Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CO[C:3]([CH:5]1[CH:19]=[C:18]2[C@@H:8]([CH2:9][C:10]3[C:20]4[C:13](=[CH:14][CH:15]=[CH:16][C:17]2=4)[NH:12][CH:11]=3)[N:7]([C:21]#[N:22])[CH2:6]1)=[O:4].[NH2:23][NH2:24].[Cl-].[Na+].C(Cl)Cl>C(Cl)(Cl)Cl>[C:21]([N:7]1[C@H:8]2[C:18]([C:17]3[CH:16]=[CH:15][CH:14]=[C:13]4[C:20]=3[C:10]([CH2:9]2)=[CH:11][NH:12]4)=[CH:19][CH:5]([C:3]([NH:23][NH2:24])=[O:4])[CH2:6]1)#[N:22]
Reactant: COC(=O)C1C=C2c3cccc4[nH]cc(c34)C[C@H]2N(C#N)C1
Reactant: NN
Agent: [Cl-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: ClCCl
Product: N#CN1CC(C(=O)NN)C=C2c3cccc4[nH]cc(c34)C[C@H]21

Procedure:
950 mg of 6-cyano-9,10-didehydroergolinecarboxylic acid methyl ester (3.2 mmol) is dissolved in 100 ml of chloroform and 18 ml of anhydrous hydrazine and stirred for one hour in an ice bath and for 3 hours at room temperature. The mixture is distributed between saturated sodium chloride solution and methylene chloride; the organic phase is washed with water, dried with magnesium sulfate, and evaporated (crude product 739 mg). The product is chromatographed on silica gel with methylene chloride, ethyl acetate, and methanol, yielding the pure 6-cyano-9,10-didehydroergolinecarboxylic acid hydrazide. A solution of 950 mg (3.2 mmol) of this hydrazide in 100 ml of tetrahydrofuran is cooled in an ice bath and combined in succession with 11 ml of a saturated solution of hydrogen chloride in toluene (about 0.7N), 3.5 ml of a 1N lithium nitrite solution in tetrahydrofuran, and 22 ml of the above hydrogen chloride solution. Under ice cooling, the mixture is agitated for 20 minutes, then diluted with 140 ml of dioxane, and heated for 30 minutes in an oil bath preheated to 80° C. After cooling in an ice bath, 20 ml of 0.2N hydrochloric acid is added thereto, the mixture is allowed to stand for 20 minutes and evaporated to dryness. The residue is made into a solution with a small amount of methanol, distributed between chloroform and sodium bicarbonate, the aqueous phase is washed with chloroform, the organic phase respectively several times with water, dried with magnesium sulfate, and evaporated. 1.0 g of the crude 8-amino-6-cyano-9,10-didehydroergoline is dissolved in 15 ml of pyridine, combined with 0.6 ml of acetyl chloride, and ice is added after one hour; the mixture is distributed between saturated bicarbonate solution and methylene chloride; the organic phase is dried and evaporated.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)O)=[CH:4][CH:3]=1.C(O)(=O)[CH2:23][C:24]([OH:26])=[O:25]>C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:23][C:24]([OH:26])=[O:25])=[CH:4][CH:3]=1
Reactant: O=C(O)CC(=O)O
Reactant: OC(c1ccccc1)(c1ccccc1)c1ccc(Cl)cc1
Solvent: CCO
Product: O=C(O)CC(c1ccccc1)(c1ccccc1)c1ccc(Cl)cc1

Procedure:
A mixture of 2 parts of (p-chlorophenyl)diphenyl carbinol and 8 parts of malonic acid are heated at 170° for 31 hours. This mixture is cooled and then dissolved in hot ethanol, affording 3-p-chlorophenyl-3,3-diphenylpropionic acid. 1 Part of 3-(p-chlorophenyl)3,3-triphenylpropionic acid is then refluxed with 5 parts of thionyl chloride for 4 hours and the excess thionyl chloride is removed in vacuum to provide the crude 3-(p-chlorophenyl)3,3-diphenylpropionyl chloride. 9 Parts of this 3-(p-chlorophenyl)-3,3-triphenylpropionyl chloride are then reacted with 27.0 parts of 4-benzyl-4-hydroxypiperidine in the presence of 4 parts of triethylamine in benzene. The resulting amide is reduced with 5 parts of lithium aluminum hydride in ether at reflux for 2.5 hours. The reaction mixture is cooled and treated with 15% aqueous sodium hydroxide solution to decompose any unreacted lithium aluminum hydride. The reaction mixture is then filtered and washed with ether. The ether solution is evaporated to give an oil. This oil is then slurried in 10% HCl and extracted with ether. The aqueous phase which contains an insoluble oil is extracted with methylene chloride, and the methylene chloride extract dried over anhydrous sodium sulfate. Evaporation of this methylene chloride solution gives a solid which is taken up in acetone and precipitated with ether which affords 1-[3-p-chlorophenyl)-3,3-diphenylpropyl]-4-benzyl-4-hydroxypiperidine hydrochloride having the following structural formula ##STR20##
Reaction SMILES: [C@H:1]12[CH2:7][C@H:4]([NH:5][CH2:6]1)[CH2:3][S:2]2(=[O:9])=[O:8].P([O-])([O-])([O-])=O.[K+].[K+].[K+].Br[CH2:19][CH2:20][OH:21].[I-].[K+]>C(#N)C>[OH:21][CH2:20][CH2:19][N:5]1[CH2:6][C@@H:1]2[CH2:7][C@H:4]1[CH2:3][S:2]2(=[O:9])=[O:8]
Reactant: O=S1(=O)C[C@@H]2C[C@H]1CN2
Reactant: OCCBr
Agent: O=P([O-])([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC#N
Product: O=S1(=O)C[C@@H]2C[C@H]1CN2CCO
Temperature: 120 °C
Yield: 71 %

Procedure:
A mixture of (1S,4S)-2-thia-5-azabicyclo[2.2.1]heptane 2,2-dioxide (65 mg, 0.442 mmol), potassium phosphate (375 mg, 1.766 mmol), 2-bromoethanol (221 mg, 1.766 mmol) and potassium iodide (147 mg, 0.883 mmol) in acetonitrile (2 mL) was heated up at 120° C. for 4 hours. The reaction mixture was concentrated under reduced pressure and purified in silica gel with 0-15% methanol/ethyl acetate to provide the title product (60 mg, 71% yield) as a white solid. LCMS: m/e 192.07 (M+H)+, 0.87 min (method 2)
Reaction SMILES: [F:1][C:2]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:3]=1[NH2:4].Br[CH:11]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:12]([O:14][CH2:15][CH3:16])=[O:13].CCN(C(C)C)C(C)C>C(#N)C>[F:1][C:2]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:3]=1[NH:4][CH:11]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:12]([O:14][CH2:15][CH3:16])=[O:13]
Reactant: Nc1cc(F)ccc1F
Reactant: CCOC(=O)C(Br)c1ccccc1
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)C(Nc1cc(F)ccc1F)c1ccccc1
Temperature: 100 °C
Reaction time: 4 h
Yield: 67 %

Procedure:
2,5-Difluoroaniline (0.19 ml, 1.85 mmol), ethyl 2-bromo-2-phenylacetate (0.22 ml, 1.23 mmol), and DIPEA (0.32 ml, 1.85 mmol) were dissolved in acetonitrile (3 ml) and heated under MW irradiation at 100° C. for 6 hours and then at 110° C. for 4 hours. Acetonitrile was evaporated, and the crude product was purified by flash chromatography (Petroleum ether/EtOAc=97/3) to obtain intermediate I19 (240 mg, 67% yield).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([O:19][C:20]2[CH:25]=[CH:24][C:23]([CH:26]([CH3:28])[CH3:27])=[CH:22][CH:21]=2)[C:10]([O:12][CH2:13][CH2:14][Si:15]([CH3:18])([CH3:17])[CH3:16])=[O:11])=[CH:4][CH:3]=1.CS(O[CH2:34][CH2:35][NH:36][C:37](=[O:43])[O:38][C:39]([CH3:42])([CH3:41])[CH3:40])(=O)=O.C(=O)([O-])[O-].[K+].[K+]>>[C:39]([O:38][C:37]([NH:36][CH2:35][CH2:34][O:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([O:19][C:20]2[CH:21]=[CH:22][C:23]([CH:26]([CH3:28])[CH3:27])=[CH:24][CH:25]=2)[C:10]([O:12][CH2:13][CH2:14][Si:15]([CH3:17])([CH3:18])[CH3:16])=[O:11])=[CH:4][CH:3]=1)=[O:43])([CH3:42])([CH3:41])[CH3:40]
Reactant: CC(C)c1ccc(O[C@H](Cc2ccc(O)cc2)C(=O)OCC[Si](C)(C)C)cc1
Reactant: CC(C)(C)OC(=O)NCCOS(C)(=O)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Product: CC(C)c1ccc(O[C@H](Cc2ccc(OCCNC(=O)OC(C)(C)C)cc2)C(=O)OCC[Si](C)(C)C)cc1
Yield: 88 %

Procedure:
In a similar manner to that described in Reference example 25, a reaction was carried out using 2-trimethylsilylethyl (R)-3-(4-hydroxyphenyl)-2-(4-isopropylphenoxy)propionate (221 mg), which is the product of Reference example 30(e), t-butyl 2-methanesulfonyloxyethylcarbamate (330 mg) and potassium carbonate (381 mg) and the reaction mixture was treated to afford the desired compound (264 mg) as a colorless oil.
Reaction SMILES: [NH2:1][C@@H:2]([C:7]([NH:9][CH2:10][C:11]([NH:13][C@H:14]([C:22]([NH:24][C:25]1[CH:33]=[CH:32][C:28]([N+:29]([O-:31])=[O:30])=[CH:27][CH:26]=1)=[O:23])[CH2:15][CH2:16][CH2:17][NH:18][C:19](=[NH:21])[NH2:20])=[O:12])=[O:8])[CH2:3][CH:4]([CH3:6])[CH3:5].[S:34](Cl)([C:37]1[CH:43]=[CH:42][C:40]([CH3:41])=[CH:39][CH:38]=1)(=[O:36])=[O:35].N(CC)(CC)CC.[BrH:52].N(CC)(CC)CC.Cl>CN(C=O)C.CCN(CC)CC>[NH:1]([S:34]([C:37]1[CH:43]=[CH:42][C:40]([CH3:41])=[CH:39][CH:38]=1)(=[O:36])=[O:35])[C@@H:2]([C:7]([NH:9][CH2:10][C:11]([NH:13][C@H:14]([C:22]([NH:24][C:25]1[CH:26]=[CH:27][C:28]([N+:29]([O-:31])=[O:30])=[CH:32][CH:33]=1)=[O:23])[CH2:15][CH2:16][CH2:17][NH:18][C:19](=[NH:20])[NH2:21])=[O:12])=[O:8])[CH2:3][CH:4]([CH3:5])[CH3:6].[BrH:52]
Reactant: CC(C)C[C@@H](N)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)Nc1ccc([N+](=O)[O-])cc1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: Br
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Cc1ccc(S(=O)(=O)N[C@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCNC(=N)N)C(=O)Nc2ccc([N+](=O)[O-])cc2)cc1

Procedure:
6.26 g (10 mM) of 2HBr.H-D-Leu-Gly-Arg-pNA (prepared according to Example 7f, see Table 3) were dissolved in 30 ml of distilled DMF. The solution was cooled to -15°, and first 2.80 ml (20 mM) of Et3N and immediately afterwards 1.91 g (10 mM) of tosyl chloride were added, while stirring, in the absence of humidity. After a reaction time of about 2 to 3 hours at -15°, the reaction mixture was allowed to further react overnight at room temperature. The reaction mixture was again cooled to -15°. The precipitated mixture of Et3N.HBr and Et3N.HCl was removed by filtration and washed with a small amount of cold DMF. The filtrate and the washing solution were combined and concentrated to dryness in vacuo at 50°. The residue was dissolved in 75 ml of 50% AcOH. The solution was purified on a column of "Sephadex" G-15 equilibrated with 50% AcOH. The main fraction of the AcOH eluate which was split by treatment with trypsin with release of p-nitroaniline was concentrated to dryness in vacuo at 40°. The residue was dissolved in 100 ml of MeOH, and the solution was again concentrated to dryness. The residue was dried in a vacuum desiccator at 60° over P2O5 to obtain 6.65 g (95.0% of the theory) of amorphous compound Tos-D-Leu-Gly-Arg-pNA.HBr which was homogeneous in the SS as shown by TLC. Elementary analysis and calculation from the empirical formula C27H39N8SO7Br gave the following values: C=46.85% (46.35%), H=5.66% (5.62%), N=16.28% (16.02%), S=4.43% (4.58%) and Br=11.22% (11.42%).
Reaction SMILES: [OH:1][C:2]1[CH:12]=[CH:11][C:5]2[C:6](=[O:10])[CH2:7][CH2:8][O:9][C:4]=2[C:3]=1[CH2:13][CH2:14][CH3:15].C[O:17][C:18](=[O:49])[CH2:19][CH2:20][C:21]1[C:26]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]OS(C)(=O)=O)=[CH:25][CH:24]=[CH:23][C:22]=1[O:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][C:45]([O:47]C)=[O:46]>>[C:45]([CH2:44][CH2:43][CH2:42][CH2:41][CH2:40][CH2:39][O:38][C:22]1[CH:23]=[CH:24][CH:25]=[C:26]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][O:1][C:2]2[CH:12]=[CH:11][C:5]3[C:6](=[O:10])[CH2:7][CH2:8][O:9][C:4]=3[C:3]=2[CH2:13][CH2:14][CH3:15])[C:21]=1[CH2:20][CH2:19][C:18]([OH:49])=[O:17])([OH:47])=[O:46]
Reactant: COC(=O)CCCCCCOc1cccc(CCCCCCOS(C)(=O)=O)c1CCC(=O)OC
Reactant: CCCc1c(O)ccc2c1OCCC2=O
Product: CCCc1c(OCCCCCCc2cccc(OCCCCCCC(=O)O)c2CCC(=O)O)ccc2c1OCCC2=O

Procedure:
Using the procedure of example 184, 2,3-dihydro-7-hydroxy-8-propyl-4H-1-benzopyran-4-one was converted into the title compound by alkylation with 2-[(7-methoxy-7-oxoheptyl)oxy]-6-[6-(methylsulfonyl)oxyhexyl]benzenepropanoic acid methyl ester from the preceding example, followed by saponification, in 55% overall yield. The product was a colorless solid, mp 91°-93° C., recrystallized from hexane-ethyl acetate.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:11])[CH2:9][CH3:10])=[CH:4][CH:3]=1.[CH2:12]=[O:13].C(=O)([O-])[O-].[K+].[K+]>CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8](=[O:11])[CH:9]([CH3:10])[CH2:12][OH:13])=[CH:6][CH:7]=1
Reactant: C=O
Reactant: CCC(=O)c1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: CC(CO)C(=O)c1ccc(F)cc1

Procedure:
A mixture of 45.7 g. (0.3 moles) of 4'-fluoropropiophenone, 9 g. (0.3 moles) of paraformaldehyde, 4 g. (0.03 mole) of anhydrous potassium carbonate and 200 ml. of methyl alcohol is stirred at 35°C for two days. The reaction is quenched in water and acidified with hydrochloric acid. The product is extracted into benzene. The benzene layer is washed with water and concentrated in vacuo to give 4'-fluoro-3-hydroxy-2-methylpropiophenone.
Reaction SMILES: Cl[C:2]1[C:3]2[CH:10]=[CH:9][N:8]([CH2:11][CH2:12][O:13][CH3:14])[C:4]=2[N:5]=[CH:6][N:7]=1.[NH2:15][C:16]1[CH:17]=[C:18]([C:22]#[CH:23])[CH:19]=[CH:20][CH:21]=1>CO>[C:22]([C:18]1[CH:17]=[C:16]([NH:15][C:2]2[C:3]3[CH:10]=[CH:9][N:8]([CH2:11][CH2:12][O:13][CH3:14])[C:4]=3[N:5]=[CH:6][N:7]=2)[CH:21]=[CH:20][CH:19]=1)#[CH:23]
Reactant: C#Cc1cccc(N)c1
Reactant: COCCn1ccc2c(Cl)ncnc21
Solvent: CO
Product: C#Cc1cccc(Nc2ncnc3c2ccn3CCOC)c1
Yield: 81 %

Procedure:
Following a procedure analogous to that described in Example 11, the title product was prepared in 81% yield from 4-chloro7-(2-methoxy-ethyl)-7H-pyrrolo[2,3-d]pyrimidine (1.0 eq) and m-aminophenyl acetylene (1.2 eq) in methanol: MP: 240-241° C.; LC-MS: 292 (MH+); anal. RP18-HPLC RT: 4.16 minutes.
Reaction SMILES: [C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[CH:13]=[C:12]([N:14]([CH2:16][CH:17]([CH3:19])[CH3:18])[CH3:15])[C:11]([Cl:20])=[CH:10][C:9]=1[NH2:21])([CH3:4])([CH3:3])[CH3:2].C([O:27][C:28](=O)[CH2:29][C:30](=[O:42])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([N:37]2[CH:41]=[N:40][CH:39]=[N:38]2)[CH:32]=1)(C)(C)C>>[C:1]([O:5][C:6](=[O:22])[NH:7][C:8]1[CH:13]=[C:12]([N:14]([CH2:16][CH:17]([CH3:18])[CH3:19])[CH3:15])[C:11]([Cl:20])=[CH:10][C:9]=1[NH:21][C:28](=[O:27])[CH2:29][C:30](=[O:42])[C:31]1[CH:36]=[CH:35][CH:34]=[C:33]([N:37]2[CH:41]=[N:40][CH:39]=[N:38]2)[CH:32]=1)([CH3:3])([CH3:2])[CH3:4]
Reactant: CC(C)CN(C)c1cc(NC(=O)OC(C)(C)C)c(N)cc1Cl
Reactant: CC(C)(C)OC(=O)CC(=O)c1cccc(-n2cncn2)c1
Product: CC(C)CN(C)c1cc(NC(=O)OC(C)(C)C)c(NC(=O)CC(=O)c2cccc(-n3cncn3)c2)cc1Cl

Procedure:
The title compound was prepared from [2-amino-4-chloro-5-(isobutyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J27) (500 mg, 1.53 mmol) and 3-oxo-3-(3-[1,2,4]triazol-1-yl-phenyl)-propionic acid tert-butyl ester (Example K25) (438 mg, 1.53 mmol) according to the general procedure M. Obtained as a light orange foam (700 mg, 85%).
Reaction SMILES: Cl.[CH3:2][C:3]1([CH3:26])[CH2:12][CH2:11][C:10]([CH3:14])([CH3:13])[C:9]2[CH:8]=[C:7]([C:15]3[N:19]=[C:18]([N:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]4)[S:17][N:16]=3)[CH:6]=[CH:5][C:4]1=2.[OH:27][CH2:28][CH2:29][CH2:30][CH2:31][CH:32]=O>>[CH3:2][C:3]1([CH3:26])[CH2:12][CH2:11][C:10]([CH3:13])([CH3:14])[C:9]2[CH:8]=[C:7]([C:15]3[N:19]=[C:18]([N:20]4[CH2:21][CH2:22][N:23]([CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][OH:27])[CH2:24][CH2:25]4)[S:17][N:16]=3)[CH:6]=[CH:5][C:4]1=2
Reactant: CC1(C)CCC(C)(C)c2cc(-c3nsc(N4CCNCC4)n3)ccc21
Reactant: O=CCCCCO
Agent: Cl
Product: CC1(C)CCC(C)(C)c2cc(-c3nsc(N4CCN(CCCCCO)CC4)n3)ccc21

Procedure:
The preparation was carried out as already described starting from 65 mg (0.17 mmol) of 1-[3-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1,2,4-thiadiazol-5-yl]piperazine hydrochloride and 17 mg (0.165 mmol) of 5-hydroxypentanal.
Reaction SMILES: Cl[C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[F:9][C:10]([F:17])([F:16])[C:11]1[CH:15]=[CH:14][NH:13][N:12]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Cl:8][C:7]1[C:2]([N:13]2[CH:14]=[CH:15][C:11]([C:10]([F:17])([F:16])[F:9])=[N:12]2)=[N:3][CH:4]=[CH:5][CH:6]=1
Reactant: Clc1cccnc1Cl
Reactant: FC(F)(F)c1cc[nH]n1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: FC(F)(F)c1ccn(-c2ncccc2Cl)n1
Temperature: 117.5 °C
Yield: 75.1 %

Procedure:
To a mixture of 2,3-dichloropyridine (99.0 g, 0.67 mol) and 3-(trifluoromethyl)-pyrazole (83 g, 0.61 mol) in dry N,N-dimethylformamide (300 mL) was added potassium carbonate (166.0 g, 1.2 mol) and the reaction was then heated to 110-125° C. over 48 hours. The reaction was cooled to 100° C. and filtered through Celite® diatomaceous filter aid to remove solids. N,N-dimethylformamide and excess dichloropyridine were removed by distillation at atmospheric pressure. Distillation of the product at reduced pressure (b.p. 139-141° C., 7 mm) afforded the desired intermediate as a clear yellow oil (113.4 g).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[N:5]=[N:6][CH:7]=1.ClC1C=CC=C(C(OO)=[O:22])C=1>C(Cl)(Cl)Cl>[CH3:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)[N:5]=[N+:6]([O-:22])[CH:7]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: Cc1cnnc(-c2ccccc2)c1
Solvent: ClC(Cl)Cl
Product: Cc1cc(-c2ccccc2)n[n+]([O-])c1
Yield: 73.1 %

Procedure:
To a solution of 5-methyl-3-phenylpyridazine (2.0 g) in 40 mL of CHCl3 is added m-chloroperbenzoic acid (2.9 g, 80% pure). The solution is permitted to stand at room temperature until the reaction is complete. The precipitate which forms during the reaction period is removed by filtration, and the filtrate diluted with ether. The ether solution is then washed sequentially with 10% aqueous sodium sulfite, saturated sodium bicarbonate, and saturated brine. The washed liquid is dried over MgSO4 and then concentrated in vacuo to give 1.6 g (73%) of a pale yellow crystalline solid having a melting point of 112°-114° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:14])[CH2:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][CH:6]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[Cl:39][C:40]1[CH:45]=[CH:44][C:43]([CH2:46][CH2:47][NH2:48])=[CH:42][CH:41]=1>C(#N)C.C(N(CC)C(C)C)(C)C>[Cl:39][C:40]1[CH:45]=[CH:44][C:43]([CH2:46][CH2:47][NH:48][C:9]([C:8]2[CH:7]=[CH:6][C:5]([CH2:4][C:3]([O:2][CH3:1])=[O:14])=[CH:13][CH:12]=2)=[O:11])=[CH:42][CH:41]=1
Reactant: COC(=O)Cc1ccc(C(=O)O)cc1
Reactant: NCCc1ccc(Cl)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CC#N
Product: COC(=O)Cc1ccc(C(=O)NCCc2ccc(Cl)cc2)cc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of 4-(2-methoxy-2-oxoethyl)benzoic acid (1.00 g) in acetonitrile (50 ml), N,N-diisopropyl ethyl amine (2.63 ml), O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (2.94 g) and 2-(4-chlorophenyl)ethylamine (790 ml) were added, and the mixed solution was stirred at room temperature for 16 hours. The solvent was removed by evaporation under reduced pressure, and the resulting crude product was purified by column chromatography (neutral OH type silica gel, ethyl acetate/n-hexane=30 to 50%) to give methyl (4-{[2-(4-chlorophenyl)ethyl]carbamoyl}phenyl)acetate (2.02 g).
Reaction SMILES: [CH2:1]([NH:8][C:9]([C:11]1[CH:12]=[CH:13][C:14]2[O:18][C:17]([C:19]([O:21]CC)=[O:20])=[CH:16][C:15]=2[CH:24]=1)=[NH:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].[ClH:27]>O1CCCC1>[ClH:27].[CH2:1]([NH:8][C:9]([C:11]1[CH:12]=[CH:13][C:14]2[O:18][C:17]([C:19]([OH:21])=[O:20])=[CH:16][C:15]=2[CH:24]=1)=[NH:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1cc2cc(C(=N)NCc3ccccc3)ccc2o1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: N=C(NCc1ccccc1)c1ccc2oc(C(=O)O)cc2c1
Temperature: 25 °C
Reaction time: 0.75 h
Yield: 53 %

Procedure:
Tetrahydrofuran (5 ml) was added to ethyl 5-benzylamidino-2-benzofurancarboxylate (325 mg, 1.21 mmol) and a 0.5N aqueous sodium hydroxide solution (10 ml, 5 mmol) was added. The mixture was stirred at room temperature for 45 minutes. 1N Hydrochloric acid was added to the reaction mixture to adjust its pH to 2-3 and low boiling matters were distilled away under reduced pressure. The resulting precipitate was collected by filtration, and washed with water to give 213 mg of 5-benzylamidino-2-benzofurancarboxylic acid hydrochloride as a colorless solid (53%).
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[C:4]([Br:10])[CH:3]=1.[Li]CCCC.CN([CH:19]=[O:20])C.O>CCOCC>[Br:10][C:4]1[CH:3]=[C:2]([CH:7]=[C:6]([O:8][CH3:9])[CH:5]=1)[CH:19]=[O:20]
Reactant: COc1cc(Br)cc(Br)c1
Reactant: CN(C)C=O
Agent: [Li]CCCC
Solvent: CCOCC
Solvent: O
Product: COc1cc(Br)cc(C=O)c1
Temperature: 25 °C
Yield: 96.5 %

Procedure:
A solution of 1,3-dibromo-5-methoxybenzene (15 g, 56.40 mmol) in anhydrous Et2O (200 mL) under nitrogen was cooled to −78° C. n-BuLi (38.80 mL of a 1.6 M solution in Et2O, 62.00 mmol) was added dropwise, and the solution was aged at −78° C. for 45 m. To the resulting heterogeneous mixture was added anhydrous DMF (4.78 mL, 62.00 mmol), and the solution was slowly warmed to RT. The mixture was poured into H2O (200 mL), and the aqueous phase was extracted with Et2O (3×125 mL). The combined organic fractions were washed with brine (100 mL) and dried over anhydrous MgSO4. Evaporation of the solvent provided 11.70 g (96%) of 3-bromo-5-methoxybenzaldehyde (115).
Reaction SMILES: [C:1]1(=[O:7])[O:6][C:4](=[O:5])[CH:3]=[CH:2]1.[CH:8]1[CH:13]=CC=[CH:10][CH:9]=1>CC1C=CC=CC=1C>[C:4]1(=[O:5])[O:6][C:1](=[O:7])[C:2]2=[CH:13][CH:8]=[CH:9][CH:10]=[C:3]12
Reactant: O=C1C=CC(=O)O1
Reactant: c1ccccc1
Solvent: Cc1ccccc1C
Product: O=C1OC(=O)c2ccccc21

Procedure:
These objectives are realized in the present invention by employing compressed air as a propellant for the jet pumps maintaining the vacuum as hereinbefore described and by introducing this air, charged with sucked organic-containing vapors, into the gas scrubbing zone. The entire quantity of organic-containing vapors and gases withdrawn from the maleic anhydride processing stages is sucked into the vacuum lines by the jet pumps, after which a large portion of such vapors, primarily water vapor, is condensed in a surface condenser(s). The propellant air, which is admixed with the remaining sucked gases and vapors recovered from the maleic anhydride processing stages, is introduced into the gas scrubbing solution, along with those reaction gases which are being treated and which contain residual maleic anhydride. Such reaction gases can be formed, for example, in the production of maleic anhydride from benzene or C-4 hydrocarbons, preferably after partial condensation of the maleic anhydride from the gas. Such reaction gases can also be formed in the production of phthalic anhydride from o-xylene after separation of the phthalic anhydride therefrom.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([CH2:15]Br)[CH:8]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].[N:17]1([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O.CN(C=O)C>[C:1]([C:5]1[CH:6]=[C:7]([CH2:15][N:20]2[CH2:19][CH2:18][N:17]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:22][CH2:21]2)[CH:8]=[C:9]([C:11]([CH3:14])([CH3:13])[CH3:12])[CH:10]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)c1cc(CBr)cc(C(C)(C)C)c1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CC(C)=O
Product: CC(C)(C)OC(=O)N1CCN(Cc2cc(C(C)(C)C)cc(C(C)(C)C)c2)CC1
Reaction time: 8 h
Yield: 56.1 %

Procedure:
3,5-Bis(t-butyl)-1-(bromomethyl)benzene (170 mg, 0.60 mmol), t-butyl piperazine carboxylate (102 mg, 0.55 mmol) and potassium carbonate (151 mg, 1.10 mmol) were dissolved in a solvent mixture of acetone (2 ml) and DMF (0.2 ml), and the mixture was stirred overnight while heated under reflux. The reaction mixture was extracted with ethyl acetate, dried over sodium sulfate, and then the filtrate was evaporated under reduced pressure. The concentrate was subjected to silica gel column chromatography (n-hexane:ethyl acetate=4:1) to give 120 mg (yield: 56%) of the title compound as a white solid.