Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([S:10](Cl)(=[O:12])=[O:11])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[CH2:14]([O:17][C:18]([NH:20][CH:21]([C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([NH2:34])[CH:29]=1)[CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])=[O:19])[CH:15]=[CH2:16]>N1C=CC=CC=1>[CH2:14]([O:17][C:18]([NH:20][CH:21]([C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([NH:34][S:10]([C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)(=[O:12])=[O:11])[CH:29]=1)[CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])=[O:19])[CH:15]=[CH2:16]
Reactant: C=CCOC(=O)NC(CC(=O)OCC)c1cccc(N)c1
Reactant: O=[N+]([O-])c1cccc(S(=O)(=O)Cl)c1
Solvent: c1ccncc1
Product: C=CCOC(=O)NC(CC(=O)OCC)c1cccc(NS(=O)(=O)c2cccc([N+](=O)[O-])c2)c1

Procedure:
3-Nitrobenzenesulphonyl chloride (9.9 g) was added at 0° C. to a solution of ethyl 3-allyloxycarbonylamino-3-(3-aminophenyl)-propionate from II.1d (10.9 g) in 100 ml of pyridine. After a reaction time of 2 h at 0° C., the mixture was concentrated, treated with 1 N HCl (150 ml) and extracted with dichloromethane. After drying (MgSO4), the solvent was removed, and 16.8 g of product were obtained.
Reaction SMILES: [CH3:1][S:2][C:3]1[C:4]([N+:10]([O-:12])=[O:11])=[C:5]([CH:7]=[CH:8][CH:9]=1)[NH2:6].N1C=CC=CC=1.[CH3:19][O:20][CH2:21][C:22](Cl)=[O:23].N>CC(N(C)C)=O.O.CO>[CH3:19][O:20][CH2:21][C:22]([NH:6][C:5]1[CH:7]=[CH:8][CH:9]=[C:3]([S:2][CH3:1])[C:4]=1[N+:10]([O-:12])=[O:11])=[O:23]
Reactant: CSc1cccc(N)c1[N+](=O)[O-]
Reactant: COCC(=O)Cl
Agent: N
Solvent: c1ccncc1
Solvent: CC(=O)N(C)C
Solvent: O
Product: COCC(=O)Nc1cccc(SC)c1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 2 h
Yield: 91 %

Procedure:
[step 2] 3-(Methylthio)-2-nitroaniline (1.0 g, 5.4 mmol) obtained in step 1 was dissolved in DMA (5.4 mL), pyridine (0.44 mL, 5.4 mmol) and 2-methoxyacetyl chloride (1.49 mL, 16 mmol) were added, and the mixture was stirred at room temperature for 2 hr. To the reaction solution were added methanol and aqueous ammonia, and the mixture was stirred at room temperature for 30 min. Water was added, and the crystals were collected by filtration, and dried to give 2-methoxy-N-[3-(methylthio)-2-nitrophenyl]acetamide (1.26 g, 91%).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[C:7]([N+:12]([O-:14])=[O:13])[CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[C:15]([O:17][CH2:18][CH3:19])=[O:16].Cl.[CH3:21][NH:22][CH3:23].C(N(CC)CC)C>O1CCOCC1.C(OCC)(=O)C>[CH3:21][N:22]([CH3:23])[C:2]1[C:11]2[C:6](=[C:7]([N+:12]([O-:14])=[O:13])[CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[C:15]([O:17][CH2:18][CH3:19])=[O:16]
Reactant: CCOC(=O)c1cnc2c([N+](=O)[O-])cccc2c1Cl
Reactant: CNC
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: CCOC(=O)c1cnc2c([N+](=O)[O-])cccc2c1N(C)C
Yield: 59.5 %

Procedure:
A mixture of 4-chloro-3-ethoxycarbonyl-8-nitroquinoline (199 mg), dimethylamine hydrochloride (63.6 mg) and triethylamine (78.9 mg) in dioxane was refluxed for 3 hours. After cooling, the mixture was diluted with ethyl acetate, washed with water, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel (ethyl acetate:n-hexane, 1:2, v/v) to give 4-dimethylamino-3-ethoxycarbonyl-8-nitroquinoline (122 mg).
Reaction SMILES: [C:1]([CH:3]([C:11]1([CH3:15])[CH2:14][O:13][CH2:12]1)[NH:4]S(C(C)(C)C)=O)#[N:2].Cl.O1CCOCC1.C(N(CC)CC)C>CO>[NH2:4][CH:3]([C:11]1([CH3:15])[CH2:14][O:13][CH2:12]1)[C:1]#[N:2]
Reactant: CC1(C(C#N)NS(=O)C(C)(C)C)COC1
Agent: Cl
Solvent: C1COCCO1
Solvent: CCN(CC)CC
Solvent: CO
Product: CC1(C(N)C#N)COC1
Temperature: 0 °C
Reaction time: 2 h
Yield: 104 %

Procedure:
To a solution of N-[cyano-(3-methyloxetan-3-yl)methyl]-2-methyl-propane-2-sulfinamide (example 251a, 1.5 g, 6.51 mmol) in methanol (40 ml) cooled at 0° C. was added a solution of hydrochloric acid in dioxane (2.44 ml, 9.77 mmol) and the reaction mixture was stirred at 0° C. for 2 hours. Triethylamine (1.32 g, 1.82 ml, 13.0 mmol) was added to the reaction mixture which was then concentrated in vacuo. The residue was directly purified by flash chromatography on silica eluting with a dichloromethane/methanol gradient to yield the title compound (854 mg) as a yellow oil which was not totally pure and was used without any further purification. MS (ESI, m/z): 127.1 (M+H+).
Reaction SMILES: [CH3:1][CH:2]([CH3:20])[CH:3]([C:5]1[CH:6]=[CH:7][C:8]2[O:17][C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[C:10](=[O:18])[C:9]=2[CH:19]=1)[OH:4].[Mn]([O-])(=O)(=O)=O.[K+]>CC(C)=O>[C:3]([C:5]1[CH:6]=[CH:7][C:8]2[O:17][C:12]3=[N:13][CH:14]=[CH:15][CH:16]=[C:11]3[C:10](=[O:18])[C:9]=2[CH:19]=1)(=[O:4])[CH:2]([CH3:20])[CH3:1]
Reactant: CC(C)C(O)c1ccc2oc3ncccc3c(=O)c2c1
Agent: O=[Mn](=O)(=O)[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CC(C)C(=O)c1ccc2oc3ncccc3c(=O)c2c1

Procedure:
A mixture of 2.7 g of 2-methyl-1-(5-oxo-5H-[1]benzopyrano[2,3-b]pyridin-7-yl)-1-propanol, 60 ml of acetone and 1.5 g of potassium permanganate is refluxed for 6 hours. The reaction mixture is filtered, and the residue is washed thoroughly was chloroform. The filtrate and washings are concentrated, and the residue is purified by column chromatography on silica gel with chloroform as eluent, and further by recrystallization from ethanol to give 7-isobutyryl-5-oxo-5H-[1]benzopyrano[2,3-b]pyridine melting at 155°-156°C.
Reaction SMILES: [CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH2:15][CH2:16][NH2:17])[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:5][CH2:4][CH2:3][CH2:2]1.C[Si]([N:22]=[C:23]=[O:24])(C)C.[Cl-].[NH4+]>O1CCCC1>[CH:1]1([O:6][C:7]2[CH:8]=[C:9]([CH2:15][CH2:16][NH:17][C:23]([NH2:22])=[O:24])[CH:10]=[CH:11][C:12]=2[O:13][CH3:14])[CH2:2][CH2:3][CH2:4][CH2:5]1
Reactant: COc1ccc(CCN)cc1OC1CCCC1
Reactant: C[Si](C)(C)N=C=O
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: COc1ccc(CCNC(N)=O)cc1OC1CCCC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 2-(3-cyclopentyloxy-4-methoxyphenyl)ethylamine (0.47 g, 2.0 mmol) in tetrahydrofuran (10 mL) under an argon atmosphere was added trimethylsilyl isocyanate (0.42 mL, 3.1 mmol). The resulting mixture was heated at reflux for 1 h, was allowed to cool to room temperature and then was stirred overnight. The reaction mixture was again heated to reflux for an additional 5 h and allowed to cool to room temperature. Ammonium chloride was added, and the mixture was concentrated under reduced pressure. The residue was partitioned between methylene chloride and water. The organic extract was washed successively with 10%. hydrochloric acid and water and dried (potassium carbonate). Removal of the solvent in vacuo and purification of the residue by flash chromatography, eluting with 3% methanol/methylene chloride, provided the urea as a white solid: m.p. 136°-37° C. Analysis Calc. for C15H22 N2O3 : C 64.73, H 7.97, N 10.06; found: C 64.66, H 7.97, N 10.28.
Reaction SMILES: [CH2:1]([N:8]1[CH:12]=[C:11]([CH:13]=[O:14])[N:10]=[C:9]1[CH3:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:16][Mg]Cl.[Cl-].[NH4+]>O1CCCC1>[CH2:1]([N:8]1[CH:12]=[C:11]([CH:13]([OH:14])[CH3:16])[N:10]=[C:9]1[CH3:15])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Cc1nc(C=O)cn1Cc1ccccc1
Reactant: C[Mg]Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: Cc1nc(C(C)O)cn1Cc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 7.2 g (0.306 mole) of 1-benzyl-2-methylimidazol-4-carboxaldehyde in 100 ml of tetrahydrofuran was added 15 ml of 2.9M methyl magnesium chloride (0.044 mole) in tetrahydrofuran. A white precipitate formed immediately. The mixture was stirred at room temperature for 30 minutes and then heated with 50 ml of 25% aqueous ammonium chloride solution. The precipitate was filtered off, washed with tetrahydrofuran and air dried. The combined filtrate and wash solutions were dried (Na2SO4) and concentrated in vacuo to a solid residue. The residue was dissolved in 300 ml of boiling ethyl acetate, dried (Na2SO4) and concentrated to half volume under reduced pressure. The solid which separated upon cooling was filtered off and air dried. Total yield=7.1 g (90%); m.p. 162.5°-167.5° C.
Reaction SMILES: C(C1C=CC(C(=O)C)=CC=1)(=O)C.O.NN.[C:16]([C:19]1[CH:37]=[CH:36][C:22]([O:23][CH2:24][CH2:25][O:26][C:27]2[CH:32]=[CH:31][C:30]([C:33](O)=[O:34])=[CH:29][CH:28]=2)=[CH:21][CH:20]=1)(O)=[O:17].[H-].[Al+3].[Li+].[H-].[H-].[H-]>O1CCCC1>[OH:34][CH2:33][C:30]1[CH:29]=[CH:28][C:27]([O:26][CH2:25][CH2:24][O:23][C:22]2[CH:36]=[CH:37][C:19]([CH2:16][OH:17])=[CH:20][CH:21]=2)=[CH:32][CH:31]=1
Reactant: O=C(O)c1ccc(OCCOc2ccc(C(=O)O)cc2)cc1
Agent: CC(=O)c1ccc(C(C)=O)cc1
Agent: NN
Agent: [Al+3]
Solvent: O
Solvent: C1CCOC1
Product: OCc1ccc(OCCOc2ccc(CO)cc2)cc1

Procedure:
A bishydrazone was used in Ex. 26. It may be prepared by refluxing (48 hr) 1,4-diacetylbenzene with excess hydrazine hydrate in 2B alcohol, then cooling the reaction mixture to yield the product, m.p. = 184° C (dec.). The dialdehyde used in Ex. 35 is prepared by first reducing the dimethyl ester of 1,2-bis(4-carboxyphenoxy)ethane with lithium aluminum hydride in tetrahydrofuran to form 1,2-bis(4-hydroxymethylphenoxy)ethane; m.p. = 174°-176° C. The latter is oxidized to the desired dialdehyde with ceric ammonium nitrate in glacial acetic acid/water following the general procedure described in J. Org. Chem. 32, 3865-8 (1967); m.p. = 112.5°-114° C.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][CH:8]=1)=[O:6].[NH:15]1[CH2:20][CH2:19][CH:18]([C:21]2[CH:22]=[C:23]([NH:27][C:28](=[O:31])[CH2:29][CH3:30])[CH:24]=[CH:25][CH:26]=2)[CH2:17][CH2:16]1>>[CH3:14][O:13][C:10]1[CH:11]=[CH:12][C:7]([C:5](=[O:6])[CH2:4][CH2:3][CH2:2][N:15]2[CH2:20][CH2:19][CH:18]([C:21]3[CH:22]=[C:23]([NH:27][C:28](=[O:31])[CH2:29][CH3:30])[CH:24]=[CH:25][CH:26]=3)[CH2:17][CH2:16]2)=[CH:8][CH:9]=1
Reactant: CCC(=O)Nc1cccc(C2CCNCC2)c1
Reactant: COc1ccc(C(=O)CCCCl)cc1
Product: CCC(=O)Nc1cccc(C2CCN(CCCC(=O)c3ccc(OC)cc3)CC2)c1

Procedure:
Prepared by Procedure K and Scheme B1 using 4-chloro-1-(4-methoxyphenyl)-1-butanone and N-[3-(4-piperidinyl)phenyl]propanamide: ESMS m/e: 409.2 (M+H)+.
Reaction SMILES: [CH:1]([N-]C(C)C)(C)C.[Li+].C1CCCCC1.[S:15]1[CH:19]=[CH:18][C:17]([C:20]([OH:22])=[O:21])=[CH:16]1.CI.Cl>C1COCC1>[CH3:1][C:16]1[S:15][CH:19]=[CH:18][C:17]=1[C:20]([OH:22])=[O:21]
Reactant: CC(C)[N-]C(C)C
Reactant: O=C(O)c1ccsc1
Agent: Cl
Agent: [Li+]
Solvent: CI
Solvent: C1CCOC1
Solvent: C1CCCCC1
Product: Cc1sccc1C(=O)O
Temperature: -70 °C
Reaction time: 2 h

Procedure:
To a solution of 1.5M-lithium diisopropylamide/cyclohexane solution (600 ml) and THF (300 ml) was dropwise added 3-thiophenecarboxylic acid (50.0 g)/THF (150 ml) under vigorous stirring at −70° C. After the reaction mixture was stirred, as it was, at −70° C. for 2 hr, methyl iodide (60.0 g) was added dropwise to the reaction mixture. After the dry ice/acetone bath was removed, the mixture was reacted overnight. The resulting reaction solution was acidified by adding 5N hydrochloric acid thereto, and then extracted with ethyl acetate. The organic layer was washed with water and brine, dried and evaporated, to give 54 g of the title compound. (290-2) 2-Methyl-3-thiophenecarboxylate chloride
Reaction SMILES: [O:1]1[CH2:5][CH2:4][O:3][CH:2]1[CH2:6][CH2:7][CH2:8][C:9]1[S:13][C:12]([C:14]([OH:16])=[O:15])=[CH:11][CH:10]=1.[C:17](=O)([O-])[O-].[K+].[K+].CI.O>CN(C)C=O>[CH3:17][O:15][C:14]([C:12]1[S:13][C:9]([CH2:8][CH2:7][CH2:6][CH:2]2[O:3][CH2:4][CH2:5][O:1]2)=[CH:10][CH:11]=1)=[O:16]
Reactant: O=C([O-])[O-]
Reactant: O=C(O)c1ccc(CCCC2OCCO2)s1
Agent: [K+]
Solvent: CI
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1ccc(CCCC2OCCO2)s1
Temperature: 25 °C
Reaction time: 17 h
Yield: 94.4 %

Procedure:
To a solution of 5-(3-[1,3-dioxolan-2-yl]propyl)-2-thiophene carboxylic acid (58.0 g, 239 mmol) in 300 mL of dimethylformamide was added potassium carbonate (41.4 g, 299 mmol) followed by methyl iodide (51.0 g, 359 mmol). The slurry was stirred at ambient temperature for 17 hours and then poured into 600 mL of water. The resulting suspension was extracted twice with 500 mL of t-butylmethylether and the combined extracts were washed with water, dried over magnesium sulfate, filtered, and concentrated by rotory evaporation to afford 57.84 g (94.3%) of the title compound which was of sufficient purity for use in Preparation 3. IR (CHCl3, cm−1) 3021, 1707, 1541, 1463, 1296, 1101. 1H NMR (300 MHz, CDCl3) d 1.75 (m, 4H), 2.84 (t, J=7.4 Hz, 2H), 3.81 (s, 3H), 3.82 (m, 2H), 3.92 (m, 2H), 4.84 (t, J=4.3 Hz, 1H), 6.76 (d, J=3.9 Hz, 1H), 7.58 (d, J=3.7 Hz, 1H).
Reaction SMILES: [Cl:1][C:2]1[N:6]([CH3:7])[N:5]=[C:4]([C:8]([OH:10])=O)[CH:3]=1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.Cl.[CH3:34][NH:35][O:36][CH3:37]>ClCCl.O.C(N(CC)CC)C>[Cl:1][C:2]1[N:6]([CH3:7])[N:5]=[C:4]([C:8]([N:35]([O:36][CH3:37])[CH3:34])=[O:10])[CH:3]=1
Reactant: Cn1nc(C(=O)O)cc1Cl
Reactant: CNOC
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: CON(C)C(=O)c1cc(Cl)n(C)n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 91.5 %

Procedure:
5-Chloro-1-methyl-1H-pyrazole-3-carboxylic acid (982 mg) was added to a solution of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (2.39 g), 1-hydroxybenzotriazole (252 mg), and N,O-dimethylhydroxylamine hydrochloride (1.21 g) in dichloromethane (50 ml). Triethylamine (2.4 ml) was added dropwise to the mixture, and the resulting mixture was stirred overnight at room temperature. The reaction solution was diluted with dichloromethane (20 ml). Water (50 ml) was added to the dilution to separate the aqueous and organic layers. The organic layer was washed with water (50 ml). The organic layer was dried over anhydrous magnesium sulfate. After filtration, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane-ethyl acetate) to obtain the title compound (1.14 g).
Reaction SMILES: [N:1]1([CH:6]2[C:15](=[CH2:16])[C:14]3[CH:13]=[C:12]([C:17]([O:19]CC)=[O:18])[CH:11]=[CH:10][C:9]=3[CH2:8][CH2:7]2)[CH:5]=[CH:4][N:3]=[CH:2]1.[OH-].[Na+].C(O)C>O>[N:1]1([CH:6]2[C:15](=[CH2:16])[C:14]3[CH:13]=[C:12]([C:17]([OH:19])=[O:18])[CH:11]=[CH:10][C:9]=3[CH2:8][CH2:7]2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: C=C1c2cc(C(=O)OCC)ccc2CCC1n1ccnc1
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: C=C1c2cc(C(=O)O)ccc2CCC1n1ccnc1
Yield: 84.5 %

Procedure:
A mixture of ethyl 5,6,7,8-tetrahydro-7-(1H-imidazol-1-yl)-8-methylene-2-naphthalenecarboxylate (0.46 g), sodium hydroxide (0.8 g), ethanol (40 ml) and water (5 ml) is heated under reflux for 2 hours. The solution is evaporated, the residue is dissolved in water and the solution, acidified with acetic acid, is extracted with methylene chlorid. The organic layer is dried over sodium sulfate and evaporated to give 0.35 g of 5,6,7,8-tetrahydro-7-(1H-imidazol-1-yl)-8-methylene-2-naphthalenecarboxylic acid.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[N:5][N:6]2[C:11]([CH3:12])=[CH:10][C:9]([C:13]3[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][CH:14]=3)=[N:8][C:7]=12)#[CH:2].Br[C:24]1[CH:25]=[C:26]([S:30]([NH2:33])(=[O:32])=[O:31])[CH:27]=[CH:28][CH:29]=1>>[CH3:12][C:11]1[N:6]2[N:5]=[CH:4][C:3]([C:1]#[C:2][C:24]3[CH:25]=[C:26]([S:30]([NH2:33])(=[O:32])=[O:31])[CH:27]=[CH:28][CH:29]=3)=[C:7]2[N:8]=[C:9]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:21])([F:22])[F:20])=[CH:15][CH:14]=2)[CH:10]=1
Reactant: C#Cc1cnn2c(C)cc(-c3ccc(C(F)(F)F)cc3)nc12
Reactant: NS(=O)(=O)c1cccc(Br)c1
Product: Cc1cc(-c2ccc(C(F)(F)F)cc2)nc2c(C#Cc3cccc(S(N)(=O)=O)c3)cnn12

Procedure:
The title compound was prepared from 3-ethynyl-7-methyl-5-(4-trifluoromethyl-phenyl)-pyrazolo[1,5-a]pyrimidine (example C.12) (75 mg, 0.25 mmol) and 3-bromo-benzenesulfonamide (59 mg, 0.25 mmol) according to general procedure II. Obtained as a yellow solid (48 mg, 42%). MS (ISN) 454.9 [(M−H)−]; mp 214-216° C.
Reaction SMILES: C([O-])(=[O:3])C.[Cs+].Cl[CH2:7][C:8]1[NH:17][C:16](=[O:18])[C:15]2[C:10](=[CH:11][C:12]3[CH2:21][CH2:20][CH2:19][C:13]=3[CH:14]=2)[N:9]=1>CN(C=O)C>[OH:3][CH2:7][C:8]1[NH:17][C:16](=[O:18])[C:15]2[C:10](=[CH:11][C:12]3[CH2:21][CH2:20][CH2:19][C:13]=3[CH:14]=2)[N:9]=1
Reactant: CC(=O)[O-]
Reactant: O=c1[nH]c(CCl)nc2cc3c(cc12)CCC3
Agent: [Cs+]
Solvent: CN(C)C=O
Product: O=c1[nH]c(CO)nc2cc3c(cc12)CCC3
Temperature: 40 °C
Reaction time: 2 h

Procedure:
A solution of caesium acetate (14.4 g, 75.2 mmol) in dry DMF (40 ml) was heated to 60° C. under argon for 30 min. The mixture was cooled to 40° C. and a suspension of 2-chloromethyl-3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-4-one (L. Skelton, V. Bavetsias, A. Jackman, WO 00/050417-A1; 2.2 g, 9.4 mmol) in dry DMF (60 ml) was added via a cannula. The mixture was heated to 80° C. under argon for 16 h. The mixture was cooled to room temperature and the solvent was removed in vacuo. The residue was suspended in water (50 ml) and MeOH (20 ml). The pH was adjusted to 12.5 with 1M sodium hydroxide solution and the brown suspension was stirred for 2 h at room temperature. The insoluble brown solid was removed by filtration and the resulting solution was acidified to pH 5 with 1M hydrochloric acid.
Reaction SMILES: [Br:1][C:2]1[CH:12]=[N:11][C:10]2[O:9][CH:8]([CH2:13][CH2:14][Cl:15])[CH2:7][N:6]([CH3:16])[C:5](=O)[C:4]=2[CH:3]=1.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:19]>C(#N)C.C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:12]=[N:11][C:10]2[O:9][CH:8]([CH2:13][CH2:14][Cl:15])[CH2:7][N:6]([CH3:16])[C:5](=[S:19])[C:4]=2[CH:3]=1
Reactant: CN1CC(CCCl)Oc2ncc(Br)cc2C1=O
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Solvent: Cc1ccccc1
Solvent: CC#N
Product: CN1CC(CCCl)Oc2ncc(Br)cc2C1=S
Yield: 59.6 %

Procedure:
To a solution of 5.9 g (0.016 mole) of 7-bromo-2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f]-1,4-oxazepin-5(4H)-one in 25 ml of acetonitrile was added 2.07 g (0.005 mole) of phosphorus pentasulfide. The mixture was heated to reflux for 3 hr. The reaction mixture was diluted with 100 ml of toluene and filtered. The filtrate was washed with 3×50 ml of saturated sodium bicarbonate and 50 ml of water, dried over sodium sulfate, filtered, and concentrated by rotary evaporation to ~5-10 ml. Crystallization ensued and 3.0 g of crystals were collected. The mother liquor was concentrated giving 1.0 g additional crystals. The two crops were combined and recrystallized from diisopropylether/toluene to give ~3 g (56%) of yellow crystals, m.p. 138°-141° C.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:19]=[CH:20][CH:21]=1)[C:7]([C:9]1[C:14]([C:15]([O:17]C)=O)=[CH:13][CH:12]=[CH:11][N:10]=1)=O)([O-:3])=[O:2].Cl.[CH2:23]([NH:30][NH2:31])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C(O)C>[CH2:23]([N:30]1[C:15](=[O:17])[C:14]2[CH:13]=[CH:12][CH:11]=[N:10][C:9]=2[C:7]([C:6]2[CH:19]=[CH:20][CH:21]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)=[N:31]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: COC(=O)c1cccnc1C(=O)c1cccc([N+](=O)[O-])c1
Reactant: NNCc1ccccc1
Agent: Cl
Solvent: CCO
Product: O=c1c2cccnc2c(-c2cccc([N+](=O)[O-])c2)nn1Cc1ccccc1
Temperature: 85 °C
Yield: 40.9 %

Procedure:
To a solution of 2-(3-nitrobenzoyl)-3-methoxycarbonylpyridine (0.20 g, 0.75 mmoles) dissolved in ethanol (50 ml), was added benzylhydrazine hydrochloride (0.36 g, 1.86 mmoles). The mixture was heated to 85° C. for 144 hours. The mixture was purified by chromatography yielding 0.11 g of 6-benzyl-8-(3-nitrophenyl)pyrido[2,3-d]pyridazin-5-one (41%), mp 132° C.
Reaction SMILES: C[O:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:15]=[CH:14][C:13]([CH2:16][O:17]C)=[CH:12][CH:11]=2)=[CH:6][CH:5]=1.Br([O-])(=O)=O.[Na+]>>[CH:16]([C:13]1[CH:12]=[CH:11][C:10]([C:7]2[CH:8]=[CH:9][C:4]([CH:3]=[O:2])=[CH:5][CH:6]=2)=[CH:15][CH:14]=1)=[O:17]
Reactant: COCc1ccc(-c2ccc(COC)cc2)cc1
Agent: [Na+]
Agent: [O-][Br+2]([O-])[O-]
Product: O=Cc1ccc(-c2ccc(C=O)cc2)cc1

Procedure:
In the same manner as in Example 3, the operation was conducted, except that 0.53 g (2 mmols) of bismethoxymethylbiphenyl was used in place of m-methoxybenzyl alcohol and also 0.2 g (1.35 mmols) of sodium bromate was used. With respect to the components in the reaction solution, 4,4′-bisformylbiphenyl was produced in an area ratio, as determined by gas chromatography, of 93.3% and 6.7% of bismethoxymethylbiphenyl as a raw material was remained.
Reaction SMILES: [CH3:1][C:2]1[C:3]([CH:8]2[CH2:13][CH2:12][CH2:11][CH:10]([C:14]3[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][N:15]=3)[NH:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.Br[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[C:29]1([CH3:34])[O:33][CH2:32][CH2:31][O:30]1.CCN(C(C)C)C(C)C>CN(C=O)C>[CH3:1][C:2]1[C:3]([CH:8]2[CH2:13][CH2:12][CH2:11][CH:10]([C:14]3[C:19]([CH3:20])=[CH:18][CH:17]=[CH:16][N:15]=3)[N:9]2[CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[C:29]2([CH3:34])[O:30][CH2:31][CH2:32][O:33]2)=[N:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC1(c2ccccc2CBr)OCCO1
Reactant: Cc1cccnc1C1CCCC(c2ncccc2C)N1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1cccnc1C1CCCC(c2ncccc2C)N1Cc1ccccc1C1(C)OCCO1
Yield: 89.5 %

Procedure:
Using General Procedure A: A solution of 3,3″-dimethyl-1′,2′,3′,4′,5′,6′-hexahydro-[2,2′;6′,2″]terpyridine (0.547 g, 2.04 mmol), 2-(2-bromomethyl-phenyl)-2-methyl-[1,3]dioxolane (1.03 g, 3.99 mmol), KI (73 mg, 0.42 mmol), and DIPEA (0.70 mL, 4.02 mmol) in DMF (10 mL) was heated at 60° C. for 24 hours. Purification of the crude material by column chromatography on silica gel (40:1:1 CH2Cl2—CH3OH—NH4OH) provided 0.81 g (90%) of 3,3″-dimethyl-1′-[2-(2-methyl-[1,3]dioxolan-2-yl)-benzyl]-1′,2′,3′,4′,5′,6′-hexahydro-[2,2′;6′,2″]terpyridine as a white solid. 1H NMR (CDCl3) δ 1.46 (s, 3H), 1.60-1.83 (m, 3H), 2.15-2.20 (m, 1H), 2.47-2.57 (m, 8H), 3.26-3.31 (m, 2H), 3.82-3.87 (m, 2H), 4.01 (s, 2H), 4.44 (d, 2H, J=10.8 Hz), 6.72-6.82 (m, 4H), 7.05 (dd, 1H, J=7.2, 1.5 Hz), 7.21 (d, 2H, J=7.2 Hz), 7.46 (d, 1H, J=6.9 Hz), 8.19 (d, 2H, J=4.8 Hz); ES-MS m/z 444 (M+H).
Reaction SMILES: [Si:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([CH:19]([C:21]1[N:22]=[CH:23][N:24]([C:26]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:25]=1)[OH:20])[CH:13]=[CH:12]2)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]>ClCCl.O=[Mn]=O>[Si:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([C:19]([C:21]1[N:22]=[CH:23][N:24]([C:26]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)([C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=3)[CH:25]=1)=[O:20])[CH:13]=[CH:12]2)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc2cc(C(O)c3cn(C(c4ccccc4)(c4ccccc4)c4ccccc4)cn3)ccc2c1
Agent: O=[Mn]=O
Solvent: ClCCl
Product: CC(C)(C)[Si](C)(C)Oc1ccc2cc(C(=O)c3cn(C(c4ccccc4)(c4ccccc4)c4ccccc4)cn3)ccc2c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 92.8 %

Procedure:
To a solution of (6-tert-butyldimethylsilyloxy-2-naphthyl)(1-trityl-1H-imidazol-4-yl)methanol (49.0 g) in dichloromethane (400 mL) was added MnO2 (150 g) and the mixture was stirred for 3 h at room temperature. The reaction mixture was filtered and the filtrate was concentrated to give the titled compound (45.3 g) as a pale yellow powder.