Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:9]2[C:14](=[O:15])[C:13]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)=[C:12]([C:23]3[CH:28]=[CH:27][C:26]([S:29](C)(=[O:31])=[O:30])=[CH:25][CH:24]=3)[CH:11]=[N:10]2)[CH:5]=[CH:6][C:7]=1[F:8].[NH3:33]>>[F:1][C:2]1[CH:3]=[C:4]([N:9]2[C:14](=[O:15])[C:13]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)=[C:12]([C:23]3[CH:28]=[CH:27][C:26]([S:29]([NH2:33])(=[O:31])=[O:30])=[CH:25][CH:24]=3)[CH:11]=[N:10]2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: N
Reactant: CS(=O)(=O)c1ccc(-c2cnn(-c3ccc(F)c(F)c3)c(=O)c2-c2ccc(F)cc2)cc1
Product: NS(=O)(=O)c1ccc(-c2cnn(-c3ccc(F)c(F)c3)c(=O)c2-c2ccc(F)cc2)cc1

Procedure:
The title compound was prepared according to Example 384 substituting 2-(3,4-difluorophenyl)-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (Example 182) in place of 2-benzyl-4-(4-fluorophenyl)-5-[4-(methylsulfonyl)phenyl]-3(2H)-pyridazinone (yield: 950 mg, 54%). mp 177-181° C. 1H NMR (300 MHz, DMSO-d6) δ 7.15 (t, 2H), 7.29 (m, 2H), 7.43 (s, 1H), 7.45 (bs, 2H), 7.59 (m, 2H), 7.76 (d, J=9 Hz, 2H), 7.85 (m, 1H), 8.27 (s, 1H). MS (DCI/NH3) m/z 458 (M+H)+, 475 (M+NH4)+. Anal. calc. for C22H14F3N3O3S: C, 57.77; H, 3.08; N, 9.19. Found, C, 57.22; H, 3.28; N, 8.99.
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[C:7]2[CH2:9][CH2:10][CH2:11][C:6]2=[CH:5][C:4]=1[NH:12][C:13](=[S:21])OC1C=CC=CC=1.[CH3:22][O:23][C:24]1[CH:25]=[C:26]([N:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)[CH:27]=[C:28]([O:30][CH3:31])[CH:29]=1>>[CH3:1][O:2][C:3]1[N:8]=[C:7]2[CH2:9][CH2:10][CH2:11][C:6]2=[CH:5][C:4]=1[NH:12][C:13]([N:35]1[CH2:34][CH2:33][N:32]([C:26]2[CH:25]=[C:24]([O:23][CH3:22])[CH:29]=[C:28]([O:30][CH3:31])[CH:27]=2)[CH2:37][CH2:36]1)=[S:21]
Reactant: COc1cc(OC)cc(N2CCNCC2)c1
Reactant: COc1nc2c(cc1NC(=S)Oc1ccccc1)CCC2
Product: COc1cc(OC)cc(N2CCN(C(=S)Nc3cc4c(nc3OC)CCC4)CC2)c1
Yield: 55 %

Procedure:
Phenyl N-(2-methoxy-6,7-dihydro-5H-cyclopenta[b]pyridin-3-yl)thiocarbamate and 1-(3,5-dimethoxyphenyl)piperazine were reacted by the same way with the example 22 to obtain the titled compound.
Reaction SMILES: CS(C)=O.[CH2:5]([N:7]([C:15]1[S:27][C@@H:26]2[C@@H:17]([C@@H:18]3[C@@H:23]([C@@H:24]([CH2:28][OH:29])[O:25]2)[O:22][C:21]([O:31][CH3:32])([CH3:30])[C:20]([O:34][CH3:35])([CH3:33])[O:19]3)[N:16]=1)[C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH3:6].C(N(CC)CC)C>ClCCl>[CH2:5]([N:7]([C:15]1[S:27][C@@H:26]2[C@@H:17]([C@@H:18]3[C@@H:23]([C@@H:24]([CH:28]=[O:29])[O:25]2)[O:22][C:21]([O:31][CH3:32])([CH3:30])[C:20]([O:34][CH3:35])([CH3:33])[O:19]3)[N:16]=1)[C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])[CH3:6]
Reactant: CCN(C(=O)OC(C)(C)C)C1=N[C@@H]2[C@H]3OC(C)(OC)C(C)(OC)O[C@@H]3[C@@H](CO)O[C@@H]2S1
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CS(C)=O
Product: CCN(C(=O)OC(C)(C)C)C1=N[C@@H]2[C@H]3OC(C)(OC)C(C)(OC)O[C@@H]3[C@@H](C=O)O[C@@H]2S1
Temperature: -30 °C
Reaction time: 4 h
Yield: 60.1 %

Procedure:
A solution of DMSO (40 g, 0.52 mol) in anhydrous dichloromethane (1.5 L) was treated with oxallyl dichloride (49 g, 0.39 mol) at −78° C. for 1 hour, followed by addition of 123 (30 g, 65 mmol). The resulting solution was stirred for 4 hours at −30° C. and then cooled down to −78° C. again at which time triethylamine (86 g, 0.85 mol) was added. After 1 hour at −50° C., the reaction mixture was quenched by H2O (500 mL), washed with brine (3×100 mL), dried over anhydrous sodium sulfate and concentrated under vacuum to give a residue, which was purified by a short silica gel column, eluted with 30% ethyl acetate in petroleum ether to give 124 as a brown syrup (18 g, 60%). (ES, m/z) [M+H]+ 461.0; 1H NMR (300 MHz, CDCl3) δ 8.93 (s, 1H), 8.90 (s, 1H), 6.15-6.18 (m, 2H), 4.41-4.45 (m, 1H), 4.28-4.30 (m, 1H), 3.76-4.09 (m, 13H), 3.38 (s, 3H), 3.32 (s, 3H), 3.28 (s, 3H), 3.26 (s, 3H), 1.58 (s, 9H), 1.47 (s, 3H), 1.43 (s, 3H), 1.39 (s, 3H), 1.37 (s, 3H), 1.14-1.21 (m, 6H).
Reaction SMILES: [NH2:1][CH2:2][CH:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[OH:4].[OH:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20](=O)[CH3:21])=[CH:14][C:13]=1[CH2:23][C:24]([O:26][CH3:27])=[O:25].C1C=CC=CC=1.C([BH3-])#N.[Na+]>CO>[CH3:27][O:26][C:24]([CH2:23][C:13]1[CH:14]=[C:15]([CH:16]=[CH:17][C:12]=1[OH:11])[O:18][CH2:19][CH:20]([NH:1][CH2:2][CH:3]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[OH:4])[CH3:21])=[O:25]
Reactant: COC(=O)Cc1cc(OCC(C)=O)ccc1O
Reactant: NCC(O)c1ccccc1
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Solvent: c1ccccc1
Product: COC(=O)Cc1cc(OCC(C)NCC(O)c2ccccc2)ccc1O
Yield: 3.7 %

Procedure:
Following a procedure similar to that described in Example 6, but using 0.72 g of 2-amino-1-phenylethanol, 1.5 g of methyl 2-hydroxy-5-(2-oxopropoxy)phenylacetate (prepared as described in Preparation 21), 60 ml of benzene, 50 ml of absolute methanol and 1.9 g of sodium cyanoborohydride, and then purifying the reaction product by column chromatography through silica gel, using a 10:1 by volume mixture of ethyl acetate and ethanol as the eluent, 0.07 g of the title compound was obtained having an Rf=0.40 (thin layer chromatography over silica gel, using a 10:1 by volume mixture of ethyl acetate and ethanol as the developing solvent).
Reaction SMILES: [CH3:1][C:2]1[S:3][C:4]([C:7]([NH:9][NH2:10])=O)=[CH:5][N:6]=1.Cl.[CH3:12][NH:13][C:14](=NC)[CH2:15][CH2:16][CH2:17][CH:18]=[CH2:19]>>[CH3:12][N:13]1[C:14]([CH2:15][CH2:16][CH2:17][CH:18]=[CH2:19])=[N:10][N:9]=[C:7]1[C:4]1[S:3][C:2]([CH3:1])=[N:6][CH:5]=1
Reactant: C=CCCCC(=NC)NC
Reactant: Cc1ncc(C(=O)NN)s1
Agent: Cl
Product: C=CCCCc1nnc(-c2cnc(C)s2)n1C
Yield: 43 %

Procedure:
The title compound was prepared in analogy to the method described in Preparation 11 starting from 2-methyl-1,3-thiazole-5-carbohydrazide and N,N′-dimethyl-5-hexenimidamide hydrochloride in 43% yield by column chromatography.
Reaction SMILES: [C:1]([C:5]1[CH:15]=[C:14]([S:16][C:17]([S:20][C:21]2[CH:26]=[C:25]([C:27]([CH3:30])([CH3:29])[CH3:28])[C:24]([OH:31])=[C:23]([C:32]([CH3:35])([CH3:34])[CH3:33])[CH:22]=2)([CH3:19])[CH3:18])[CH:13]=[C:12]([C:36]([CH3:39])([CH3:38])[CH3:37])[C:6]=1[O:7][CH2:8][C:9](O)=[O:10])([CH3:4])([CH3:3])[CH3:2].B>C1COCC1>[C:32]([C:23]1[CH:22]=[C:21]([S:20][C:17]([S:16][C:14]2[CH:13]=[C:12]([C:36]([CH3:37])([CH3:38])[CH3:39])[C:6]([O:7][CH2:8][CH2:9][OH:10])=[C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[CH:15]=2)([CH3:19])[CH3:18])[CH:26]=[C:25]([C:27]([CH3:30])([CH3:29])[CH3:28])[C:24]=1[OH:31])([CH3:33])([CH3:34])[CH3:35]
Reactant: CC(C)(Sc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1)Sc1cc(C(C)(C)C)c(OCC(=O)O)c(C(C)(C)C)c1
Agent: B
Solvent: C1CCOC1
Product: CC(C)(Sc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1)Sc1cc(C(C)(C)C)c(OCCO)c(C(C)(C)C)c1
Temperature: 0 °C
Reaction time: 4 h
Yield: 64.4 %

Procedure:
A 100 mL, 2-neck round bottom flask equipped with a nitrogen adapter and a temperature probe was charged with 5.0 g (8.7 mmol, 1 eq) of {2,6-Di-tert-butyl-4-[1-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-1-methyl-ethylsulfanyl]-phenoxy}-acetic acid and 40 mL of anhydrous THF. The solution was cooled to 0° C. using an ice bath and 26.1 mL of 1.0 M (26.1 mmol, 3 eq) borane in THF at a rate such that the maximum temperature was less than 30° C. The solution was warmed to 30° C. and consumption of starting material was monitored by TLC. After 4 hours, the flask was cooled to 0° C. using an ice bath and 75 mL of methanol was slowly added. The resulting solution was concentrated under reduced pressure. The resulting oil was dissolved in 50 mL of methanol and concentrated under reduced pressure two more times. The residue was slurried in 50 mL of hexanes and concentrated under reduced pressure a total of 4 times. The residue was taken up in 50 mL of hexanes and the product was allowed to slowly precipitate. The precipitate was collected by vacuum filtration, washed with 10 mL of hexanes and dried in vacuo to yield 3.1 g (5.6 mmol, 64% yield) of the title compound as a white powder, mp 146–147° C.; 1H NMR (300 MHz, CDCl3) d 7.56 (s, 2H), 7.45 (s, 2H), 5.37 (s, 1H), 4.03 (t, J=5.2 Hz, 2H), 2H), 3.92 (t, J=5.1 Hz, 2H), 1.47 (s, 6H), 1.46 (s, 18H), 1.45 (s, 18H). Anal. calcd for C33H52O3S2: C70.66, H9.34, S11.43; found: C70.36, H9.37, S11.35. HRMS (EI+), m/z: calc. 560.3358; Found 560.3347
Reaction SMILES: [C:1]([N:4]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH:9]=[CH:8][C:7]2[N:16]=[C:17](Cl)[C:18]([F:20])=[CH:19][C:6]=2[CH2:5]1)(=[O:3])[CH3:2].CC1(C)C(C)(C)OB([C:30]2[CH:31]=[CH:32][C:33]([N:36]3[CH2:41][CH2:40][O:39][CH2:38][CH2:37]3)=[N:34][CH:35]=2)O1.C(N1C2C=CC=CC=2C=CC2N=C(C3C=NC(OC)=CC=3)C(F)=CC=2C1)(=O)C>>[C:1]([N:4]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[CH:9]=[CH:8][C:7]2[N:16]=[C:17]([C:30]3[CH:35]=[N:34][C:33]([N:36]4[CH2:37][CH2:38][O:39][CH2:40][CH2:41]4)=[CH:32][CH:31]=3)[C:18]([F:20])=[CH:19][C:6]=2[CH2:5]1)(=[O:3])[CH3:2]
Reactant: CC(=O)N1Cc2cc(F)c(Cl)nc2C=Cc2ccccc21
Reactant: CC1(C)OB(c2ccc(N3CCOCC3)nc2)OC1(C)C
Agent: COc1ccc(-c2nc3c(cc2F)CN(C(C)=O)c2ccccc2C=C3)cn1
Product: CC(=O)N1Cc2cc(F)c(-c3ccc(N4CCOCC4)nc3)nc2C=Cc2ccccc21
Yield: 72.2 %

Procedure:
Compound 5B (20.5 mg, 72.2%) was prepared from 1D (20.0 mg, 0.066 mmol) and 5A (28.7 mg, 0.099 mmol) by a route analogous to that used for the preparation of 2B. HPLC Rt=2.336 min; LCMS Found: (M+H)+=431.
Reaction SMILES: [CH2:1]([NH:15][C:16](=[O:22])[C:17]([O:19]CC)=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][NH:7][C:8](=[O:14])[C:9]([O:11]CC)=O.[CH2:23]([NH2:35])[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]>C(Cl)(Cl)Cl>[CH2:6]([NH:7][C:8](=[O:14])[C:9]([NH:35][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])=[O:11])[CH2:5][CH2:4][CH2:3][CH2:2][CH2:1][NH:15][C:16](=[O:22])[C:17]([NH:35][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])=[O:19]
Reactant: CCCCCCCCCCCCN
Reactant: CCOC(=O)C(=O)NCCCCCCNC(=O)C(=O)OCC
Solvent: ClC(Cl)Cl
Product: CCCCCCCCCCCCNC(=O)C(=O)NCCCCCCNC(=O)C(=O)NCCCCCCCCCCCC

Procedure:
Diethyl 2,2′-(hexane-1,6-diylbis(azanediyl))bis(2-oxoacetate) (5.00 g, 15.8 mmol) and dodecyl amine (5.85 g, 31.64 mmol) were dissolved in 100 ml of CHCl3. Subsequently the mixture was heated at reflux temperature for 24 hours. The solvent was removed by filtering the product. The remaining solid was washed two times with CHCl3 and two times with diethyl ether and dried in vacuum. The product was obtained as a white powder.
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[C:14]1([CH:20]([CH3:22])[CH3:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.CC(C)=[O:25]>>[C:14]1([CH:20]([CH3:22])[CH3:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[C:1]([O:7][OH:25])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)([CH3:6])[CH3:2].[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(C)=O
Reactant: c1ccccc1
Solvent: CC(C)c1ccccc1
Solvent: Oc1ccccc1
Product: CC(C)(OO)c1ccccc1

Procedure:
The industrial synthesis of phenol comprises the alkylation steps of benzene to cumene, the oxidation of cumene to cumyl hydroperoxide and the subsequent rearrangement to give phenol and acetone.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[CH:4][N:3]=1.[CH:9]([C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1)=[O:10]>[Pd]>[Cl:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([C:14]2[CH:15]=[CH:16][C:11]([CH:9]=[O:10])=[CH:12][CH:13]=2)[N:7]=1
Reactant: O=Cc1ccc(B(O)O)cc1
Reactant: Clc1ccnc(Cl)n1
Agent: [Pd]
Product: O=Cc1ccc(-c2nccc(Cl)n2)cc1

Procedure:
The compound was prepared by palladium-catalyzed arylation of 2,4-dichloropyrimidine and 4-formylphenyl boronic acid: 1H NMR (400 MHz, CDCl3) δ 10.13 (s, 1H), 8.74 (d, J=5.0 Hz, 1H), 8.27 (d, J=7.8 Hz, 2H), 8.04 (d, J=7.9 Hz, 2H), 7.74 (m, 1H); EIMS m/z 218 (M+).
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12](=[O:14])[CH3:13])=[CH:7][CH:6]=1)([O:3][CH3:4])=[O:2].[CH2:15](O)[CH2:16][OH:17].C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C1C=CC=CC=1>[CH2:16]1[O:17][C:12]([CH3:13])([CH2:11][C:8]2[CH:9]=[CH:10][C:5]([C:1]([O:3][CH3:4])=[O:2])=[CH:6][CH:7]=2)[O:14][CH2:15]1
Reactant: OCCO
Reactant: COC(=O)c1ccc(CC(C)=O)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: c1ccccc1
Product: COC(=O)c1ccc(CC2(C)OCCO2)cc1

Procedure:
A mixture of 1-(4-carbomethoxyphenyl)propan-2-one (17.3 g), ethan-1,2-diol (5.6 g) and p-toluenesulphonic acid (200 ml) in benzene (150 ml) was refluxed under a Dean and Stark head until the theoretical amount of water had been collected (ca. 4 hours). The solvent was evaporated and the residue was partitioned between sodium bicarbonate solution and ether. The ethereal extract was washed with water, dried, evaporated and distilled to give 15.7 g (74%), bp 136-140/1.5 mm.
Reaction SMILES: [NH2:1][C@@H:2]([CH:5]([CH3:7])[CH3:6])[CH2:3]O.[CH3:8][S:9](Cl)(=[O:11])=[O:10]>>[CH:5]([C@H:2]1[CH2:3][CH2:8][S:9](=[O:11])(=[O:10])[NH:1]1)([CH3:7])[CH3:6]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)[C@H](N)CO
Product: CC(C)[C@H]1CCS(=O)(=O)N1

Procedure:
Using (S)-2-amino-3-methyl-1-butanol (5.0 g) and methanesulfonyl chloride (7.7 mL) and by the reaction and treatment in the same manner as in Preparation Example 1, the title compound (1.55 g) was obtained.
Reaction SMILES: [I:1][C:2]1[NH:6][N:5]=[C:4]([C:7](OCC)=[O:8])[C:3]=1[CH3:12].[OH-].[NH4+:14]>CO>[I:1][C:2]1[NH:6][N:5]=[C:4]([C:7]([NH2:14])=[O:8])[C:3]=1[CH3:12]
Reactant: CCOC(=O)c1n[nH]c(I)c1C
Reactant: [NH4+]
Agent: [OH-]
Solvent: CO
Product: Cc1c(C(N)=O)n[nH]c1I
Temperature: 60 °C
Reaction time: 8 h
Yield: 89 %

Procedure:
Into a 100-mL round-bottom flask, was placed a solution of ethyl 5-iodo-4-methyl-1H-pyrazole-3-carboxylate (compound 258.1, 500 mg, 1.79 mmol) in methanol (5 mL). Then ammonium hydroxide (15 mL, 25% aq.) was added and the resulting solution was stirred overnight at 60° C. The mixture was concentrated under reduced pressure to obtain the title compound as a white solid (400 mg, 89%).
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:14]=3[C:15]([O:17][CH3:18])=[O:16])=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.[CH3:24][N:25]([CH2:27]CO)[CH3:26].C1(C)C=CC=CC=1.[H-].[Na+]>C(O)(=O)C>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:14]=3[C:15]([O:17][CH2:18][CH2:24][N:25]([CH3:27])[CH3:26])=[O:16])=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1
Reactant: CN(C)CCO
Reactant: COC(=O)c1cc(F)ccc1Nc1ccnc2cc(Cl)ccc12
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CC(=O)O
Product: CN(C)CCOC(=O)c1cc(F)ccc1Nc1ccnc2cc(Cl)ccc12
Temperature: 50 °C

Procedure:
A mixture of 4 g of the ester of Example 1, 2.45 ml of dimethylaminoethanol and 50 ml of anhydrous toluene was heated to reflux and then cooled to 50° C. and 95 mg of a 50% sodium hydride oil suspension was added thereto. The mixture was again heated to reflux and was then cooled to 40° C. and 0.2 ml of acetic acid were added thereto. The mixture was evaporated to dryness and the residue was dissolved in methylene chloride. The solution was filtered and the filtrate was washed with water, dried and filtered. The filtrate was evaporated to dryness to obtain 4.01 g of 2-dimethylaminoethyl 2-(7-chloro-4-quinolinylamino)-5-fluorobenzoate.
Reaction SMILES: [NH2:1]N.[CH3:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH:5]1[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]C1C=CC=C2C(NC(=O)C=12)=O>CO>[CH3:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH:5]1[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH2:1]
Reactant: NN
Reactant: CN1CCNCC1CCCCCCCCc1cccc2c1C(=O)NC2=O
Solvent: CO
Product: CN1CCNCC1CCCCCCCCN

Procedure:
Hydrazine (aqueous solution at 35% by wt.) (0.15 ml; 1.6 mmoles) was added to 8-(N-methylpiperazinyl)octylphthalimide (285 mg; 0.8 mmoles) in methanol (5 ml) and the resulting solution was refluxed. Reaction times and process as per Example 1.
Reaction SMILES: Cl.[CH3:2][NH:3][CH:4]1[CH2:19][C:8]2[C:9]3[NH:10][C:11](=[O:18])[C:12](=[O:17])[NH:13][C:14]=3[CH:15]=[CH:16][C:7]=2[CH2:6][CH2:5]1.[N+:20]([O-])([OH:22])=[O:21]>FC(F)(F)C(O)=O>[CH3:2][NH:3][CH:4]1[CH2:19][C:8]2[C:9]3[NH:10][C:11](=[O:18])[C:12](=[O:17])[NH:13][C:14]=3[CH:15]=[C:16]([N+:20]([O-:22])=[O:21])[C:7]=2[CH2:6][CH2:5]1
Reactant: CNC1CCc2ccc3[nH]c(=O)c(=O)[nH]c3c2C1
Reactant: O=[N+]([O-])O
Agent: Cl
Solvent: O=C(O)C(F)(F)F
Product: CNC1CCc2c([N+](=O)[O-])cc3[nH]c(=O)c(=O)[nH]c3c2C1

Procedure:
9-Methylamino-1,2,3,4,7,8,9,10-octahydrobenzo[f]quinoxaline-2,3-dione hydrochloride (1 g, 3.5 mmol) was nitrated using fuming nitric acid (1 mL) and trifluoroacetic acid (30 mL) from 0° C. to room temperature for 1 h. The solvent was removed and their residue triturated in acetone:water and collected by filtration and dried to give the product (1.1 g). Calc'd for C13H14N4O4.HCl: C, 47.79; H, 4.63; N, 17.15; found: C, 43.36; H, 4.22; N, 18.85. MS M+1 (291).
Reaction SMILES: [Cl-].[Li+].C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([Si]([O:35][CH2:36][CH2:37][CH2:38][C:39]#[C:40][Si](CC)(CC)CC)(CC)CC)C.I[C:49]1[CH:55]=[C:54]([CH2:56][N:57]2[CH:61]=[N:60][CH:59]=[N:58]2)[CH:53]=[CH:52][C:50]=1[NH2:51]>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[N:57]1([CH2:56][C:54]2[CH:53]=[C:52]3[C:50](=[CH:49][CH:55]=2)[NH:51][CH:40]=[C:39]3[CH2:38][CH2:37][CH2:36][OH:35])[CH:61]=[N:60][CH:59]=[N:58]1
Reactant: Nc1ccc(Cn2cncn2)cc1I
Reactant: CC[Si](C#CCCCO[Si](CC)(CC)CC)(CC)CC
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: O=C([O-])[O-]
Solvent: CN(C)C=O
Product: OCCCc1c[nH]c2ccc(Cn3cncn3)cc12
Temperature: 100 °C
Yield: 56 %

Procedure:
A mixture of palladium acetate (0.78 g), lithium chloride (1.47 g), sodium carbonate (18.49 g), triphenylphosphine (1.8 g), 5-triethylsilyl-4-pentyn-1-ol triethylsilyl ether (16.3 g) and 2-iodo-4-[(1,2,4-triazol-1-yl)methyl]aniline (10.0 g) in degassed anhydrous dimethylformamide (400 ml) was heated at 100° C. for 10 h, under nitrogen. After cooling, the reaction was filtered, concentrated, and the residue was partitioned between water and ethyl acetate. The organic phase was dried (MgSO4), concentrated and the residue was treated with 5N hydrochloric acid/methanol (1:3; 400 ml) for 3 h at room temperature. The methanol was removed under vacuum, the aqueous residue was basified with sodium carbonate solution and it was extracted with ethyl acetate. The combined organic extracts were dried (MgSO4) and concentrated. Flash chromatography of the residue (silica gel, dichloromethane/methanol, 95:5) followed by trituration with petroleum ether, gave the title compound (56%) as a beige solid. δH (360 MHz, DMSO-d6) 1.74-1.82 (2H, m), 2.66-2.70 (2H, m), 3.43-3.49 (2H, m), 4.41-4.44 (1H, m), 5.42 (2H, s), 7.01-7.04 (1H, m), 7.11-7.12 (1H, m), 7.28-7.30 (1H, m), 7.51 (1H, s), 7.93 (1H, s), 8.60 (1H, s), 10.79 (1H, s).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:18]/[CH:19]=[CH:20]/[C:21]1[CH:26]=[CH:25][C:24]([B:27]2[O:31][C:30]([CH3:33])([CH3:32])[C:29]([CH3:35])([CH3:34])[O:28]2)=[CH:23][CH:22]=1)[C:10]([O:12][CH:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[C:37]1C=CC(I)=C(C)C=1>>[C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:18]/[CH:19]=[CH:20]/[C:21]1[CH:26]=[CH:25][C:24]([B:27]2[O:31][C:30]([CH3:33])([CH3:32])[C:29]([CH3:35])([CH3:34])[O:28]2)=[CH:23][C:22]=1[CH3:37])[C:10]([O:12][CH:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1)=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N[C@@H](C/C=C/c1ccc(B2OC(C)(C)C(C)(C)O2)cc1)C(=O)OC1CCCC1
Reactant: Cc1cc(Br)ccc1I
Product: Cc1cc(B2OC(C)(C)C(C)(C)O2)ccc1/C=C/C[C@H](NC(=O)OC(C)(C)C)C(=O)OC1CCCC1

Procedure:
Synthesised by analogous methods to Intermediate 5a, using 4-bromo-2-methyl-iodobenzene at Stage 2 of Scheme 4. m/z 500 [M+H]+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[N:11]3[N:18]=[CH:19][C:20]([C:21](O)=[O:22])=[C:10]3[N:9]=2)=[CH:4][CH:3]=1.[NH2:24][C:25]1[N:30]=[CH:29][C:28]([C:31]([NH:33]O)=[NH:32])=[CH:27][N:26]=1>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([C:14]([F:17])([F:16])[F:15])[N:11]3[N:18]=[CH:19][C:20]([C:21]4[O:22][N:33]=[C:31]([C:28]5[CH:27]=[N:26][C:25]([NH2:24])=[N:30][CH:29]=5)[N:32]=4)=[C:10]3[N:9]=2)=[CH:4][CH:3]=1
Reactant: O=C(O)c1cnn2c(C(F)(F)F)cc(-c3ccc(Cl)cc3)nc12
Reactant: N=C(NO)c1cnc(N)nc1
Product: Nc1ncc(-c2noc(-c3cnn4c(C(F)(F)F)cc(-c5ccc(Cl)cc5)nc34)n2)cn1

Procedure:
The title compound was prepared from 5-(4-chloro-phenyl)-7-trifluoromethyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C.4) (171 mg, 0.5 mmol) and 2-amino-N-hydroxy-pyrimidine-5-carboxamidine (example B.5) (115 mg, 0.75 mmol) according to general procedure II. Obtained after flash chromatography on silica gel (ethyl acetate/heptane) and further purification by crystallization (dichloromethane/hexane) as a yellow solid (165 mg, 72%). MS (EI) 458.1 [(M)+]; mp 268° C.
Reaction SMILES: [CH3:1][C:2]1[C:3]([CH3:28])=[CH:4][C:5]2[N:11]([C:12](=[O:21])[CH2:13][N:14]([CH2:18][CH2:19][CH3:20])[CH2:15][CH2:16][CH3:17])[C:10]3[N:22]=[CH:23][CH:24]=[CH:25][C:9]=3[C:8](=O)[NH:7][C:6]=2[CH:27]=1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:30]>N1C=CC=CC=1>[CH3:1][C:2]1[C:3]([CH3:28])=[CH:4][C:5]2[N:11]([C:12](=[O:21])[CH2:13][N:14]([CH2:18][CH2:19][CH3:20])[CH2:15][CH2:16][CH3:17])[C:10]3[N:22]=[CH:23][CH:24]=[CH:25][C:9]=3[C:8](=[S:30])[NH:7][C:6]=2[CH:27]=1
Reactant: CCCN(CCC)CC(=O)N1c2cc(C)c(C)cc2NC(=O)c2cccnc21
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Solvent: c1ccncc1
Product: CCCN(CCC)CC(=O)N1c2cc(C)c(C)cc2NC(=S)c2cccnc21

Procedure:
In the manner given in Example 1, 8,9-dimethyl-6,11-dihydro-11-[(dipropylamino)acetyl]-5H-pyrido[2,3-b][1,5]benzodiazepin-5-one is reacted with phosphorus pentasulfide in pyridine to give 8,9-dimethyl-6,11-dihydro-11-[(dipropylamino)acetyl]-5H-pyrido[2,3-b][1,5]benzodiazepin-5-thione.
Reaction SMILES: [C:1]([OH:24])(=[O:23])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH:21]=[CH2:22].C1(BC2CCCCC2)CCCCC1.C([O-])(=O)C.[Na+].[I-:43].[Na+].CC1C=CC(S(NCl)(=O)=O)=CC=1>>[I:43][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][C:1]([OH:24])=[O:23]
Reactant: [I-]
Reactant: C=CCCCCCCCCCCCCCCCCCCCC(=O)O
Agent: B(C1CCCCC1)C1CCCCC1
Agent: CC(=O)[O-]
Agent: Cc1ccc(S(=O)(=O)NCl)cc1
Product: O=C(O)CCCCCCCCCCCCCCCCCCCCCI

Procedure:
21-Docosenoic acid (55mg. 0.16 mmol) was hydroborated with dicyclohexylborane (0.32 mmol) at 0° C. The organoborane was iodinated with a mixture of sodium aceate (0.32 mmol), sodium iodide (0.16 mmol), and chloramine-T (0.32 mmol). The product was isolated by a column chromotography on silica gel (10% ethyl acetate:hexane):yield 68 mg (91%); mp 71°-2° C.; m/e 466.5 (calcd 466.5); NMR (CDCl3), 1.2 δ (s, 36H, alkane), 2.1 (m, 4H, --CH2 --CO2H and --CH2CH2I), 3.0 (t, 2H, --CH2I, 11.9 (s, 1H, --CO2H).
Reaction SMILES: [C:1]([C:5]1[CH:19]=[CH:18][C:8]([O:9][C:10]2[CH:11]=[C:12]([CH:15]=[CH:16][CH:17]=2)[CH:13]=O)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[C@@H:20]1([NH2:30])[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:23][CH2:22][CH2:21]1>>[C:1]([C:5]1[CH:19]=[CH:18][C:8]([O:9][C:10]2[CH:11]=[C:12]([CH:15]=[CH:16][CH:17]=2)[CH2:13][NH:30][C@@H:20]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[CH2:23][CH2:22][CH2:21]2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)c1ccc(Oc2cccc(C=O)c2)cc1
Reactant: N[C@H]1CCCc2ccccc21
Product: CC(C)(C)c1ccc(Oc2cccc(CN[C@H]3CCCc4ccccc43)c2)cc1

Procedure:
3-(4-tert-Butylphenoxy)benzaldehyde and (1S)-1,2,3,4-tetrahydro-1-naphthalenylamine were processed as described in Example 1A to provide the title compound.