Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: F[C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[C:10]1([C:12](=[CH:14][CH:15]=[CH:16][CH:17]=1)[OH:13])[OH:11]>CN(C=O)C>[C:4]([C:3]1[CH:6]=[CH:7][CH:8]=[CH:9][C:2]=1[O:11][C:10]1[CH:17]=[CH:16][CH:15]=[CH:14][C:12]=1[O:13][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5])#[N:5]
Reactant: N#Cc1ccccc1F
Reactant: Oc1ccccc1O
Solvent: CN(C)C=O
Product: N#Cc1ccccc1Oc1ccccc1Oc1ccccc1C#N
Yield: 84.6 %

Procedure:
The compound 1,2-Bis(2-cyanophenoxy)benzene was synthesized in the same manner as for 1,2-bis-(4-4-cyanophenoxy)benzene according to Example 1 above, but from 2-fluorobenzonitrile and catechol, except that the synthesis was performed in DMF at 125° C. and over a period of 10 hours. The precipitate was filtered off and washed several times with deionised water. The white product was recrystallized from methanol/water (8:1). The yield was 84.6% of the title compound with the formula: ##STR6##
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:17]3[C:12](=[CH:13][C:14]([F:20])=[C:15](F)[C:16]=3[F:18])[C:11](=[O:21])[C:10]([C:22]([OH:24])=[O:23])=[CH:9]2)=[CH:4][CH:3]=1.[F:25][C:26]1[CH:34]=[CH:33][CH:32]=[C:31]2[C:27]=1[CH2:28][NH:29][CH2:30]2>CN(C=O)C>[F:25][C:26]1[CH:34]=[CH:33][CH:32]=[C:31]2[C:27]=1[CH2:28][N:29]([C:15]1[C:16]([F:18])=[C:17]3[C:12]([C:11](=[O:21])[C:10]([C:22]([OH:24])=[O:23])=[CH:9][N:8]3[C:5]3[CH:6]=[CH:7][C:2]([F:1])=[CH:3][CH:4]=3)=[CH:13][C:14]=1[F:20])[CH2:30]2
Reactant: Fc1cccc2c1CNC2
Reactant: O=C(O)c1cn(-c2ccc(F)cc2)c2c(F)c(F)c(F)cc2c1=O
Solvent: CN(C)C=O
Product: O=C(O)c1cn(-c2ccc(F)cc2)c2c(F)c(N3Cc4cccc(F)c4C3)c(F)cc2c1=O
Yield: 82.9 %

Procedure:
170 mg of 1-(4-fluorophenyl)-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, 210 mg of 4-fluoroisoindoline, and 1.5 ml of anhydrous DMF were processed in the same manner as in Example 20 to produce 190 mg of the target compound.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:14])([F:13])[C:9]([F:12])([F:11])[F:10])=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16].N1CCCC1.CO[CH:25](OC)[N:26]([CH3:28])[CH3:27]>C1(C)C=CC=CC=1>[CH3:25][N:26]([CH3:28])/[CH:27]=[CH:1]/[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:13])([F:14])[C:9]([F:12])([F:11])[F:10])=[CH:4][C:3]=1[N+:15]([O-:17])=[O:16]
Reactant: Cc1ccc(C(F)(F)C(F)(F)F)cc1[N+](=O)[O-]
Reactant: COC(OC)N(C)C
Solvent: C1CCNC1
Solvent: Cc1ccccc1
Product: CN(C)/C=C/c1ccc(C(F)(F)C(F)(F)F)cc1[N+](=O)[O-]
Temperature: 25 °C

Procedure:
To a solution of 1-methyl-2-nitro-4-(perfluoroethyl)benzene (10.0 g, 39.2 mmol) and pyrollidine (2.79 g, 39.2 mmol) in toluene (250 mL) was added dimethyl formamide dimethyl acetal (4.96 g, 39.2 mmol). The mixture was heated to reflux for 16 hours. After cooling to room temperature the mixture was concentrated under vacuum and the resulting oil was immediately used in the next reaction.
Reaction SMILES: C(OC(=O)[NH:7][CH:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]([C:16]2[CH:36]=[CH:35][C:19]3[N:20]([CH3:34])[C:21]([C:23]4[N:31]([CH2:32][CH3:33])[C:26]5=[N:27][CH:28]=[CH:29][CH:30]=[C:25]5[CH:24]=4)=[N:22][C:18]=3[CH:17]=2)=[O:15])[CH2:9]1)(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl>[NH2:7][CH:8]1[CH2:13][CH2:12][CH2:11][N:10]([C:14]([C:16]2[CH:36]=[CH:35][C:19]3[N:20]([CH3:34])[C:21]([C:23]4[N:31]([CH2:32][CH3:33])[C:26]5=[N:27][CH:28]=[CH:29][CH:30]=[C:25]5[CH:24]=4)=[N:22][C:18]=3[CH:17]=2)=[O:15])[CH2:9]1
Reactant: CCn1c(-c2nc3cc(C(=O)N4CCCC(NC(=O)OC(C)(C)C)C4)ccc3n2C)cc2cccnc21
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCn1c(-c2nc3cc(C(=O)N4CCCC(N)C4)ccc3n2C)cc2cccnc21
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of tert-butyl(1-(2-(1-ethyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-methyl-1H-benzo[d]imidazole-5-carbonyl)piperidin-3-yl)carbamate (104 mg, 0.207 mmol) in dichloromethane (DCM) (1 mL) was added TFA (0.367 mL, 4.76 mmol) and the reaction stirred at room temperature for 2 h. LCMS (A1) showed no desired product but reaction had progressed to 1 major product. The reaction mixture was concentrated in vacuo to afford a colourless oil. This was dissolved in methanol and loaded onto an SCX cartridge (5 g). It was eluted with methanol (3 column volumes) and product eluted as free base with 2M ammonia in methanol. The filtrate from the ammonia fractions was concentrated in vacuo to yield a yellow solid—(3-aminopiperidin-1-yl)(2-(1-ethyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-1-methyl-1H-benzo[d]imidazol-5-yl)methanone (81 mg, 0.201 mmol, 97% yield).
Reaction SMILES: [CH:1]1[CH:6]=[CH:5][C:4](/[CH:7]=[C:8](/[N+:17]([O-:19])=[O:18])\[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[O:10])=[CH:3][CH:2]=1.[CH:20]1[CH2:24][CH:23]=[CH:22][CH:21]=1>C(Cl)Cl>[C:9]([C@:8]1([N+:17]([O-:19])=[O:18])[C@H:7]([C:4]2[CH:3]=[CH:2][CH:1]=[CH:6][CH:5]=2)[C@@H:22]2[CH2:23][C@H:24]1[CH:20]=[CH:21]2)(=[O:10])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: C1=CCC=C1
Reactant: O=C(/C(=C\c1ccccc1)[N+](=O)[O-])c1ccccc1
Solvent: ClCCl
Product: O=C(c1ccccc1)[C@@]1([N+](=O)[O-])[C@@H]2C=C[C@@H](C2)[C@H]1c1ccccc1
Temperature: 45 °C
Reaction time: 24 h
Yield: 80.9 %

Procedure:
A solution of (E)α-nitrochalcone [Dornow et al., Ann., 588:40 (1954); Yamamura et al., Bull. Chem. Soc., Jpn. 44:2440 (1971)] (Compound 7, 5.35 g, 21.1 mmol) in a minimum amount of CH2Cl2 (2-3 mL) was treated with freshly cracked cyclopentadiene (15.7 mL, 190 mmol, 9.0 equiv. ). The reaction mixture was stirred at 45° C. for 24 hours before the mixture was partitioned between CH2Cl2 (200 mL) and H2O (200 mL). The CH2Cl2 layer was dried (Na2SO4) and concentrated under reduced pressure. Chromatography (SiO2, 5×15 cm, 5 percent Et2O-hexane eluant) afforded Compound 9 (5.45 g, 6.73 g theoretical, 81 percent) as a white crystalline solid: mp 119°-120° C. (Et2O-hexane, colorless needles); 1H NMR (CDCl3, 250 MHz) δ 7.33 (d, 2H, J=8.0 Hz), 7.25-6.97 (m, 8H), 6.72 (m, 1H, C6-H), 5.99 (m, 1H, C5-H), 4.24 (d, 1H, J=2.7 Hz, C3-H), 3.84 (s, 1H, C1-H), 2.93 (s, 1H, C4-H), 2.65 (d, 1H, J=9.8 Hz, C7-H syn to ketone), 1.86 (d, 1H, J=9.9 Hz, C7-H anti to ketone); 13C NMR (CDCl3, 62.5 MHz) δ192.5, 144.3, 137.9, 134.2, 133.7, 133.0, 129.0, 128.6, 128.4, 127.9, 127.5, 105.4, 54.8, 53.5, 51.1, 48.5; IR (neat) vmax 3004, 2970, 1685, 1540, 1465, 1354, 1240 cm-1 ; FABHRMS (NBA-NaI) m/e 342.1101 (C20H17NO3 +Na+ requires 342.1106). A mixture of minor diastereomers (<3 percent) was isolated in trace amounts. Anal. Calcd for C20H17NO3 : C, 75.22; H, 5.37; N, 4.39. Found: C, 74.85; H, 5.29; N, 4.55.
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[CH3:13][O:14][C:15](=[O:30])[CH2:16][CH:17]1[CH2:22][CH2:21][N:20]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:19][CH2:18]1.[H-].[Na+].[F:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([CH:40]=[O:41])[C:35]=1[NH:42][C:43](=[O:48])[C:44]([CH3:47])([CH3:46])[CH3:45]>O1CCCC1>[F:33][C:34]1[C:35]([NH:42][C:43](=[O:48])[C:44]([CH3:46])([CH3:45])[CH3:47])=[C:36]([CH:40]([OH:41])[CH:16]([CH:17]2[CH2:18][CH2:19][N:20]([C:23]([O:25][C:26]([CH3:27])([CH3:29])[CH3:28])=[O:24])[CH2:21][CH2:22]2)[C:15]([O:14][CH3:13])=[O:30])[CH:37]=[CH:38][CH:39]=1
Reactant: COC(=O)CC1CCN(C(=O)OC(C)(C)C)CC1
Reactant: CC(C)(C)C(=O)Nc1c(F)cccc1C=O
Agent: [H-]
Agent: [Li]CCCC
Agent: [Na+]
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: COC(=O)C(C1CCN(C(=O)OC(C)(C)C)CC1)C(O)c1cccc(F)c1NC(=O)C(C)(C)C
Temperature: -78 °C
Reaction time: 0.33 h
Yield: 81 %

Procedure:
Diisopropylamine (3.40 mL, 24.2 mmol) was dissolved in tetrahydrofuran (70 mL). The mixture was cooled to −78° C. Butyllithium (2 M in cyclohexane, 12.2 μL, 24.4 mmol) was added dropwise to the reaction. The mixture was held at −78° C. with stirring and held for 20 minutes. A solution of tert-butyl 4-(2-methoxy-2-oxoethyl)piperidine-1-carboxylate (5.20 g, 20.2 mmol) in tetrahydrofuran (15 mL) was added to the mixture dropwise. The mixture was held at −78° C. with stirring and held for 45 min. In a separate flask, sodium hydride (60% in mineral oil, 970 mg, 24.3 mmol) was washed with hexanes then suspended in tetrahydrofuran (50 mL). The mixture was cooled to 0° C. A solution of N-(2-Fluoro-6-formylphenyl)pivalamide (4.50 g, 20.2 mmol) in tetrahydrofuran (20 mL) was added to the mixture dropwise. The mixture was held at 0° C. with stirring and held for 1 h. The above prepared aldehyde mixture was added to the ester mixture dropwise over 1.25 h. The mixture was held at −78° C. with stirring and held for 1 h. The reaction was quenched with aqueous ammonium chloride, warmed to room temperature, and diluted with water. The mixture was extracted ethyl acetate (2×) and the aqueous phase was discarded. The material was dried (magnesium sulfate), filtered, and concentrated to dryness. Silica gel chromatography gave the title compound as white foam in 81% yield. Mass spec.: 381.2 (M-C4H8O2+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[NH:7][C:6]([CH:12](C(C)(C)C(C)C)O[SiH](C)C)=[CH:5]2.[C:23]([O:27][C:28]([N:30]1[CH2:34][C@H:33]([CH3:35])OS1(=O)=O)=[O:29])([CH3:26])([CH3:25])[CH3:24]>>[C:23]([O:27][C:28]([N:30]1[CH2:34][C@@H:33]([CH3:35])[N:7]2[C:8]3[CH:9]=[C:10]([F:11])[C:2]([Br:1])=[CH:3][C:4]=3[CH:5]=[C:6]2[CH2:12]1)=[O:29])([CH3:26])([CH3:25])[CH3:24]
Reactant: CC(C)C(C)(C)C(O[SiH](C)C)c1cc2cc(Br)c(F)cc2[nH]1
Reactant: C[C@H]1CN(C(=O)OC(C)(C)C)S(=O)(=O)O1
Product: C[C@@H]1CN(C(=O)OC(C)(C)C)Cc2cc3cc(Br)c(F)cc3n21

Procedure:
The title compound, ISP-MS: m/e=383.2 ([M+H]+) and m.p. 116-118° C., was prepared in accordance with the general method of example 81e and f) from 5-bromo-2[dimethyl-(1,1,2-trimethyl-propyl)-silanyloxymethyl]-6-fluoro-1H-indole and (S)-5-methyl-2,2-dioxo-[1,2,3]oxathiazolidine-3-carboxylic acid tert-butyl ester.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([OH:8])[CH:5]=[CH:6][CH:7]=1.O[C@H:10]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:11][N:12]1[CH2:17][CH2:16][CH:15]([C:18]2[CH:19]=[C:20]([NH:24][C:25](=[O:29])[CH:26]([CH3:28])[CH3:27])[CH:21]=[CH:22][CH:23]=2)[CH2:14][CH2:13]1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[O:8][C@@H:10]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH2:11][N:12]1[CH2:17][CH2:16][CH:15]([C:18]2[CH:19]=[C:20]([NH:24][C:25](=[O:29])[CH:26]([CH3:28])[CH3:27])[CH:21]=[CH:22][CH:23]=2)[CH2:14][CH2:13]1
Reactant: Oc1cccc(Cl)c1
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(C[C@H](O)c3ccccc3)CC2)c1
Product: CC(C)C(=O)Nc1cccc(C2CCN(C[C@@H](Oc3cccc(Cl)c3)c3ccccc3)CC2)c1

Procedure:
Prepared by Procedure B and Scheme B1 using 3-chlorophenol and N-(3-{1-[(2R)-2-hydroxy-2-phenylethyl]-4-piperidinyl}phenyl)-2-methylpropanamide: ESMS m/e: 477.1 (M+H)+.
Reaction SMILES: [H-].[Na+].[CH2:3]([O:5][C:6]1[CH:7]=[C:8]([CH:28]=[C:29]([OH:31])[CH:30]=1)[CH2:9][N:10]1[CH:14]=[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:12]([CH2:21][CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:11]1)[CH3:4].Cl[CH2:33][C:34]1[N:35]=[C:36]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=2)[O:37][C:38]=1[CH3:39].O>CN(C)C=O>[CH2:3]([O:5][C:6]1[CH:7]=[C:8]([CH:28]=[C:29]([O:31][CH2:33][C:34]2[N:35]=[C:36]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[O:37][C:38]=2[CH3:39])[CH:30]=1)[CH2:9][N:10]1[CH:14]=[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:12]([CH2:21][CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])=[CH:11]1)[CH3:4]
Reactant: Cc1oc(-c2ccccc2)nc1CCl
Reactant: CCOC(=O)CCc1cn(Cc2cc(O)cc(OCC)c2)cc1-c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)CCc1cn(Cc2cc(OCC)cc(OCc3nc(-c4ccccc4)oc3C)c2)cc1-c1ccccc1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 88.1 %

Procedure:
Sodium hydride (60%, oily, 50.0 mg) was added to a solution of ethyl 3-[1-(3-ethoxy-5-hydroxybenzyl)-4-phenyl-3-pyrrolyl]propionate (492 mg) in N,N-dimethylformamide (10 ml) at 0° C., and the mixture was stirred at room temperature for 15 minutes. 4-Chloromethyl-5-methyl-2-phenyloxazole (260 mg) was added to the mixture, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured into water, and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated. The residue was subjected to silica gel column chromatography to obtain ethyl 3-[1-[3-ethoxy-5-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-4-phenyl-3-pyrrolyl]propionate (622 mg, yield: 88%) as a colorless oily substance from the fraction eluted with ethyl acetate-hexane (1:3, volume ratio).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[CH:4][C:3]=1[C:17]1[CH:18]=[N:19][C:20]([NH2:23])=[N:21][CH:22]=1.Br[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[C:31]([N:33]1[CH2:38][CH2:37][O:36][CH2:35][CH2:34]1)=[O:32]>>[F:1][C:2]1[CH:7]=[C:6]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=2[C:31]([N:33]2[CH2:34][CH2:35][O:36][CH2:37][CH2:38]2)=[O:32])[CH:5]=[CH:4][C:3]=1[C:17]1[CH:22]=[N:21][C:20]([NH2:23])=[N:19][CH:18]=1
Reactant: O=C(c1ccccc1Br)N1CCOCC1
Reactant: CC1(C)OB(c2ccc(-c3cnc(N)nc3)c(F)c2)OC1(C)C
Product: Nc1ncc(-c2ccc(-c3ccccc3C(=O)N3CCOCC3)cc2F)cn1

Procedure:
The title compound was prepared using methods analogous to those described in Example 369 using 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine and (2-bromophenyl)(morpholino)methanone. MS (ESI): mass calcd. for C21H19FN4O2, 378.15; m/z found, 379.2 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.56 (d, J=1.4, 2H), 7.54-7.41 (m, 5H), 7.36 (dd, J=8.0, 1.8, 1H), 7.32 (dd, J=11.5, 1.8, 1H), 5.20 (s, 2H), 3.74-3.58 (m, 3H), 3.49-3.30 (m, 2H), 3.15-3.01 (m, 1H), 2.94-2.77 (m, 2H).
Reaction SMILES: [Br-].[CH3:2][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[NH2-].[Na+].[F:24][C:25]1([F:32])[CH2:30][CH2:29][C:28](=O)[CH2:27][CH2:26]1>CCOCC>[F:24][C:25]1([F:32])[CH2:30][CH2:29][C:28](=[CH2:2])[CH2:27][CH2:26]1
Reactant: O=C1CCC(F)(F)CC1
Reactant: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Agent: [NH2-]
Agent: [Na+]
Solvent: CCOCC
Product: C=C1CCC(F)(F)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
A methyl triphenyl phosphonium bromide/sodium amide mixture (MTP instant ylide, 0.49 g, 1.24 mmol) was suspended in anhydrous Et2O (3 mL) stirring for 1 h at r.t. Afterwards, the reaction mixture was cooled at 0° C. and a solution of 4,4-difluorocyclohexanone (0.145 g, 1.08 mmol) in 3 mL of Et2O was added dropwise into. Stirring at r.t. was maintained for 16 h, then the reaction mixture was filtered and the filtrate was used in the next step without further purification.
Reaction SMILES: [H-].[Na+].Cl.[OH:4][CH2:5][C:6]1[C:7]([CH3:14])=[C:8]([OH:13])[C:9]([CH3:12])=[N:10][CH:11]=1.[Cl:15][C:16]1[CH:21]=[C:20]([N+]([O-])=O)[CH:19]=[CH:18][N:17]=1>CN(C=O)C.O>[Cl:15][C:16]1[CH:21]=[C:20]([O:13][C:8]2[C:7]([CH3:14])=[C:6]([CH2:5][OH:4])[CH:11]=[N:10][C:9]=2[CH3:12])[CH:19]=[CH:18][N:17]=1
Reactant: O=[N+]([O-])c1ccnc(Cl)c1
Reactant: Cc1ncc(CO)c(C)c1O
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ncc(CO)c(C)c1Oc1ccnc(Cl)c1
Temperature: 25 °C
Reaction time: 2 h
Yield: 78.7 %

Procedure:
A suspension of sodium hydride (5.27 g, 209 mmol) in DMF (100 mL) was carefully charged with 5-(hydroxymethyl)-2,4-dimethylpyridin-3-ol hydrochloride (18 g, 95 mmol). The mixture stirred at room temperature for 2 hours. 2-chloro-4-nitropyridine (15 g, 95 mmol) was then added and the reaction stirred overnight at room temperature. The material was diluted with water and extracted with ethylacetate. The organic layer was dried, and concentrated. Flash chromatography (dichloromethane/methanol 20:1) gave (5-(2-chloropyridin-4-yloxy)-4,6-dimethylpyridin-3-yl)methanol (19.8 g, 79%) as colorless oil.
Reaction SMILES: [C:1]([C:3]1[CH:11]=[CH:10][C:6]2[N:7]=[CH:8][NH:9][C:5]=2[CH:4]=1)#[N:2].[C:12]([NH:16][S:17]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:26]1[CH:31]=[CH:30][C:29]([NH:32][C:33]([CH2:35]Cl)=[O:34])=[CH:28][CH:27]=1)(=[O:19])=[O:18])([CH3:15])([CH3:14])[CH3:13].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[C:12]([NH:16][S:17]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[C:26]1[CH:27]=[CH:28][C:29]([NH:32][C:33]([CH2:35][C:8]2[NH:9][C:5]3[CH:4]=[C:3]([C:1]#[N:2])[CH:11]=[CH:10][C:6]=3[N:7]=2)=[O:34])=[CH:30][CH:31]=1)(=[O:18])=[O:19])([CH3:15])([CH3:13])[CH3:14]
Reactant: N#Cc1ccc2nc[nH]c2c1
Reactant: CC(C)(C)NS(=O)(=O)c1ccccc1-c1ccc(NC(=O)CCl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)(C)NS(=O)(=O)c1ccccc1-c1ccc(NC(=O)Cc2nc3ccc(C#N)cc3[nH]2)cc1
Yield: 16.4 %

Procedure:
Alkylation of 5-cyanobenzimidazole (2 mmol) with (4-(2-tert-butylaminosulfonylphenyl)phenyl-aminocarbonyl]methylene chloride (2 mmol) in DMF (10 mL) and K2CO3 (4 mmol) at r.t. over 16 hours, followed by purification on thin layer TLC plates, and further isolation by HPLC gave [4-(2-tert-butylaminosulfonylphenyl)phenylaminocarbonyl]methyl-6-cyanobenzimidazole (240 mg, 56%) and [4-(2-tert-butylaminosulfonylphenyl)phenylaminocarbonyl]methyl-5-cyanobenzimidazole (160 mg, 37%).
Reaction SMILES: [C:1]1([CH:7]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:8]2[CH2:11][CH:10]([NH:12][CH2:13][C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[N+:20]([O-])=O)[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>CO.[Rh].C>[NH2:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[CH2:13][NH:12][CH:10]1[CH2:9][N:8]([CH:7]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:11]1
Reactant: O=[N+]([O-])c1ccccc1CNC1CN(C(c2ccccc2)c2ccccc2)C1
Agent: [Rh]
Solvent: CO
Product: Nc1ccccc1CNC1CN(C(c2ccccc2)c2ccccc2)C1

Procedure:
A solution of 20.0 g (0.5355 mol) of 1-(diphenylmethyl)-3-[(2-nitrophenylmethyl)amino]-azetidine in 200 ml of methanol was hydrogenated in the presence of 4 g of 5% rhodium/charcoal for 5 hours at ambient temperature. The catalyst was filtered off, the filtrate was concentrated by evaporation in vacuo. 17.7 g (96% of theoretical) of a colourless, highly viscous oil were obtained, which was further processed without any additional purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([CH:13]([P:22]([O:27]CC)(=[O:26])[O:23]CC)[P:14]([O:19]CC)(=[S:18])[O:15]CC)[CH:7]=[CH:6]2.C[Si](Br)(C)C>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[CH:9]=[C:8]([CH:13]([P:22]([OH:26])(=[O:23])[OH:27])[P:14]([OH:19])(=[S:18])[OH:15])[CH:7]=[CH:6]2
Reactant: CCOP(=O)(OCC)C(c1ccc2cc(OC)ccc2c1)P(=S)(OCC)OCC
Agent: C[Si](C)(C)Br
Solvent: ClCCl
Product: COc1ccc2cc(C(P(=O)(O)O)P(O)(O)=S)ccc2c1
Yield: 80.6 %

Procedure:
Following the same method described as in Example 2, 7.15 g (15 mmol) of tetraethyl 6-methoxy-2-naphthylthiomethanediphosphonate obtained in Example 3 in dry methylene chloride was treated with trimethylsilyl bromide, and then hydrolyzed to obtain 4.21 g of the title compound as white crystals. The yield was 77%.
Reaction SMILES: C(O[C:6](=O)[CH2:7][CH2:8][N:9]([CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[Cl:26])[CH2:10][CH2:11][C:12]([O:14]C(C)(C)C)=O)(C)(C)C.[CH2:28](Br)[CH:29]=C>C1(C)C=CC=CC=1>[Cl:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[CH2:19][N:9]1[CH2:10][CH2:11][C:12](=[O:14])[CH:7]([CH2:6][CH:28]=[CH2:29])[CH2:8]1
Reactant: C=CCBr
Reactant: CC(C)(C)OC(=O)CCN(CCC(=O)OC(C)(C)C)Cc1ccccc1Cl
Solvent: Cc1ccccc1
Product: C=CCC1CN(Cc2ccccc2Cl)CCC1=O
Temperature: 40 °C
Reaction time: 0.33 h

Procedure:
16.60 g (0.145 mol) of K-tert-butylate was introduced and warmed to 75° to 80° C. Then 50 g (0.125 mol) of di-tert-butyl-N-[(2-chlorophenyl)methyl]-3,3'-iminodipropionate in 100 ml of toluene was added within 10 minutes. After 20 minutes, the toluene was practically completely evaporated at 75° C. and 220 mbars. Then 400 ml of tert-butanol was added to 40° C. 17.94 g (0.145 mol) of allylbromide was added to the resulting suspension at 40° C. in 10 minutes. It was allowed to stir for 45 minutes more at 40° C. The reaction mixture was then completely concentrated by evaporation and then the solid residue was dissolved in 500 ml each of H2O plus 300 ml of ether. The aqueous phase was again extracted twice with 100 ml each of ether. The combined ether phases was washed with 50 ml of saturated Na2SO4 and then concentrated by evaporation. Then 500 ml of 0.5 n HCl was added to the resulting oil and refluxed for 30 to 45 minutes (CO2 development). The reaction mixture was cooled to room temperature and mixed again with 20 ml of HCl conc. It was extracted three times with 100 ml of ether and the ether phase was dried with MgSO4 and evaporated. The acidic water phase was made basic with NaOH and extracted three times with 200 ml of ether. The ether phases were combined and dried with MGSO4 and evaporated. A yellowish oil resulted. The yield was 28.66 g (87 percent). Data concerning the compound was:
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:8]2[C:13]([C:14]([O:16][CH3:17])=[O:15])=[C:12]([CH3:18])[NH:11][C:10]([CH3:19])=[C:9]2[C:20]([O:22][CH3:23])=[O:21])[CH:5]=[CH:6][CH:7]=1.[Cl:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29](Cl)=[O:30]>C1COCC1>[Cl:24][CH2:25][CH2:26][CH2:27][CH2:28][C:29]([NH:1][C:2]1[CH:3]=[C:4]([CH:8]2[C:9]([C:20]([O:22][CH3:23])=[O:21])=[C:10]([CH3:19])[NH:11][C:12]([CH3:18])=[C:13]2[C:14]([O:16][CH3:17])=[O:15])[CH:5]=[CH:6][CH:7]=1)=[O:30]
Reactant: O=C(Cl)CCCCCl
Reactant: COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1c1cccc(N)c1
Solvent: C1CCOC1
Product: COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1c1cccc(NC(=O)CCCCCl)c1
Temperature: 0 °C
Reaction time: 1 h
Yield: 99.8 %

Procedure:
4-(3-Aminophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid, dimethyl ester (2.3 g, 7.28 mmol) was dissolved in THF (50 mL) and cooled to 0° C. 5-Chlorovaleryl chloride (1.13 g, 7.28 mmol) was dissolved in THF (15 mL) and added dropwise to the mixture over 15 min. The mixture was stirred at 0° C. for 1 h., the solvent removed in vacuo, and the residue was extracted using CH2Cl2 /water. The CH2Cl2 layer was dried over Na2SO4, filtered, and concentrated in vacuo. Silica gel chromatography (1:1 to 1:0 EtOAc:hexane gradient) of the concentrate gave the title compound (3.16 g, 100%) as a pale yellow foam.
Reaction SMILES: [SH:1][C:2]1[N:7]([NH2:8])[C:6](=[O:9])[C:5]([C:10]([CH3:13])([CH3:12])[CH3:11])=[N:4][N:3]=1.[CH3:14]I>[OH-].[Na+].CO>[CH3:14][S:1][C:2]1[N:7]([NH2:8])[C:6](=[O:9])[C:5]([C:10]([CH3:13])([CH3:12])[CH3:11])=[N:4][N:3]=1
Reactant: CI
Reactant: CC(C)(C)c1nnc(S)n(N)c1=O
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CSc1nnc(C(C)(C)C)c(=O)n1N
Temperature: 20 °C
Reaction time: 4 h
Yield: 82 %

Procedure:
4 parts by weight of 3-mercapto-4-amino-6tert.-butyl-1,2,4-triazin-5-(4H)-one are dissolved in a mixture of 11 parts by weight of 2 normal sodium hydroxide solution and 4 parts by weight of methanol and the solution is treated at 0° C with 3.2 parts by weight of methyl iodide. The reaction mixture is then stirred at 20° C for a further 4 hours. The reaction product crystallizes out, is filtered off, dried and recrystallized from benzene. 3.52 parts by weight of 3-methylthio-4-amino-6-tert.-butyl-1,2,4-triazin-5(4H)-one (XV) of melting point 126°-127° are obtained. Yield: 82% of theory.