Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][CH:2]([F:25])[C:3]1[N:8]2[N:9]=[CH:10][C:11]([C:12](O)=[O:13])=[C:7]2[N:6]=[C:5]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=2)[CH:4]=1.[OH:26][CH2:27][C:28]([NH:31][S:32]([C:35]1[S:36][C:37]([CH3:41])=[C:38]([NH2:40])[CH:39]=1)(=[O:34])=[O:33])([CH3:30])[CH3:29]>>[OH:26][CH2:27][C:28]([NH:31][S:32]([C:35]1[S:36][C:37]([CH3:41])=[C:38]([NH:40][C:12]([C:11]2[CH:10]=[N:9][N:8]3[C:3]([CH:2]([F:1])[F:25])=[CH:4][C:5]([C:15]4[CH:16]=[CH:17][C:18]([C:21]([F:24])([F:22])[F:23])=[CH:19][CH:20]=4)=[N:6][C:7]=23)=[O:13])[CH:39]=1)(=[O:34])=[O:33])([CH3:30])[CH3:29]
Reactant: O=C(O)c1cnn2c(C(F)F)cc(-c3ccc(C(F)(F)F)cc3)nc12
Reactant: Cc1sc(S(=O)(=O)NC(C)(C)CO)cc1N
Product: Cc1sc(S(=O)(=O)NC(C)(C)CO)cc1NC(=O)c1cnn2c(C(F)F)cc(-c3ccc(C(F)(F)F)cc3)nc12

Procedure:
The title compound was prepared from 7-difluoromethyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (example C.1) and 4-amino-5-methyl-thiophene-2-sulfonic acid (2-hydroxy-1,1-dimethyl-ethyl)-amide (example B.12) according to general procedure II. Yellow solid. MS (ISP) 602.2 [(M−H)−]; mp 180° C.
Reaction SMILES: Br[C:2]1[C:3]2[N:4]([N:8]=[C:9]([Cl:11])[N:10]=2)[CH:5]=[CH:6][CH:7]=1.[NH2:12][C:13]1[CH:25]=[CH:24][CH:23]=[CH:22][C:14]=1[CH2:15][N:16]([CH3:21])[S:17]([CH3:20])(=[O:19])=[O:18]>>[Cl:11][C:9]1[N:10]=[C:3]2[C:2]([NH:12][C:13]3[CH:25]=[CH:24][CH:23]=[CH:22][C:14]=3[CH2:15][N:16]([CH3:21])[S:17]([CH3:20])(=[O:19])=[O:18])=[CH:7][CH:6]=[CH:5][N:4]2[N:8]=1
Reactant: CN(Cc1ccccc1N)S(C)(=O)=O
Reactant: Clc1nc2c(Br)cccn2n1
Product: CN(Cc1ccccc1Nc1cccn2nc(Cl)nc12)S(C)(=O)=O

Procedure:
171 c) N-[2-(2-Chloro-[1,2,4]triazolo[1,5-a]pyridin-8-ylamino)-benzyl]-N-methyl-methanesulfonamide was prepared from 8-bromo-2-chloro-[1,2,4]triazolo[1,5-a]pyridine (500.0 mg, 2.151 mmol) and N-(2-amino-benzyl)-N-methyl-methanesulfonamide (507.0 mg, 2.366 mmol) in a manner analogous to Exmaple 2d. Product isolated as a tan foam (0.53 g, 67%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.01 (d, J=6.4 Hz, 1H), 7.48-7.41 (m, 2H), 7.38 (t, J=7.4 Hz, 1H), 7.21 (t, J=7.4 Hz, 1H), 7.10 (s, 1H), 6.90-6.81 (m, 2H), 4.36 (s, 2H), 3.02 (s, 3H), 2.76 (s, 3H). MS=366 (MH)+.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][CH2:12][C@H:11]([NH:15][C@@H:16]3[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]3[NH:22][C:23]3[CH:28]=[C:27](/[CH:29]=[CH:30]\[C:31](O)=[O:32])[CH:26]=[CH:25][N:24]=3)[CH2:10]2)=[CH:5][CH:4]=1)#[N:2].CC[N:36](CC)CC.ClC(OCC(C)C)=O.N>CO.C1COCC1>[C:1]([C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:14][CH2:13][CH2:12][C@H:11]([NH:15][C@@H:16]3[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]3[NH:22][C:23]3[CH:28]=[C:27](/[CH:29]=[CH:30]\[C:31]([NH2:36])=[O:32])[CH:26]=[CH:25][N:24]=3)[CH2:10]2)=[CH:7][CH:8]=1)#[N:2]
Reactant: N#Cc1ccc(N2CCC[C@H](N[C@@H]3CCCC[C@H]3Nc3cc(/C=C\C(=O)O)ccn3)C2)cc1
Reactant: CCN(CC)CC
Agent: CC(C)COC(=O)Cl
Agent: N
Solvent: CO
Solvent: C1CCOC1
Product: N#Cc1ccc(N2CCC[C@H](N[C@@H]3CCCC[C@H]3Nc3cc(/C=C\C(N)=O)ccn3)C2)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 22.2 %

Procedure:
To a round bottom flask was added (Z)-3-(2-(((1R,2R)-2-(((S)-1-(4-cyanophenyl)piperidin-3-yl)amino)cyclohexyl)amino)pyridin-4-yl)acrylic acid (35 mg, 0.063 mmol), THF (0.8 mL) and Et3N (0.026 mL, 0.188 mmol). The reaction was cooled to 0° C. Then isobutyl chloroformate (9.04 μl, 0.069 mmol) was added to the reaction and the reaction was stirred at 0° C. for 15 mins before ammonia (0.045 mL, 0.313 mmol) in methanol was added to the reaction. The reaction was stirred at 0° C. for 30 mins. The reaction was concentrated and purified using RP prep-HPLC. The desired fraction was concentrated to give (Z)-3-(2-(((1R,2R)-2-(((S)-1-(4-cyanophenyl)piperidin-3-yl)amino)cyclohexyl)amino)pyridin-4-yl)acrylamide (8 mg, 0.014 mmol, 21.98% yield) as a light brown film. Anal. Calcd. for C26H32N6O m/z 444.3, found: 445.5 (M+H)+; 1H NMR (400 MHz, METHANOL-D4) δ ppm 7.87 (d, J=6.6 Hz, 1H), 7.47 (d, J=8.8 Hz, 2H), 7.00-6.89 (m, 3H), 6.84 (br. s., 1H), 6.67 (d, J=12.6 Hz, 1H), 6.35 (d, J=12.6 Hz, 1H), 3.88-3.67 (m, 2H), 3.63-3.52 (m, 1H), 3.50-3.42 (m, 1H), 3.40-3.33 (m, 2H), 3.18-3.08 (m, 1H), 2.34 (d, J=12.6 Hz, 1H), 2.14 (dd, J=9.6, 3.0 Hz, 2H), 1.91-1.72 (m, 4H), 1.66-1.53 (m, 1H), 1.52-1.40 (m, 3H), 1.33-1.26 (m, 1H)
Reaction SMILES: Cl[C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][C:12]=3Cl)[C:7](=[O:18])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH2:19]([N:21]([CH2:25][CH3:26])[CH2:22][CH2:23][NH2:24])[CH3:20]>>[CH2:19]([N:21]([CH2:25][CH3:26])[CH2:22][CH2:23][NH:24][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][C:12]=3[NH:24][CH2:23][CH2:22][N:21]([CH2:25][CH3:26])[CH2:19][CH3:20])[C:7](=[O:18])[C:6]=2[CH:5]=[CH:4][CH:3]=1)[CH3:20]
Reactant: O=C1c2cccc(Cl)c2C(=O)c2c(Cl)cccc21
Reactant: CCN(CC)CCN
Product: CCN(CC)CCNc1cccc2c1C(=O)c1c(NCCN(CC)CC)cccc1C2=O
Yield: 41.6 %

Procedure:
A mixture of 5.52 g (0.02 mol) of 1,8-dichloroanthraquinone and 23.2 g (0.2M) 2-(diethylamino)ethylamine is heated under reflux for 3 hours. The reaction product is washed up as described in Example 1 except that the oily residue is only washed with water and then dried to yield 3.63 g of the title compound as the free base in the form of a purple solid, m.p. 103.5°-106.5° C.; λmax (deionised water) (E/cm/M) 236 nm (54940), 542 nm (13200).
Reaction SMILES: [C:1]([N:11]1[CH2:17][CH2:16][CH2:15][C@H:12]1[CH2:13][OH:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].C(N(CC)CC)C>CS(C)=O>[C:1]([N:11]1[CH2:17][CH2:16][CH2:15][C@H:12]1[CH:13]=[O:14])([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2]
Reactant: O=C(OCc1ccccc1)N1CCC[C@H]1CO
Solvent: CS(C)=O
Solvent: CCN(CC)CC
Product: O=C[C@@H]1CCCN1C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 70 %

Procedure:
To a stirred solution of N-Cbz-L-prolinol (5 g, 21.26 mmol, from steps 24b or 24c above)in 20 mL of anhydrous DMSO were added 8.89 mL (63.79 mmol) of triethylamine and 10.75 g (63.79 mmol) of SO3 -pyridine complex in 35 mL of DMSO. The reaction mixture was stirred at room temperature for 10 min, then poured into 200 mL of ice water. The mixture was extracted with ether, the extract was dried over Na2SO4 and concentrated to afford the title product, 3.058 g (70% yield).
Reaction SMILES: [N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][CH:2]=1.[H-].[Na+].Cl[CH2:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[O:21][CH:22]=[C:23]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:24]=2)=[CH:16][CH:15]=1>CN(C=O)C>[N:1]1([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:20]3[O:21][CH:22]=[C:23]([C:25]([O:27][CH2:28][CH3:29])=[O:26])[N:24]=3)=[CH:18][CH:19]=2)[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[CH:2]1
Reactant: CCOC(=O)c1coc(-c2ccc(CCl)cc2)n1
Reactant: c1ccc2[nH]cnc2c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCOC(=O)c1coc(-c2ccc(Cn3cnc4ccccc43)cc2)n1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 92.4 %

Procedure:
To a solution of benzimidazole (1.5 eq) in DMF was added portionwise sodium hydride (60% suspension in mineral oil, 1.5 eq) and the reaction mixture was allowed to stir for 45 min at room temperature. The reaction mixture was then added to a solution of ethyl 2-[4-(chloromethyl)phenyl]-1,3-oxazole-4-carboxylate (1 eq) in DMF and the reaction mixture was allowed to stir at room temperature for 2 h. The reaction mixture was poured into ice/water, stirred for 30 min, and the resulting precipitate filtered through a coarse filter without vacuum suction (if the filtration is bad, it is possible to decant the aqueous/DMF layer from the organic precipitate), the precipitate dissolved in methylene chloride, washed with aq. ammonium chloride, water, dried over sodium sulphate, evaporated, triturated with MTBE, filtered, dried in the oven at 40° C. overnight. The product (92.4% yield) was obtained as off-white crystals; m.p. 150-152° C. 1H NMR (300 MHz, DMSO-D6, δ): 8.92 (s, 1H), 8.45 (d, 2H, J=8.5 Hz), 7.99 (d, 2H, J=8.5 Hz), 7.68 (m, 1H), 7.51 (m, 1H), 7.46 (d, 2H, J=8.5 Hz), 7.21 (m, 2H), 5.61 (s, 2H), 4.31 (m, 2H, J=7.2 Hz), 3.32 (s, 2H), 130 (t, 3H, J=7.2 Hz).
Reaction SMILES: C1CCN(C(N=NC(N2CCCCC2)=O)=O)CC1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:38][O:39][CH2:40][C:41]1[CH:46]=[CH:45][C:44]([CH2:47][CH2:48][OH:49])=[CH:43][CH:42]=1.O[C:51]1[CH:64]=[CH:63][C:54]([CH2:55][CH:56]([CH2:61][CH3:62])[C:57]([O:59][CH3:60])=[O:58])=[CH:53][CH:52]=1>ClCCl.C(OCC)(=O)C>[CH3:38][O:39][CH2:40][C:41]1[CH:46]=[CH:45][C:44]([CH2:47][CH2:48][O:49][C:51]2[CH:64]=[CH:63][C:54]([CH2:55][CH:56]([CH2:61][CH3:62])[C:57]([O:59][CH3:60])=[O:58])=[CH:53][CH:52]=2)=[CH:43][CH:42]=1
Reactant: CCC(Cc1ccc(O)cc1)C(=O)OC
Reactant: COCc1ccc(CCO)cc1
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CCC(Cc1ccc(OCCc2ccc(COC)cc2)cc1)C(=O)OC
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 23.2 %

Procedure:
ADDP (1,23 g, 4,89 mmole) and triphenylphosphine (1,03 g, 3,92 mmole) were added to a solution of 2-[4-(methoxymethyl)phenyl]ethanol (0,54 g, 3,26 mmole) and methyl 2-(4-hydroxybenzyl)butanoate (0,68 g, 3,26 mmole) in dry dichloromethane (10 ml) under argon. After 5 minutes, more dichloromethane (10 ml) was added. The reaction mixture was stirred at room temperature for 5.5 hours and then filtered. Purification by chromatography on silica gel using heptan:ethyl acetate (1:1) as eluent gave a mixture of product and starting material wich was dissolved in ethyl acetate and washed 3 times with 1 N sodium hydroxide. The organic phase was washed with brine, dried (sodium sulphate), filtered and solvent was evaporated to give 0,27 g (yield 60%) of the desired product.
Reaction SMILES: [Cl:1][C:2]1[C:7]([I:8])=[CH:6][C:5]([NH:9][CH2:10][C:11]([OH:13])=O)=[C:4]([O:14][CH3:15])[CH:3]=1.[N:16]1([CH:22]2[CH2:25][N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:23]2)[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.CCN(CC)CC>CN(C=O)C>[Cl:1][C:2]1[C:7]([I:8])=[CH:6][C:5]([NH:9][CH2:10][C:11]([N:19]2[CH2:20][CH2:21][N:16]([CH:22]3[CH2:23][N:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:25]3)[CH2:17][CH2:18]2)=[O:13])=[C:4]([O:14][CH3:15])[CH:3]=1
Reactant: COc1cc(Cl)c(I)cc1NCC(=O)O
Reactant: CC(C)(C)OC(=O)N1CC(N2CCNCC2)C1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COc1cc(Cl)c(I)cc1NCC(=O)N1CCN(C2CN(C(=O)OC(C)(C)C)C2)CC1
Temperature: 25 °C
Reaction time: 16 h
Yield: 67.4 %

Procedure:
To a solution of 2-(4-chloro-5-iodo-2-methoxyphenylamino)acetic acid (2.0 g, 5.88 mmol), tert-butyl 3-(piperazin-1-yl)azetidine-1-carboxylate (1.84 g, 7.64 mmol), EDCI.HCl (2.26 g, 11.76 mmol), and HOBt (1.59 g, 11.76 mmol) in DMF (3 mL) at 0° C., Et3N (3.28 mL, 23.52 mmol) was added. The resulting mixture was stirred at RT for 16 h and then partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was washed by a mixture of ethyl acetate/petroleum ether=1:5 to afford the desired product (2.24 g, 67% yield) as a white solid. ESI-MS m/z: 565.4[M+H]+.
Reaction SMILES: C([O:8][C:9]1[CH:36]=[CH:35][C:34]([N:37]([CH3:46])[CH2:38][CH2:39][N:40]2[CH2:45][CH2:44][O:43][CH2:42][CH2:41]2)=[CH:33][C:10]=1[C:11]([NH:13][C:14]1[CH:26]=[C:25]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:24]=[CH:23][C:15]=1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[O:12])C1C=CC=CC=1>CO.C(OCC)(=O)C.[C].[Pd]>[OH:8][C:9]1[CH:36]=[CH:35][C:34]([N:37]([CH3:46])[CH2:38][CH2:39][N:40]2[CH2:41][CH2:42][O:43][CH2:44][CH2:45]2)=[CH:33][C:10]=1[C:11]([NH:13][C:14]1[CH:26]=[C:25]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:24]=[CH:23][C:15]=1[C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])=[O:12]
Reactant: CN(CCN1CCOCC1)c1ccc(OCc2ccccc2)c(C(=O)Nc2cc(-c3ccccc3)ccc2C(=O)OC(C)(C)C)c1
Agent: [Pd]
Solvent: CO
Solvent: CCOC(C)=O
Product: CN(CCN1CCOCC1)c1ccc(O)c(C(=O)Nc2cc(-c3ccccc3)ccc2C(=O)OC(C)(C)C)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 72.1 %

Procedure:
To a solution mixture of the obtained tert-butyl 2-(2-(benzyloxy)-5-(methyl(2-(morpholin-4-yl)ethyl)amino)benzamido)-4-phenylbenzoate (0.12 g) in methanol (1.5 mL) and ethyl acetate (1.5 mL), 10% palladium-carbon (0.12 g) was added, followed by stirring under a hydrogen atmosphere at room temperature for 2 hours and 30 minutes. Ethyl acetate was added to the reaction mixture. The insoluble substance was removed by filtration, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [Kanto Chemical Co., Inc., silica gel 60 (spherical), eluent: 100-95% chloroform/methanol] to obtain 0.074 g of tert-butyl 2-(2-hydroxy-5-(methyl(2-(morpholin-4-yl)ethyl)amino)benzamido)-4-phenylbenzoate.
Reaction SMILES: Cl[CH2:2][C:3](=[O:7])[CH2:4][CH2:5][CH3:6].[CH3:8][C:9]1[N:14]=[C:13]([NH:15][C:16](=[S:18])[S-:17])[CH:12]=[CH:11][CH:10]=1.C([NH+](CC)CC)C.C1CCCCC1>C(#N)C>[OH:7][C:3]1([CH2:4][CH2:5][CH3:6])[CH2:2][S:18][C:16](=[S:17])[N:15]1[C:13]1[CH:12]=[CH:11][CH:10]=[C:9]([CH3:8])[N:14]=1
Reactant: CCCC(=O)CCl
Reactant: Cc1cccc(NC(=S)[S-])n1
Agent: CC[NH+](CC)CC
Solvent: CC#N
Solvent: C1CCCCC1
Product: CCCC1(O)CSC(=S)N1c1cccc(C)n1
Temperature: 10 °C
Reaction time: 2 h
Yield: 80.6 %

Procedure:
1-Chloropentan-2-one (12.1 g) is added to a suspension of triethylammonium (6-methylpyrid-2-yl)dithiocarbamate (28.5 g) in anhydrous acetonitrile (200 cc) at a temperature between 15° and 25° C. The reaction is continued for 2 hours at 20°-25° C. The insoluble triethylamine hydrochloride is removed by filtration and washed twice with diethyl ether (60 cc. total). The solvents are evaporated under reduced pressure (20 mm.Hg) at 40° C. The residual oil is dissolved in a mixture of diethyl ether (100 cc) and methylene chloride (50 cc); the organic solution is washed twice with distilled water (total 100 cc), dried over sodium sulphate and evaporated. The crystals obtained (25.4 g; m.p. about 70° C.) are dissolved in boiling cyclohexane (500 cc) and the boiling solution is filtered. After cooling for 1 hour at about 10° C., the resulting crystals are separated by filtration, washed twice with cyclohexane (total 120 cc) cooled to 10° C., and dried under reduced pressure (0.1 mm.Hg) at 40° C. 4-Hydroxy-3-(6-methylpyrid-2-yl)-4-propylthiazolidine-2-thione (21.6 g), melting at 83° C., is thus obtained.
Reaction SMILES: Br[C:2]1[CH:3]=[N:4][N:5]([CH3:9])[C:6]=1[O:7][CH3:8].[Cl:10][C:11]1[C:16]([F:17])=[CH:15][CH:14]=[C:13]([O:18][CH3:19])[C:12]=1[C@H:20]([C:22]1[C:30]2[C:25](=[N:26][CH:27]=[C:28](B3OC(C)(C)C(C)(C)O3)[CH:29]=2)[NH:24][CH:23]=1)[CH3:21].C(=O)([O-])[O-].[K+].[K+].ClCCl>O1CCOCC1>[Cl:10][C:11]1[C:16]([F:17])=[CH:15][CH:14]=[C:13]([O:18][CH3:19])[C:12]=1[C@H:20]([C:22]1[C:30]2[C:25](=[N:26][CH:27]=[C:28]([C:2]3[CH:3]=[N:4][N:5]([CH3:9])[C:6]=3[O:7][CH3:8])[CH:29]=2)[NH:24][CH:23]=1)[CH3:21]
Reactant: COc1c(Br)cnn1C
Reactant: COc1ccc(F)c(Cl)c1[C@@H](C)c1c[nH]c2ncc(B3OC(C)(C)C(C)(C)O3)cc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: ClCCl
Product: COc1ccc(F)c(Cl)c1[C@@H](C)c1c[nH]c2ncc(-c3cnn(C)c3OC)cc12
Temperature: 100 °C

Procedure:
A solution of 4-bromo-5-methoxy-1-methyl-1H-pyrazole (0.0133 g, 0.0697 mmol), 3-[(1S)-1-(2-chloro-3-fluoro-6-methoxyphenyl)ethyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (0.020 g, 0.046 mmol), potassium carbonate (0.0193 g, 0.139 mmol) 1,1′-bis(diphenylphosphino)ferrocenepalladium(II) dichloride, dichloromethane (3.79 mg, 0.00464 mmol) in previously degassed 4:1 dioxane:water (1.0 mL) was evacuated and charged with N2 (2×) and heated under microwave conditions [Biotage, 100° C., 30 min, high absorption]. This was further purified by Gilson HPLC. The combined fractions were concentrated in vacuo resulting in the title compound an off-white solid. 1H NMR (400 MHz, CD3OD): δ=1.80 (d, J=7.3 Hz, 3H), 3.63 (s, 3H), 3.67 (br. s., 2H), 3.72 (s, 3H), 5.07-5.16 (m, 1H), 6.91 (dd, J=4.2, 9.0 Hz, 1H), 7.10 (dd, J=8.8, 8.8 Hz, 1H), 7.34 (d, J=1.3 Hz, 1H), 7.52 (s, 2H), 7.67 (s, 1H). MS (ES+): m/z 415.09, 417.07 [MH+]. HPLC: tR=3.95 min (polar—5 min, ZQ3)
Reaction SMILES: [CH2:1]([C:3]1[CH:4]=[C:5]2[C:14](=[C:15]3[C:20]=1[CH:19]=[CH:18][CH:17]=[CH:16]3)[CH:13]=[CH:12][C:11]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]2=1)[CH3:2].C1C2C=CC3C(=CC([CH:39]=[O:40])=C4C=3C=CC=C4)C=2C=CC=1>C(Cl)Cl>[CH2:1]([C:3]1[C:20]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[C:14]2[C:5](=[C:6]3[C:11](=[C:12]([CH:39]=[O:40])[CH:13]=2)[CH:10]=[CH:9][CH:8]=[CH:7]3)[CH:4]=1)[CH3:2]
Reactant: O=Cc1cc2c3ccccc3ccc2c2ccccc12
Reactant: CCc1cc2c3ccccc3ccc2c2ccccc12
Solvent: ClCCl
Product: CCc1cc2c3ccccc3c(C=O)cc2c2ccccc12
Yield: 76 %

Procedure:
6-Ethylchrysene (Cambridge Chemical, Inc., 60 g, 0.234 mol) was formylated according to the procedure outlined in 1A, except that CH2Cl2 (1 L) was used as the reaction solvent. The crude material was chromatographed on a plug of SiO2 (1 kg) using PhCH3 as the eluting solvent, afforded 50.38 g (76%) of 12-ethyl-6-chrysenecarbaldehyde mp 138°-139°, (C,H).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:16])[C:5]1[CH:10]=[CH:9][C:8]([OH:11])=[C:7]([O:12][C:13](=[O:15])[CH3:14])[CH:6]=1)[CH3:2].[C:17]1([CH3:26])[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23][CH2:24]O)[CH:18]=1>>[CH2:1]([O:3][C:4](=[O:16])[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH2:24][CH2:23][C:19]2[CH:18]=[C:17]([CH3:26])[CH:22]=[CH:21][CH:20]=2)=[C:7]([O:12][C:13](=[O:15])[CH3:14])[CH:6]=1)[CH3:2]
Reactant: Cc1cccc(CCO)c1
Reactant: CCOC(=O)c1ccc(O)c(OC(C)=O)c1
Product: CCOC(=O)c1ccc(OCCc2cccc(C)c2)c(OC(C)=O)c1

Procedure:
The compound of step 1 (350 mg, 1.56 mmol) was reacted with 2-m-tolyl-ethanol in analogy to step 3 of example 15 to yield 450 mg of the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:8]=[C:7]([OH:9])[C:6]([Br:10])=[CH:5][C:3]=1[OH:4].[OH-].[Na+].[CH2:13](Br)[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]>C(O)C>[Br:1][C:2]1[CH:8]=[C:7]([O:9][CH2:24][CH2:23][CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH3:13])[C:6]([Br:10])=[CH:5][C:3]=1[OH:4]
Reactant: Oc1cc(Br)c(O)cc1Br
Reactant: CCCCCCCCCCCCBr
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CCCCCCCCCCCCOc1cc(Br)c(O)cc1Br
Temperature: 55 °C
Reaction time: 10 h
Yield: 60 %

Procedure:
2,5-Dibromohydroquinone 3 (40.2 g, 0.15 mol) was dissolved in a solution of sodium hydroxide (9.2 g, 0.23 mol) in 1.5 L of absolute ethanol at room temperature under nitrogen atmosphere. The reaction mixture was warmed to 50-60° C. with constant stirring. The dodecylbromide (36 ml, 0.15 mol) was added drop wise to the above reaction mixture at 60° C. After 10 h of stirring under nitrogen atmosphere, the reaction mixture was cooled and the precipitate formed was filtered and washed with methanol. This precipitate was identified as dialleylated-2,5-dibromohydroquinone as a side product. The filtrate was evaporated to remove the solvent. 2 L of distilled water was added to the residue and the mixture was acidified with 36% HCl, boiled gently for 1 h and cooled. The resulting precipitate was collected by filtration, washed with water and dried in vacuo. The crude product was purified by column chromatography using a mixture of solvents (CH2Cl2: hexanes, 4:6) to get the pure product in 60% yield.
Reaction SMILES: [CH2:1]([S:4]([C:7]1[C:17]2[NH:16][C:15](=S)[CH2:14][N:13]=[C:12]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:11]=2[CH:10]=[C:9]([CH3:25])[CH:8]=1)(=[O:6])=[O:5])[CH2:2][CH3:3].[C:26]([NH:30][NH2:31])(=O)[CH2:27][CH3:28]>C(O)C>[CH2:1]([S:4]([C:7]1[C:17]2[N:16]3[C:26]([CH2:27][CH3:28])=[N:30][N:31]=[C:15]3[CH2:14][N:13]=[C:12]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:11]=2[CH:10]=[C:9]([CH3:25])[CH:8]=1)(=[O:6])=[O:5])[CH2:2][CH3:3]
Reactant: CCC(=O)NN
Reactant: CCCS(=O)(=O)c1cc(C)cc2c1NC(=S)CN=C2c1ccccc1
Solvent: CCO
Product: CCCS(=O)(=O)c1cc(C)cc2c1-n1c(CC)nnc1CN=C2c1ccccc1
Temperature: 250 °C

Procedure:
In the manner given in Example 2, 9-(propylsulfonyl)-7-methyl-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepine-2-thione is heated in ethanol with propionic acid hydrazide and the resulting product heated to 250° C. to give 10-(propylsulfonyl)-8-methyl-1-ethyl-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:7]2[N:11]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[C:14]([Br:19])[CH:13]=3)[C:10](=[O:20])[O:9][N:8]=2)=[N:4][O:5][N:6]=1.CO[CH:23](OC)[CH2:24][NH:25][S:26]([NH:29][C:30](=[O:39])[O:31][CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)(=[O:28])=[O:27].FC(F)(F)C(O)=O.C([SiH](CC)CC)C>ClCCCl>[Br:19][C:14]1[CH:13]=[C:12]([N:11]2[C:10](=[O:20])[O:9][N:8]=[C:7]2[C:3]2[C:2]([NH:1][CH2:23][CH2:24][NH:25][S:26]([NH:29][C:30](=[O:39])[O:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)(=[O:27])=[O:28])=[N:6][O:5][N:4]=2)[CH:17]=[CH:16][C:15]=1[F:18]
Reactant: Nc1nonc1-c1noc(=O)n1-c1ccc(F)c(Br)c1
Reactant: COC(CNS(=O)(=O)NC(=O)OCc1ccccc1)OC
Agent: CC[SiH](CC)CC
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCCl
Product: O=C(NS(=O)(=O)NCCNc1nonc1-c1noc(=O)n1-c1ccc(F)c(Br)c1)OCc1ccccc1
Temperature: 0 °C
Reaction time: 2 h
Yield: 104.5 %

Procedure:
A mixture of 3-(4-amino-1,2,5-oxadiazol-3-yl)-4-(3-bromo-4-fluorophenyl)-1,2,4-oxadiazol-5(4H)-one (68 mg, 0.20 mmol; from Step D) and benzyl {[(2,2-dimethoxyethyl)amino]sulfonyl}carbamate (191 mg, 0.60 mmol, 3.0 equiv.) in 1,2-dichloroethane (3.0 mL) was cooled to 0° C. To this mixture was added trifluoroacetic acid (1.0 mL, 13.0 mmol) and triethylsilane (105 μL, 0.66 mmol, 3.3 equiv.) drop-wise. This reaction mixture was stirred at 0° C. for 2 h. HPLC indicated reaction completion. The reaction mixture was cooled to 0° C. and quenched with saturated sodium bicarbonate to pH ˜8. and the quenched reaction mixture was extracted with EtOAc (3×10 mL). The combined organic extracts were washed with brine, dried over sodium sulfate and concentrated. The residue was then stirred in a mixture of heptane and diethyl ether overnight. The solids were collected by filtration, washed with heptane and dried in vacuum to give the desired product (125 mg, 99%) as a crude off-white solid. 1H NMR (300 MHz, DMSO-d6) δ 11.31 (s, 1H), 8.05 (m, 1H), 7.87 (m, 1H), 7.68 (m, 1H), 7.56 (m, 1H), 7.32 (m, 5H), 6.54 (m, 1H), 5.07 (s, 2H), 3.29 (m, 2H), 3.09 (m, 2H); C20H17BrFN7O7S (MW 598.36), LCMS m/e 598/600 (M++H).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:16]([CH2:21][CH2:22][C:23]3[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=3)[C:17]([CH3:20])=[CH:18][CH:19]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:30]([CH:35]1[CH2:40][CH2:39][CH:38]([CH2:41]O)[CH2:37][CH2:36]1)[CH2:31][CH2:32][CH2:33][CH3:34].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1(C)C=CC=CC=1.O>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:16]([CH2:21][CH2:22][C:23]3[CH:28]=[CH:27][C:26]([O:29][CH2:41][CH:38]4[CH2:39][CH2:40][CH:35]([CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])[CH2:36][CH2:37]4)=[CH:25][CH:24]=3)[C:17]([CH3:20])=[CH:18][CH:19]=2)=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1ccc(-c2ccc(OCc3ccccc3)cc2)n1CCc1ccc(O)cc1
Reactant: CCCCCC1CCC(CO)CC1
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: CCCCCC1CCC(COc2ccc(CCn3c(C)ccc3-c3ccc(OCc4ccccc4)cc3)cc2)CC1
Temperature: 80 °C
Reaction time: 12 h
Yield: 79.9 %

Procedure:
To a solution of 4-{2-[2-(4-benzyloxyphenyl)-5-methyl-1H-pyrrol-1-yl]ethyl}phenol (970 mg, 2.53 mmol), 4-pentylcyclohexylmethanol (699 mg, 3.79 mmol) and triphenylphosphine (994 mg, 3.79 mmol) in toluene (2 ml) was added 1,1′-(azodicarbonyl)dipiperidine (956 mg, 3.79 mmol) and the mixture was stirred at 80° C. for 12 hours. The reaction solution was poured into water and the mixture was extracted with ethyl acetate. The extract was dried over magnesium sulfate anhydride and the solvent was removed under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=30:1) to give the object compound as a solid. 1.11 g (yield: 79.9%)