Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([N:8]([CH2:10][C:11]([OH:13])=O)[CH3:9])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.Cl.[CH3:30][O:31][C:32](=[O:64])[C@H:33]([CH2:56][C:57]1[CH:62]=[CH:61][C:60]([OH:63])=[CH:59][CH:58]=1)[NH:34][C:35](=[O:55])[C@H:36]([CH:52]([CH3:54])[CH3:53])[NH:37][C:38](=[O:51])[C@H:39]([CH2:44][CH2:45][CH2:46][NH:47][C:48](=[NH:50])[NH2:49])[NH:40][N+:41]([O-:43])=[O:42]>C(Cl)Cl>[CH3:30][O:31][C:32](=[O:64])[C@H:33]([CH2:56][C:57]1[CH:62]=[CH:61][C:60]([OH:63])=[CH:59][CH:58]=1)[NH:34][C:35](=[O:55])[C@H:36]([CH:52]([CH3:54])[CH3:53])[NH:37][C:38](=[O:51])[C@H:39]([CH2:44][CH2:45][CH2:46][NH:47][C:48](=[NH:49])[NH2:50])[N:40]([C:11](=[O:13])[CH2:10][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH3:9])[N+:41]([O-:43])=[O:42]
Reactant: CN(CC(=O)O)C(=O)OC(C)(C)C
Reactant: COC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)N[N+](=O)[O-])C(C)C
Agent: CC(C)COC(=O)Cl
Agent: Cl
Solvent: CN1CCOCC1
Solvent: ClCCl
Product: COC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(=N)N)N(C(=O)CN(C)C(=O)OC(C)(C)C)[N+](=O)[O-])C(C)C
Temperature: -70 °C
Reaction time: 0.08 h

Procedure:
8.84 g of t-butoxycarbonylsarcosine is dissolved in 200 ml of methylene chloride. 10.5 ml of N-methylmorpholine is added to the solution. The solution is cooled to -70° C. 6.1 ml of isobutyl chloroformate is then added. The reaction mixture is warmed up to -15° C. and stirred for 5 minutes. The reaction mixture is again cooled to -70° C. 25.5 g of nitroarginylvalyltyrosine methyl ester hydrochloride is added to the reaction mixture. The reaction mixture is allowed to warm to room temperature, and then is stirred for 16 hours. The reaction mixture is extracted three times with 0.5 M potassium bisulfate and once with brine. The methylene chloride solution is dried over anhydrous sodium sulfate, filtered and stripped of solvent. The residue is dissolved in 200 ml of ethyl ether. The ether solution is added to cold rapidly stirring Skellysolve B. The white precipitate is filtered and dried to afford the product t-butoxycarbonylsarcosylnitroarginylvalyltyrosine methyl ester.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([SH:9])[CH:5]=[CH:6][C:7]=1[Cl:8].[CH2:10]=[C:11]([CH2:19][CH2:20][CH2:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13].C(O)C>CO>[Cl:1][C:2]1[CH:3]=[C:4]([S:9][CH2:10][CH:11]([CH2:19][CH2:20][CH2:21][C:22]([O:24][C:25]([CH3:26])([CH3:28])[CH3:27])=[O:23])[C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: Sc1ccc(Cl)c(Cl)c1
Reactant: C=C(CCCC(=O)OC(C)(C)C)C(=O)OC(C)(C)C
Solvent: CO
Solvent: CCO
Product: CC(C)(C)OC(=O)CCCC(CSc1ccc(Cl)c(Cl)c1)C(=O)OC(C)(C)C
Temperature: 170 °C
Reaction time: 17 h

Procedure:
A mixture of 3,4-dichlorobenzenethiol (0.20 ml), di-tert-butyl 2-methyleneadipate (350 mg), ethanol (2 ml), and triton B (40% methanol solution, 2 drops) was stirred at 170° C. in a sealed tube for 17 hours. After the reaction mixture was concentrated in vacuo, the resulting residue was dissolved in chloroform, washed with a 0.5% sodium hydroxide solution, water and a saturated sodium chloride solution respectively, and dried over MgSO4. The solvent was evaporated at reduced pressure, and the residue was purified by flash column chromatography on silica by eluting with diethyl ether/hexane (1:10) to give 430 mg of di-tert-butyl 2-(3,4-dichlorophenylthiomethyl)adipate as an oil.
Reaction SMILES: [C:1](=[O:8])([O:5][CH2:6][CH3:7])[O:2][CH2:3]Cl.[C:9]1([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[CH:14]=[CH:13][C:12]([CH2:15][C@@H:16]([NH:25]C(OC(C)(C)C)=O)[CH2:17][C@:18]([CH2:23][OH:24])([CH3:22])[C:19]([OH:21])=[O:20])=[CH:11][CH:10]=1.CCN(CC)CC>CC(C)=O>[CH2:6]([O:5][C:1]([O:2][CH2:3][O:21][C:19](=[O:20])[C@@:18]([CH2:23][OH:24])([CH3:22])[CH2:17][C@H:16]([NH2:25])[CH2:15][C:12]1[CH:13]=[CH:14][C:9]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[CH:10][CH:11]=1)=[O:8])[CH3:7]
Reactant: CCOC(=O)OCCl
Reactant: CC(C)(C)OC(=O)N[C@H](Cc1ccc(-c2ccccc2)cc1)C[C@@](C)(CO)C(=O)O
Solvent: CC(C)=O
Solvent: CCN(CC)CC
Product: CCOC(=O)OCOC(=O)[C@](C)(CO)C[C@H](N)Cc1ccc(-c2ccccc2)cc1

Procedure:
Chloromethyl ethyl carbonate (54 mg, 387 μmol) was added to a mixture of (2S,4R)-5-biphenyl-4-yl-4-t-butoxycarbonylamino-2-hydroxymethyl-2-methyl-pentanoic acid (100 mg, 242 μmol) and Et3N (35 μL, 254 μmol) in acetone (10 mL). The mixture was refluxed for 24 hours and the reaction monitored for completion. When the reaction was complete, the product was purified ((Interchim reverse phase chromatography column) the solvent was removed under vacuum to yield (2S,4R)-4-amino-5-biphenyl-4-yl-2-hydroxymethyl-2-methyl-pentanoic acid ethoxycarbonyloxymethyl ester.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]3[N:13]=[C:14]([O:17][CH3:18])[CH:15]=[CH:16][C:11]3=[N:10][C:9]=2[C:19]2[CH:20]=[CH:21][C:22]([CH3:26])=[C:23]([CH:25]=2)[NH2:24])=[CH:4][CH:3]=1.N1C=CC=CC=1.[CH3:33][C:34]([CH3:39])([CH3:38])[C:35](Cl)=[O:36]>C(#N)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]3[N:13]=[C:14]([O:17][CH3:18])[CH:15]=[CH:16][C:11]3=[N:10][C:9]=2[C:19]2[CH:20]=[CH:21][C:22]([CH3:26])=[C:23]([NH:24][C:35](=[O:36])[C:34]([CH3:39])([CH3:38])[CH3:33])[CH:25]=2)=[CH:4][CH:3]=1
Reactant: CC(C)(C)C(=O)Cl
Reactant: COc1ccc2nc(-c3ccc(C)c(N)c3)c(-c3ccc(F)cc3)n2n1
Solvent: CC#N
Solvent: c1ccncc1
Product: COc1ccc2nc(-c3ccc(C)c(NC(=O)C(C)(C)C)c3)c(-c3ccc(F)cc3)n2n1
Temperature: 25 °C
Reaction time: 4 h
Yield: 89.9 %

Procedure:
A stirred solution of 5-(3-(4-fluorophenyl)-6-methoxyimidazo[1,2-b]pyridazin-2-yl)-2-methylaniline (0.025 g, 0.072 mmol) in acetonitrile (1 mL) containing pyridine (0.215 mmol) is added trimethylacetylchloride (0.072 mmol). The mixture is stirred at room temperature for 4 hours, then concentrated to dryness and purified via chromatography (hexanes to EtOAc) to afford the title compound (0.028 g, 90%) as a yellow solid: Rf 0.28 (1:1 EtOAc:hexanes); LCMS (m/z)=433.5 [M+H]+, tR=2.74 min. (compound same as Example 114)
Reaction SMILES: C([C:3]1[CH:8]=[CH:7][C:6]([N:9]2C(=O)C(C)(C)[N:11]([CH2:17][CH2:18][CH2:19][C:20](O)=O)[C:10]2=O)=[CH:5][C:4]=1C(F)(F)F)#N.[C:28](O)(C)(C)[CH3:29]>CN(C)C1C=CN=CC=1.C(Cl)Cl.CC(C)=O>[CH:17]1([N:11]=[C:10]=[N:9][CH:6]2[CH2:5][CH2:4][CH2:3][CH2:8][CH2:7]2)[CH2:18][CH2:19][CH2:20][CH2:29][CH2:28]1
Reactant: CC1(C)C(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C(=O)N1CCCC(=O)O
Reactant: CC(C)(C)O
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CC(C)=O
Product: C(=NC1CCCCC1)=NC1CCCCC1

Procedure:
By carrying out the esterification of the product of Example 62, with terbutanol in the presence of dicyclohexylcarbodiimide and 4-dimethylamino-pyridine as in Example 60, the expected product melting at 96°-97° C. with a Rf=0.32 (eluant: methylene chloride-acetone (98-2)) was obtained.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]=[CH:8][C:9]([OH:11])=O.[F:12][C:13]([F:25])([F:24])[O:14][C:15]1[CH:16]=[C:17]([CH:21]([NH2:23])[CH3:22])[CH:18]=[CH:19][CH:20]=1.CCN=C=NCCCN(C)C.Cl.C(N(CC)CC)C>C(Cl)Cl.CN(C1C=CN=CC=1)C>[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]=[CH:8][C:9]([NH:23][CH:21]([C:17]1[CH:18]=[CH:19][CH:20]=[C:15]([O:14][C:13]([F:12])([F:24])[F:25])[CH:16]=1)[CH3:22])=[O:11]
Reactant: CC(N)c1cccc(OC(F)(F)F)c1
Reactant: O=C(O)C=Cc1ccccn1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(NC(=O)C=Cc1ccccn1)c1cccc(OC(F)(F)F)c1
Temperature: 25 °C
Reaction time: 12 h

Procedure:
To a solution of 3-(pyridin-2-yl)acrylic acid, Preparation 16 (50 mg) in CH2Cl2 (2 mL) at room temperature were added (±)-1-(3-trifluoromethoxy phenyl)ethylamine, Preparation 15 (76 mg), EDC hydrochloride (129 mg), DMAP (41 mg), and triethylamine (0.2 mL), and the resulting solution was stirred at room temperature for 12 hours. The crude product was purified by silica gel chromatography eluting with ethyl acetate to provide the title compound as the racemate (96 mg). This racemate was separated by HPLC using AD column eluting with hexanes/ethanol (9:1) to give the title compound as an enantiomer of undetermined chirality.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]([C:11]1[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=1)=[O:10].[CH3:17][C:18]([C:25]1[CH:30]=[CH:29][C:28]([S:31](Cl)(=[O:33])=[O:32])=[CH:27][CH:26]=1)([C:20]1[N:21]=[CH:22][O:23][CH:24]=1)[CH3:19]>N1C=CC=CC=1>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][S:31]([C:28]2[CH:27]=[CH:26][C:25]([C:18]([CH3:19])([C:20]3[N:21]=[CH:22][O:23][CH:24]=3)[CH3:17])=[CH:30][CH:29]=2)(=[O:32])=[O:33])=[C:3]([C:9]([C:11]2[CH:16]=[CH:15][N:14]=[CH:13][CH:12]=2)=[O:10])[CH:4]=1
Reactant: Nc1ccc(Cl)cc1C(=O)c1ccncc1
Reactant: CC(C)(c1ccc(S(=O)(=O)Cl)cc1)c1cocn1
Solvent: c1ccncc1
Product: CC(C)(c1ccc(S(=O)(=O)Nc2ccc(Cl)cc2C(=O)c2ccncc2)cc1)c1cocn1

Procedure:
Following the general procedure for synthesis of N-arylbenzenesulfonamides, 73 mg (0.32 mmol) of (2-Amino-5-chloro-phenyl)-pyridin-4-yl-methanone and 36 mg (0.13 mmol) of 4-(1-Methyl-1-oxazol-4-yl-ethyl)-benzenesulfonyl chloride were combined in 1 ml of anhydrous pyridine at 60° C. to give, after purification, the title product as a pale yellow solid: 1H NMR (CDCl3): δ (ppm): 1.61 (s, 6H), 7.26-7.66 (m, 12H), 8.90 (br, 1H), 10.13 (br, 1H) ppm; MS: (M+H)/z=482.0.
Reaction SMILES: Br[C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[CH:10]1([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]#[CH:23])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1>C(N(CC)CC)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:10]1([CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][C:22]#[C:23][C:2]2[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=2[CH:4]=[O:5])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1
Reactant: C#CCCCCCCC1CCCCC1
Reactant: O=Cc1ccccc1Br
Agent: Cl[Pd]Cl
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Product: O=Cc1ccccc1C#CCCCCCCC1CCCCC1

Procedure:
To an ice cold solution of 1-hexyne (49.6 mmoles) in freshly distilled tetrahydrofuran (50 ml) containing a trace of triphenylmethane was added dropwise n-butyl lithium in hexane (49.5 mmoles). About 10 minutes after the addition was stopped, sieve dried hexamethylphosphoramide (57.5 mmoles) was added and the solution stirred for 10 minutes. A solution of 2-cyclohexylethyl bromide (51.3 mmoles) in tetrahydrofuran (10 ml) was added and the reaction mixture was stirred for about 3 hours as the temperature rose to room temperature. The mixture was taken up in ether (100 ml) and washed with water (3×100 ml) and sodium chloride solution (100 ml). The organic phase was dried over magnesium sulfate and evaporated to leave an oil which was purified by flash chromatography to give 1-cyclohexyloct-3-yne. This compound (20.8 mmoles) was treated with potassium hydride (36.8 mmoles) in propylene diamine to obtain the isomeric 8-cyclohexyloct-1-yne as an oil. A mixture of 2-bromobenzaldehyde (12.59 mmoles), 8-cyclohexyloct-1-yne (14.87 mmoles), cuprous iodide (0.17 mmoles) and bis(triphenylphosphine) palladium (II) chloride (0.26 mmoles) in triethylamine (35 ml) was refluxed under argon for 1.5 hours. The reaction mixture was cooled, filtered and the filtrate evaporated. The resulting residue was dissolved in ether (100 ml), washed with 3N hydrochloric acid (50 ml) and saturated sodium chloride solution (50 ml) and then dried over anhydrous magnesium sulfate and charcoal. The solution was evaporated to afford an oil which was purified by flash chromatography (2% ether/hexane) to yield 2-(8-cyclohexyl-1-octynyl)benzaldehyde as an oil. This benzaldehyde (10.22 mmoles) was hydrogenated with 10% palladium on charcoal in ethyl acetate to give the desired product as an oil, after chromatography (3% ether/hexane).
Reaction SMILES: [C:1]([NH:6][C:7]1[C:12]([N+:13]([O-])=O)=[C:11]([CH3:16])[CH:10]=[CH:9][N:8]=1)(=O)[CH2:2][CH2:3][CH3:4]>C(O)(=O)C.C(O)C.[Fe]>[CH3:16][C:11]1[CH:10]=[CH:9][N:8]=[C:7]2[NH:6][C:1]([CH2:2][CH2:3][CH3:4])=[N:13][C:12]=12
Reactant: CCCC(=O)Nc1nccc(C)c1[N+](=O)[O-]
Agent: [Fe]
Solvent: CCO
Solvent: CC(=O)O
Product: CCCc1nc2c(C)ccnc2[nH]1
Temperature: 90 °C
Reaction time: 3 h
Yield: 65.5 %

Procedure:
A solution of 2-butyrylamino-4-methyl-3-nitropyridine (7.0 g) and iron powder (17.5 g) in a mixture of acetic acid (14 ml) and ethanol (100 ml) was stirred at 90° C. for 3 hours under nitrogen atmosphere. After being cooled to room temperature, the reaction mixture was filtered through Celite and the filtrate was evaporated in vacuo. Ethyl acetate and saturated aqueous sodium hydrogencarbonate were added to the residue until pH 7~8 and the resulting suspension was filtered through Celite. The organic layer of the filtrate was separated, washed with brine and dried over magnesium sulfate. The solvent was evaporated in vacuo and the residue was purified with silica gel column chromatography (eluent:ethyl acetate) to give 7-methyl-2-propyl-3H-imidazo[4,5-b]pyridine (3.6 g).
Reaction SMILES: [CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8]([S:10]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=2[C:20]([F:23])([F:22])[F:21])(=[O:12])=[O:11])[CH2:7][NH:6]1)=[O:4].[C:24](OC(C)(C)C)(=[O:29])[CH2:25][C:26]([CH3:28])=[O:27]>>[CH3:1][O:2][C:3]([C@@H:5]1[CH2:9][C@@H:8]([S:10]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=2[C:20]([F:23])([F:21])[F:22])(=[O:11])=[O:12])[CH2:7][N:6]1[C:24](=[O:29])[CH2:25][C:26](=[O:27])[CH3:28])=[O:4]
Reactant: COC(=O)[C@@H]1C[C@@H](S(=O)(=O)c2ccc(F)cc2C(F)(F)F)CN1
Reactant: CC(=O)CC(=O)OC(C)(C)C
Product: COC(=O)[C@@H]1C[C@@H](S(=O)(=O)c2ccc(F)cc2C(F)(F)F)CN1C(=O)CC(C)=O

Procedure:
In analogy to the procedure described in example 192f, (2S,4R)-4-(4-fluoro-2-trifluoromethyl-benzenesulfonyl)-pyrrolidine-2-carboxylic acid methyl ester was reacted with tert-butyl acetoacetate to give the title compound as yellow oil. MS (ESI): m/z=440.2 [M+H]+.
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].[NH:7]1[CH:11]=[N:10][CH:9]=[N:8]1.CC1C=CC(S(O[CH2:23][C@@H:24]2[C@@H:29]([OH:30])[C@H:28]([OH:31])[C@@H:27]([OH:32])[C@H:26]([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]4[S:42][C:43]([C:46]5[O:47][CH:48]=[CH:49][CH:50]=5)=[CH:44][N:45]=4)[CH:34]=3)[O:25]2)(=O)=O)=CC=1.O>CN(C=O)C>[N:7]1([CH2:23][C@@H:24]2[C@@H:29]([OH:30])[C@H:28]([OH:31])[C@H:27]([OH:32])[C@H:26]([C:33]3[CH:38]=[CH:37][C:36]([Cl:39])=[C:35]([CH2:40][C:41]4[S:42][C:43]([C:46]5[O:47][CH:48]=[CH:49][CH:50]=5)=[CH:44][N:45]=4)[CH:34]=3)[O:25]2)[CH:11]=[N:10][CH:9]=[N:8]1
Reactant: Cc1ccc(S(=O)(=O)OC[C@H]2O[C@@H](c3ccc(Cl)c(Cc4ncc(-c5ccco5)s4)c3)[C@H](O)[C@@H](O)[C@@H]2O)cc1
Reactant: c1nc[nH]n1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Product: O[C@H]1[C@H](O)[C@@H](Cn2cncn2)O[C@@H](c2ccc(Cl)c(Cc3ncc(-c4ccco4)s3)c2)[C@H]1O
Temperature: 0 °C
Reaction time: 1 h
Yield: 14 %

Procedure:
Cesium carbonate (660 mg, 2.02 mmol) was added to the solution of 1,2,4-triazole (140 mg, 2.02 mmol) in DMF (2.0 mL) at 0° C. The reaction mixture was stirred at 0° C. for 1 h. The solution of toluenesulfonate 90 (240 mg, 0.41 mmol) in DMF (1.0 mL) was added to the reaction mixture. The reaction mixture was warmed up to room temperature, stirred at room temperature for 3 d. H2O was added to the reaction mixture and then extracted with EtOAc. The organic extract was dried over anhydrous MgSO4, filtered and concentrated in vacuo. Purification by prep HPLC (C18) provided desired triazole 97 (28 mg, 14%) as a solid.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[C:12]([CH3:14])[CH:11]=[C:10]([C:15]3[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=3)[N:9]=2)[CH:5]=[CH:4][N:3]=1.[N+:25]([C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][CH:33]=1)([O-:27])=[O:26]>>[CH3:14][C:12]1[CH:11]=[C:10]([C:15]2[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=2)[N:9]=[C:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([C:32]3[CH:31]=[CH:30][CH:29]=[C:28]([N+:25]([O-:27])=[O:26])[CH:33]=3)[CH:7]=2)[CH:13]=1
Reactant: Cc1cc(-c2ccc(C(F)(F)F)cc2)nc(-c2ccnc(Cl)c2)c1
Reactant: O=[N+]([O-])c1cccc(B(O)O)c1
Product: Cc1cc(-c2ccc(C(F)(F)F)cc2)nc(-c2ccnc(-c3cccc([N+](=O)[O-])c3)c2)c1

Procedure:
The 4-methyl-2′-(3-nitro-phenyl)-6-(4-trifluoromethyl-phenyl)-[2,4′]bipyridinyl was prepared from 2′-chloro-4-methyl-6-(4-trifluoromethyl-phenyl)-[2,4′]bipyridinyl (example E.94) (1.25 g, 3.6 mmol) and commercially available 3-nitrophenylboronic acid (0.718 g, 4.3 mmol) according to the general procedure VI. Obtained as a light brown solid (1.03 g, 66%). MS (ISP) 436.1 [(M+H)+]; mp 91° C.
Reaction SMILES: [CH3:1][C:2]([C:4]12O[C:5]1([CH3:13])[CH2:6][CH2:7][CH2:8][C:9]2([CH3:11])[CH3:10])=[O:3]>O1CCOCC1>[CH3:1][C:2]([C:4]1[C:9]([CH3:11])([CH3:10])[CH2:8][CH:7]=[CH:6][C:5]=1[CH3:13])=[O:3]
Reactant: CC(=O)C12OC1(C)CCCC2(C)C
Solvent: C1COCCO1
Product: CC(=O)C1=C(C)C=CCC1(C)C
Yield: 72.1 %

Procedure:
2.0 g (0.011 M) of 2,6,6-trimethyl-1,2-epoxy-cyclohexyl methyl ketone have been treated with 0.5 g of acidic diatomaceous earth in 10 ml of dioxane at 100° to give, after the usual treatments as described in Example 6, 1.3 g (yield 72%) of the desired product (purity 80%).
Reaction SMILES: BrC[CH:3](CBr)[C:4]1[C:5]([C:10]([OH:12])=O)=[CH:6][CH:7]=[CH:8][CH:9]=1.[CH3:15][NH:16][NH2:17]>C(O)C>[CH3:15][N:16]1[N:17]=[CH:3][C:4]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:10]1=[O:12]
Reactant: O=C(O)c1ccccc1C(CBr)CBr
Reactant: CNN
Solvent: CCO
Product: Cn1ncc2ccccc2c1=O
Yield: 74.9 %

Procedure:
A solution of 29.4 g (0.1 mole) of α,α-dibromomethyl-o-toluic acid and 14.7 g (0.32 mole) of methylhydrazine in 100 ml of ethanol was heated under reflux for 3 hours. The solvent was evaporated under reduced pressure, and the residue recrystalized from ethanol to give 12.0 g (yield: 75%) of 2-methyl-1-phthalazinone having a melting point of 111°-112° C.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[S-:10][C:11]#[N:12].[NH4+].OOS([O-])=O.[K+]>CO>[N:12]([C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][CH:2]=1)=[C:11]=[S:10]
Reactant: c1ccc2[nH]ccc2c1
Reactant: N#C[S-]
Agent: O=S([O-])OO
Agent: [K+]
Agent: [NH4+]
Solvent: CO
Product: S=C=Nc1c[nH]c2ccccc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 73.8 %

Procedure:
A solution of indole (2.0 g, 17.1 mmol) and ammonium thiocyanate (1.95 g, 25.6 mmol) in methanol (150 mL) was treated with oxone (15.7 g, 25.6 mmol) and allowed to stir at RT for overnight till TLC showed all starting material consumed. The reaction solution was evaporated in vacuum. The residue was purified by chromatography on silica gel (EtOAc:PE=5/95) to afford 2.2 g of 3-isothiocyanato-1H-indole as yellow solid (yield: 73%). MS obsd. (ESI+) [(M+H)+] 175.1, 1H NMR: (400 MHz, CDCl3) δ ppm: 8.67 (brs, 1H), 7.82-7.80 (m, 1H), 7.52 (d, J=3.0 Hz, 1H), 7.44-7.43 (m, 1H), 7.34-7.30 (m, 2H).
Reaction SMILES: [C:1](=[N:14][OH:15])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[CH2:17][C:18]1[CH:23]=[CH:22][C:21]([S:24][C:25]2[CH:26]=[C:27]([C:32]3([O:38][CH3:39])[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)[CH:28]=[C:29]([F:31])[CH:30]=2)=[CH:20][CH:19]=1>>[F:31][C:29]1[CH:28]=[C:27]([C:32]2([O:38][CH3:39])[CH2:33][CH2:34][O:35][CH2:36][CH2:37]2)[CH:26]=[C:25]([S:24][C:21]2[CH:22]=[CH:23][C:18]([CH2:17][O:15][N:14]=[C:1]([C:8]3[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=3)[C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:19][CH:20]=2)[CH:30]=1
Reactant: ON=C(c1ccccc1)c1ccccc1
Reactant: COC1(c2cc(F)cc(Sc3ccc(CCl)cc3)c2)CCOCC1
Product: COC1(c2cc(F)cc(Sc3ccc(CON=C(c4ccccc4)c4ccccc4)cc3)c2)CCOCC1
Yield: 44 %

Procedure:
Using an analogous procedure to that described in Example 1, benzophenone oxime was reacted with 4-[3-(4-chloromethylphenylthio)-5fluorophenyl]-4-methoxytetrahydropyran to give benzophenone O-{4-[5-fluoro-3-(4-methoxytetrahydropyran-4-yl)phenylthio]benzyl}oxime as an oil in 44% yield.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=2)[C:10](C=CC(OC)=O)=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[O:25]1CCC[CH2:26]1>O.I([O-])(=O)(=O)=O.[Na+].[Os](=O)(=O)(=O)=O>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=2)[C:10]([CH:26]=[O:25])=[N:9]1)=[O:7])([CH3:3])([CH3:2])[CH3:4]
Reactant: C1CCOC1
Reactant: COC(=O)C=Cc1nn(C(=O)OC(C)(C)C)c2ccc(OC)cc12
Agent: O=[Os](=O)(=O)=O
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: O
Product: COc1ccc2c(c1)c(C=O)nn2C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A solution of 5-methoxy-3-(2-methoxycarbonyl-vinyl)-indazole-1-carboxylic acid tert-butyl ester [282 mg, Reference Example 21(a)] in tetrahydrofuran (4 ml) and water (1.5 ml) was treated with a solution of osmium tetroxide in water (54 μL, 4 wt %) and sodium periodate (400 mg). The reaction mixture was stirred at ambient temperature for 16 hours and then filtered. The filtrate was evaporated and the residue was partitioned between ethyl acetate and water. The organic layer was dried over magnesium sulfate and then evaporated. The residue was subjected to flash column chromatography on silica eluting with a mixture of ethyl acetate and petrol (1:9, v/v) to yield 3-formyl-5-methoxy-indazole-1-carboxylic acid tert-butyl ester (162 mg) as a white solid. LC-MS (METHOD B): RT=2.97 minutes; 277 (M+H)+.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6](S(C)=O)[C:5]([C:11]#[N:12])=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[N:3]=1.[C:19]1([NH:25][CH2:26][CH2:27][NH2:28])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>COCCOC>[NH2:1][C:2]1[N:7]=[C:6]([NH:28][CH2:27][CH2:26][NH:25][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[C:5]([C:11]#[N:12])=[C:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[N:3]=1
Reactant: NCCNc1ccccc1
Reactant: CS(=O)c1nc(N)nc(-c2ccccn2)c1C#N
Solvent: COCCOC
Product: N#Cc1c(NCCNc2ccccc2)nc(N)nc1-c1ccccn1

Procedure:
From 2-amino-4-methanesulfinyl-6-pyridin-2-yl-pyrimidine-5-carbonitrile and N-phenylethylenediamine in DME. ES-MS m/e (%): 332 (M+H+, 100).
Reaction SMILES: [OH:1][CH2:2][CH2:3][O:4][C:5]1[CH:6]=[C:7]([C:11]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)([O:21][CH2:22][CH2:23][CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)[C:12]2[CH:20]=[CH:19][C:15]([C:16]([OH:18])=[O:17])=[CH:14][CH:13]=2)[CH:8]=[CH:9][CH:10]=1.C1(N=C=NC2CCCCC2)CCCCC1.O[N:53]1[C:57](=[O:58])[CH2:56][CH2:55][C:54]1=[O:59]>C1COCC1.CN(C1C=CN=CC=1)C.CCOCC>[O:59]=[C:54]1[CH2:55][CH2:56][C:57](=[O:58])[N:53]1[O:17][C:16](=[O:18])[C:15]1[CH:19]=[CH:20][C:12]([C:11]([C:7]2[CH:8]=[CH:9][CH:10]=[C:5]([O:4][CH2:3][CH2:2][OH:1])[CH:6]=2)([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[O:21][CH2:22][CH2:23][CH2:24][C:25]2[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=2)=[CH:13][CH:14]=1
Reactant: O=C1CCC(=O)N1O
Reactant: O=C(O)c1ccc(C(OCCCc2ccccc2)(c2ccccc2)c2cccc(OCCO)c2)cc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: C1CCOC1
Solvent: CCOCC
Product: O=C(ON1C(=O)CCC1=O)c1ccc(C(OCCCc2ccccc2)(c2ccccc2)c2cccc(OCCO)c2)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a stirred solution of trityl acid 8 (200 mg, 0.42 mM) in dry THF (6 mL) was added dicyclohexyl carbodiimide (DDC, 206 mg, 1 mM). The reaction mixture was stirred for 30 min at r.t., and N-hydroxysuccinimide (70 mg, 0.6 mM) and a catalytic amount of DMAP added and was allowed to stir for overnight. The solvent was removed under rotaevaporator and the solid obtained was dissolved in dry ether. The precipitated DCU was filtered and the solvent ether was evaporated. The crude solid obtained was separated by silica column chromatography using CH2Cl2. Yield: about 120 mg. 1H-NMR (500 MHz, CDCl3) δ ppm: 1.70 (m, 2H), 1.9 (t, 2H), 2.9 (s, 4H), 3.5 (m, 2H), 3.9 (t, 2H), 4.0 (t, 2H), 6.85 (m, 4H), 7.25 (m, 4H), 7.32 (m, 5H), 7.51 (m, 3H), 8.09 (d, 2H).