Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH:11]=O)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[NH:13]1[CH2:17][CH2:16][CH2:15][CH2:14]1.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].O>ClC(Cl)C.CC(O)=O>[I:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2([CH2:11][N:13]3[CH2:17][CH2:16][CH2:15][CH2:14]3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1
Reactant: C1CCNC1
Reactant: O=CC1(c2ccc(I)cc2)CC1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Solvent: CC(Cl)Cl
Product: Ic1ccc(C2(CN3CCCC3)CC2)cc1
Temperature: 25 °C
Reaction time: 0.33 h

Procedure:
Part A. 1-(4-Iodophenyl)cyclopropane carboxylic acid (0.64 g, 2.25 mmol) was stirred in THF (10 mL) at 0° C. under N2. Et3N (0.47 mL, 3.37 mmol) was added, followed by dropwise addition of ClCO2Et (0.28 mL, 2.93 mmol). The reaction mixture was then stirred at 0° C. for 30 min. TLC showed the completion of the reaction. The mixture was filtered through a filter funnel and rinsed with anhydrous THF. The THF filtrate (ca.15 mL) was stirred at 0° C. under N2. NaBH4 (0.41 g, 10.8 mmol) was added, followed by addition of MeOH (3 mL). The resulting mixture was stirred at 0° C. for 30 min. Analytical LC-MS showed completion of the reaction. Sat'd Na2SO4 was then added. The mixture was extracted with EtOAc (2×). The organic layer was washed with H2O (2×) and brine (2×), dried over Na2SO4, filtered, and concentrated to dryness. The resulting alcohol was stirred in anhydrous CH2Cl2 (10 mL) at RT under N2. NaOAc (0.42 g, 5.12 mmol) and molecular sieves (4 Å, 0.75 g) were added, followed by the addition of PCC (0.83 g, 3.84 mmol). The resulting slurry was stirred at RT for 1.5 h. Analytical LC-MS showed completion of the reaction. The mixture was filtered through Celite, and rinsed with CH2Cl2. The filtrate was washed with H2O (2×) and brine (2×), dried over Na2SO4, filtered, and concentrated in vacuo to give almost pure 4-iodophenylcyclopropanecarbaldehyde. This aldehyde and pyrrolidine (0.37 mmol) were stirred in dichloroethane (6 mL) at RT under N2. NaBH(OAc)3 (1.37 mg, mmol) was added, followed by addition of several drops of HOAc. The reaction mixture was stirred at RT for 20 min. Analytical LC-MS showed completion of the reaction. H2O was added. The mixture was extracted with EtOAc; and the organic extracts were washed with H2O (2×) and brine (2×), dried over Na2SO4, filtered, and concentrated to dryness to give almost pure 1-{[1-(4-iodophenyl)cyclopropyl]methyl}pyrrolidine (0.41 g, yield % for 3 steps). LC/MS (ESI+) 328.2 (M+H)+. (10–90% CH3CN/H2O in a 4-min run, tR=1.77 min).
Reaction SMILES: [C:1]([NH:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].[C:13]1([P:19](Cl)(Cl)=[O:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>>[C:13]1([P:19]2(=[O:20])[C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=3[CH2:6][N:5]2[C:1]([CH3:4])([CH3:2])[CH3:3])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: O=P(Cl)(Cl)c1ccccc1
Reactant: CC(C)(C)NCc1ccccc1
Product: CC(C)(C)N1Cc2ccccc2P1(=O)c1ccccc1
Yield: 16 %

Procedure:
The procedure of Example 1 was employed utilizing N-t-butyl-N-benzylamine and phenyl phosphonic dichloride. The reaction of the dilithio compound and the phenyl phosphonic dichloride was conducted at 0° C. The crude product produced as a result of the chromatographic separation was distilled at 160° C. and 0.2 mm to yield a colorless oil. The colorless oil was slurried in petroleum ether to yield 1-phenyl-2-(t-butyl)-2,3-dihydro-1H-2,1-benzazaphosphole-1-oxide (2.75 g, 16% yield) as a white solid having a melting point of 89°-91° C. and the following analysis:
Reaction SMILES: [C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[O:15][C:14]([C:16]3[CH:17]=[C:18]([C:22]4[O:26][C:25]([C:27]5[CH:28]=[C:29]([OH:33])[CH:30]=[CH:31][CH:32]=5)=[N:24][N:23]=4)[CH:19]=[CH:20][CH:21]=3)=[N:13][N:12]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].CC1C=CC(S(O[CH2:45][CH:46]2[CH2:51][CH:50]3[CH2:52][CH:47]2[CH:48]=[CH:49]3)(=O)=O)=CC=1.C([O-])([O-])=O.[Cs+].[Cs+].O>CN(C=O)C.ClCCl.CO>[CH:47]12[CH2:52][CH:50]([CH:49]=[CH:48]1)[CH2:51][CH:46]2[CH2:45][O:33][C:29]1[CH:28]=[C:27]([C:25]2[O:26][C:22]([C:18]3[CH:19]=[CH:20][CH:21]=[C:16]([C:14]4[O:15][C:11]([C:8]5[CH:9]=[CH:10][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:6][CH:7]=5)=[N:12][N:13]=4)[CH:17]=3)=[N:23][N:24]=2)[CH:32]=[CH:31][CH:30]=1
Reactant: CC(C)(C)c1ccc(-c2nnc(-c3cccc(-c4nnc(-c5cccc(O)c5)o4)c3)o2)cc1
Reactant: Cc1ccc(S(=O)(=O)OCC2CC3C=CC2C3)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CO
Solvent: CN(C)C=O
Product: CC(C)(C)c1ccc(-c2nnc(-c3cccc(-c4nnc(-c5cccc(OCC6CC7C=CC6C7)c5)o4)c3)o2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 3-(5-(3-(5-(4-tert-butylphenyl)-1,3,4-oxadiazol-2-yl)phenyl)-1,3,4-oxadiazol-2-yl)phenol (0.92 g, 2.10 mmol) and bicyclo[2,2,1]hept-5-en-2-ylmethyl 4-methylbenzenesulfonate (1.6 g, 5.75 mmol) in DMF (45.0 ml), was added Cs2CO3 (4.5 g, 13.81 mmol) at room temperature under nitrogen. The reaction was carried out at 100° C. for 2 hours. After cooling down to room temperature, water (100.0 ml) was added into the reaction mixture. A brown solid precipitate was collected by filtration and washed with methanol and then dried under vacuum. The crude product was purified by a silica gel column using dichloromethane/ethyl acetate, ratio (9.3:0.7), as the eluent. After removal of the solvents, a pure white solid product was obtained in 0.97 g (85.1%) yield by recrystallization from dichloromethane/methanol. 1H NMR (400 MHz, CDCl3) δ: 8.86 (m, 1H), 8.34 (dd, 2H, J1=8.0 Hz, J2=1.6 Hz), 8.11 (d, 2H, J=8.4 Hz), 7.73 (m, 2H), 7.67 (m, 1H), 7.58 (d, 2H, J=8.4 Hz), 7.45 (m, 1H), 7.12 (m, 1H), 6.22-5.99 (m, 2H, C═C—H, endo and exo), 4.17-3.64 (m, 2H, OCH2, endo and exo), 3.09 (s, br), 2.91 (m, br), 2.61 (m, br), 1.95 (m), 1.52 (m), 1.39 (s, 9H, 3×CH3), 1.40-1.23 (m), 0.68 (m) ppm. 13C NMR (100 MHz, CDCl3) δ: 165.14, 163.65, 163.38, 159.57, 155.67, 137.68, 136.90, 136.38, 132.29, 130.26, 129.99, 129.77, 129.71, 126.92, 126.13, 125.13, 124.98, 124.94, 124.61, 120.73, 119.31, 119.22, 118.90, 112.29, 72.57, 71.78, 49.42, 45.06, 43.87, 43.69, 42.23, 41.60, 38.54, 38.32, 35.12, 31.10, 29.62, 28.99 ppm. MS (m/z): [M+1]+ calcd for C34H32N4O3 545.3. found 545.2. Anal. Calcd for C34H32N4O3: C, 74.98; H, 5.92; N, 10.29. Found: C, 74.77; H, 6.02; N, 10.27.
Reaction SMILES: [OH:1][C:2]1[N:11]=[C:10]([OH:12])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[N:3]=1>O=[Pt]=O.FC(F)(F)C(O)=O>[OH:1][C:2]1[N:11]=[C:10]([OH:12])[C:9]2[CH2:8][CH2:7][CH2:6][CH2:5][C:4]=2[N:3]=1
Reactant: Oc1nc(O)c2ccccc2n1
Agent: O=[Pt]=O
Solvent: O=C(O)C(F)(F)F
Product: Oc1nc(O)c2c(n1)CCCC2
Yield: 34.5 %

Procedure:
A mixture solution of 2,4-dihydroxyquinazoline(39.2 g, 0.24 mol), platinium oxide(4 g) and trifluoroacetic acid(300 ml) was hydrogenated by Parr reactor for 2 hours. Platinium was filtered and the filtrate was concentrated, diluted with water, and basified with 1N-NaOH solution. The resulting solid was filtered and dried to give 13.76 g of the titled compound. (Yield: 34.5%)
Reaction SMILES: [O-:1][CH2:2][CH3:3].[Na+].Cl[C:6]1[N:19]=[C:18]([O:20][CH2:21][C:22]([F:25])([F:24])[F:23])[CH:17]=[CH:16][C:7]=1[C:8]([O:10][CH2:11][C:12](F)(F)F)=[O:9].O>O1CCCC1>[CH2:2]([O:1][C:6]1[N:19]=[C:18]([O:20][CH2:21][C:22]([F:25])([F:23])[F:24])[CH:17]=[CH:16][C:7]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH3:3]
Reactant: CC[O-]
Reactant: O=C(OCC(F)(F)F)c1ccc(OCC(F)(F)F)nc1Cl
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CCOC(=O)c1ccc(OCC(F)(F)F)nc1OCC
Temperature: 25 °C
Reaction time: 1 h
Yield: 87.4 %

Procedure:
Sodium ethoxide (1.4 mL, 3.55 mmol, 20% in ethanol) is added to a solution of 2,2,2-trifluoroethyl 2-chloro-6-(2,2,2-trifluoroethoxy)nicotinate (400 mg, 1.19 mmol, Step-1 of Amine-37) in tetrahydrofuran (15 mL) and stirred at room temperature for 1 hour. The reaction mixture is poured into water and extracted with ethyl acetate and dried over sodium sulfate and concentrated in vacuo. The residue is purified by column chromatography on silica gel eluting with n-Hexane/ethyl acetate (7:1) to give 305 mg (88% yield) of title compound as a white solid.
Reaction SMILES: [CH3:1][C:2]1[NH:3][CH:4]=[CH:5][N:6]=1.[F:7][C:8]([F:19])([F:18])[C:9]1[CH:14]=[CH:13][C:12](B(O)O)=[CH:11][CH:10]=1>C1COCC1>[CH3:1][C:2]1[N:3]([C:12]2[CH:13]=[CH:14][C:9]([C:8]([F:19])([F:18])[F:7])=[CH:10][CH:11]=2)[CH:4]=[CH:5][N:6]=1
Reactant: OB(O)c1ccc(C(F)(F)F)cc1
Reactant: Cc1ncc[nH]1
Solvent: C1CCOC1
Product: Cc1nccn1-c1ccc(C(F)(F)F)cc1
Reaction time: 8 h

Procedure:
2-Methylimidazole (1.0 g, 12 mmol) was dissolved in 35 mL THF. 4-(Trifluoromethyl)phenylboronic acid (2.66 g, 14 mmol) and [Cu(OH)TMEDA]2Cl2 (1.13 g, 2 mmol) were added. Oxygen was bubbled through the reaction mixture for 30 minutes and stirring was continued at room temperature overnight. The reaction mixture was filtered through a dicalite speed plus pad, washed with 80 ml THF and evaporated. The crude product was purified by flash chromatography on silica gel with ethyl acetate. The desired compound was obtained as a light yellow solid (1.6 g, 58%), MS: m/e=227.2 (M+H+).
Reaction SMILES: [CH:1]1([N:4]2[C:13]3[C:8](=[C:9]([NH2:17])[C:10]([F:16])=[C:11](F)[C:12]=3[F:14])[C:7](=[O:18])[C:6]([C:19]([OH:21])=[O:20])=[CH:5]2)[CH2:3][CH2:2]1.[CH3:22][N:23]1[CH2:27][CH2:26][CH:25]([CH2:28][OH:29])[CH2:24]1.CN(C=O)C.[H-].[Na+]>C(O)(=O)C>[CH3:22][N:23]1[CH2:27][CH2:26][CH:25]([CH2:28][O:29][C:11]2[C:12]([F:14])=[C:13]3[C:8]([C:7](=[O:18])[C:6]([C:19]([OH:21])=[O:20])=[CH:5][N:4]3[CH:1]3[CH2:3][CH2:2]3)=[C:9]([NH2:17])[C:10]=2[F:16])[CH2:24]1
Reactant: Nc1c(F)c(F)c(F)c2c1c(=O)c(C(=O)O)cn2C1CC1
Reactant: CN1CCC(CO)C1
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CN(C)C=O
Product: CN1CCC(COc2c(F)c(N)c3c(=O)c(C(=O)O)cn(C4CC4)c3c2F)C1
Temperature: 25 °C

Procedure:
To a mixture of 596 mg of 1-cyclopropyl-5-amino-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, 460 mg of 1-methyl-3-hydroxymethylpyrrolidine and 5 ml of DMF was added 262 mg of 55% sodium hydride while the former was stirred at room temperature. After the resultant mixture was stirred for 1 hour at room temperature, 360 mg of acetic acid was added and DMF was distilled off under reduced pressure. The residue was purified by chromatography on silica gel (chloroform/methanol: 3/1), followed by recrystallization from ethanol. The title compound was obtained as pale green powder (yield: 240 mg).
Reaction SMILES: C([O:3][C:4](=[O:27])[CH2:5][S:6][C:7]1[S:8][C:9]([NH:12][C:13]([N:15]([CH:21]2[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]2)[CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[O:14])=[N:10][N:11]=1)C.C1(NC2CCCC2)CCCCC1.C(OC(=O)CSC1SC(N)=NN=1)C>>[CH:21]1([N:15]([CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[C:13](=[O:14])[NH:12][C:9]2[S:8][C:7]([S:6][CH2:5][C:4]([OH:27])=[O:3])=[N:11][N:10]=2)[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]1
Reactant: CCOC(=O)CSc1nnc(NC(=O)N(C2CCCCC2)C2CCCC2)s1
Agent: C1CCC(NC2CCCC2)CC1
Agent: CCOC(=O)CSc1nnc(N)s1
Product: O=C(O)CSc1nnc(NC(=O)N(C2CCCCC2)C2CCCC2)s1

Procedure:
[5-(3-Cyclohexyl-3-cyclopentyl-ureido)-[1,3,4]thiadiazol-2-ylsulfanyl]-acetic acid ethyl ester prepared as described in general procedures (A) and (B) using cyclohexyl-cyclopentyl-amine and ethyl-2-[5-amino-1,3,4-thiadiazol-2-yl-thio]acetate. Hydrolysis using general procedure (F) gave the title compound.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:14]=[O:15]>C(O)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([CH2:2][C:1]([CH3:4])([CH3:3])[CH2:14][OH:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: C=O
Solvent: CC(=O)O
Product: CC(C)(CO)CN1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 94 %

Procedure:
2.9 g of N-(tert-butyloxycarbonyl)piperazine and 1.6 ml of 35% formalin were dissolved in 8 ml of acetic acid, and the resulting solution was stirred at room temperature for 30 minutes. Then, 1.5 ml of isobutylaldehyde was added, and the resulting mixture was stirred at 50° C. for 12 hours. After concentration under reduced pressure, the residue was extracted with ethyl acetate and washed with saturated aqueous sodium bicarbonate. After drying with anhydrous sodium sulfate, the solvent was evaporated under reduced pressure to give 3.9 g of a colorless powdery crystal (yield: 94%). The IR and NMR data of the compound thus obtained are as follows: ##STR51##
Reaction SMILES: C([NH:4][C:5]1[CH:6]=[C:7]([C:11]2[N:12]([CH3:17])[N:13]=[N:14][C:15]=2[SH:16])[CH:8]=[CH:9][CH:10]=1)(=O)C>Cl>[NH2:4][C:5]1[CH:6]=[C:7]([C:11]2[N:12]([CH3:17])[N:13]=[N:14][C:15]=2[SH:16])[CH:8]=[CH:9][CH:10]=1
Reactant: CC(=O)Nc1cccc(-c2c(S)nnn2C)c1
Agent: Cl
Product: Cn1nnc(S)c1-c1cccc(N)c1
Reaction time: 3 h

Procedure:
150 ml of 12N hydrochloric acid was added to 10 g of 4-(3-acetylaminophenyl)-3-methyl-5-mercaptotriazole (4) thus obtained. The system was then heated under reflux. After 3 hours, the system was cooled. Water was then distilled off by a rotary evaporator to obtain crystals of crude 4-(3-aminophenyl)-3-methyl-5-mercaptotriazole (5). 100 ml of acetonitrile was added to this crystal. 12 g of pyridine was then added to the system. The system was stirred. 7.5 g of phenyl chlorocarbonate was added dropwise to the system while the system was kept at a temperature of 5° C. or lower in an iced-water bath. After completion of the dropwise addition, the system was allowed to undergo reaction over 10 minutes. 20 ml of water was added to the reaction solution. The solvent was then distilled off by a rotary evaporator. The resulting concentrated solution was extracted with ethyl acetate. The extract was then washed with saturated aqueous solution of sodium chloride, and dried with sodium sulfate anhydride. The solvent was distilled off to obtain a crystals of crude 4-(3-phenoxycarbonylaminophenyl)-3-methyl-5-mercaptotriazole (6). The crude crystals were recrystallized from ethyl acetate to obtain 13 g of Compound (6). (Yield: 98%; m.p. 188° C.)
Reaction SMILES: [Cl:1][C:2]1[C:7]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[O:15][CH3:16])=[C:6](Cl)[N:5]=[C:4]([C:18]2[CH:23]=[CH:22][N:21]=[C:20]([C:24]#[N:25])[CH:19]=2)[N:3]=1.[CH:26]([C:29]1[CH:30]=[CH:31][C:32]([S:35]([NH2:38])(=[O:37])=[O:36])=[N:33][CH:34]=1)([CH3:28])[CH3:27].C(=O)([O-])[O-].[K+].[K+].Cl>CC(C)=O.C1N2CCN(CC2)C1.C(C1C=CC(S(N)(=O)=O)=NC=1)(C)C.O>[Cl:1][C:2]1[N:3]=[C:4]([C:18]2[CH:23]=[CH:22][N:21]=[C:20]([C:24]#[N:25])[CH:19]=2)[N:5]=[C:6]([NH:38][S:35]([C:32]2[CH:31]=[CH:30][C:29]([CH:26]([CH3:28])[CH3:27])=[CH:34][N:33]=2)(=[O:37])=[O:36])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:15][CH3:16]
Reactant: CC(C)c1ccc(S(N)(=O)=O)nc1
Reactant: COc1ccccc1Oc1c(Cl)nc(-c2ccnc(C#N)c2)nc1Cl
Agent: C1CN2CCN1CC2
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CC(C)=O
Solvent: O
Product: COc1ccccc1Oc1c(Cl)nc(-c2ccnc(C#N)c2)nc1NS(=O)(=O)c1ccc(C(C)C)cn1
Temperature: 40 °C
Reaction time: 20 h
Yield: 102.4 %

Procedure:
8.95 g (24 mmol) of 4-[4,6-dichloro-5-(2-methoxy-phenoxy)-pyrimidine-2-yl]-pyridine-2-carbonitrile were suspended in 100 ml of acetone. At a temperature of 20° C., 5.04 g (25 mmol) of 5-isopropyl-pyridine-2-sulfonamide, 1 ml of de-ionized water, 10.6 g (77 mmol) of potassium carbonate and 135 mg (1.2 mmol) 1,4-diazobicyclo[2.2.2]octane were added. The mixture was stirred at 40° C. for 20 hr. Thereafter, another 240 mg (1.2 mmol) of 5-isopropyl-pyridine-2-sulfonamide and 80 mg (0.7 mmol) of 1,4-diazobicyclo[2.2.2]octane were added. The reaction mixture was stirred for 24 hr at 40° C. followed by cooling to 20° C. Then 50 ml of de-ionized water and 45 ml of 3 N aqueous hydrochloric acid were added slowly until pH=1. The acetone was removed by distillation and the resulting suspension was stirred at 20° C. for 1.5 hr. The solid was filtered off under suction, washed first with 100 ml of de-ionized water and thereafter with 50 ml of t-butylmethylether. Then the solid was dried at 70° C., 2000 Pa for 20 hr. There were obtained 13.2 g (102% of theory) of 5-isopropyl-pyridin 2-sulfonic acid [6-chloro-2-(2-cyano-pyridine-4-yl)-5-(2-methoxy-phenoxy)-pyrimidine-4-yl]-amide with a HPLC purity of 87.8% (w/w).
Reaction SMILES: [CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:47]=[CH:46][C:16]([CH2:17][N:18]([C:33]3[CH:45]=[CH:44][C:36]4[O:37]C(C)(C)[O:39][C:40](=[O:41])[C:35]=4[CH:34]=3)[C:19](=[O:32])[C:20]3[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[CH:22][CH:21]=3)=[CH:15][CH:14]=2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4].[OH-].[Na+]>CCO>[CH2:1]([C:5]1[CH:6]=[CH:7][C:8]([C:11]#[C:12][C:13]2[CH:47]=[CH:46][C:16]([CH2:17][N:18]([C:19](=[O:32])[C:20]3[CH:25]=[CH:24][C:23]([CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH3:31])=[CH:22][CH:21]=3)[C:33]3[CH:45]=[CH:44][C:36]([OH:37])=[C:35]([CH:34]=3)[C:40]([OH:41])=[O:39])=[CH:15][CH:14]=2)=[CH:9][CH:10]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCCCc1ccc(C(=O)N(Cc2ccc(C#Cc3ccc(CCCC)cc3)cc2)c2ccc3c(c2)C(=O)OC(C)(C)O3)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CCCCCCc1ccc(C(=O)N(Cc2ccc(C#Cc3ccc(CCCC)cc3)cc2)c2ccc(O)c(C(=O)O)c2)cc1

Procedure:
The titled compound was prepared following the procedure C using N-{4-[(4-butylphenyl)ethynyl]benzyl}-N-(2,2-dimethyl-4-oxo-4H-1,3-benzodioxin-6-yl)-4-hexylbenzamide and NaOH 5M aq. in the presence of EtOH as a grey powder (43%). 1H NMR (CDCl3, 300 MHz) δ 10.46 (s, 1H), 7.46 (m, 5H), 7.27 (m, 4H), 7.16 (d, J=7.9 Hz, 2H), 7.00 (m, 3H), 6.76 (d, J=9.0 Hz, 1H), 5.10 (s, 2H), 2.62 (t, J=7.6 Hz, 2H), 2.52 (t, J=7.7 Hz, 2), 1.58 (m, 4H), 1.36 (m, 2H), 1.24 (brs, 6H), 0.93 (t, J=7.2 Hz, 3H), 0.85 (t, J=6.8 Hz, 3H). M− (ESI): 586.3; M1(ESI): 588.2. HPLC, Rt: 6.04 min (Purity: 98.3%).
Reaction SMILES: [C:1]1([CH:7]=[CH:8][CH2:9][CH:10]2[NH:16][C:15](=[O:17])[CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.F[B-](F)(F)F.[CH3:23][O+](C)C>C(Cl)Cl>[CH3:23][O:17][C:15]1[CH2:14][CH2:13][CH2:12][CH2:11][CH:10]([CH2:9][CH:8]=[CH:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:16]=1
Reactant: O=C1CCCCC(CC=Cc2ccccc2)N1
Reactant: C[O+](C)C
Agent: F[B-](F)(F)F
Solvent: ClCCl
Product: COC1=NC(CC=Cc2ccccc2)CCCC1
Yield: 99 %

Procedure:
The title material of Example 32 (0.50 g, 2.2 mmol) in CH2Cl2 (15 mL) and in the presence of 3A molecular sieves (1.0 g) was reacted with trimethyloxonium tetrafluoroborate (0.39 g, 2.6 mmol) by the method of Example 3 to produce 0.53 g (99%) of the title material.
Reaction SMILES: [CH3:1][N:2](C)C=O.[Si:6]([O:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:21]2[CH:26]=[CH:25][N:24]=[C:23](Cl)[N:22]=2)=[CH:16][CH:15]=1)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7]>[C-]#N.[Zn+2].[C-]#N.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[Si:6]([O:13][C:14]1[CH:19]=[CH:18][C:17]([NH:20][C:21]2[CH:26]=[CH:25][N:24]=[C:23]([C:1]#[N:2])[N:22]=2)=[CH:16][CH:15]=1)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7]
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(Nc2ccnc(Cl)n2)cc1
Reactant: CN(C)C=O
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [C-]#N
Agent: [Zn+2]
Solvent: O
Product: CC(C)(C)[Si](C)(C)Oc1ccc(Nc2ccnc(C#N)n2)cc1
Temperature: 120 °C
Reaction time: 2 h

Procedure:
Anhydrous N,N-dimethylformamide (10 mL) is placed under nitrogen in a flask and then the compound of Step A (670 mg, 2.0 mmol) is added. Zinc cyanide (468 mg, 4.0 mmol) and tetrakis(triphenylphosphine)palladium(0) (404 mg, 0.3 mmol) are subsequently added. Nitrogen is bubbled through the solution for 5 minutes and then the reaction mixture is stirred at 120° C. for 2 hours under a nitrogen atmosphere. The reaction, monitored by LC-MS, is complete. The mixture is cooled to ambient temperature, and then water (15 mL) is added thereto. The product is extracted with AcOEt (3×25 mL). The organic phases are combined and washed with water (4×25 mL), and then with brine (1×25 mL). The organic phase is dried over MgSO4, filtered and concentrated in vacuo. The residue is purified by chromatography over silica gel using ethyl acetate and heptane as eluants to obtain the expected compound in the form of a solid.
Reaction SMILES: [CH3:1][N:2]([CH2:6][CH2:7][CH:8]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1)[CH2:3][CH2:4][NH2:5].[C:21]([NH:23][C:24](=[N:32][CH2:33][CH2:34][CH2:35][O:36][C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([CH2:43][N:44]2[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]2)[CH:38]=1)OC1C=CC=CC=1)#[N:22]>C(OCC)(=O)C>[C:21]([NH:23][C:24]([NH:5][CH2:4][CH2:3][N:2]([CH2:6][CH2:7][CH:8]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=1)[CH3:1])=[N:32][CH2:33][CH2:34][CH2:35][O:36][C:37]1[CH:42]=[CH:41][CH:40]=[C:39]([CH2:43][N:44]2[CH2:45][CH2:46][CH2:47][CH2:48][CH2:49]2)[CH:38]=1)#[N:22]
Reactant: N#CNC(=NCCCOc1cccc(CN2CCCCC2)c1)Oc1ccccc1
Reactant: CN(CCN)CCC(c1ccccc1)c1ccccn1
Solvent: CCOC(C)=O
Product: CN(CCNC(=NCCCOc1cccc(CN2CCCCC2)c1)NC#N)CCC(c1ccccc1)c1ccccn1

Procedure:
Preparation is effected analogously to Example 1, using 0.7 g (2.6 mmol) of N-methyl-N-[3-phenyl-3-(2-pyridyl)propyl]-1,2-ethanediamine and 1 g (2.5 mmol) of N-cyano-O-phenyl-N'-[3-[3-(piperidinomethyl)phenoxy]propyl]isourea as starting materials. Working up by chromatography (eluant: ethyl acetate) analogously to Example 1 yields the purified title compound in the form of a viscous oil; MS (+FAB method): m/z (rel. int.[%])=568 ([M+H]+ 3), 196 (100).
Reaction SMILES: [N:1]1([C:7]2[N:12]3[N:13]=[C:14]([C:16]4[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=4)[CH:15]=[C:11]3[N:10]=[C:9]([NH:22][NH2:23])[CH:8]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH:24]([C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][CH:34]=1)[CH:30]=O)([CH3:26])[CH3:25]>C(O)C>[CH:24]([C:27]1[CH:28]=[C:29]([CH:32]=[CH:33][CH:34]=1)[CH:30]=[N:23][NH:22][C:9]1[CH:8]=[C:7]([N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)[N:12]2[N:13]=[C:14]([C:16]3[CH:17]=[CH:18][N:19]=[CH:20][CH:21]=3)[CH:15]=[C:11]2[N:10]=1)([CH3:26])[CH3:25]
Reactant: NNc1cc(N2CCOCC2)n2nc(-c3ccncc3)cc2n1
Reactant: CC(C)c1cccc(C=O)c1
Solvent: CCO
Product: CC(C)c1cccc(C=NNc2cc(N3CCOCC3)n3nc(-c4ccncc4)cc3n2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 26.5 %

Procedure:
There was dissolved, in ethanol (2 mL), (7-morpholin-4-yl-2-pyridin-4-yl-pyrazolo[1,5-a]pyrimidin-5-yl)-hydrazine (30.1 mg, 0.0967 mM), then 3-isopropyl-benzaldehyde (14.3 mg, 0.0967 mM) was added to the solution and the mixture was stirred at room temperature overnight. The solvent was distilled off from this reaction liquid, the resulting residue was purified by the reversed phase HPLC and then subjected to a desalting treatment to thus give the title compound (11.3 mg, yield: 26%).
Reaction SMILES: [CH3:1][C:2]1([CH3:14])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[NH:4][C:3]1=[O:13].Cl[CH2:16][CH2:17][S:18][CH3:19].[Na]>C(O)(C)C>[CH3:1][C:2]1([CH3:14])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[N:4]([CH2:16][CH2:17][S:18][CH3:19])[C:3]1=[O:13]
Reactant: CC1(C)C(=O)NC(=O)c2ccccc21
Reactant: CSCCCl
Agent: [Na]
Solvent: CC(C)O
Product: CSCCN1C(=O)c2ccccc2C(C)(C)C1=O

Procedure:
5.7 gm of 4,4-dimethyl-2H,4H-isoquinoline-1,3-dione and 3.3 gm of 1-chloro-2-methylmercapto-ethane were added to a solution of 0.7 gm of sodium in 200 ml of isopropanol. After refluxing the mixture for 3 hours the solvent was removed in vacuo, and the residue was taken up in water and chloroform. The separated organic phase was worked up as described in Example 1. Yield: 7 gm (88.6% of theory).