Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2](Cl)([C:25]#[N:26])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[S:10]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH2:19][C:20]([C:23]#[N:24])(Cl)[Cl:21])(=[O:12])=[O:11].ClC(=CS(C1C=CC=CC=1)(=O)=O)C#N>O>[Cl:21][CH:20]([C:23]#[N:24])[CH2:19][C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][C:13]=1[S:10]([C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=1[CH2:3][CH:2]([C:25]#[N:26])[Cl:1])(=[O:12])=[O:11]
Reactant: N#CC(Cl)(Cl)Cc1ccccc1S(=O)(=O)c1ccccc1CC(Cl)(Cl)C#N
Agent: N#CC(Cl)=CS(=O)(=O)c1ccccc1
Solvent: O
Product: N#CC(Cl)Cc1ccccc1S(=O)(=O)c1ccccc1CC(Cl)C#N

Procedure:
The addition of 40 ppm of β,β-dichloro-β-cyano-ethyl-phenyl-sulphone or α-chloro-β-phenylsulphonyl-acrylonitrile to a back water sample, from a paper factory, which contained 9.3 × 107 germs (predominantly slime-forming organisms) per ml, caused complete destruction of the germs within 2 to 5 hours, whilst even 70 ppm of β-chloro-β-cyano-ethyl-phenyl-sulphone only gave a reduction to 2.5 × 107 germs per ml.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]([CH:7]=[O:8])[S:5][CH:6]=1.[Cl:9][CH2:10][CH2:11][O:12][CH2:13][Mg]Cl.[Cl-].[NH4+].Cl.C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C>[CH3:1][C:2]1[N:3]=[C:4]([CH:7]([OH:8])[CH2:13][O:12][CH2:11][CH2:10][Cl:9])[S:5][CH:6]=1
Reactant: Cc1csc(C=O)n1
Reactant: ClCCOC[Mg]Cl
Agent: Cl
Agent: O=C([O-])O
Agent: [Cl-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Cc1csc(C(O)COCCCl)n1
Temperature: -30 °C
Reaction time: 1 h

Procedure:
1.6 g of 4-methyl-2-formylthiazole was dissolved in 30 ml of tetrahydrofuran. The solution was cooled to -30° C. Thereto was dropwise added, in 10 minutes, 10 ml of a tetrahydrofuran solution containing 1.6M of 2-chloroethoxymethylmagnesium chloride. The mixture was stirred for 1 hour with ice cooling. The reaction mixture was added to a mixture of 50 ml of ice water, 50 ml of ethyl acetate and 2 g of ammonium chloride. The resulting mixture was adjusted to pH 2 with 6N hydrochloric acid and stirred at the same temperature for 5 minutes. The reaction mixture was adjusted to pH 6 with a saturated aqueous sodium hydrogencarbonate solution. The organic layer was separated, washed with water and a saturated aqueous sodium chloride solution in this order, and dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure. The residue thus obtained was purified by column chromatography (eluant:toluene/ethyl acetate=4/1) to obtain 1.3 g of oily 1-(4-methyl-2-thiazolyl)-2-(2-chloroethoxy)ethanol.
Reaction SMILES: Cl.[CH2:2]([O:9][C:10]1[CH:11]=[C:12]([NH:16][NH2:17])[CH:13]=[CH:14][CH:15]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[C:18](#[N:21])[CH:19]=[CH2:20]>[O-]CC.[Na+]>[NH2:21][C:18]1[CH2:19][CH2:20][N:16]([C:12]2[CH:13]=[CH:14][CH:15]=[C:10]([O:9][CH2:2][C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH:11]=2)[N:17]=1
Reactant: C=CC#N
Reactant: NNc1cccc(OCc2ccccc2)c1
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Product: NC1=NN(c2cccc(OCc3ccccc3)c2)CC1
Temperature: 25 °C
Yield: 18.8 %

Procedure:
To an ethanolic sodium ethoxide solution (prepared from 0.29 g of sodium and 20 mL of ethanol) was added 2 g of 3-benzyloxyphenylhydrazine hydrochloride and 0.51 g of acrylonitrile. The reaction mixture was refluxed for 5 h and then cooled to room temperature. Solvent was removed in vacuo, residue washed well with water and ether to give 0.4 g of solid. Recrystallization from CH2C12 -Hexane gave 0.3 g of pure product: mp 135°-136° C.
Reaction SMILES: [CH2:1]([C:4]1[C:10]([OH:11])=[CH:9][CH:8]=[C:7]([CH2:12][CH:13]=[CH2:14])[C:5]=1[OH:6])[CH:2]=[CH2:3]>CO.[Pd]>[CH2:1]([C:4]1[C:5]([OH:6])=[C:7]([CH2:12][CH2:13][CH3:14])[CH:8]=[CH:9][C:10]=1[OH:11])[CH2:2][CH3:3]
Reactant: C=CCc1ccc(O)c(CC=C)c1O
Agent: [Pd]
Solvent: CO
Product: CCCc1ccc(O)c(CCC)c1O

Procedure:
The product 2,6-bis-allylresorcinol (33.5 gm) was dissolved in methanol and hydrogenated under H2 Pressure (initial pressure 45 psig) over 10% Pd on carbon (300 mg). The reaction mixture was filtered through celite and reduced i. vac. The crude oil was flushed through a short SiO2 gel column eluting with ethyl ether. The resulting oil was purified by crystallization from hexanes:ether.
Reaction SMILES: CC1C=CC(CO[N:8]=[C:9]([C:11]2[N:12]=[CH:13][N:14]([C@@H:17]3[O:23][C@H:22]([CH2:24][OH:25])[C@@H:20]([OH:21])[C@H:18]3[OH:19])[C:15]=2[NH2:16])[NH2:10])=CC=1.C(O)C.[C:31](=S)=[S:32]>>[CH:13]1[N:14]([C@@H:17]2[O:23][C@H:22]([CH2:24][OH:25])[C@@H:20]([OH:21])[C@H:18]2[OH:19])[C:15]2[C:11](=[C:9]([NH2:10])[NH:8][C:31]([N:16]=2)=[S:32])[N:12]=1
Reactant: Cc1ccc(CON=C(N)c2ncn([C@@H]3O[C@H](CO)[C@@H](O)[C@H]3O)c2N)cc1
Reactant: S=C=S
Solvent: CCO
Product: Nc1[nH]c(=S)nc2c1ncn2[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O
Yield: 76 %

Procedure:
0.45 g of 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide O-(p-methylbenzyl)-oxime was dissolved in 8 ml of an aqueous solution containing 1 ml of ethanol, and 2 ml of carbon disulfide was added to the solution. The resulting mixture was allowed to react in an autoclave at 130° C for 5 hours under autogenous pressure (about 10 Kg/cm2), and the reaction product was worked up in the same manner as described in Example 1 to obtain 0.288 g of 2-thioadenosine having a melting point of 198° C (with decomposition) in a 76% yield.
Reaction SMILES: C1(N=C=NC2CCCCC2)CCCCC1.Cl.[NH2:17][CH2:18][C:19](O)=[O:20].[NH2:22][C:23]1[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][C:24]=1[C:25](=[N:33][CH2:34][CH2:35][OH:36])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[F:32]>CN(C)C=O.O.O1CCCC1>[NH2:17][CH2:18][C:19]([NH:22][C:23]1[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][C:24]=1[C:25](=[N:33][CH2:34][CH2:35][OH:36])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[F:32])=[O:20]
Reactant: NCC(=O)O
Reactant: Nc1ccc(Cl)cc1C(=NCCO)c1ccccc1F
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Solvent: C1CCOC1
Solvent: CN(C)C=O
Solvent: O
Product: NCC(=O)Nc1ccc(Cl)cc1C(=NCCO)c1ccccc1F
Yield: 44.5 %

Procedure:
To a solution of 4.5g of N,N'-dicyclohexylcarbodiimide in 100ml of dimethylformamide is added a solution of 2.2g of glycine hydrochloride in 2.2ml of water in a period of about 30 seconds under stirring and ice-cooling. Immediately a solution of 3.2g of 2-{[2-amino-5-chloro-α-(2-fluorophenyl)benzylidene]amino}ethanol in 10ml of tetrahydrofuran is added dropwise to the above solution and the mixture is stirred for further 3 hours. After completion of the reaction, the reaction mixture is treated by the same manner as described in the Example 1, yielding 1.7g of the desired product melting at 128°-132° C.
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.B(O)(O)O.[S:12](=[O:16])(=O)(O)[OH:13]>O>[OH:7][C:1]1[CH:6]=[CH:5][C:4]([S:12]([C:4]2[CH:5]=[CH:6][C:1]([OH:7])=[CH:2][CH:3]=2)(=[O:16])=[O:13])=[CH:3][CH:2]=1
Reactant: Oc1ccccc1
Reactant: O=S(=O)(O)O
Agent: OB(O)O
Solvent: O
Product: O=S(=O)(c1ccc(O)cc1)c1ccc(O)cc1
Yield: 82 %

Procedure:
470.6 g (5.0 moles) of phenol and 6.2 g (0.1 mole) of boric acid were placed in a glass flask having a capacity of 2 liters. While the mixture was heated to 180°-186° C., 102.2 g (1.0 mole) of 96% sulfuric acid were added dropwise, after which the water of reaction was removed at 180°-186° C. The phenol was then distilled off over a period of 2 hours at a temperature of from 160° to 200° C. Analysis of the crude product revealed the following composition: 3% phenol, 1% isomeric sulfone and 97% bis(4-hydroxyphenyl) sulfone. Further purification was conducted as described in Example 1. There were obtained 205 g (0.82 mole; yield 82%) of bis(4-hydroxylphenyl) sulfone showing a purity of >99%.
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11](O)=O)=[CH:6][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])C=O>N1CCCCC1>[Cl:14][C:15]1[CH:16]=[CH:17][C:20]([CH:11]=[CH:10][C:7]2[CH:8]=[CH:9][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)=[CH:21][C:22]=1[Cl:23]
Reactant: O=Cc1ccc(Cl)c(Cl)c1
Reactant: O=C(O)Cc1ccc([N+](=O)[O-])cc1
Solvent: C1CCNCC1
Product: O=[N+]([O-])c1ccc(C=Cc2ccc(Cl)c(Cl)c2)cc1
Temperature: 155 °C
Yield: 27.5 %

Procedure:
A mixture of p-nitrophenylacetic acid (51.23 g, 0.28 mol) and 3,4-dichlorobenzaldehyde (49.50 g, 0.28 mol) in piperidine (50 mL) was heated to 150-160° C. for 5 hours under a N2 atmosphere. After cooling the reaction mixture, the precipitate was triturated in boiling methanol (MeOH) (50 mL) and then cooled to −5° C. for 12 hours. The crystalline precipitate was filtered off, rinsed with cold MeOH and dried at room temperature in a vacuum oven overnight to yield an orange solid, 22.71 g (0.077 mol, 27%) of the desired product.
Reaction SMILES: [CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9]1(=[O:15])[O:14][C:12](=[O:13])[CH2:11][CH2:10]1.CCN(CC)CC>C1COCC1>[CH2:1]([O:8][C:9](=[O:15])[CH2:10][CH2:11][C:12]([OH:14])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C1CCC(=O)O1
Reactant: OCc1ccccc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: O=C(O)CCC(=O)OCc1ccccc1
Reaction time: 18 h
Yield: 82.8 %

Procedure:
To a solution of 4.13 mL (4.32 g, 40 mmol) of benzyl alcohol and 4.40 g (44 mmol) of succinic anhydride in 100 mL of THF at 0° C. was added at once 12.24 mL (8.90 g, 88 mmol) of Et3N. The mixture was allowed to come to room temperature and stirred for 18 h at which time it was concentrated under vacuum to a viscous oil and partitioned between 100 mL of 1 N HCl and 100 mL of EtOAc. The EtOAc layer was extracted with 84 mL of 5% NaHCO3 solution. The aqueous layer was acidified with concentrated HCl solution to pH 1 and extracted with two 50 mL portions of EtOAc. The EtOAc layers were combined and washed with brine, dried (MgSO4), filtered, and concentrated to give 6.9 g (83%) of 21 as a white chunky solid: 1H NMR (CDCl3) 2.70 (s, 4H), 5.22 (s, 2H), 7.38 (s, 5H).
Reaction SMILES: Cl[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:11][N:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.C(=O)([O-])[O-].[Cs+].[Cs+]>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].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.O1CCOCC1>[CH3:11][N:12]1[CH2:17][CH2:16][N:15]([C:2]2[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=2)[CH2:14][CH2:13]1
Reactant: CN1CCNCC1
Reactant: O=[N+]([O-])c1cccnc1Cl
Agent: [Pd]
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: CN1CCN(c2ncccc2[N+](=O)[O-])CC1
Temperature: 90 °C
Yield: 92.7 %

Procedure:
To a microwave vial was added 2-chloro-3-nitropyridine (LXXXI) (1.00 g, 6.31 mmol), 1-methylpiperazine (LXXXII) (0.758 g, 7.57 mmol), cesium carbonate (2.88 g, 8.83 mmol), Pd2(dba)3 (0.173 g, 0.189 mmol), xanthphos (0.109 g, 0.189 mmol), and dioxane (5 mL) The reaction vial was capped and purged with argon. The solution into the reaction vial was heated under microwave irradiation for 2 h at 90° C. The solution was filtered through a pad of Celite and concentrated to a residue under vacuum. The residue was purified by column chromatography (1:99 MeOH:CHCl3→8:92 MeOH:CHCl3) to afford 1-methyl-4-(3-nitro-pyridin-2-yl)-piperazine (LXXXIII) (1.30 g, 5.85 mmol, 93% yield) as a brown oil.
Reaction SMILES: [OH:1][CH:2]1[CH2:5][N:4]([C:6]2[CH:7]=[C:8]([C:12]3[N:13]=[C:14]4[C:20]([C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:19][N:18](COCC[Si](C)(C)C)[C:15]4=[N:16][CH:17]=3)[CH:9]=[CH:10][CH:11]=2)[CH2:3]1.[ClH:35]>CO>[Cl:35][CH2:3][CH:2]([OH:1])[CH2:5][NH:4][C:6]1[CH:7]=[C:8]([C:12]2[N:13]=[C:14]3[C:20]([C:21](=[O:26])[C:22]([CH3:25])([CH3:24])[CH3:23])=[CH:19][NH:18][C:15]3=[N:16][CH:17]=2)[CH:9]=[CH:10][CH:11]=1
Reactant: Cl
Reactant: CC(C)(C)C(=O)c1cn(COCC[Si](C)(C)C)c2ncc(-c3cccc(N4CC(O)C4)c3)nc12
Solvent: CO
Product: CC(C)(C)C(=O)c1c[nH]c2ncc(-c3cccc(NCC(O)CCl)c3)nc12
Temperature: 90 °C
Reaction time: 0.25 h
Yield: 35 %

Procedure:
A solution of 1-[2-[3-(3-hydroxy-azetidin-1-yl)-phenyl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-7-yl]-2,2-dimethyl-propan-1-one (36 mg, 0.075 mmol), in MeOH (1 ml), was treated with 18.5% HCl aq (1.75 ml). The reaction mixture was capped and heated to 90° C. for 1.5 hours. The reaction mixture was concentrated to dryness, and the resulting residue was taken up in 10 ml of EtOAc and 5 ml of sat. NaHCO3 aq. The reaction mixture was allowed to stir for 15 minutes and then extracted into EtOAc. The organic layers were collected, dried over MgSO4, filtered, concentrated. Silica gel chromatography using 0-10% MeOH in EtOAc as eluant gave 10 mg (35%) of 1-{2-[3-(3-chloro-2-hydroxy-propylamino)-phenyl]-5H-pyrrolo[2,3-b]pyrazin-7-yl}-2,2-dimethyl-propan-1-one as a yellow solid. M+H=387.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([O:8][CH:9]2[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][CH2:10]2)[CH:5]=[CH:6][CH:7]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([O:8][CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)[CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N1CCC(Oc2cccc(F)c2)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Fc1cccc(OC2CCNCC2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 111.8 %

Procedure:
A solution of 1,1-dimethylethyl 4-[(3-fluorophenyl)oxy]-1-piperidinecarboxylate (D11) (16.4 g, 55 mmol) in DCM (200 ml) at 0° C. was treated with TFA (17 ml). The reaction was warmed to room temperature and stirred overnight. The solvent was then removed in vacuo and the residue partitioned between DCM and 2M NaOH solution. The aqueous was further extracted with DCM (×2) and the combined organics concentrated in vacuo. The residue was re-dissolved in DCM and extracted with 2M HCl (×2) which was then basified with 2M NaOH and re-extracted with DCM (×3). The combined organics were concentrated in vacuo to give the title compound (12 g). δH (CDCl3, 250 MHz) 1.66 (2H, m), 2.01 (2H, m), 2.73 (2H, m), 3.14 (2H, m), 4.34 (1H, m), 6.68 (3H, m), 7.19 (1H, m), MS (ES): MH+ 196. This whole was diluted with MeOH and treated with 1M HCl in Et2O to give the hydrochloride salt of the title compound (8.0 g).
Reaction SMILES: [CH3:1][C:2](=[N:10][O:11][CH2:12][CH2:13][C:14]([OH:16])=O)[C:3]1[CH:8]=[CH:7][C:6]([Cl:9])=[CH:5][CH:4]=1.[NH3:17]>CO>[CH3:1][C:2](=[N:10][O:11][CH2:12][CH2:13][C:14]([NH2:17])=[O:16])[C:3]1[CH:8]=[CH:7][C:6]([Cl:9])=[CH:5][CH:4]=1
Reactant: N
Reactant: CC(=NOCCC(=O)O)c1ccc(Cl)cc1
Solvent: CO
Product: CC(=NOCCC(N)=O)c1ccc(Cl)cc1
Temperature: 70 °C

Procedure:
15.6 g of the ethyl ester of 3[(α-methyl-4-chlorobenzylidene amino)oxy] propionic acid obtained by the method described in Example 13 was dissolved in 100 ml of methanol saturated with ammonia at 25° C. This solution was heated at 70° C. in an autoclave for 7 hours. It was then concentrated by evaporation in a vacuum at 40° C. and the semisolid residue was dissolved by means of 200 ml of diethyl ether, 100 ml of benzene, 200 ml of chloroform and 200 ml of methylene chloride. The resulting solution was extracted thrice with dilute sodium hydroxide, then dried over anhydrous sodium sulfate and finally concentrated by evaporation in a vacuum. The residue obtained was recrystallized from a mixture of 50 ml of benzene, 50 ml of chloroform and 25 ml of petroleum ether. Melting point 149° C.-150° C.
Reaction SMILES: [C:1]1([C:7]#[C:8][C:9]2[CH:10]=[C:11]([NH:23][C:24](=[O:46])[C@@H:25]([NH:38]C(=O)OC(C)(C)C)[CH2:26][CH2:27][CH2:28][CH2:29][NH:30]C(=O)OC(C)(C)C)[CH:12]=[C:13]([C:15]#[C:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:14]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>C(O)(C(F)(F)F)=O>[NH2:38][C@@H:25]([CH2:26][CH2:27][CH2:28][CH2:29][NH2:30])[C:24]([NH:23][C:11]1[CH:10]=[C:9]([C:8]#[C:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH:14]=[C:13]([C:15]#[C:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:12]=1)=[O:46]
Reactant: CC(C)(C)OC(=O)NCCCC[C@H](NC(=O)OC(C)(C)C)C(=O)Nc1cc(C#Cc2ccccc2)cc(C#Cc2ccccc2)c1
Solvent: O=C(O)C(F)(F)F
Product: NCCCC[C@H](N)C(=O)Nc1cc(C#Cc2ccccc2)cc(C#Cc2ccccc2)c1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
(S)-di-tert-butyl (6-((3,5-bis(phenylethynyl) phenyl)amino)-6-oxohexane-1,5-diyl)dicarbamate (0.35 g, 0.56 mmol) was reacted with neat TFA (10 mL) and the solution was stirred for 5 hours at room temperature. TFA was evaporated and the product (0.34 mg, 93%) was purified by recrystallization with ethanol: 1H-NMR (400 MHz, CD3OD) δ 7.80 (d, J=1.4 Hz, 2H), 7.52-7.55 (m, 4H), 7.45 (t, J=1.4 Hz, 1H), 7.38-7.41 (m, 6H), 4.06 (t, J=6.5 Hz, 1H), 2.96 (t, J=15.4 Hz, 2H), 1.96-2.06 (m, 2H), 1.70-1.78 (m, 2H), 1.50-1.60 (m, 2H).
Reaction SMILES: [Cl:1][C:2]1[C:3]2[C:4]3[CH2:15][N:14]([CH3:16])[CH2:13][CH2:12][C:5]=3[NH:6][C:7]=2[C:8]([F:11])=[CH:9][CH:10]=1.[H-].[Na+].CC1C=CC(S(O[CH2:30][CH2:31][C:32]2[CH:33]=[N:34][C:35]([CH3:38])=[CH:36][CH:37]=2)(=O)=O)=CC=1>CN(C=O)C>[Cl:1][C:2]1[C:3]2[C:4]3[CH2:15][N:14]([CH3:16])[CH2:13][CH2:12][C:5]=3[N:6]([CH2:30][CH2:31][C:32]3[CH:33]=[N:34][C:35]([CH3:38])=[CH:36][CH:37]=3)[C:7]=2[C:8]([F:11])=[CH:9][CH:10]=1
Reactant: Cc1ccc(S(=O)(=O)OCCc2ccc(C)nc2)cc1
Reactant: CN1CCc2[nH]c3c(F)ccc(Cl)c3c2C1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1ccc(CCn2c3c(c4c(Cl)ccc(F)c42)CN(C)CC3)cn1
Temperature: 60 °C
Reaction time: 0.5 h

Procedure:
To a solution of 9-chloro-6-fluoro-2,3,4,5-tetrahydro-2-methyl-1H-pyrido[4,3-b]indole (500 mg, 2.1 mmol) in DMF (5 mL), sodium hydride (252 mg, 6.3 mmol) was added. After stirring at 60° C. for 30 min., 2-(6-methylpyridin-3-yl)ethyl 4-methylbenzenesulfonate (1.5 g, 5.25 mmol) was added to the reaction mixture and stirred at the same temperature for 1 h. The progress of reaction was monitored by TLC and LCMS. The reaction mixture was quenched with water and extracted with EtOAc. The organic layer was washed with water, dried over anhydrous sodium sulfate and concentrated to obtain the crude product, which was purified by reverse phase HPLC to obtain the 9-chloro-6-fluoro-2,3,4,5-tetrahydro-2-methyl-5-(2-(6-methylpyridin-3-yl)ethyl)-1H-pyrido[4,3-b]indole. 1H NMR (CD3OD, TFA) δ (ppm): 8.37 (s, 1H), 8.12 (d, 1H), 7.73 (d, 1H), 7.02 (dd, 1H), 6.86 (t, 1H), 5.1 (m, 1H), 4.57 (t, 2H), 4.56 (m, 1H), 3.85 (m, 1H), 3.6 (m, 1H), 3.27 (m, 3H), 3.2 m (2,H), 3.1 (s, 3H), 2.69 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[OH:9].[Cl:10][C:11]1[CH:18]=[CH:17][C:14]([CH2:15]Cl)=[CH:13][CH:12]=1.O>C(Cl)(Cl)Cl.[Cl-].[Cl-].[Zn+2]>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:15][C:14]2[CH:17]=[CH:18][C:11]([Cl:10])=[CH:12][CH:13]=2)[CH:5]=[C:4]([CH3:8])[C:3]=1[OH:9]
Reactant: ClCc1ccc(Cl)cc1
Reactant: Cc1cccc(Cl)c1O
Agent: [Cl-]
Agent: [Zn+2]
Solvent: O
Solvent: ClC(Cl)Cl
Product: Cc1cc(Cc2ccc(Cl)cc2)cc(Cl)c1O

Procedure:
178.1 g (1.25 mol) 2-chloro-6-methylphenol and 80.5 g (0.5 mol) 4-chlorobenzyl chloride are dissolved in 300 ml dry chloroform. 40 g water-free, finely mortared ZnCl2 are subsequentlyadded.
Reaction SMILES: O=[N+]([O-])[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[O-][N+](=O)[O-].[Ce+4].[NH4+].[NH4+].C(#N)C.[OH:31][CH2:32][C:33]1([CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][OH:58])[CH2:41][C:40]2[C:35](=[C:36]([O:48]C)[C:37]([O:46][CH3:47])=[C:38]([O:44][CH3:45])[C:39]=2[O:42]C)[CH2:34]1>O>[OH:31][CH2:32][C:33]1([CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][OH:58])[CH2:41][C:40]2[C:39](=[O:42])[C:38]([O:44][CH3:45])=[C:37]([O:46][CH3:47])[C:36](=[O:48])[C:35]=2[CH2:34]1
Reactant: COc1c2c(c(OC)c(OC)c1OC)CC(CO)(CCCCCCCCO)C2
Agent: O=[N+]([O-])[O-]
Agent: [Ce+4]
Agent: [NH4+]
Solvent: O
Solvent: CC#N
Product: COC1=C(OC)C(=O)C2=C(CC(CO)(CCCCCCCCO)C2)C1=O
Reaction time: 0.25 h
Yield: 25.7 %

Procedure:
A water (1.0 ml) solution of CAN (509 mg, 0.928 mmols) was dropwise added to an acetonitrile (4.0 ml) solution of 8-(2-hydroxymethyl-4,5,6,7-tetramethoxyindan-2-yl)octanol (147 mg, 0.371 mmols) with cooling with ice and stirring was continued for 15 minutes. Water was added to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium chloride solution, and then dried. The solvent was evaporated in vacuo, and the resulting crude product was purified by silica gel column chromatography (hexane:ethyl acetate=2:1 to 1:2) followed by recrystallization from hexane-ethyl acetate to obtain the entitled compound (35 mg) as crystals.
Reaction SMILES: [CH2:1]([C:13]1[N:14]=[N:15][N:16]([CH:18]([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])[C:19]([O:21]CC)=[O:20])[N:17]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].C(C1N=NN(C(C2C=CC=CC=2)C(OCC)=O)N=1)CCCCCCCCC>>[CH2:1]([C:13]1[N:14]=[N:15][N:16]([CH:18]([CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])[C:19]([OH:21])=[O:20])[N:17]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCCCc1nnn(C(CCCCCCCCCCCC)C(=O)OCC)n1
Agent: CCCCCCCCCCc1nnn(C(C(=O)OCC)c2ccccc2)n1
Product: CCCCCCCCCCCCc1nnn(C(CCCCCCCCCCCC)C(=O)O)n1

Procedure:
When in the general procedure of Example 79 an appropriate amount of ethyl (±)-5-dodecyl-α-dodecyl-2H-tetrazole-2-acetate was substituted for ethyl (±)-5-decyl-α-phenyl-2H-tetrazole-2-acetate, the title compound was obtained, mp 57°-59° C.
Reaction SMILES: [C:1]1(=[O:8])[O:7][C:5](=[O:6])[CH:4]=[C:2]1[CH3:3].[OH:9][C:10]([CH3:18])([CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[CH2:11][SH:12].C(NC(C)C)(C)C>>[CH3:3][C:2]1([CH2:4][C:5]([OH:7])=[O:6])[S:12][CH2:11][C:10]([CH3:18])([CH2:13][CH2:14][CH2:15][CH2:16][CH3:17])[O:9][C:1]1=[O:8]
Reactant: CCCCCC(C)(O)CS
Reactant: CC1=CC(=O)OC1=O
Solvent: CC(C)NC(C)C
Product: CCCCCC1(C)CSC(C)(CC(=O)O)C(=O)O1

Procedure:
Analogously to Example 1, from citraconic acid anhydride and 2-hydroxy-2-methylheptane-1-thiol in the presence of diisopropylamine and the usual working up of the reaction mixture, 3,6-dimethyl-2-oxo-6-pentyl-1,4-oxathiane-3-acetic acid is obtained. Using chromatographic purification it can be separated into two isomers:
Reaction SMILES: ClCC[CH2:4][OH:5].NCCNC(NC1C=CC=CC=1)=O.[OH:19][CH2:20][CH2:21][CH2:22][NH:23][CH2:24][CH2:25][NH:26][C:27]([NH:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:28].C(=O)(OCC)OCC>>[O:5]=[C:4]1[N:23]([CH2:24][CH2:25][NH:26][C:27]([NH:29][C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)=[O:28])[CH2:22][CH2:21][CH2:20][O:19]1
Reactant: OCCCCl
Reactant: O=C(NCCNCCCO)Nc1ccccc1
Agent: NCCNC(=O)Nc1ccccc1
Solvent: CCOC(=O)OCC
Product: O=C(NCCN1CCCOC1=O)Nc1ccccc1

Procedure:
When 3-chloropropanol is reacted with 1-(2-aminoethyl)-3-phenylurea and the resulting 1-[2-(3-hydroxypropylamino)ethyl]-3-phenylurea is reacted with diethyl carbonate according to the general processes of steps 1 and 2 of Example 2, there is obtained 1-[2-(tetrahydro-2-oxo-1,3-oxazin-3-yl)ethyl]-3-phenylurea.
Reaction SMILES: [CH3:1][C@@:2]1([OH:32])[C:17]2[CH:18]=[CH:19][CH:20]=[C:21]([OH:22])[C:16]=2[C:15]([OH:23])=[C:14]2[C@@H:3]1[CH2:4][C@@H:5]1[C@:11]([OH:24])([C:12]2=[O:13])[C:10]([OH:25])=[C:9]([C:26]([NH2:28])=[O:27])[C:7](=[O:8])[C@H:6]1[N:29]([CH3:31])[CH3:30]>O>[CH3:1][C@:2]1([OH:32])[C@@H:3]2[C:14](=[C:12]([OH:13])[C@:11]3([OH:24])[C:10](=[O:25])[C:9]([C:26]([NH2:28])=[O:27])=[C:7]([OH:8])[C@@H:6]([N:29]([CH3:31])[CH3:30])[C@@H:5]3[CH2:4]2)[C:15](=[O:23])[C:16]2[C:21]([OH:22])=[CH:20][CH:19]=[CH:18][C:17]1=2
Reactant: CN(C)[C@@H]1C(=O)C(C(N)=O)=C(O)[C@@]2(O)C(=O)C3=C(O)c4c(O)cccc4[C@@](C)(O)[C@H]3C[C@@H]12
Solvent: O
Product: CN(C)[C@@H]1C(O)=C(C(N)=O)C(=O)[C@@]2(O)C(O)=C3C(=O)c4c(O)cccc4[C@@](C)(O)[C@H]3C[C@@H]12

Procedure:
The second tetracycline labelling solution was prepared by dissolving 288 mg of tetracycline base (Sigma) in 40 ml of deionized water to yield a concentration of 7.2 mg of tetracycline per ml.