Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O-])([O-])=O.[K+].[K+].[CH2:7]([N:9]([CH2:14][CH3:15])[C:10](=[O:13])[CH2:11]Cl)[CH3:8].CN(C=O)C.[Cl:21][C:22]1[C:31]([OH:32])=[C:30]([S:33]([CH2:36][CH3:37])(=[O:35])=[O:34])[CH:29]=[CH:28][C:23]=1[C:24]([O:26][CH3:27])=[O:25]>O>[Cl:21][C:22]1[C:31]([O:32][CH2:11][C:10]([N:9]([CH2:14][CH3:15])[CH2:7][CH3:8])=[O:13])=[C:30]([S:33]([CH2:36][CH3:37])(=[O:35])=[O:34])[CH:29]=[CH:28][C:23]=1[C:24]([O:26][CH3:27])=[O:25]
Reactant: CCS(=O)(=O)c1ccc(C(=O)OC)c(Cl)c1O
Reactant: CCN(CC)C(=O)CCl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCN(CC)C(=O)COc1c(S(=O)(=O)CC)ccc(C(=O)OC)c1Cl
Temperature: 120 °C

Procedure:
0.922 g (7.2 mmol) of K2CO3, 0.179 g (1.10 mmol) of Kl and 0.644 g (4.3 mmol) of N,N-diethylchloroacetamide were introduced into 30 ml of DMF. 1.000 g (3.6 mmol) of methyl 2-chloro-3-hydroxy-4-ethylsulfonylbenzoate were added at RT and the mixture was then heated for 7 hours at 120° C. The mixture was then poured into water and extracted with diisopropyl ether. The organic phases were washed with water, dried over Na2SO4 and concentrated completely. Chromatography on silica gel (eluent: n-heptane/ethyl acetate 1:1) gave methyl 2-chloro-3-(N,N-diethylaminocarbonylmethoxy) -4-ethylsulfonylbenzoate as a colorless viscous oil.
Reaction SMILES: [H-].[Na+].[CH3:3][N:4]1[C:8]([CH3:9])=[CH:7][C:6]([C:10]([O:12][CH3:13])=[O:11])=[C:5]1[CH2:14][C:15]([O:17][CH3:18])=[O:16].[CH:19](OC)=[O:20].CO>O1CCCC1>[CH:19]([CH:14]([C:5]1[N:4]([CH3:3])[C:8]([CH3:9])=[CH:7][C:6]=1[C:10]([O:12][CH3:13])=[O:11])[C:15]([O:17][CH3:18])=[O:16])=[O:20]
Reactant: COC(=O)Cc1c(C(=O)OC)cc(C)n1C
Reactant: COC=O
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: COC(=O)c1cc(C)n(C)c1C(C=O)C(=O)OC
Temperature: 10 °C

Procedure:
Sodium hydride (2.29 g, 60% dispersion in mineral oil) was added portionwise to a stirred solution of methyl 1,5-dimethyl-2-[2-(methyloxy)-2-oxoethyl]-1H-pyrrole-3-carboxylate (2.37 g) in tetrahydrofuran (30 ml) at 20° C. After fifteen minutes the reaction mixture was cooled to 10° C. and methyl formate (1.0 ml) added. After ten minutes a mixture of methanol (0.05 ml) and tetrahydrofuran (1 ml) was added. The reaction mixture was stirred at room temperature for sixteen hours. After cooling to 10° C., methanol (0.1 ml) was added, the mixture was stirred at room temperature for two hours. After cooling in an ice bath, methanol (8.4 ml) was added dropwise, the mixture was stirred for a further fifteen minutes, then evaporated. The residue was partitioned between ethyl acetate and aqueous ammonium chloride, and then acidified by addition of 5N hydrochloric acid. The aqueous phase was extracted with a second portion of ethyl acetate. The combined organic extracts were washed with water, then brine, dried (MgSO4) and evaporated. The solid residue washed with hexane and then dried to give the title compound 2.59 g as a tautomeric mixture.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[N+:4]([O-])[C:5]2[CH2:10][CH2:9][CH2:8][C:6]=2[CH:7]=1.[C:12]([O:15]C(=O)C)(=[O:14])[CH3:13]>>[C:12]([O:15][CH:10]1[C:5]2[N:4]=[CH:3][C:2]([Cl:1])=[CH:7][C:6]=2[CH2:8][CH2:9]1)(=[O:14])[CH3:13]
Reactant: [O-][n+]1cc(Cl)cc2c1CCC2
Reactant: CC(=O)OC(C)=O
Product: CC(=O)OC1CCc2cc(Cl)cnc21
Reaction time: 20 h
Yield: 71 %

Procedure:
A solution of 3-chloro-6,7-dihydro-5H-cyclopentapyridine 1-oxide (1 g, 5.9 mmole) in acetic anhydride (30 ml) was heated to 110° C. and stirred at this temperature for 20 h. The solvent was evaporated and the residue was partitioned between aqueous saturated NaHCO3 solution and dichloromethane. The organic layer was dried, evaporated and the residue was purified by flash chromatography over silica using EtOAc/n-heptane (gradient from 0% to 30% EtOAc) to give the title compound as a red liquid (880 mg, 71% yield). MS (ESI): m/z=212.0 [M+H]+.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1([CH2:9][NH2:10])[CH2:8][CH2:7]1.[CH:11]1[N:16]=[C:15](Cl)[C:14]2[N:18]=[CH:19][N:20]([C@@H:21]3[O:25][C@H:24]([CH2:26][OH:27])[C@@H:23]([OH:28])[C@H:22]3[OH:29])[C:13]=2[N:12]=1.C(N(CC)CC)C>>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]1([CH2:9][NH:10][C:15]2[C:14]3[N:18]=[CH:19][N:20]([C:13]=3[N:12]=[CH:11][N:16]=2)[C@@H:21]2[O:25][C@H:24]([CH2:26][OH:27])[C@@H:23]([OH:28])[C@H:22]2[OH:29])[CH2:8][CH2:7]1
Reactant: OC[C@H]1O[C@@H](n2cnc3c(Cl)ncnc32)[C@H](O)[C@@H]1O
Reactant: NCC1(c2cccs2)CC1
Solvent: CCN(CC)CC
Product: OC[C@H]1O[C@@H](n2cnc3c(NCC4(c5cccs5)CC4)ncnc32)[C@H](O)[C@@H]1O

Procedure:
Reaction of the above amine (1.53 g, 10 mmol) with 6-chloropurine riboside (2.87 g, 10 mmol) and triethylamine (2.02 g, 20 mmol) as described in Example 1 gives, after a second crystallization from ethanol, N6((1-thien-2-ylcyclopropyl)methyl)adenosine (2.90 g, 71%) as a fluffy off-white solid m.p. 136°-138.5° C. Found: C, 53.78; H, 5.45; N, 17.28; S, 7.52%. C18H21N5O4S calculated requires: C, 53.60; H, 5.21; N, 17.37; S, 7.94%.
Reaction SMILES: [NH:1]([C:3]1[N:8]([CH2:9][CH:10]([CH3:12])[CH3:11])[C:7](=[O:13])[N:6]([CH3:14])[C:5](=[O:15])[CH:4]=1)[NH2:2].[Cl:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[NH:22][C:21]([CH3:26])=[C:20]2[CH:27]=O.[CH3:29][N:30]1[CH:34]=[CH:33][N:32]=[C:31]1[CH:35]=O>>[Cl:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[NH:22][C:21]([CH3:26])=[C:20]2[CH2:27][N:2]1[C:35]([C:31]2[N:30]([CH3:29])[CH:34]=[CH:33][N:32]=2)=[C:4]2[C:3]([N:8]([CH2:9][CH:10]([CH3:11])[CH3:12])[C:7](=[O:13])[N:6]([CH3:14])[C:5]2=[O:15])=[N:1]1
Reactant: CC(C)Cn1c(NN)cc(=O)n(C)c1=O
Reactant: Cn1ccnc1C=O
Reactant: Cc1[nH]c2ccc(Cl)cc2c1C=O
Product: Cc1[nH]c2ccc(Cl)cc2c1Cn1nc2c(c1-c1nccn1C)c(=O)n(C)c(=O)n2CC(C)C

Procedure:
This compound was made following the procedure described above, starting with 6-hydrazino-1-isobutyl-3-methylpyrimidine-2,4(1H,3H)-dione, and condensing first with 5-chloro-2-methyl-1H-indole-3-carbaldehyde, followed by 1-methyl-1H-imidazole-2-carbaldehyde. Mass: 480.10 (M+H).
Reaction SMILES: [CH3:1][N:2]([CH3:33])[CH2:3][CH2:4][CH2:5][C:6]([O:8][C:9]1[CH:32]=[CH:31][C:12]2[NH:13][C:14]([C:16]3[C:28]4[C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[C:21](=[N:29]O)[C:20]=4[CH:19]=[CH:18][CH:17]=3)=[N:15][C:11]=2[CH:10]=1)=[O:7].O.[C:35](O)(=O)C>C(O)C.[Zn]>[CH:9]([O:8][CH:6]([CH3:5])[CH3:35])([CH3:10])[CH3:32].[CH3:33][N:2]([CH3:1])[CH2:3][CH2:4][CH2:5][C:6]([O:8][C:9]1[CH:32]=[CH:31][C:12]2[NH:13][C:14]([C:16]3[C:28]4[C:27]5[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=5)[CH:21]([NH2:29])[C:20]=4[CH:19]=[CH:18][CH:17]=3)=[N:15][C:11]=2[CH:10]=1)=[O:7]
Reactant: CN(C)CCCC(=O)Oc1ccc2[nH]c(-c3cccc4c3-c3ccccc3C4=NO)nc2c1
Reactant: CC(=O)O
Agent: [Zn]
Solvent: O
Solvent: CCO
Product: CC(C)OC(C)C
Product: CN(C)CCCC(=O)Oc1ccc2[nH]c(-c3cccc4c3-c3ccccc3C4N)nc2c1

Procedure:
The procedure used in Example 216 is followed. In a 20 ml round-bottomed flask under an argon atmosphere, dissolve 468 mg of 4-{5-[(3-dimethylaminopropyl)carbonyloxy]-1H-benzimidazol-2-yl}-9H-fluoren-9-one oxime (Z,E), obtained in the previous stage, in a mixture of 2.5 ml of ethanol, 2.5 ml of water and 2.5 ml acetic acid, at room temperature. Add 278 mg of zinc in three stages. Between each addition, stir for approximately one hour to two hours. Add Celite 545 and filter. The filtrate is concentrated under pressure. After purification by flash chromatography on silica gel (40-63 μm), eluting with a mixture of dichloromethane and ammonia as a 7N solution in methanol (9/1 by volume), and then formation of a paste with diisopropyl ether, in this way we obtain 327 mg of 4-{5-[(3-dimethylaminopropyl)-carbonyloxy]-1H-benzimidazol-2-yl}-9H-fluorene-9(R,S)-amine, in the form of an off-white solid, which is used as it is in the following stage, with the following characteristics:
Reaction SMILES: [CH2:1]([N:8]1[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([OH:18])[CH:16]=2)[CH2:11][CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[F:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[N:33]=[C:34]=[O:35]>O1CCCC1>[F:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[NH:33][C:34](=[O:35])[O:18][C:15]1[CH:16]=[C:17]2[C:12]([CH2:11][CH2:10][CH2:9][N:8]2[CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[CH:13][CH:14]=1
Reactant: O=C=Nc1ccccc1F
Reactant: Oc1ccc2c(c1)N(Cc1ccccc1)CCC2
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C(Nc1ccccc1F)Oc1ccc2c(c1)N(Cc1ccccc1)CCC2
Temperature: 35 °C

Procedure:
A mixture of 1-benzyl-1,2,3,4-tetrahydroquinolin-7-ol (805 mg, 3.36 mM) and triethylamine (0.6 mL) in dry tetrahydrofuran (THF, 5 ml) was stirred for half an hour under nitrogen atmosphere at room temperature (35° C.). To the stirred reaction mixture, 2-fluorophenyl isocyanate (565 mg/ml, 5.04 mM) was added at once and then the reaction mixture was further stirred for 72 hours under N2 atmosphere at RT. The reaction mixture was concentrated under vacuum and then was added distilled water (15 mL) followed by the extraction with ether (3×15 mL). The ether layer was dried over sodium sulphate and concentrated under vacuum to afford the crude product, which was finally chromatographed using chloroform-hexane (1:9) to give 8c as oil. Yield: 1.02 g, 80.56%.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:16]=[CH:17][C:18]=1[O:19][CH3:20])[C:5]([C:7]1[CH:15]=[CH:14][CH:13]=[CH:12][C:8]=1[C:9](O)=[O:10])=O.C1(C)C=CC=CC=1.[CH3:28][NH:29][NH2:30]>O>[CH3:28][N:29]1[N:30]=[C:5]([C:4]2[CH:16]=[CH:17][C:18]([O:19][CH3:20])=[C:2]([Cl:1])[CH:3]=2)[C:7]2[C:8](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:9]1=[O:10]
Reactant: COc1ccc(C(=O)c2ccccc2C(=O)O)cc1Cl
Reactant: CNN
Solvent: Cc1ccccc1
Solvent: O
Product: COc1ccc(-c2nn(C)c(=O)c3ccccc23)cc1Cl
Yield: 68.7 %

Procedure:
A mixture of 2-(3-chloro-4-methoxybenzoyl)benzoic acid (10.46 g, 0,036 mol), toluene (50 mL) and methyl hydrazine (2.1 mL) was refluxed in the presence of a Dean Stark trap until the theoretical amount of water had been collected. The reaction mixture was cooled, and the product was collected by filtration to afford 7.42 g (68.7%) of 2-methyl-4-(3-chloro-4-methoxyphenyl)-1-(2H)-phthalazinone, m.p. 195°-195° C. An additional 1.89 g of product was also collected from the filtrate for a total of 9.31 g (86.2%).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([O:10][CH3:11])[C:5]([O:8][CH3:9])=[CH:6][CH:7]=1.C([O:14][CH:15]=[C:16]([C:22](OCC)=O)[C:17]([O:19][CH2:20][CH3:21])=[O:18])C>C1(OC2C=CC=CC=2)C=CC=CC=1.CCCCCC>[C:17]([C:16]1[CH:22]=[N:1][C:2]2[C:7]([C:15]=1[OH:14])=[CH:6][C:5]([O:8][CH3:9])=[C:4]([O:10][CH3:11])[CH:3]=2)([O:19][CH2:20][CH3:21])=[O:18]
Reactant: COc1ccc(N)cc1OC
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Solvent: c1ccc(Oc2ccccc2)cc1
Solvent: CCCCCC
Product: CCOC(=O)c1cnc2cc(OC)c(OC)cc2c1O
Temperature: 165 °C

Procedure:
A mixture of 30.6 g of 4-aminoveratrole and 43.2 g of diethyl ethoxymethylenemalonate was heated at 100 for 2 h and at 165° C. for 0.75 h. The intermediate thus obtained was dissolved in 600 ml of diphenyl ether, and the resulting solution was heated at reflux temperature for 2 h, cooled, and diluted with hexane. The resulting solid was filtered, washed with hexane followed by ether, and dried to provide the title compound as a brown solid, mp 275-285° C.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH:9]1[CH2:14][N:13]([C:15]([O-])=O)[CH2:12][C:11]([F:19])([F:18])[CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.ClC1[CH:35]=[CH:34][N:33]=[CH:32][C:31]=1[N+:36]([O-:38])=[O:37]>CO.CCOC(C)=O.[Pd]>[F:18][C:11]1([F:19])[CH2:12][N:13]([C:15]2[CH:35]=[CH:34][N:33]=[CH:32][C:31]=2[N+:36]([O-:38])=[O:37])[CH2:14][C@@H:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])[CH2:10]1
Reactant: CC(C)(C)OC(=O)NC1CN(C(=O)[O-])CC(F)(F)C1
Reactant: O=[N+]([O-])c1cnccc1Cl
Agent: [Pd]
Solvent: CO
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N[C@@H]1CN(c2ccncc2[N+](=O)[O-])CC(F)(F)C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 19 %

Procedure:
To a solution of 5-(tert-butoxycarbonylamino)-3,3-difluoropiperidine-1-carboxylate (1 eq) in 5 mL of methanol and 5 mL of EtOAc was added 10% Pd/C (0.1 eq). The resulting suspension was stirred at H2 atmosphere overnight. The crude solids were filtered through a pad of Celite on a paper lined Buchner funnel, washed with MeOH, then concentrated in vacuo. The residue was dissolved in 5 mL of isopropanol and DIPEA (2.0 eq) and 4-chloro-3-nitropyridine (1.5 eq) were added. The reaction mixture was stirred at 70° C. for 3 hours, at which point the reaction mixture was allowed to cool to room temperature and concentrated under reduced pressure. The residue was diluted with 120 mL of EtOAc, washed with brine, then dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (5% methanol in EtOAc:hexanes=1:1) to yield (S)-tert-butyl 5,5-difluoro-1-(3-nitropyridin-4-yl)piperidin-3-ylcarbamate (19%). LC/MS (m/z): 359.0 (MH+), Rt: 0.65 min.
Reaction SMILES: [NH2:1][CH:2]1[CH:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH:6]=[CH:5][N:4]([CH3:15])[C:3]1=[O:16].[C:17]([O:21][C:22]([NH:24][C@H:25]([C:27](O)=[O:28])[CH3:26])=[O:23])([CH3:20])([CH3:19])[CH3:18].O.OC1C2N=NNC=2C=CC=1.C(N(C(C)C)CC)(C)C.Cl.CN(C)CCCN=C=NCC>O.ClCCl>[C:17]([O:21][C:22](=[O:23])[NH:24][C@H:25]([C:27](=[O:28])[NH:1][CH:2]1[CH:8]=[C:7]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:6]=[CH:5][N:4]([CH3:15])[C:3]1=[O:16])[CH3:26])([CH3:18])([CH3:19])[CH3:20]
Reactant: CN1C=CC(c2ccccc2)=CC(N)C1=O
Reactant: C[C@H](NC(=O)OC(C)(C)C)C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: Oc1cccc2[nH]nnc12
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Product: C[C@H](NC(=O)OC(C)(C)C)C(=O)NC1C=C(c2ccccc2)C=CN(C)C1=O
Temperature: 10 °C
Reaction time: 3.5 h
Yield: 96.7 %

Procedure:
3-Amino-1-methyl-5-phenyl-1,3-dihydro-azepin-2-one (330 g, 1.54 mol) is combined with dichloromethane (3 L), N-(tert-butoxycarbonyl)-L-alanine (291.4 g, 1.54 mol), and hydroxybenzotriazole hydrate (259.5 g, 1.617 mol). The solution is cooled to about 10° C. To this solution is added diisopropylethylamine (335.4 mL, 1.925 mol) followed by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (310.1 g, 1.617 mol) and the contents are allowed to gradually warm to room temperature. After 3.5 hours, the reaction contents are poured into water (1000 mL) and the layers are allowed to separate. The organic layer is further washed with water (1000 mL), 0.1 N HCl (1000 mL), saturated NaHCO3 solution (1000 mL) and finally saturated aqueous sodium chloride solution. The dichloromethane layer is dried over Na2SO4, filtered, and concentrated via rotary evaporation to provide the title compound (about 574 g, 97%) as a tan foam. The material is of sufficient purity to use directly in the next step.
Reaction SMILES: [N+:1]([O-:4])([OH:3])=O.C(O)(=O)C.[CH3:9][C:10]1([CH3:22])[O:14][C:13]2[CH:15]=[CH:16][C:17]([N+:19]([O-:21])=[O:20])=[CH:18][C:12]=2[O:11]1>O>[CH3:9][C:10]1([CH3:22])[O:11][C:12]2[CH:18]=[C:17]([N+:19]([O-:21])=[O:20])[C:16]([N+:1]([O-:4])=[O:3])=[CH:15][C:13]=2[O:14]1
Reactant: CC1(C)Oc2ccc([N+](=O)[O-])cc2O1
Reactant: O=[N+]([O-])O
Solvent: O
Solvent: CC(=O)O
Product: CC1(C)Oc2cc([N+](=O)[O-])c([N+](=O)[O-])cc2O1
Reaction time: 0.25 h
Yield: 82 %

Procedure:
A solution of 90% (fuming) nitric acid (22 ml) and glacial acetic acid (11 ml) cooled at 12° C. was treated in portions with solid compound from Example 3B (5.4 g, 27.7 mmoles) so as to maintain the temperature of <17° C. After the addition, stirring was continued for 15 minutes, when the internal temperature began to fall. The mixture was diluted to 100 ml with water, the yellow solid filtered, washed with water, taken up in CH2Cl2, dried (Na2SO4) and evaporated to give 5.43 g (82%) of pure title compound.
Reaction SMILES: [CH:1]1[C:18]2=[C:19]3[C:8]([C:9]4[C:20]5[C:13](=[CH:14][CH:15]=[CH:16][C:17]2=5)[CH:12]=[CH:11][CH:10]=4)=[CH:7][CH:6]=[C:5]2[C:21]([O:23][C:24](=O)[C:3](=[C:4]23)[CH:2]=1)=[O:22].[NH2:26][CH:27]([CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45])[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36].N1C=CN=C1.C(C(N1C(=O)C2C3C4C(=CC=2)C2C5C(C=CC=2)=CC=CC=5C=4C=CC=3C1=O)CCCCCC)CCCCC>C(Cl)(Cl)Cl>[CH2:28]([CH:27]([N:26]1[C:24](=[O:23])[C:3]2[C:4]3[C:19]4[C:18](=[CH:1][CH:2]=2)[C:17]2[C:20]5[C:13]([CH:14]=[CH:15][CH:16]=2)=[CH:12][CH:11]=[CH:10][C:9]=5[C:8]=4[CH:7]=[CH:6][C:5]=3[C:21]1=[O:22])[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45])[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36]
Reactant: O=C1OC(=O)c2ccc3c4cccc5cccc(c6ccc1c2c63)c54
Reactant: CCCCCCCCCC(N)CCCCCCCCC
Agent: CCCCCCC(CCCCCC)N1C(=O)c2ccc3c4cccc5cccc(c6ccc(c2c36)C1=O)c54
Agent: c1c[nH]cn1
Solvent: ClC(Cl)Cl
Product: CCCCCCCCCC(CCCCCCCCC)N1C(=O)c2ccc3c4cccc5cccc(c6ccc(c2c36)C1=O)c54

Procedure:
230 mg (0.70 mmol) of perylene-3,4-dicarboxylic anhydride are reacted with 400 mg (1.40 mmol) of 10-aminononadecane (prepared according to DE-A 4,007,618) and 1.0 g of imidazole under an argon inert atmosphere as in 2c, followed by workup. After chromatography on silica gel using chloroform, the reaction product is applied to silica gel using petroleum ether, and the purely aliphatic by-products are washed off with about 11 of petroleum ether. The reaction product is then eluted with toluene, and is then recrystallized by extraction with pentane. Yield 400 mg (85%), m.p. 143°-143.5° C. Rf (silica gel/CHCl3)=0.94. UV (CHCl3): λmax (ε)=507 nm (31319), 482 (32213), 453 (sh, 17450). Fluorescence (CHCl3, exc. 507 nm) λmax (Irel)=539 (1), 557 (0.47).
Reaction SMILES: [C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl[CH2:15][C:16]#[N:17]>ClCCl.C(N(CC)CC)C>[C:16]([CH2:15][N:11]1[CH2:10][CH2:9][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:13][CH2:12]1)#[N:17]
Reactant: N#CCCl
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)OC(=O)N1CCN(CC#N)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirred solution of N-Boc piperazine (5 g) in dry dichloromethane (100 ml), triethyl amine (10 ml) followed by chloro acetonitrile (25.02 ml) were added dropwise. The reaction mixture was allowed to stir at room temperature for overnight. The solvent was removed under vacuum and residue was diluted with dichloromethane (200 ml). The organic layer was washed with water, brine and concentrated to dryness under reduced pressure to afford tert-butyl 4-(cyanomethyl)piperazine-1-carboxylate, which was used for the next reaction without further purification.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-:11])=[O:10])=[C:6]([CH:8]=1)[NH2:7].[CH3:12][NH:13][CH2:14][CH2:15][OH:16].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C(=O)C>[NH2:7][C:6]1[CH:8]=[C:2]([N:13]([CH3:12])[CH2:14][CH2:15][OH:16])[CH:3]=[CH:4][C:5]=1[N+:9]([O-:11])=[O:10]
Reactant: CNCCO
Reactant: Nc1cc(Cl)ccc1[N+](=O)[O-]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Solvent: O
Product: CN(CCO)c1ccc([N+](=O)[O-])c(N)c1
Temperature: 125 °C
Reaction time: 24 h
Yield: 88.2 %

Procedure:
A mixture of 5-chloro-2-nitroaniline (5 g, 29 mmol), 2-Methylamino-ethanol (7 mL, 87 mmol) and anhydrous potassium carbonate (5.3 g, 38 mmol) in N,N-dimethylacetamide (10 ml) were stirred at 125° C. under nitrogen for 1 day. Sample NMR analysis showed complete conversion of the starting material. The resultant mixture was then cooled to room temperature, poured onto cold water (30 mL), stirred vigorously and incubated at 4° C. overnight. The resulting yellow precipitate was collected by filtration, washed well with water then dried on the filter funnel. This was then slurried in diethyl ether, filtered, washed with additional diethyl ether, dried to afford 2-[(3-Amino-4-nitro-phenyl)-methyl-amino]-ethanol (5.4 g, 88% yield) as a yellow solid and used in the next step without further purification.
Reaction SMILES: [S:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4](=[O:11])[CH2:3][CH2:2]1.[CH2:12]=[O:13].[C:14](=[O:17])([O-])[O-].[K+].[K+]>CO.O>[OH:13][CH2:12][C:3]1([CH2:14][OH:17])[C:4](=[O:11])[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[S:1][CH2:2]1
Reactant: C=O
Reactant: O=C1CCSc2ccccc21
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: O
Product: O=C1c2ccccc2SCC1(CO)CO
Temperature: 40 °C
Reaction time: 2 h

Procedure:
A solution of thiochroman-4-one (2.0 g, 12 mmol) in MeOH (40 ml) and water (8 ml) was admixed with 35% eq. formalin solution (8 ml) and potassium carbonate (200 mg). The reaction mixture was stirred at 40° C. for 2 h and then at RT for 2 h, the solvent was removed under reduced pressure and the residue was admixed with water. The aqueous solution was extracted repeatedly with EtOAc, the combined organic phases were dried over sodium sulfate and the solvent was removed under reduced pressure. After column chromatography purification of the residue (silica gel, 1:1 cyclohexane/EtOAc), the desired product was obtained as a white solid (1.71 g, 63% of theory, m.p. 136-139° C.).
Reaction SMILES: [CH:1]12[NH:7][CH:4]([CH2:5][CH2:6]1)[CH2:3][CH:2]2[NH:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][N:13]=[CH:12]2.[CH:18]([C:20]1[CH:21]=[CH:22][C:23]([CH3:31])=[C:24]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[CH:25]=1)=O>>[NH:14]1[C:15]2[C:11](=[CH:10][C:9]([NH:8][CH:2]3[CH2:3][CH:4]4[N:7]([CH2:18][C:20]5[CH:21]=[CH:22][C:23]([CH3:31])=[C:24]([NH:26][S:27]([CH3:30])(=[O:29])=[O:28])[CH:25]=5)[CH:1]3[CH2:6][CH2:5]4)=[CH:17][CH:16]=2)[CH:12]=[N:13]1
Reactant: Cc1ccc(C=O)cc1NS(C)(=O)=O
Reactant: c1cc2[nH]ncc2cc1NC1CC2CCC1N2
Product: Cc1ccc(CN2C3CCC2C(Nc2ccc4[nH]ncc4c2)C3)cc1NS(C)(=O)=O

Procedure:
Reaction of Intermediate 24 with N-(5-formyl-2-methylphenyl)methanesulfonamide affords the title compound.
Reaction SMILES: [CH2:1]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:25])[CH:16]([CH:18](C(O)=O)[C:19]([OH:21])=[O:20])[CH3:17])=[CH:11][C:10]=1[OH:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)COCCO.COC.C(OC(C)C)(C)C.Cl>O>[CH2:1]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:25])[CH:16]([CH3:17])[CH2:18][C:19]([OH:21])=[O:20])=[CH:11][C:10]=1[OH:26])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C(=O)c1ccc(NCc2ccccc2)c(O)c1)C(C(=O)O)C(=O)O
Agent: COC
Agent: Cl
Solvent: OCCOCCO
Solvent: O
Solvent: CC(C)OC(C)C
Product: CC(CC(=O)O)C(=O)c1ccc(NCc2ccccc2)c(O)c1
Temperature: 140 °C
Reaction time: 3 h

Procedure:
78.9 g (220.8 mmol) 2-[2-(4-benzylamino-3-hydroxy-phenyl)-1-methyl-2-oxo-ethyl]-malonic acid are combined with 200 ml diethyleneglycol-dimethylether and stirred for 3 h at 140° C. The mixture is combined with water and diisopropylether, then it is adjusted with 6N hydrochloric acid to pH=2 and extracted with DCM. The org. phase is separated off and dried on magnesium sulphate, then the solv. is eliminated by rotary evaporation i.V., the residue is stirred with diisopropylether and filtered off.
Reaction SMILES: C([N:5]1[C:12](=O)[N:11]2[C:7](=[N:8][C:9]3[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=32)[S:6]1)CCC.C([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][N:21]=1)#N>ClCCl>[N:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[C:12]1[N:11]2[C:7](=[N:8][C:9]3[CH:17]=[CH:16][CH:15]=[CH:14][C:10]=32)[S:6][N:5]=1
Reactant: N#Cc1ccccn1
Reactant: CCCCn1sc2nc3ccccc3n2c1=O
Solvent: ClCCl
Product: c1ccc(-c2nsc3nc4ccccc4n23)nc1
Temperature: 25 °C
Reaction time: 72 h
Yield: 67.9 %

Procedure:
A mixture of 2-butyl-1,2,4-thiadiazolo[4,5-a]benzimidazole-3(2H)-one (15.0 g, 60.7 mmole) and 2-cyanopyridine (13.3 g, 0.13 mole) in 150 mL of dichloromethane was stirred at room temperature for 72 h. The precipitate was filtered and washed with dichloromethane to give 10.4 g (68%) of 3-(2-pyridyl)-1,2,4-thiadiazolo[4,5-a]benzimidazole as a white solid: mp 173-174° C.; 1H NMR (CDCl3) δ 8.90 (d, 1H), 8.70 (d, 1H), 8.30 (d, 1H), 7.99 (t, 1H), 7.80 (d, 1H), 7.57 (t, 1H) 7.47 (t, 1H), 7.37 (t, 1H) ppm; 13C NMR (CDCl3) δ 166.10, 151.09, 150.11, 148.74, 147.73, 137.38, 130.50, 125.85, 125.24, 124.52, 121.41, 119.11, 116.33 ppm; IR (KBr) ν 3419, 3054, 1611, 1587, 1501, 1463, 1446, 727 cm-1. HRMS calcd for C13H8N4S 252.0470, found 252.0882. Anal. Calcd for C13H8N4S: C, 61.89; H, 3.20; N, 22.21. Found: C, 61.48; H, 3.30; N, 22.24.