-thiopheneboronic acid (2.4 g, 15.1 mmol) in water (15 mL) are added to a solution of 2-bromopyrimidine (2 g, 12.58 mmol) and tetrakis(triphenylphosphine)palladium(0) (480 mg, 0.46 mmol) in DME (30 mL) and the mixture is heated to reflux for 24 hr. The cooled reaction mixture is diluted with dichloromethane, washed with sat. aq. NaHCO3 and brine, dried (MgSO4), and concentrated. Purification by chromatography yields the title compound. MS 191 (M+H)+.
Reaction SMILES: CS[C:3]1[N:8]=[C:7]2[N:9]=[C:10]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[O:20][CH2:21][CH2:22][CH3:23])[NH:11][C:12](=[O:13])[C:6]2=[CH:5][N:4]=1.O.[NH2:25][NH2:26]>C(O)C>[NH:25]([C:3]1[N:8]=[C:7]2[N:9]=[C:10]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[O:20][CH2:21][CH2:22][CH3:23])[NH:11][C:12](=[O:13])[C:6]2=[CH:5][N:4]=1)[NH2:26]
Reactant: CCCOc1ccccc1-c1nc2nc(SC)ncc2c(=O)[nH]1
Reactant: NN
Solvent: O
Solvent: CCO
Product: CCCOc1ccccc1-c1nc2nc(NN)ncc2c(=O)[nH]1

Procedure:
A stirred mixture of 7-methylthio-4-oxo-2-(2-propoxyphenyl)-3,4-dihydropyrimido[4,5-d]pyrimidine (1.31 g) and hydrazine hydrate (3 ml) in ethanol (30 ml) was heated under reflux for 3 hours to yield a yellow precipitate. The reaction mixture was cooled overnight and the yellow precipitate was collected and washed with ethanol and water to yield the title compound, 0.80 g, m.p. 219-220° C.
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+].[CH2:10]([CH:12]1O[CH2:13]1)Cl.O>C(O)C.CO>[O:7]([CH2:10][CH2:12][CH3:13])[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: Oc1ccccc1
Reactant: ClCC1CO1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Solvent: CO
Product: CCCOc1ccccc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
1.840 g (0.008 mole) of 4- (2-nitroxy)ethoxymethyl!phenol, dissolved in a mixture of 10.6 ml of ethanol and 10 ml (0.010 mole) of 1N NaOH, were added slowly to a solution of 15.970 g (13.5 ml, 0.172 mole) of epichlorohydrin in 7 ml of methanol. The mixture was stirred for 16 hours at room temperature. 50 ml of water were added and the mixture was concentrated at reduced pressure at 40° C. The residue was extracted with a mixture of 100 ml of ethyl acetate and 100 ml of water. It was decanted and the aqueous phase was extracted a further two times with 25 ml of ethyl acetate. The organic extracts were pooled and washed with 75 ml of 1N HCl and 75 ml of water. It was dried over anhydrous sodium sulphate, was filtered and was concentrated at reduced pressure. 2.030 g (0.007 mole) of 2,3-epoxy-1- 4-(2-nitroxy)ethoxymethyl!phenoxy propane were obtained in the form of a yellowish oil which was mixed with 4.476 g (6.45 ml, 0.075 mole) of isopropylamine in 25 ml of anhydrous methanol and was heated under reflux for two hours. It was concentrated at reduced pressure at 40° C. 100 ml of water were added and it was extracted three times with 50 ml of ethyl acetate. The organic extracts were pooled and extracted three times with 100 ml of 1N HCl. The acid extracts were pooled and were alkalized to pH=12 by addition of 1N NaOH. It was extracted four times with 50 ml of ethyl acetate. The extracts were pooled and washed with 60 ml of water. It was dried over anhydrous sodium sulphate, was filtered and the solvent was removed at reduced pressure until a constant weight was obtained. 1.714 g (61%) of the product were obtained in the form of an oil.
Reaction SMILES: [C:1](/[C:3](=[C:5]1/[C:6]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:7]=2[O:8][CH2:9][C:10]2[CH:15]=[C:14]([CH2:16][N:17]3[C:21]4[CH:22]=[CH:23][CH:24]=[C:25]([C:26]([OH:28])=O)[C:20]=4[N:19]=[C:18]3[CH2:29][CH2:30][CH3:31])[CH:13]=[CH:12][C:11]/1=2)/[CH3:4])#[N:2].C(N1C=CN=C1)([N:39]1C=CN=C1)=O.N.Cl>C1COCC1.O>[C:1](/[C:3](=[C:5]1/[C:6]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:7]=2[O:8][CH2:9][C:12]2[CH:13]=[C:14]([CH2:16][N:17]3[C:21]4[CH:22]=[CH:23][CH:24]=[C:25]([C:26]([NH2:39])=[O:28])[C:20]=4[N:19]=[C:18]3[CH2:29][CH2:30][CH3:31])[CH:15]=[CH:10][C:11]/1=2)/[CH3:4])#[N:2]
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: CCCc1nc2c(C(=O)O)cccc2n1Cc1ccc2c(c1)COc1cc(F)ccc1/C2=C(\C)C#N
Agent: Cl
Agent: N
Solvent: O
Solvent: C1CCOC1
Product: CCCc1nc2c(C(N)=O)cccc2n1Cc1ccc2c(c1)COc1cc(F)ccc1/C2=C(\C)C#N
Temperature: 50 °C
Reaction time: 4 h
Yield: 100.9 %

Procedure:
[step 5] (E)-1-{[11-(1-cyanoethylidene)-3-fluoro-6,11-dihydrodibenzo[b,e]oxepin-8-yl]methyl}-2-propyl-1H-benzo[d]imidazole-4-carboxylic acid (97 mg, 0.20 mmol) obtained in step 4 was dissolved in THF (1.0 mL), 1,1′-carbonyldiimidazole (130 mg, 0.80 mmol) was added, and the mixture was stirred at 50° C. for 4 hr. After cooling to room temperature, 25% aqueous ammonia solution (55 μL, 0.80 mmol) was added, and the mixture was stirred at room temperature for 17 hr. To the mixture were added 1 mol/L hydrochloric acid and water, and the mixture was extracted 3 times with chloroform. The combined organic layers were washed with saturated aqueous sodium hydrogen carbonate, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform/methanol=100/0 v/v-93/7 v/v) to give the title compound (97 mg, 100%).
Reaction SMILES: [CH:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:7]([C:9]1C=CC=CC=1)[CH3:8]>O>[C:1]1([CH:7]([CH3:9])[CH3:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: c1ccccc1
Reactant: CCc1ccccc1
Solvent: O
Product: CC(C)c1ccccc1

Procedure:
The benzene column 140 receives feed from the bottoms of the depropanizer column 130 in the line 136 after it is mixed with transalkylation effluent in a line 152. The benzene column 140 produces a benzene column overhead stream comprising benzene in a line 142 and a benzene column bottom stream comprising ethylbenzene and PEBs in a line 144. The overhead benzene stream in the line 142 may be provided with a water concentration of about 50 to about 150 wppm and a temperature of at least about 120° C. and preferably greater than 125° C. and no more than about 170° C. The depropanizer intermediate stream in the line 132 has similar properties, and is combined with stream 142 and delivered to a hot adsorbent vessel 160 by line 161. The hot adsorbent vessel 160 contains a bed of acidic molecular sieve adsorbent for the removal of ONCs, including nitrites from the mixed benzene stream in the line 161. The denitrogenated benzene effluent in a line 164 is delivered to both the alkylation reactor 120 by the line 102 and to a transalkylation reactor 150 by a line 166. The benzene stream in the line 166 is mixed with an intermediate stream comprising diisopropylbenzene (DIB) in a line 168 from a heavies column 190. The mixture of benzene and DIB in a line 154 are delivered to the transalkylation reactor 150. The DIB transalkylates with benzene over a transalkylation catalyst bed 156 in the transalkylation reactor 150 to produce cumene. Transalkylation effluent in the line 152 has a greater concentration of cumene and a smaller concentration of benzene and DIB than in the line 154.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:30]=[C:29]([C:31]([O:33]C)=[O:32])[C:28]([N+:35]([O-:37])=[O:36])=[CH:27][C:4]=1[O:5][C:6]([O:11][C:12]1[CH:17]=[C:16]([N+:18]([O-:20])=[O:19])[C:15]([C:21]([O:23]C)=[O:22])=[CH:14][C:13]=1[O:25][CH3:26])([CH2:9][CH3:10])[CH2:7][CH3:8]>[OH-].[Na+].C1COCC1>[C:21]([C:15]1[C:16]([N+:18]([O-:20])=[O:19])=[CH:17][C:12]([O:11][C:6]([O:5][C:4]2[CH:27]=[C:28]([N+:35]([O-:37])=[O:36])[C:29]([C:31]([OH:33])=[O:32])=[CH:30][C:3]=2[O:2][CH3:1])([CH2:9][CH3:10])[CH2:7][CH3:8])=[C:13]([O:25][CH3:26])[CH:14]=1)([OH:23])=[O:22]
Reactant: CCC(CC)(Oc1cc([N+](=O)[O-])c(C(=O)OC)cc1OC)Oc1cc([N+](=O)[O-])c(C(=O)OC)cc1OC
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CCC(CC)(Oc1cc([N+](=O)[O-])c(C(=O)O)cc1OC)Oc1cc([N+](=O)[O-])c(C(=O)O)cc1OC
Yield: 104.4 %

Procedure:
A suspension of the ester 52 (9.0 g, 17.2 mmol) in aqueous sodium hydroxide (1 M, 180 mL) and THF (180 mL) was allowed to stir until a homogenous solution was obtained (2 days). THF was evaporated under reduced pressure and the resulting aqueous suspension was filtered to remove any unreacted starting material. The filtrate was adjusted to pH 1, the precipitated product was collected by filtration and air dried to afford the desired bis-acid (53) (8.88 g). A higher than theoretical yield was obtained due to the inclusion of the sodium salt of acid. The salt may be removed by dissolving the bulk of the material in THF and removing the insoluble material by filtration: 1H NMR (400 MHz, CDCl3) δ 7.39 (s, 2H), 7.16 (s, 2H), 4.12 (t, 4H, J=6.59 Hz), 3.95 (s, 6H), 2.00-1.85 (m, 4H), 1.75-1.67 (m, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=2)[CH2:16]Cl)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].[NH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:13]2[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=2)[CH2:16][N:21]2[CH2:26][CH2:25][N:24]([CH2:16][C:15]3[CH:18]=[CH:19][CH:20]=[C:13]([C:5]4[CH:6]=[C:7]([O:11][CH3:12])[C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=4)[CH:14]=3)[CH2:23][CH2:22]2)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10]
Reactant: COc1cc(-c2cccc(CCl)c2)cc(OC)c1OC
Reactant: C1CNCCN1
Product: COc1cc(-c2cccc(CN3CCN(Cc4cccc(-c5cc(OC)c(OC)c(OC)c5)c4)CC3)c2)cc(OC)c1OC

Procedure:
3-(3,4,5-Trimethoxyphenyl)benzyl chloride (120 mg) and piperazine (17 mg) were reacted in the same manner as in Example 1 to obtain the title compound as a free base.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[CH:12][C:7]2[NH:8][C:9]([SH:11])=[N:10][C:6]=2[CH:5]=1)([O-:3])=[O:2].[Cl:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=1[Cl:23])[CH2:18]Br>C(O)C>[Cl:14][C:15]1[CH:16]=[C:17]([CH:20]=[CH:21][C:22]=1[Cl:23])[CH2:18][S:11][C:9]1[NH:8][C:7]2[CH:12]=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][C:6]=2[N:10]=1
Reactant: O=[N+]([O-])c1ccc2[nH]c(S)nc2c1
Reactant: Clc1ccc(CBr)cc1Cl
Solvent: CCO
Product: O=[N+]([O-])c1ccc2[nH]c(SCc3ccc(Cl)c(Cl)c3)nc2c1
Yield: 64.9 %

Procedure:
A mixture of 5-nitro-1H-benzoimidazol-2-thiol (1.95 g, 0.01 mol) and 3,4-dichlorobenzylbromide (2.4 g, 0.01 mol) was heated at reflux in ethanol (100 mL) for a period of 20 hours. The mixture was then concentrated. The solid was collected by filtration. The solid was dissolved in a mixture of EtOAc/H2O. Sodium bicarbonate was added until basic. The organic phase was separated and the solvent evaporated. The residue was dissolved in ethanol. The solution was saturated with hydrogen chloride. The solution was then concentrated to the precipitation point. The solid was then collected to give the title compound (2.3 g, 59% yield) as a mono-hydrochloride, off-white solid, m.p. 232°-234° C. (dec.). Mass spectrum (EI; M+) m/z 353/355/347. Anal. Calcd. for C14H9Cl2N3O2 S.HCl: C, 43.04; H, 2.58; N, 10.76. Found: C, 43.24; H, 2.47; N, 10.69. 1H-NMR (DMSO-d6 ; 400 MHz): δ 8.32 (s, 1H), 8.07 (d, 1H), 7.78 (s, 1H), 7.62 (d, 1H), 7.56 (d, 1H), 7.49 (d, 1H), and 4.64 ppm (s, 2H).
Reaction SMILES: [NH2:1]/[C:2](/[N:5]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=1)[CH2:6][CH2:7][C:8]1[CH:22]=[CH:21][C:11]([O:12][C:13]([CH3:20])([CH3:19])[C:14]([O:16]CC)=[O:15])=[CH:10][CH:9]=1)=[N:3]\[OH:4].[Cl:34][C:35]1[CH:36]=[C:37]([CH:41]=[CH:42][CH:43]=1)[C:38](Cl)=O>>[Cl:34][C:35]1[CH:36]=[C:37]([C:38]2[O:4][N:3]=[C:2]([N:5]([CH2:23][C:24]3[CH:29]=[CH:28][C:27]([C:30]([F:31])([F:32])[F:33])=[CH:26][CH:25]=3)[CH2:6][CH2:7][C:8]3[CH:22]=[CH:21][C:11]([O:12][C:13]([CH3:19])([CH3:20])[C:14]([OH:16])=[O:15])=[CH:10][CH:9]=3)[N:1]=2)[CH:41]=[CH:42][CH:43]=1
Reactant: CCOC(=O)C(C)(C)Oc1ccc(CCN(Cc2ccc(C(F)(F)F)cc2)/C(N)=N/O)cc1
Reactant: O=C(Cl)c1cccc(Cl)c1
Product: CC(C)(Oc1ccc(CCN(Cc2ccc(C(F)(F)F)cc2)c2noc(-c3cccc(Cl)c3)n2)cc1)C(=O)O

Procedure:
Similarly prepared from ethyl 2-[4-(2-{[(E)-amino(hydroxyimino)methyl][4-(trifluoromethyl)benzyl]amino}ethyl)phenoxy]-2-methylpropanoate and 3-chlorobenzoyl chloride.
Reaction SMILES: [C:1]([O:42]N1C(=O)CCC1=O)(=O)[CH2:2][CH2:3][O:4][CH2:5][CH2:6][O:7][CH2:8][CH2:9][O:10][CH2:11][CH2:12][O:13][CH2:14][CH2:15][O:16][CH2:17][CH2:18][O:19][CH2:20][CH2:21][O:22][CH2:23][CH2:24][O:25][CH2:26][CH2:27][O:28][CH2:29][CH2:30][C:31]([O:33]N1C(=O)CCC1=O)=O.[NH2:50][CH2:51][CH2:52][O:53][CH2:54][CH2:55][O:56][CH2:57][CH2:58][O:59][CH2:60][CH2:61][O:62][CH2:63][CH2:64][O:65][CH2:66][CH2:67][O:68][CH2:69][CH2:70][O:71][CH2:72][CH2:73][O:74][CH2:75][CH2:76][O:77][CH2:78][CH2:79][O:80][CH2:81][CH2:82][NH:83][S:84]([C:87]1[CH:92]=[CH:91][CH:90]=[C:89]([CH:93]2[C:102]3[C:97](=[C:98]([Cl:104])[CH:99]=[C:100]([Cl:103])[CH:101]=3)[CH2:96][N:95]([CH3:105])[CH2:94]2)[CH:88]=1)(=[O:86])=[O:85]>>[Cl:103][C:100]1[CH:101]=[C:102]2[C:97](=[C:98]([Cl:104])[CH:99]=1)[CH2:96][N:95]([CH3:105])[CH2:94][CH:93]2[C:89]1[CH:88]=[C:87]([S:84]([NH:83][CH2:82][CH2:81][O:80][CH2:79][CH2:78][O:77][CH2:76][CH2:75][O:74][CH2:73][CH2:72][O:71][CH2:70][CH2:69][O:68][CH2:67][CH2:66][O:65][CH2:64][CH2:63][O:62][CH2:61][CH2:60][O:59][CH2:58][CH2:57][O:56][CH2:55][CH2:54][O:53][CH2:52][CH2:51][NH:50][C:31](=[O:33])[CH2:30][CH2:29][O:28][CH2:27][CH2:26][O:25][CH2:24][CH2:23][O:22][CH2:21][CH2:20][O:19][CH2:18][CH2:17][O:16][CH2:15][CH2:14][O:13][CH2:12][CH2:11][O:10][CH2:9][CH2:8][O:7][CH2:6][CH2:5][O:4][CH2:3][CH2:2][C:1]([NH:50][CH2:51][CH2:52][O:53][CH2:54][CH2:55][O:56][CH2:57][CH2:58][O:59][CH2:60][CH2:61][O:62][CH2:63][CH2:64][O:65][CH2:66][CH2:67][O:68][CH2:69][CH2:70][O:71][CH2:72][CH2:73][O:74][CH2:75][CH2:76][O:77][CH2:78][CH2:79][O:80][CH2:81][CH2:82][NH:83][S:84]([C:87]2[CH:92]=[CH:91][CH:90]=[C:89]([CH:93]3[C:102]4[C:97](=[C:98]([Cl:104])[CH:99]=[C:100]([Cl:103])[CH:101]=4)[CH2:96][N:95]([CH3:105])[CH2:94]3)[CH:88]=2)(=[O:86])=[O:85])=[O:42])(=[O:86])=[O:85])[CH:92]=[CH:91][CH:90]=1
Reactant: O=C(CCOCCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)ON1C(=O)CCC1=O)ON1C(=O)CCC1=O
Reactant: CN1Cc2c(Cl)cc(Cl)cc2C(c2cccc(S(=O)(=O)NCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCN)c2)C1
Product: CN1Cc2c(Cl)cc(Cl)cc2C(c2cccc(S(=O)(=O)NCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)NCCOCCOCCOCCOCCOCCOCCOCCOCCOCCOCCNS(=O)(=O)c3cccc(C4CN(C)Cc5c(Cl)cc(Cl)cc54)c3)c2)C1
Yield: 49.8 %

Procedure:
Compound 217 was prepared following the procedure outlined in Example 168 using bis(2,5-dioxopyrrolidin-1-yl) 4,7,10,13,16,19,22,25,28-nonaoxahentriacontane-1,31-dioate (69.1 mg, 0.0975 mmol) and N-(32-amino-3,6,9,12,15,18,21,24,27,30-decaoxadotriacontyl)-3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)benzenesulfonamide (Compound 214, 166.2 mg, 0.195 mmol). Purification by preparative HPLC gave the title compound (106.3 mg) as a TFA salt. 1H-NMR (400 MHz, CD3OD): δ 7.88 (d, 2H), 7.76 (s, 2H), 7.66 (t, 2H), 7.56 (m, 4H), 6.86 (s, 2H), 3.90 (m, 2H), 3.82 (t, 2H), 3.76 (m, 6H), 3.62-3.41 (m, 28H), 3.38 (m, 6H), 3.35-3.28 (m, 56H), 3.15 (s, 6H), 3.05 (t, 4H), 2.43 (t, 4H). MS (m/z): 1094.37 [(M+2H)/2]+.
Reaction SMILES: C(O[C:5](=[O:7])[CH3:6])(=O)C.[CH2:8]([N:20]1[CH2:25][CH2:24][CH:23]([C:26]([CH3:31])([CH3:30])[CH2:27][NH:28][CH3:29])[CH2:22][CH2:21]1)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].[OH-].[Na+].CC1C=CC(S([O-])(=O)=O)=CC=1>ClCCl.C(N(CC)CC)C>[CH3:29][N:28]([CH2:27][C:26]([CH3:31])([CH:23]1[CH2:24][CH2:25][N:20]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[CH2:21][CH2:22]1)[CH3:30])[C:5](=[O:7])[CH3:6]
Reactant: CC(=O)OC(C)=O
Reactant: CCCCCCCCCCCCN1CCC(C(C)(C)CNC)CC1
Agent: Cc1ccc(S(=O)(=O)[O-])cc1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCCCCCCCCCN1CCC(C(C)(C)CN(C)C(C)=O)CC1
Temperature: 25 °C
Reaction time: 12 h
Yield: 95.2 %

Procedure:
3.4 ml (3.6×10-2 mole) of acetic anhydride was added to a solution of 8 g (2.4×10-2 mole) of 1-dodecyl-N,β,β-trimethyl-4-piperidineethanamine in 100 ml of dichloromethane and 16.8 ml of N,N-diethylethanamine. The reaction mixture was stirred for 12 hours at room temperature. The solution was poured into a 1N sodium hydroxide solution and extracted with trichloromethane. The organic phase was washed with water, dried and filtered and the solvents were evaporated off under reduced pressure. 8.7 g of N-methyl-N-[2-methyl-2-[(1-dodecyl)-4-piperidinyl]propyl]acetamide (yield: 97%) was obtained, from which the 4-methylbenzene sulphonate was prepared and recrystallised from ethyl acetate. M Pt=102°-103° C.