Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: FC(F)(F)C(O)=O.[C:8]1([C@H:14]([OH:26])[CH2:15][NH:16][C:17]2[CH:22]=[CH:21][C:20](CCN)=[CH:19][CH:18]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[OH-].[Na+]>CO>[C:8]1([C@H:14]([OH:26])[CH2:15][NH:16][C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1
Reactant: NCCc1ccc(NC[C@@H](O)c2ccccc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Product: O[C@H](CNc1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of N-(2-phenyl-2-(S)-hydroxyethyl)-4-(2-aminoethyl)aniline trifluoroacetate 31 (0.144 g, 0.3 mmole) in methanol (10 mL) was added aq. NaOH solution (1.0 M, 0.625 mL). The solution was concentrated to dryness and the residue was dissolved in anhydrous THF (5 mL). α,α-Dihydroxy-4-hydroxy-3-methoxycarbonylacetophenone 12 (0.067 g, 0.3 mmole) was added and the reaction mixture was stirred for 12 h at rt. BH3-Me2S (0.2 mL, 2 M) was added at 0° C. and the reaction mixture was heated at 75° C. for 6 h. After cooling the reaction mixture in ice bath, MeOH (5 mL) was slowly added to it to quench the reaction, and the reaction mixture was stirred for 30 min., at rt. The organics were removed and the residue was dissolved in TFA/MeOH (1/9; 20 mL), and concentrated. The crude product was dissolved in 20% MeCN/H2O, and purified by preparative HPLC: 5 to 20% MeCN/H2O; 20 mL/min; 254 nm.) to give 1-{2-[N-2-(4-hydroxy-3-hydroxymethylphenyl)-2-hydroxyethyl]amino]ethyl}-4-[N-(2-phenyl-2-(S)-hydroxyethyl)-amino]benzene 33.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][Cl:5].[CH3:6][O:7][C:8]1[CH:21]=[CH:20][C:19]2[S:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][C:16]=3[S:22](=[O:27])(=[O:26])[N:23]([CH3:25])[CH3:24])[NH:11][C:10]=2[CH:9]=1.[OH-].[K+]>C(C(C)=O)C>[CH3:6][O:7][C:8]1[CH:21]=[CH:20][C:19]2[S:18][C:17]3[C:12](=[CH:13][CH:14]=[CH:15][C:16]=3[S:22](=[O:27])(=[O:26])[N:23]([CH3:24])[CH3:25])[N:11]([CH2:2][CH2:3][CH2:4][Cl:5])[C:10]=2[CH:9]=1
Reactant: COc1ccc2c(c1)Nc1cccc(S(=O)(=O)N(C)C)c1S2
Reactant: ClCCCBr
Agent: [K+]
Agent: [OH-]
Solvent: CCC(C)=O
Product: COc1ccc2c(c1)N(CCCCl)c1cccc(S(=O)(=O)N(C)C)c1S2
Yield: 60.4 %

Procedure:
2-Methoxy-6-dimethylsulphamoyl-10-(3-chloropropyl)phenothiazine (m.p. 124°-126°C.; 62.6 g.) is prepared by reacting 1-bromo-3-chloropropane (147 g.) with 2-methoxy-6-dimethylsulphamoylphenothiazine (84.4 g.) in the presence of powdered potassium hydroxide (25.8 g.) in methyl ethyl ketone (300 cc.).
Reaction SMILES: C([Li])CCC.[C:6]1([S:12]([N:15]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]([CH:24]([O:27][CH3:28])[O:25][CH3:26])=[CH:16]2)(=[O:14])=[O:13])[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.CN(C)CCN(C)C.[CH3:37][O:38][C:39]1[CH:40]=[C:41]([CH:44]=[CH:45][C:46]=1[O:47][CH3:48])[CH:42]=[O:43]>CCCCCC.O1CCCC1.O>[C:6]1([S:12]([N:15]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[C:17]([CH:24]([O:25][CH3:26])[O:27][CH3:28])=[C:16]2[CH:42]([OH:43])[C:41]2[CH:44]=[CH:45][C:46]([O:47][CH3:48])=[C:39]([O:38][CH3:37])[CH:40]=2)(=[O:13])=[O:14])[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1
Reactant: COc1ccc(C=O)cc1OC
Reactant: COC(OC)c1cn(S(=O)(=O)c2ccccc2)c2ccccc12
Agent: CN(C)CCN(C)C
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Solvent: CCCCCC
Product: COc1ccc(C(O)c2c(C(OC)OC)c3ccccc3n2S(=O)(=O)c2ccccc2)cc1OC
Yield: 61 %

Procedure:
40 ml of 1.55M n-butyl lithium in hexane are added under stirring with cooling to a tetrahydrofuran solution of 19 g of 1-phenylsulfonyl-3-dimethoxymethylindole and 6.5 g of N,N,N',N'-tetramethylethylenediamine. The mixture is stirred at room temperature, and then a solution of 9.3 g of 3,4-dimethoxybenzaldehyde in tetrahydrofuran is added thereto under cooling. The mixture is further stirred at room temperature, poured into water, and then extracted with ethyl acetate. The extract is dried and evaporated under reduced pressure to remove the solvent. The residue is purified by using silica gel column. 17 g of 1-phenylsulfonyl-2-(α-hydroxy-3,4-dimethoxybenzyl)-3-dimethoxymethylindole are obtained as syrup.
Reaction SMILES: [CH3:1][NH:2][NH2:3].[Cl:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]([CH:15]=[O:16])[CH2:10][C:9](=[CH:17]O)[C:8]2=O.C(O)(=O)C>CO>[Cl:4][C:5]1[CH:14]=[CH:13][C:12]2[N:11]([CH:15]=[O:16])[CH2:10][C:9]3[CH:17]=[N:3][N:2]([CH3:1])[C:8]=3[C:7]=2[CH:6]=1
Reactant: CNN
Reactant: O=CN1CC(=CO)C(=O)c2cc(Cl)ccc21
Solvent: CO
Solvent: CC(=O)O
Product: Cn1ncc2c1-c1cc(Cl)ccc1N(C=O)C2
Reaction time: 1.5 h
Yield: 61.7 %

Procedure:
Methylhydrazine (52.5 g) was dropwise to a mixture of 6-chloro-1-formyl-3-hydroxymethylene-4-oxo-1,2,3,4-tetrahydroquinoline (276 g) and acetic acid (13 ml) in methanol (2.76 liters) at 10° C. to 12° C. over a period of 10 minutes. After being stirred for 1.5 hours at the same temperature, the resulting precipitate was collected by filtration, washed with methanol and dried to give 8-chloro-4,5-dihydro-5-formyl-1-methyl-1H -pyrazolo[4,3-c]quinoline (174 g).
Reaction SMILES: [NH3:1].[CH2:2]([O:4][C:5]([C:7]1[N:8]=[C:9](S(C)(=O)=O)[N:10]([CH3:22])[C:11](=[O:21])[C:12]=1[O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:6])[CH3:3]>C(#N)C>[CH2:2]([O:4][C:5]([C:7]1[N:8]=[C:9]([NH2:1])[N:10]([CH3:22])[C:11](=[O:21])[C:12]=1[O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:6])[CH3:3]
Reactant: N
Reactant: CCOC(=O)c1nc(S(C)(=O)=O)n(C)c(=O)c1OCc1ccccc1
Solvent: CC#N
Product: CCOC(=O)c1nc(N)n(C)c(=O)c1OCc1ccccc1
Reaction time: 0.5 h
Yield: 59 %

Procedure:
Gaseous ammonia was bubbled at 25° C. in a solution of 2-methanesulfonyl-5-benzyloxy-1-methyl-6-oxo-1,6-dihydro-pyrimidine-4-carboxylic acid ethyl ester (0.200 g, 0.55 mmol) in acetonitrile (4 ml). After 30 min, the solvent was evaporated in vacuo and the residue was chromatographed on silica gel (elution toluene-ethyl acetate, 6:4 to 1:1) to give 0.099 g (59% yield) of the title ester as a white solid. 1HNMR 400 MHz (DMSO-d6) δ (ppm): 1.19 (3H, t, J=7.1 Hz, CH3), 3.29 (3H, s, NCH3), 4.18 (2H, q, J=7.1 Hz, OCH2), 4.89 (2H, s, OCH2), 7.21 (2H, broad s, NH2), 7.31–7.37 (5H, m, aromatics). Anal. Calcd for C15H17N3O4: C 59.39; H, 5.64; N, 13.85. Found: C, 59.31; H, 5.46, N 13.72.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:9])[CH:4]=[C:5]1[CH2:8][O:7][CH2:6]1.[NH3:10]>CCO>[CH3:1][O:2][C:3](=[O:9])[CH2:4][C:5]1([NH2:10])[CH2:8][O:7][CH2:6]1
Reactant: COC(=O)C=C1COC1
Reactant: N
Solvent: CCO
Product: COC(=O)CC1(N)COC1

Procedure:
Oxetan-3-ylidene-acetic acid methyl ester (Angewandte Chemie, International Edition (2006), 45(46), 7736-7739) ester (1.5 g; 11.72 mmol) in EtOH (20 ml) and liquid NH3 (11 g) are heated in a steel cylinder at 800 C for 5 hours. Evaporation of the solvent delivers the title compound as yellow resin. 1H-NMR (400 MHz; DMSO-d6): 4.42 (d, 2H); 4.34 (d, 2H); 3.61 (s, 3H); 2.77 (s, 2H); 2.33 (bs, 2H). MS (m/z) ES+: 145 (MH+; 15); 96 (100).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([OH:29])[CH:9]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]([F:28])([F:27])[CH:24]([F:26])[F:25])[CH:17]=2)[C:10]([O:12]CC)=[O:11])[CH:5]=[CH:6][CH:7]=1.[OH-].[Na+].Cl>CO>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]([OH:29])[CH:9]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][C:23]([F:28])([F:27])[CH:24]([F:26])[F:25])[CH:17]=2)[C:10]([OH:12])=[O:11])[CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)C(Cc1cccc(OC(F)(F)C(F)F)c1)C(O)c1cccc(Cl)c1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)C(Cc1cccc(OC(F)(F)C(F)F)c1)C(O)c1cccc(Cl)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of ethyl (2RS,3RS)-3-(3-chlorophenyl)-3-hydroxy-2-[3-(1,1,2,2-tetrafluoroethoxy)benzyl]propanoate (6.08 g, 14.0 mmol) in methanol (30 ml) was added 2N aqueous sodium hydroxide solution (14 ml, 28 mmol), and the mixture was stirred at room temperature for 2 hrs. The reaction solution was acidified with 1N hydrochloric acid and extracted with ethyl acetate (200 ml×2). The extract was washed with water and saturated brine, dried (anhydrous magnesium sulfate) and evaporated under reduced pressure. Recrystallization of the residue from ethyl acetate-hexane gave the objective substance (4.6 g, 81%).
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[C:3]=1[CH2:4][N:5]1[CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[N:7]=[C:6]1[CH2:13]O.C(N(CC)CC)C.S(Cl)([Cl:29])=O>ClCCl>[Cl:29][CH2:13][C:6]1[N:5]([CH2:4][C:3]2[C:2]([Cl:1])=[CH:18][CH:17]=[CH:16][C:15]=2[Cl:19])[CH:9]=[C:8]([N+:10]([O-:12])=[O:11])[N:7]=1
Reactant: O=[N+]([O-])c1cn(Cc2c(Cl)cccc2Cl)c(CO)n1
Reactant: O=S(Cl)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=[N+]([O-])c1cn(Cc2c(Cl)cccc2Cl)c(CCl)n1
Temperature: 25 °C
Reaction time: 24 h

Procedure:
210 mg (0.70 mmol) of the compound from Example 37A were dissolved in 10 ml of dichloromethane, and 145 μl (1.04 mmol) of triethylamine and 61 μl (0.83 mmol) of thionyl chloride were added at 0° C. The mixture was stirred at RT for 24 h. A further 200 μl (2.72 mmol) of thionyl chloride were then added, and the mixture was stirred under reflux for 15 min. Under reduced pressure, the reaction mixture was then freed from all volatile components. This gave, in a purity of 88%, 200 mg (80% of theory) of the target compound, which was reacted further without any further purification.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([S:14][C:15]2[CH:20]=[C:19]([C:21]([CH3:24])([CH3:23])[CH3:22])[C:18]([OH:25])=[C:17]([C:26]([CH3:29])([CH3:28])[CH3:27])[CH:16]=2)[CH2:10][CH2:9]1)=O)(C)(C)C.[ClH:30]>O1CCOCC1>[ClH:30].[C:26]([C:17]1[CH:16]=[C:15]([S:14][CH:11]2[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]2)[CH:20]=[C:19]([C:21]([CH3:24])([CH3:23])[CH3:22])[C:18]=1[OH:25])([CH3:29])([CH3:28])[CH3:27]
Reactant: CC(C)(C)OC(=O)N1CCC(Sc2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)CC1
Agent: Cl
Solvent: C1COCCO1
Product: CC(C)(C)c1cc(SC2CCNCC2)cc(C(C)(C)C)c1O
Temperature: 25 °C
Reaction time: 5 h
Yield: 97 %

Procedure:
To 4-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-piperidine-1-carboxylic acid tert-butyl ester (Ex. 3b, 21 g, 50 mmol) in a 250 mL round bottom flask was added 100 mL of a 4 N HCl in dioxane. The mixture was stirred at room temperature for 5 h and concentrated under reduced pressure to about 25 mL. The solid was collected through filtration, washed with Ethyl acetate/hexanes (1:2 v/v, 50 mL), and dried under high vacuum to afford 2,6-di-tert-butyl-4-(piperidin-4-ylsulfanyl)-phenol hydrochloride as a white solid (16 g, 97%). 1H NMR (400 MHz, CD3OD): δ 7.26 (s, 2H), 3.35 (m, 2H), 3.10 (m, 1H), 3.00 (m, 2H), 2.11 (m, 2H), 1.68 (m, 2H), 1.37 (s, 18H). ESI/CI-MS m/z 322 ([M+H]+), 320 ([M−H]−). HRMS (ESI) Calcd. for C19H32ClNOS: 321.2126 (M+). Found: 321.2127. Anal. Calcd. for C19H32ClNOS, C, 63.75; H, 9.01; N, 3.91; S, 8.96. Found: C, 63.43; H, 9.08; N, 3.94; S, 8.72.
Reaction SMILES: CS([O-])(=O)=O.[C:6]1(=[O:13])[O:12][C:10](=[O:11])[CH2:9][O:8][CH2:7]1.[NH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][OH:20]>>[OH:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][NH:14][C:10](=[O:11])[CH2:9][O:8][CH2:7][C:6]([OH:12])=[O:13]
Reactant: O=C1COCC(=O)O1
Reactant: NCCCCCO
Agent: CS(=O)(=O)[O-]
Product: O=C(O)COCC(=O)NCCCCCO

Procedure:
methanesulfonate by the following sequence of steps: (a) by reacting diglycolic anhydride and 5-aminopentanol to produce [2-(5-hydroxypentyl)amino-2-oxoethoxy]acetic acid, (b) heating to cyclize the latter to obtain 4-(5-hydroxypentyl)-3,5-dioxomorpholine, (c) esterifying the latter with methanesulfonyl chloride to produce 5-(3,5-dioxomorpholino)pentyl methanesulfonate and (d) reacting the mesylate with 2-benzhydrylpiperidine.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[CH3:12])[C:8](=[O:13])[NH:7][CH:6]=[CH:5]2.[CH2:14](Br)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>O1CCCC1.C(OCC)(=O)C.C(=O)([O-])[O-].[Ag+2]>[CH2:14]([O:13][C:8]1[C:9]2[C:4](=[CH:3][C:2]([F:1])=[C:11]([CH3:12])[CH:10]=2)[CH:5]=[CH:6][N:7]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: BrCc1ccccc1
Reactant: Cc1cc2c(=O)[nH]ccc2cc1F
Agent: [Ag+2]
Agent: O=C([O-])[O-]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: Cc1cc2c(OCc3ccccc3)nccc2cc1F
Temperature: 70 °C
Reaction time: 8 h
Yield: 15.1 %

Procedure:
6-Fluoro-7-methyl-2H-isoquinolin-1-one (prepared as described in WO2007012421, 13.2 g, mmol) was dissolved in tetrahydrofurane (175 mL). After addition of silver carbonate (41.2 g), benzyl bromide (15.3 g) was added dropwise. The mixture was stirred overnight. The mixture was heated to 70° C. and another 3 mL of benzyl bromide were added. Heating was continued until no further conversion was observed. The mixture was taken up in ethyl acetate, filtered over celite, evaporated and the residue was taken up in little ethyl acetate. The formed precipitate was filtered off to give 3.0 g of (2). The mother liquor was concentrated and chromatographed on silica gel to yield another 8.6 g of (2). Rt=4.00 min (Method 2). Detected mass: 268.1 (M+H+).
Reaction SMILES: [NH2:1][C:2]1[C:11]2[C:6](=CC=CC=2)[N+:5]([O-:12])=[CH:4][CH:3]=1.N(OS(=O)(=O)O)=O.O.FC(F)(F)[C:23](O)=[O:24]>COCCO>[NH2:1][C:2]1[CH:3]=[CH:4][N+:5]([O-:12])=[CH:6][C:11]=1[O:24][CH3:23]
Reactant: O=C(O)C(F)(F)F
Reactant: Nc1cc[n+]([O-])c2ccccc12
Agent: O=NOS(=O)(=O)O
Solvent: COCCO
Solvent: O
Product: COc1c[n+]([O-])ccc1N
Reaction time: 1 h

Procedure:
A solution of 4.8 g of 4-aminoquinoline-N-oxide (Amine 6) in 40 ml of trifluoroacetic acid is diazotised at 0° C. with 4.8 ml of 40% nitrosyl sulphuric acid. After one hour. the diazonium salt solution is added dropwise at 0° C. to a solution of 22.2 g of 2,3-dimethyl-5-propyl-6-α-3-(N-5-hydroxy-1-naphthylsulphamoyl)-phenylsulphonyl]-tetradecyl-1,4-quinone (the method of preparation is described in DE-A- No. 3 344 295) in 200 ml of methyl glycol and stirring is then continued for 5 hours at 0° C. The reaction mixture is then stirred into 1000 ml of water and decanted and the smeary residue is again stirred up with 1000 ml of water. After one hour, the reaction mixture is suction filtered and washed with water. 21 g of crude dye are obtained. The dye is chromatographed on a Jobin Yvon Chromatospac Prep. 100 medium pressure-liquid chromatograph C, Instruments SA GmbH, Unterhaching, using an 80 mm×1000 mm column packed with 1.5 kg of silica gel Woelm (ICN) 32-63 nm. Detection is carried out with a preparative LC-UV Detector GOW-MAC 80-800 at a wavelength of 310 nm. A Gilson M 201 is used as fraction collector. A mixture of methylene chloride and ethyl acetate 10/1 is used for elution and working up the fractions yields 2.8 g of an isomeric reddish violet dye and 8.3 g of the desired dye in the form of a dark powder.
Reaction SMILES: [NH:1]1[CH2:4][CH:3]([C:5]2[NH:9][N:8]=[C:7]([C:10]3[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=3)[N:6]=2)[CH2:2]1.[F:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[C:24]([C:32]3[CH:39]=[CH:38][C:35]([CH:36]=O)=[CH:34][CH:33]=3)=[N:25][C:26]3[N:27]([CH:29]=[CH:30][N:31]=3)[CH:28]=2)=[CH:19][CH:18]=1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>CN1C(=O)CCC1.C(O)(=O)C.C(N(CC)CC)C>[F:16][C:17]1[CH:18]=[CH:19][C:20]([C:23]2[C:24]([C:32]3[CH:39]=[CH:38][C:35]([CH2:36][N:1]4[CH2:4][CH:3]([C:5]5[N:6]=[C:7]([C:10]6[CH:15]=[CH:14][CH:13]=[CH:12][N:11]=6)[NH:8][N:9]=5)[CH2:2]4)=[CH:34][CH:33]=3)=[N:25][C:26]3[N:27]([CH:29]=[CH:30][N:31]=3)[CH:28]=2)=[CH:21][CH:22]=1
Reactant: O=Cc1ccc(-c2nc3nccn3cc2-c2ccc(F)cc2)cc1
Reactant: c1ccc(-c2n[nH]c(C3CNC3)n2)nc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN1CCCC1=O
Solvent: CC(=O)O
Solvent: CCN(CC)CC
Product: Fc1ccc(-c2cn3ccnc3nc2-c2ccc(CN3CC(c4n[nH]c(-c5ccccn5)n4)C3)cc2)cc1
Reaction time: 1 h

Procedure:
95 mg (0.35 mmol) 2-(5-Azetidine-3-yl-[1,2,4]triazole-3-yl)-pyridine×2HCl are dissolved in 2.7 mL NMP. After addition of 0.1 mL triethylamine the reaction mixture is stirred for one hour. 100 mg (0.32 mmol) 4-[6-(4-Fluorophenyl)imidazo[1,2-a]pyrimidin-7-yl]-benzaldehyde and 0.03 mL acetic acid are added. The reaction mixture is stirred for three days at room temperature. 73 mg (0.35 mmol) NaBH(OAc)3, are added in portions and the reaction mixture is stirred at room temperature for 18 hours. The reaction mixture is treated with saturated NaHCO3 and stirred vigorously for one hour. The precipitate is filtered off, washed with water and dried. After chromatography of the precipitate on silica gel (dichloromethane/methanol) 90 mg (54%) of the desired product are obtained.
Reaction SMILES: [F:1][C:2]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:3]=1[O:4][C:5]1[CH:6]=[C:7]([CH:11]=[CH:12][C:13]=1[N+:14]([O-:16])=[O:15])[C:8](Cl)=[O:9].[CH3:22][NH2:23]>CCOCC.O>[CH3:22][NH:23][C:8](=[O:9])[C:7]1[CH:11]=[CH:12][C:13]([N+:14]([O-:16])=[O:15])=[C:5]([O:4][C:3]2[CH:17]=[CH:18][C:19]([F:21])=[CH:20][C:2]=2[F:1])[CH:6]=1
Reactant: CN
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])c(Oc2ccc(F)cc2F)c1
Solvent: O
Solvent: CCOCC
Product: CNC(=O)c1ccc([N+](=O)[O-])c(Oc2ccc(F)cc2F)c1
Temperature: 5 °C
Reaction time: 0.5 h

Procedure:
A solution of 3-(2,4-difluorophenoxy)-4-nitrobenzoyl chloride (1.1 g) in dry ether (15 ml) was added dropwise to a stirred mixture of methylamine (40% in water; 2 ml) in water (8 ml) and ether (5 ml) at 5° to 8° C. The mixture was stirred for 30 minutes at 5° C. and for 30 minutes at room temperature. Precipitates in the mixture were filtered and washed with water and ether successively to give pale brown crystals of N-methyl-3-(2,4-difluorophenoxy)-4-nitrobenzamide (0.88 g).
Reaction SMILES: [NH2:1][C:2]1[CH:15]=[CH:14][C:13]2[C:4](=[C:5]([C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=3)[C:6]3[C:11]([N:12]=2)=[CH:10][CH:9]=[CH:8][CH:7]=3)[CH:3]=1.[CH3:23][S:24](Cl)(=[O:26])=[O:25].N12CCC(CC1)CN2>C(#N)C>[CH3:23][S:24]([N:1]([C:2]1[CH:15]=[CH:14][C:13]2[C:4](=[C:5]([C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=3)[C:6]3[C:11]([N:12]=2)=[CH:10][CH:9]=[CH:8][CH:7]=3)[CH:3]=1)[S:24]([CH3:23])(=[O:26])=[O:25])(=[O:26])=[O:25]
Reactant: CS(=O)(=O)Cl
Reactant: Cc1ccc(-c2c3ccccc3nc3ccc(N)cc23)cc1
Agent: C1CN2CCC1CN2
Solvent: CC#N
Product: Cc1ccc(-c2c3ccccc3nc3ccc(N(S(C)(=O)=O)S(C)(=O)=O)cc23)cc1
Temperature: 20 °C
Reaction time: 8 h

Procedure:
5.68 pbw of 2-amino-9-(4-methylphenyl)acridine (compound 12d) were dissolved with 20.3 pbw of methanesulfonyl chloride and 22.4 pbw of diazabicyclo[2.2.2]octane in 120 pbv of acetonitrile and the solution heated for 2 hours under reflux. After cooling to 20° C., filtration was carried out and the red filtrate added dropwise to 1000 pbv of 0.5% strength ammonia solution. After standing overnight, the precipitate was filtered off by suction and crystallized from 135 pbv of ethanol. Yield: 1.76 pbw (20% of theory), light yellow needles. Mp.: 217°-219° C.
Reaction SMILES: [Cl-].[CH3:2][C:3]1[N:10]2[C:6](=[N+:7]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=3)[C:8]3[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=32)[S:5][CH:4]=1.[CH3:25][O-:26].[Na+]>CO>[CH3:6][S:5]/[CH:4]=[C:3](\[N:10]1[C:9]2[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=2[N:7]([CH2:15][C:16]2[CH:17]=[CH:18][C:19]([N+:22]([O-:24])=[O:23])=[CH:20][CH:21]=2)[C:25]1=[O:26])/[CH3:2]
Reactant: Cc1csc2n1c1ccccc1[n+]2Cc1ccc([N+](=O)[O-])cc1
Reactant: C[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: CO
Product: CS/C=C(/C)n1c(=O)n(Cc2ccc([N+](=O)[O-])cc2)c2ccccc21
Temperature: 25 °C
Yield: 87.5 %

Procedure:
163 mg of 3-methyl-9-(4-nitrobenzyl)[1,3]thiazolo[3,2-a]benzimidazol-9-ium chloride (0.450 mmol) were solubilised in methanol (30 mL), then 122 mg (5 eq) of NaOMe were added and the solution stirred at room temperature. After 48 h the solvent was evaporated, water was added (20 mL) and the mixture extracted with CH2Cl2 (3×20 mL). The organic layer was dried with MgSO4 and evaporated under reduced pressure to afford 1-[(1Z)-1-(methylsulfanyl)prop-1-en-2-yl]-3-(4-nitrobenzyl)-1,3-dihydro-2H-benzimidazol-2-one as a pale yellow oil (140 mg, 91%). Rf=0.59 (CH2Cl2/AcOEt 8:2); 1H NMR (300 MHz, CDCl3) δ=2.18 (3H, d, J=1.1, CH3), 2.27 (3H, s, SCH3), 5.19 (2H, brs, CH2), 6.29 (1H, q, J=1.1, H5), 6.77-6.85 (1H, m, Ar), 6.88-6.96 (1H, m, Ar), 6.98-7.14 (2H, m, Ar), 7.42-7.52 (2H, m, Ar), 8.12-8.23 (4H, m, Ar); 13C NMR (75 MHz, CDCl3) δ=16.88, 20.40, 44.09, 108.04, 109.35, 121.75, 121.82, 124.02 (2C), 126.23, 127.74, 128.03 (2C), 128.15, 128.90, 143.60, 147.48, 152.12; HRMS m/z C18H18N3O3S [M+H]+ calcd: 356.1063, found: 356.1067.
Reaction SMILES: [OH:1][C:2]1([CH2:9][N:10]2[CH2:15][CH2:14][C:13]3[NH:16][C:17]([CH:20]=O)=[C:18]([CH3:19])[C:12]=3[C:11]2=[O:22])[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH2:3]1.[F:23][C:24]1[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=1[C:31]1[CH:39]=[CH:38][CH:37]=[C:36]2[C:32]=1[CH2:33][C:34](=[O:40])[NH:35]2>>[F:23][C:24]1[C:29]([F:30])=[CH:28][CH:27]=[CH:26][C:25]=1[C:31]1[CH:39]=[CH:38][CH:37]=[C:36]2[C:32]=1[C:33](=[CH:20][C:17]1[NH:16][C:13]3[CH2:14][CH2:15][N:10]([CH2:9][C:2]4([OH:1])[CH2:3][CH2:4][N:5]([CH3:8])[CH2:6][CH2:7]4)[C:11](=[O:22])[C:12]=3[C:18]=1[CH3:19])[C:34](=[O:40])[NH:35]2
Reactant: O=C1Cc2c(cccc2-c2cccc(F)c2F)N1
Reactant: Cc1c(C=O)[nH]c2c1C(=O)N(CC1(O)CCN(C)CC1)CC2
Product: Cc1c(C=C2C(=O)Nc3cccc(-c4cccc(F)c4F)c32)[nH]c2c1C(=O)N(CC1(O)CCN(C)CC1)CC2
Yield: 74.98 %

Procedure:
The title compound was prepared under the same conditions as described in Example 1 with 5-(4-hydroxy-1-methyl-piperidin-4-ylmethyl)-3-methyl-4-oxo-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde and 4-(2,3-difluoro-phenyl)-1,3-dihydro-indol-2-one (prepared according to WO2002055517) as starting materials to give 2-[4-(2,3-difluoro-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidenemethyl]-5-(4-hydroxy-1-methyl-piperidin-4-ylmethyl)-3-methyl-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one (67 mg, 74.98%) as an orange solid.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:23])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][NH:10][CH2:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]2[CH:22]=[CH:21][CH:20]=[N:19]2)=[CH:14][CH:13]=1.Cl.[N:25]1[CH:30]=[CH:29][CH:28]=[C:27]([S:31](Cl)(=[O:33])=[O:32])[CH:26]=1>C(N(CC)CC)C>[CH3:1][O:2][C:3](=[O:23])[CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][N:10]([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([N:18]2[CH:22]=[CH:21][CH:20]=[N:19]2)=[CH:14][CH:13]=1)[S:31]([C:27]1[CH:26]=[N:25][CH:30]=[CH:29][CH:28]=1)(=[O:33])=[O:32]
Reactant: COC(=O)CCCCCCNCc1ccc(-n2cccn2)cc1
Reactant: O=S(=O)(Cl)c1cccnc1
Agent: Cl
Solvent: CCN(CC)CC
Product: COC(=O)CCCCCCN(Cc1ccc(-n2cccn2)cc1)S(=O)(=O)c1cccnc1

Procedure:
The title compound of Step A was prepared from 7-(4-pyrazol-1-yl-benzylamino)-heptanoic acid methyl ester, of Example 11f, Step A, and pyridine-3-sulfonyl chloride hydrochloride, of Preparation 2, following the method described in Example 1, Step B using triethylamine in place of N,N-diisopropylethylamine. 1H NMR (400 MHz, CDCl3) δ 8.70 (m, 1H), 7.99-7.87 (m, 3H), 7.71 (d, 1H), 7.63 (d, 2H), 7.46 (m, 1H), 7.42 (d, 2H), 6.46 (dd, 1H), 4.56 (s, 2H), 3.62 (s, 3H), 3.25 (t, 2H), 2.20 (t, 2H), 1.46 (m, 2H), 1.34 (m, 2H), 1.25 (m, 4H); MS 457 (M+1).
Reaction SMILES: [Cl:1][C:2]([Cl:6])=[CH:3][CH2:4]Cl.[C:7]([O-:16])(=[O:15])[CH2:8][CH2:9][CH2:10][CH2:11][C:12]([O-:14])=[O:13].[K+].[K+].[I-].[K+]>C(N(CC)CC)C>[Cl:1][CH:2]([Cl:6])[CH:3]=[CH:4][O:13][C:12](=[O:14])[CH2:11][CH2:10][CH2:9][CH2:8][C:7]([O:16][CH:4]=[CH:3][CH:2]([Cl:6])[Cl:1])=[O:15]
Reactant: O=C([O-])CCCCC(=O)[O-]
Reactant: ClCC=C(Cl)Cl
Agent: [I-]
Agent: [K+]
Solvent: CCN(CC)CC
Product: O=C(CCCCC(=O)OC=CC(Cl)Cl)OC=CC(Cl)Cl

Procedure:
62 g of 1,1,3-trichloro-propene, prepared according as described in Example 1, were reacted with 36.6 g of potassium adipate for 6 hours at 135° C. in the presence of 2 g of triethylamine and 0.3 g of potassium iodide. The reaction product was then washed and freed of the low-boiling components by means of distillation under vacuum. By a successive molecular distillation (120° C./10-4 mm Hg) 47 g of a substance were obtained which on elementary analysis showed the following composition: