Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][OH:2].[C:3]([C:5]1[CH:6]=[C:7]([CH:11]=[CH:12][CH:13]=1)[C:8]([OH:10])=[O:9])#[N:4]>CO>[OH:2][NH:1][C:3](=[NH:4])[C:5]1[CH:6]=[C:7]([CH:11]=[CH:12][CH:13]=1)[C:8]([OH:10])=[O:9]
Reactant: NO
Reactant: N#Cc1cccc(C(=O)O)c1
Solvent: CO
Product: N=C(NO)c1cccc(C(=O)O)c1

Procedure:
An aqueous 50% hydroxylamine solution was added to a methanol solution of 3-cyanobenzoic acid, followed by heating under reflux for 11 hours. The reaction liquid was concentrated, diluted with water, adjusted with 1 M hydrochloric acid to have a pH of from 2 to 3, and the precipitate was collected by filtration to obtain 3-[(hydroxyamino)(imino)methyl]benzoic acid. ES+: 181.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([OH:13])=[CH:5][CH:4]=1.C(=O)([O-])[O-].[Na+].[Na+].F[C:21]1[CH:22]=[N+:23]([O-:30])[CH:24]=[CH:25][C:26]=1[N+:27]([O-:29])=[O:28].O>CN(C=O)C>[CH3:1][O:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([O:13][C:21]2[CH:22]=[N+:23]([O-:30])[CH:24]=[CH:25][C:26]=2[N+:27]([O-:29])=[O:28])=[CH:5][CH:4]=1
Reactant: COc1ccc(O)c2ccccc12
Reactant: O=[N+]([O-])c1cc[n+]([O-])cc1F
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1ccc(Oc2c[n+]([O-])ccc2[N+](=O)[O-])c2ccccc12
Reaction time: 0.25 h

Procedure:
To a solution of 4-methoxy-1-naphthol (8.87 g) in 50 ml of DMF was added sodium carbonate (7.8 g) portionwise, and after the addition was complete the mixture was stirred for 15 minutes. Then a solution of 3-fluoro-4-nitropyridine-N-oxide (8.0 g) in 50 ml DMF was added dropwise at room temperature. The reaction was then allowed to proceed for 4 hours at room temperature. The mixture was then poured into water and extracted with ethyl acetate. The organic layer was washed with NaCl (sat) and dried (anhy. MgSO4).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[NH:7]1[CH:11]=[CH:10][CH:9]=[C:8]1[C:12](=[O:14])[CH3:13].[CH2:15]=O.[OH-].[Na+]>C(O)(=O)C.O>[N:1]1([CH2:15][C:10]2[CH:9]=[C:8]([C:12](=[O:14])[CH3:13])[NH:7][CH:11]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1
Reactant: C1COCCN1
Reactant: C=O
Reactant: CC(=O)c1ccc[nH]1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(=O)O
Product: CC(=O)c1cc(CN2CCOCC2)c[nH]1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of morpholine (22 mmoles) in acetic acid (60 ml) at 0° C. there are added 1-(1H-pyrrol-2-yl)-ethanone (20 mmoles) and formaldehyde (20 mmoles) 37% in water. The reaction mixture is stirred overnight at ambient temperature. At 0° C., the solution is brought to alkaline pH (10-12) using 20% aqueous NaOH solution and is then extracted with DCM. The organic phase is washed with water and with saturated aqueous NaCl solution, dried over sodium sulphate, filtered and evaporated to dryness. Purification by flash chromatography on silica gel (SiO2; gradient DCM/MeOH) to yield the title product.
Reaction SMILES: Br[CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=O.Cl.[CH3:13][CH:14]([N:16]1[CH:20]=[C:19]([CH2:21][C:22]([NH2:24])=[S:23])[N:18]=[CH:17]1)[CH3:15]>>[CH3:15][CH:14]([N:16]1[CH:20]=[C:19]([CH2:21][C:22]2[S:23][C:2]3[CH2:10][C:9]4[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=4[C:3]=3[N:24]=2)[N:18]=[CH:17]1)[CH3:13]
Reactant: O=C1c2ccccc2CC1Br
Reactant: CC(C)n1cnc(CC(N)=S)c1
Agent: Cl
Product: CC(C)n1cnc(Cc2nc3c(s2)Cc2ccccc2-3)c1

Procedure:
Starting compounds: 2-bromo-1-indanone, [1-(2-propyl)-4-imidazolyl]thioacetamide hydrochloride
Reaction SMILES: [CH3:1][S:2]([C:4]([S:12][CH3:13])=[CH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=O.C(N(CC)CC)C.P(Cl)(Cl)([Cl:23])=O.O>C(Cl)Cl>[CH3:1][S:2][C:4]([S:12][CH3:13])=[C:5]([Cl:23])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1
Reactant: CSC(=Cc1ccccc1)S(C)=O
Reactant: O=P(Cl)(Cl)Cl
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: CSC(SC)=C(Cl)c1ccccc1
Temperature: -15 °C
Reaction time: 1 h
Yield: 94 %

Procedure:
1-Methylsulfinyl-1-methylthio-2-phenylethylene (1.154 g) was dissolved in 15 ml of methylene chloride, and 1 ml of triethylamine was added. Under cooling at -15° C., 0.55 ml of phosphorus oxychloride was added. The mixture was stirred at -15° C. for 1 hour and then at room temperature for 2 hours. Water (30 ml) was added, and the reaction mixture was extracted three times with 30 ml of methylene chloride. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was chromatographed on a Florisil column using hexane/benzene as an eluant to afford 1.180 g of 1,1-bis(methylthio)-2-chloro-2-phenylethylene in a yield of 94%.
Reaction SMILES: [N:1]([CH2:4][C@H:5]([OH:12])[CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])=[N+:2]=[N-:3].C(N([CH2:18][CH3:19])CC)C>CN(C)C1C=CN=CC=1.O1CCCC1>[N:1]([CH2:4][C@H:5]([O:12][C:7](=[O:8])[CH2:6][CH2:5][CH2:4][CH2:18][CH3:19])[CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])=[N+:2]=[N-:3]
Reactant: CCOC(=O)C[C@@H](O)CN=[N+]=[N-]
Reactant: CCN(CC)CC
Agent: CN(C)c1ccncc1
Solvent: C1CCOC1
Product: CCCCCC(=O)O[C@@H](CN=[N+]=[N-])CC(=O)OCC
Temperature: 0 °C
Reaction time: 5 h
Yield: 186.4 %

Procedure:
In a 100 ml four-necked flask were charged 6.0 g (34.6 mmol) of ethyl (R)-4-azido-3-hydroxybutyrate, 4.2 g (41.5 mmol) of triethylamine, 0.12 g (1.04 mmol) of 4-dimethylaminopyridine, and 60 ml of tetrahydrofuran and the mixture was cooled to 0° C. 5.10 g (38.1 mmol) of hexanoyl chlrodie was slowly added thereto dropwise in a nitrogen stream. After the addition, the reaction mixture was stirred at a room temperature for 5 hours, and then 14 ml of 5% HCL was added thereto. After the liquid separation, the mixture was washed thrice with 30 ml of 5% aqueous solution of sodium chloride and then concentrated to give 8.75 g (93%) of the title compound.
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][CH:13]=O)[N:8]2[CH3:11])=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[N:3]=1.[CH:21]([N:24]1[CH2:29][CH2:28][NH:27][CH2:26][C:25]1=[O:30])([CH3:23])[CH3:22].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][CH2:13][N:27]3[CH2:28][CH2:29][N:24]([CH:21]([CH3:23])[CH3:22])[C:25](=[O:30])[CH2:26]3)[N:8]2[CH3:11])=[C:4]([N:15]2[CH2:20][CH2:19][O:18][CH2:17][CH2:16]2)[N:3]=1
Reactant: CC(C)N1CCNCC1=O
Reactant: Cn1c(CC=O)nc2c(N3CCOCC3)nc(Cl)nc21
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCCl
Product: CC(C)N1CCN(CCc2nc3c(N4CCOCC4)nc(Cl)nc3n2C)CC1=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 21.2 %

Procedure:
To a solution of (2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)acetaldehyde (167 mg, 0.57 mmol) in DCE (10 mL) was added 1-isopropylpiperazin-2-one (87 mg, 0.61 mmol) and powdered 4 Å molecular sieves. The reaction mixture was stirred at room temperature for 1 h, sodium triacetoxyborohydride (239 mg, 1.13 mmol) was added and the resulting mixture stirred for a further 16 h. The reaction mixture was filtered through Celite®, loaded onto an Isolute® SCX-2 cartridge, washed with MeOH then the desired product eluted with 2 M NH3 in MeOH. The resulting residue was purified by column chromatography (Si—PCC, 0-10% 2 M NH3/MeOH in DCM) to give the title compound as a pale yellow oil (51 mg, 33%). LCMS (Method H): RT=3.31 min, [M+H]+ 422.5
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[CH2:3][C:4]1[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=1[NH2:6].C(O)(=O)C.[N:17]([O-])=O.[Na+]>O>[F:1][C:2]([F:11])([F:12])[C:3]1[C:4]2[C:5](=[CH:7][CH:8]=[CH:9][CH:10]=2)[NH:6][N:17]=1
Reactant: Nc1ccccc1CC(F)(F)F
Reactant: O=N[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: FC(F)(F)c1n[nH]c2ccccc12
Temperature: 25 °C

Procedure:
18.9 parts of 2-(2,2,2-trifluoro-ethyl)-aniline are dissoved in 700 parts by volume of glacial acetic acid. 14 parts by volume of a 50% aqueous solution of sodium nitrite are poured at one go into this well stirred solution. The temperature of the mass rises from 20° C. 27° C. The stirring is maintained at ambient temperature for about 15 hours, after which the intermediate diazo derivative has totally disappeared. A large part of the acetic acid is eliminated by distillation in vacuum so as to give a volume of about 100 parts. Then the solution is run into 160 parts of cold water with stirring. The precipitate of 3-trifluoromethyl-indazole formed is filtered off and washed with water: crude M.p. 98° C. It is recrystallised from boiling water for analysis. White needles of M.p. 104° C. (Kofler stage) are obtained; dry weight after recrystallisation 11.4 parts.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[C:6]([N:8]=[C:9]=[S:10])[CH:7]=1.[NH3:17]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)=[C:6]([NH:8][C:9]([NH2:17])=[S:10])[CH:7]=1
Reactant: N
Reactant: Fc1ccc(N2CCOCC2)c(N=C=S)c1
Product: NC(=S)Nc1cc(F)ccc1N1CCOCC1

Procedure:
Reaction of 5-fluoro-2-morpholinophenyl isothiocyanate (5.8 g) with 33% ethanolic ammonia solution (30 ml) at room temperature for 3 hours gave 1-(5-fluoro-2-morpholinophenyl)thiourea as a white solid (m.p. 195-196).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][C:10]([C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)=[C:11]([C:13]([NH:15][C:16]3[S:17][CH:18]=[CH:19][N:20]=3)=[O:14])[N:12]=2)=[CH:4][CH:3]=1.[CH3:29][N:30]([CH3:34])[CH2:31][CH2:32]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>>[CH3:29][N:30]([CH3:34])[CH2:31][CH2:32][O:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][C:10]([C:21]3[CH:26]=[CH:25][C:24]([O:27][CH3:28])=[CH:23][CH:22]=3)=[C:11]([C:13]([NH:15][C:16]3[S:17][CH:18]=[CH:19][N:20]=3)=[O:14])[N:12]=2)=[CH:4][CH:3]=1
Reactant: CN(C)CCO
Reactant: COc1ccc(-c2[nH]c(-c3ccc(O)cc3)nc2C(=O)Nc2nccs2)cc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: COc1ccc(-c2[nH]c(-c3ccc(OCCN(C)C)cc3)nc2C(=O)Nc2nccs2)cc1

Procedure:
2-(4-Hydroxyphenyl)-5-(4-methoxyphenyl)-N-(2-thiazolyl)-imidazole-4-carboxamide, 2-dimethylaminoethanol, triphenylphosphine and diethyl azodicarboxylate are reacted and treated in the same manner as in Example 24 to give 2-(4-(2-dimethylaminoethyloxy)phenyl)-5-(4-methoxyphenyl)-N-(2-thiazolyl)imidazole-4-carboxamide.
Reaction SMILES: [F:1][C:2]1[C:10]2[N:11]([C:15]3[CH:20]=[CH:19][C:18]([I:21])=[CH:17][C:16]=3[F:22])[C:12](=[O:14])[NH:13][C:9]=2[C:8]2[O:7][CH:6]=[CH:5][C:4]=2[C:3]=1[F:23].[CH2:24]([O:31][CH2:32][CH:33]1[CH2:35][CH:34]1[S:36](Cl)(=[O:38])=[O:37])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.C(OCC)(=O)C>C(Cl)Cl.CN(C1C=CN=CC=1)C.CCCCCC>[CH2:24]([O:31][CH2:32][CH:33]1[CH2:35][CH:34]1[S:36]([IH:21][C:18]1[CH:19]=[CH:20][C:15]([N:11]2[C:10]3[C:2]([F:1])=[C:3]([F:23])[C:4]4[CH:5]=[CH:6][O:7][C:8]=4[C:9]=3[NH:13][C:12]2=[O:14])=[C:16]([F:22])[CH:17]=1)(=[O:37])=[O:38])[C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1
Reactant: O=S(=O)(Cl)C1CC1COCc1ccccc1
Reactant: O=c1[nH]c2c3occc3c(F)c(F)c2n1-c1ccc(I)cc1F
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Solvent: CCCCCC
Solvent: CCOC(C)=O
Product: O=c1[nH]c2c3occc3c(F)c(F)c2n1-c1ccc([IH]S(=O)(=O)C2CC2COCc2ccccc2)cc1F
Temperature: 30 °C
Reaction time: 12 h
Yield: 59 %

Procedure:
TEA (0.0941 g, 0.930 mmol) was added to a solution of 4,5-difluoro-3-(2-fluoro-4-iodophenyl)-1H-1-benzofuro[6,7-d]imidazol-2(3H)-one (I-32a: 0.2 g, 0.4651 mmol) in dry DCM (5 mL) at 0° C. This was followed by the addition of 2-benzyloxymethyl-cyclopropanesulfonyl chloride (0.181 g, 0.6976 mmol) and catalytic amount of DMAP (0.010 g). The reaction mass was stirred for 12 hours at 20-40° C. The reaction was monitored by TLC (30% ethyl acetate in hexane). The reaction mass was diluted with DCM (50 mL) and partitioned between water and DCM. The organic layer was washed with water, brine solution and concentrated under reduced pressure to afford the crude product. Purification by column chromatography on silica gel (15% ethyl acetate in hexane) afforded 0.180 g of the product (60% yield). 1H NMR (CDCl3, 300 MHz): δ 7.71 (d, 1H), 7.59-7.65 (m, 2H), 7.24-7.28 (m, 3H), 7.12-7.18 (m, 3H), 6.98 (d, 1H), 4.48 (s, 2H), 3.56 (dd, 1H), 3.38-3.48 (m, 1H), 3.25-3.35 (m, 1H), 2.28-2.38 (m, 1H), 1.56-1.58 (m, 1H), 1.38-1.48 (m, 1H). LCMS: 98.72%, m/z=654.9 (M+1)
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:20]([C:23]1[CH:24]=[CH:25][C:26]([O:31][CH2:32][C:33]([CH2:35]I)=[CH2:34])=[C:27]([CH:30]=1)[CH:28]=O)(=[O:22])[CH3:21].C[O-].[Na+].O>C(#N)C.CO>[CH2:34]=[C:33]1[CH:35]=[CH:28][C:27]2[CH:30]=[C:23]([C:20](=[O:22])[CH3:21])[CH:24]=[CH:25][C:26]=2[O:31][CH2:32]1
Reactant: C=C(CI)COc1ccc(C(C)=O)cc1C=O
Agent: C[O-]
Agent: [Na+]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: CO
Solvent: CC#N
Product: C=C1C=Cc2cc(C(C)=O)ccc2OC1
Reaction time: 14 h
Yield: 57.9 %

Procedure:
973 mg (3.575 mmol) of triphenylphosphine are added under argon to 1.118 g (3.25 mmol) of 5-acetyl-2-{[2-(iodomethyl)-2-propenyl]oxy}benzaldehyde in solution in 30 ml of acetonitrile. The medium is brought to reflux and is stirred for 14 hours. After cooling the solution, 0.743 ml (3.25 mmol) of a 25% solution of sodium methoxide in methanol is added. The medium is stirred at ambient temperature for 3 hours and then water is added. After concentrating the solution under vacuum, dichloromethane is added. The phases are then separated and the aqueous phase is extracted with dichloromethane. The combined organic phases are washed, are then dried and are finally concentrated under vacuum. The crude reaction product is purified by chromatography on silica gel (ethyl acetate/heptane 10/90) to give 377 mg (58%) of 1-(3-methylene-2,3-dihydro-1-benzoxepin-7-yl)ethanone in the form of a white solid; 1H NMR (300 MHz, CDCl3): 7.86 (d, J=2.1 Hz, 1H), 7.75 (dd, J=2.1 Hz and 8.4 Hz, 1H), 7.03 (d, J=8.4 Hz, 1H), 6.51 (d, J=11.7 Hz, 1H), 6.38 (d, J=11.7 Hz, 1H), 5.28 and 5.11 (2s, 2H), 4.61 (s, 2H), 2.56 (s, 3H).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[C:16]([CH3:18])[CH:15]=[C:14]([CH3:19])[CH:13]=1)[CH:6]=[CH:5]2.[Li]CCCC.Cl[Ge:26]([CH:33]([CH3:35])[CH3:34])([CH:30]([CH3:32])[CH3:31])[CH:27]([CH3:29])[CH3:28]>C1COCC1>[CH3:19][C:14]1[CH:13]=[C:12]([C:7]2[CH:6]=[CH:5][C:4]3[C:9](=[CH:10][CH:11]=[C:2]([Ge:26]([CH:33]([CH3:35])[CH3:34])([CH:30]([CH3:32])[CH3:31])[CH:27]([CH3:29])[CH3:28])[CH:3]=3)[N:8]=2)[CH:17]=[C:16]([CH3:18])[CH:15]=1
Reactant: CC(C)[Ge](Cl)(C(C)C)C(C)C
Reactant: Cc1cc(C)cc(-c2ccc3cc(Br)ccc3n2)c1
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: Cc1cc(C)cc(-c2ccc3cc([Ge](C(C)C)(C(C)C)C(C)C)ccc3n2)c1
Temperature: -78 °C
Reaction time: 0.75 h
Yield: 82.7 %

Procedure:
6-Bromo-2-(3,5-dimethylphenyl)quinoline (5.3 g, 16.98 mmol) and 150 mL anhydrous THF were added in a dry two-necked round bottom flask and cooled down to −78° C. 7.2 mL BuLi (2.5 M) was added dropwise. The solution was stirred for 45 minutes and 4.4 mL (20.37 mmol) of chlorotriisopropylgermane was slowly added with a syringe. The solution was stirred for 4 h and monitored by GC until the reaction was finished. The reaction mixture was purified by column and distillation. ˜6.1 g colorless liquid was obtained after distillation. GC-MS confirmed the desired product.
Reaction SMILES: [C:1]([NH:4][NH:5][C:6](=O)[C@@H:7]([N:10]1[C@H:15]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)[C@@H:14]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=2)[CH2:13][C@H:12]([CH2:30][CH:31]=[CH2:32])[C:11]1=[O:33])[CH2:8][CH3:9])(=[O:3])[CH3:2].CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>ClC(Cl)C.O>[CH2:30]([C@H:12]1[CH2:13][C@H:14]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[CH:24]=2)[C@@H:15]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=2)[N:10]([C@H:7]([C:6]2[O:3][C:1]([CH3:2])=[N:4][N:5]=2)[CH2:8][CH3:9])[C:11]1=[O:33])[CH:31]=[CH2:32]
Reactant: C=CC[C@H]1C[C@H](c2cccc(Cl)c2)[C@@H](c2ccc(Cl)cc2)N([C@@H](CC)C(=O)NNC(C)=O)C1=O
Agent: CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC
Solvent: O
Solvent: CC(Cl)Cl
Product: C=CC[C@H]1C[C@H](c2cccc(Cl)c2)[C@@H](c2ccc(Cl)cc2)N([C@@H](CC)c2nnc(C)o2)C1=O

Procedure:
A solution of 58 mg (0.115 mmol) of (S)—N′-acetyl-2-((3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-2-oxopiperidin-1-yl)butanehydrazide (Example 34, Step A) and Burgess' reagent (110 mg, 0.462 mmol) in dichloroethane (1154 μL) was heated in the microwave at 120° C. for 30 min. Then the reaction mixture was diluted with water and extracted with DCM. The combined organic layers were washed with sat. aq. NaCl and NaHCO3-solutions, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. Separation by reversed phase HPLC (55 to 90% MeCN/H2O in 35 min, 29 mg injection each time) provided the title compound as a colorless film. MS (ESI) 484.1 [M+H]+.
Reaction SMILES: C([CH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][C:4]1=[O:9])=O.C1(C)C=CC(S([N:19]=[N+:20]=[N-])(=O)=O)=CC=1>>[N+:19](=[C:3]1[CH2:8][CH2:7][CH2:6][CH2:5][C:4]1=[O:9])=[N-:20]
Reactant: O=CC1CCCCC1=O
Reactant: Cc1ccc(S(=O)(=O)N=[N+]=[N-])cc1
Product: [N-]=[N+]=C1CCCCC1=O

Procedure:
Reaction of a formyl cyclohexanone derivative with para-toluenesulfonylazide effects displacement of the formyl group by a diazo moiety to provide a diazocyclohexanone derivative. For example, a formyl cyclohexanone derivative such as 2-phenyl-2-(2-cyanoethyl)-6-formylcyclohexanone can be reacted with about an equimolar quantity of para-toluene-sulfonylazide in the presence of dimethylamine or diethylamine, in an organic solvent such as diethyl ether, to provide, for instance, 2-phenyl-2-(2-cyanoethyl)-6-diazocyclohexanone.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([NH2:9])[CH:4]=1.[CH3:10][O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[CH:18]([C:24](OCC)=[O:25])[C:19](OCC)=[O:20].C(OCC)C>C1(OC2C=CC=CC=2)C=CC=CC=1>[OH:25][C:24]1[C:6]2[C:5](=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=2)[NH:9][C:19](=[O:20])[C:18]=1[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[O:11][CH3:10]
Reactant: CCOC(=O)C(C(=O)OCC)c1ccccc1OC
Reactant: COc1cccc(N)c1
Solvent: CCOCC
Solvent: c1ccc(Oc2ccccc2)cc1
Product: COc1ccc2c(O)c(-c3ccccc3OC)c(=O)[nH]c2c1
Temperature: 280 °C
Yield: 90.7 %

Procedure:
A mixture of 2.7 g of m-anisidine and 5.32 g of diethyl 2-methoxyphenylmalonate in 20 ml of diphenyl ether was placed in a flask equipped with an air condenser, and heated at 270-290° C. for 2.5 hours. After cooling, to the reaction mixture there was added 80 ml of diethyl ether. The precipitates were collected by filtration, and washed with diethyl ether to obtain 5.39 g of 4-hydroxy-7-methoxy-3-(2-methoxyphenyl)-2-quinolone (yield: 90.7%).
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([Cl:9])=[CH:5][C:4]=1[C:10]1([CH2:15][C:16]([NH2:18])=[NH:17])[CH2:14][CH2:13][CH2:12][CH2:11]1.[C:19]([O:23][C:24](=[O:39])/[C:25](/O)=[C:26](\[O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)/[C:27](O)=[O:28])([CH3:22])([CH3:21])[CH3:20].C(OCC)(=O)C>CO.CCCCCC>[C:19]([O:23][C:24]([C:25]1[C:26]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[C:27]([OH:28])[N:18]=[C:16]([CH2:15][C:10]2([C:4]3[CH:5]=[C:6]([Cl:9])[CH:7]=[CH:8][C:3]=3[Cl:2])[CH2:14][CH2:13][CH2:12][CH2:11]2)[N:17]=1)=[O:39])([CH3:22])([CH3:20])[CH3:21]
Reactant: N=C(N)CC1(c2cc(Cl)ccc2Cl)CCCC1
Reactant: CC(C)(C)OC(=O)/C(O)=C(\OCc1ccccc1)C(=O)O
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: CO
Product: CC(C)(C)OC(=O)c1nc(CC2(c3cc(Cl)ccc3Cl)CCCC2)nc(O)c1OCc1ccccc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 53.5 %

Procedure:
To a stirred solution of 2-[1-(2,5-dichlorophenyl)-cyclopentyl]-acetamidine hydrochloride (2=3) (2.0, 7.407 mmol) and (E)-2-benzyloxy-3-hydroxy-but-2-enedioic acid 4-tert-butyl ester (4) (3.422 g, 11.111 mmol) in methanol (50 mL) NaOMe (25% in methanol; 4.8 mL) was added dropwise at 0° C. and stirred at room temperature for 16 h. Silica thin layer chromatography was performed (40% ethyl acetate in hexane, Rf=0.6). The reaction mixture was quenched with HCl (1N; 5 mL), methanol was removed, the product was diluted with water and the mixture was extracted with ethyl acetate. The combined organic part was dried, the product was concentrated and the crude product was purified using a normal silica gel column using a gradient eluent of 10 to 40% ethyl acetate in hexane to get pure 5-benzyloxy-2-[1-(2,5-dichlorophenyl)-cyclopentylmethyl]-6-hydroxypyrimidine-4-carboxylic acid tert-butyl ester (204) (2.1 g, 53.55%) as a yellow solid.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][CH:3]=1.[CH:10]1([C:16](OC)=O)[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11]1.[CH3:20][OH:21]>>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([C:16]([C:10]2[CH:11]=[CH:12][C:13]([O:21][CH3:20])=[CH:14][CH:15]=2)=[C:2]2[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]2)=[CH:3][CH:4]=1
Reactant: COc1ccc(Br)cc1
Reactant: COC(=O)C1CCCCC1
Reactant: CO
Product: COc1ccc(C(=C2CCCCC2)c2ccc(OC)cc2)cc1

Procedure:
The Grignard reaction of p-bromoanisole (15.0 g, 0.080 mol) and methyl cyclohexane carboxylate (Compound 26) (5.7 g, 0.040 mol) afforded the carbinol (Compound 27) which upon dehydration yielded a yellow solid. Recrystallized from absolute EtOH yielded 8.0 g (65%) of a colorless solid, mp 106°-107° C. (MIQUEL, J -F., WAHLSTAM, H., OLSSON, K. AND SUNDBECK, B. (1963), "Synthesis of unsymmetrical diphenylalkenes", Journal of Medicinal Chemistry, 6, 774), 109°-110° C. 1H NMR (CDCl3) δ 1.70 (broad s, 10H, cyclohexyl), 3.70 (s, 6H, OCH3), 7.07 (dd, 8H, ArH).
Reaction SMILES: C(C1C=C(C)C=C(C(C)(C)C)C=1[OH:16])(C)(C)C.CN(CCCN1CN(CCCN(C)C)CN(CCCN(C)C)C1)C.[Cl:41][C:42]1[CH:43]=[C:44]([N:48]=[C:49]=[O:50])[CH:45]=[CH:46][CH:47]=1.[C:51]([O:55][CH2:56][CH2:57]C(O)C)(=[O:54])[CH:52]=[CH2:53].[N-]=C=O>>[C:51]([O:55][CH2:56][CH2:57][O:50][C:49](=[O:16])[NH:48][C:44]1[CH:45]=[CH:46][CH:47]=[C:42]([Cl:41])[CH:43]=1)(=[O:54])[CH:52]=[CH2:53]
Reactant: O=C=Nc1cccc(Cl)c1
Reactant: Cc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Reactant: C=CC(=O)OCCC(C)O
Agent: CN(C)CCCN1CN(CCCN(C)C)CN(CCCN(C)C)C1
Agent: [N-]=C=O
Product: C=CC(=O)OCCOC(=O)Nc1cccc(Cl)c1
Temperature: 60 °C

Procedure:
0.15 g of 2,6-di-tert-butyl-4-methylphenol, 0.075 g of Desmorapid Z, 85.3 g of 3-chlorophenyl isocyanate were initially introduced into a 500 ml round-bottomed flask and heated to 60° C. Thereafter, 65.5 g of 3-hydroxybutyl acrylate were added dropwise and the mixture was kept further at 60° C. until the isocyanate content had fallen below 0.1%. Cooling was then effected. The product was obtained as a crystalline solid.