Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[CH2:10][CH2:11][NH:12][C:13]([NH2:15])=[S:14].[O-]CC.[Na+].[C:20]([CH2:22][C:23](OCC)=[O:24])#[N:21].S(=O)(=O)(O)O>C(O)C.O>[NH2:21][C:20]1[N:12]([CH2:11][CH2:10][C:2]2[NH:3][C:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[N:1]=2)[C:13](=[S:14])[NH:15][C:23](=[O:24])[CH:22]=1
Reactant: CCOC(=O)CC#N
Reactant: NC(=S)NCCc1nc2ccccc2[nH]1
Agent: CC[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: CCO
Solvent: O
Product: Nc1cc(=O)[nH]c(=S)n1CCc1nc2ccccc2[nH]1
Temperature: 25 °C
Reaction time: 3 h
Yield: 95.7 %

Procedure:
To a suspension of 1-[2-(1H-benzimidazol-2-yl)ethyl]thiourea (0.44 g, 2.0 mmol, obtained from Example 12(a)) in absolute ethanol (5 mL) at 80° C. were added, over 2 h, a solution of sodium ethoxide (21% w/v, 2.2 mL, 6.0 mmol) and a solution of ethyl cyanoacetate (0.64 mL, 6.0 mmol) in absolute ethanol (1.3 mL). The reaction was kept at 80° C. for an additional 3 h. After cooling to r.t., water (75 mL) was added and the pH adjusted to ˜7 using concentrated sulfuric acid. The solid that formed was collected by filtration, washed with water and dried in vacuo to give the title compound (0.55 g, 96% yield).
Reaction SMILES: [F:1][C:2]([F:29])([F:28])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19]1[CH:27]=[CH:26][C:22]([C:23]([OH:25])=[O:24])=[CH:21][CH:20]=1.[CH2:30]([O:32][CH2:33][CH2:34]O)[CH3:31].B(F)(F)F.CCOCC>C1(C)C=CC=CC=1>[F:1][C:2]([F:28])([F:29])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19]1[CH:27]=[CH:26][C:22]([C:23]([O:25][CH2:31][CH2:30][O:32][CH2:33][CH3:34])=[O:24])=[CH:21][CH:20]=1
Reactant: CCOCCO
Reactant: O=C(O)c1ccc(NCCCCCCCCCCCCCCCC(F)(F)F)cc1
Agent: FB(F)F
Solvent: CCOCC
Solvent: Cc1ccccc1
Product: CCOCCOC(=O)c1ccc(NCCCCCCCCCCCCCCCC(F)(F)F)cc1
Reaction time: 120 h

Procedure:
A solution of 11.8 g. of 4-[15-(trifluoromethyl)pentadecylamino]benzoic acid, 1.00 g. of 2-ethoxyethanol and 5.35 ml. of boron trifluoride etherate in 200 ml. of toluene is stirred under reflux for 48 hours. The solution is treated with an additional 5.35 ml. of boron trifluoride etherate and refluxing is continued for 120 hours. Dilution with water and methylene chloride followed by filtration affords the product as a white solid.
Reaction SMILES: [C:1]1([C:7]2[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-:14].[K+].[C:16]1([CH3:22])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>>[C:1]1([C:7]2[CH:8]=[CH:9][C:10]([O:13][C:20]3[C:21]4[C:22](=[O:14])[C:16]5[C:21](=[C:20]([O:13][C:10]6[CH:9]=[CH:8][C:7]([C:1]7[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=7)=[CH:12][CH:11]=6)[CH:19]=[CH:18][CH:17]=5)[C:22](=[O:14])[C:16]=4[CH:17]=[CH:18][CH:19]=3)=[CH:11][CH:12]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: Oc1ccc(-c2ccccc2)cc1
Reactant: [OH-]
Reactant: Cc1ccccc1
Agent: [K+]
Product: O=C1c2cccc(Oc3ccc(-c4ccccc4)cc3)c2C(=O)c2cccc(Oc3ccc(-c4ccccc4)cc3)c21
Reaction time: 5 h

Procedure:
Under a nitrogen atmosphere, 4.3 parts of 4-phenylphenol and 1.5 parts of potassium hydroxide were dissolved in 80 parts of toluene and the solution was refluxed under heat. After stirred for 5 hours, the solution was allowed to cool, and the precipitated solid was filtered. Then, under a nitrogen stream, the precipitate, 2 parts of 1,5-dichloroanthraquinone and 0.6 part of copper powder were dissolved in 10 parts of DMF, and the mixture was refluxed under heat for 3 hours. The reaction solution was poured into an aqueous potassiumhydroxide solution, and the precipitated solid was filtered, washed, and dried. Then, after removal of inorganic materials with toluene, the solid obtained was recrystallized from 2-ethoxyethanol, filtered, washed, and dried, to give 0.6 part of 1,5-bis(4-phenylphenoxy)anthraquinone as an intermediate.
Reaction SMILES: [F:1][C:2]([F:13])([F:12])[C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6](Cl)=[O:7].[CH3:14][N:15]1[C:20](=[O:21])[N:19]([CH3:22])[C:18](=[O:23])[C:17]([N:24]2[CH2:29][CH2:28][NH:27][CH2:26][CH2:25]2)=[N:16]1>>[CH3:14][N:15]1[C:20](=[O:21])[N:19]([CH3:22])[C:18](=[O:23])[C:17]([N:24]2[CH2:25][CH2:26][N:27]([C:6](=[O:7])[C:5]3[CH:9]=[CH:10][CH:11]=[C:3]([C:2]([F:13])([F:12])[F:1])[CH:4]=3)[CH2:28][CH2:29]2)=[N:16]1.[F:1][C:2]([F:13])([F:12])[C:9]1[CH:10]=[CH:11][C:3]([C:2]([F:13])([F:12])[F:1])=[CH:4][C:5]=1[C:6]([N:27]1[CH2:26][CH2:25][N:24]([C:17]2[C:18](=[O:23])[N:19]([CH3:22])[C:20](=[O:21])[N:15]([CH3:14])[N:16]=2)[CH2:29][CH2:28]1)=[O:7]
Reactant: Cn1nc(N2CCNCC2)c(=O)n(C)c1=O
Reactant: O=C(Cl)c1cccc(C(F)(F)F)c1
Product: Cn1nc(N2CCN(C(=O)c3cc(C(F)(F)F)ccc3C(F)(F)F)CC2)c(=O)n(C)c1=O
Product: Cn1nc(N2CCN(C(=O)c3cccc(C(F)(F)F)c3)CC2)c(=O)n(C)c1=O
Yield: 75 %

Procedure:
The compound 44 (solid) is prepared from 3-trifluoromethyl-benzoyl chloride and from the intermediate 12a according to the synthesis method 2 under the operating conditions described for Example 40 (yield: 75%).
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([I:16])=[CH:12][C:11]=2[F:17])[C:5]([NH2:18])=[CH:4][CH:3]=1.[CH:19]([S:23](Cl)(=[O:25])=[O:24])([CH2:21][CH3:22])[CH3:20]>>[F:8][C:7]1[C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([I:16])=[CH:12][C:11]=2[F:17])=[C:5]([NH:18][S:23]([CH:19]([CH2:21][CH3:22])[CH3:20])(=[O:25])=[O:24])[CH:4]=[CH:3][C:2]=1[F:1]
Reactant: CCC(C)S(=O)(=O)Cl
Reactant: Nc1ccc(F)c(F)c1Nc1ccc(I)cc1F
Product: CCC(C)S(=O)(=O)Nc1ccc(F)c(F)c1Nc1ccc(I)cc1F
Yield: 22 %

Procedure:
According to the general procedure A, 5,6-difluoro-N1-(2-fluoro-4-iodophenyl)benzene-1,2-diamine was reacted with sec-butylsulfonyl chloride to obtain the desired product. Yield: 22%. 1H-NMR (500 MHz, MeOH[d4]): δ=7.60-7.40 (m, 3H), 7.18-7.00 (q, 1H), 6.55-6.45 (m, 1H), 3.55-3.50 (m, 1H), 2.20-2.00 (m, 1H), 1.80-1.60 (m, 1H), 1.43-1.40 (d, 3H), 1.06-1.04 (t, 3H); m/z=483 [M−1]−.
Reaction SMILES: [Cl:1]C(OC(Cl)C)=O.C([N:21]1[CH2:24][CH:23]([O:25][CH2:26][C:27]2[S:28][CH:29]=[C:30]([Cl:32])[CH:31]=2)[CH2:22]1)(C1C=CC=CC=1)C1C=CC=CC=1.C(O)C>ClCCl>[ClH:1].[Cl:32][C:30]1[CH:31]=[C:27]([CH2:26][O:25][CH:23]2[CH2:22][NH:21][CH2:24]2)[S:28][CH:29]=1
Reactant: Clc1csc(COC2CN(C(c3ccccc3)c3ccccc3)C2)c1
Reactant: CC(Cl)OC(=O)Cl
Solvent: CCO
Solvent: ClCCl
Product: Cl
Product: Clc1csc(COC2CNC2)c1
Temperature: 0 °C
Reaction time: 1 h
Yield: 90.9 %

Procedure:
1-Chloroethyl chloroformate (218 μL, 2.0 mmol) was added to a solution of 1-benzhydryl-3-((4-chlorothiophen-2-yl)methoxy)-azetidine (793 mg, 1.91 mmol) in dichloromethane (10 mL) at 0° C. The reaction mixture was stirred for 1 hour at 0° C. and for an additional 1 hour at room temperature. Ethanol (10 mL) was added and the reaction mixture was stirred overnight. After concentration to dryness, the crude mixture was precipitated from a mixture dichloromethane/diethyl ether to afford the title compound as a white solid (417 mg, 77%) which was used without further purification.
Reaction SMILES: [NH3:1].CCO.F[C:6]1[C:13]([N+:14]([O-:16])=[O:15])=[CH:12][CH:11]=[C:10]([F:17])[C:7]=1[C:8]#[N:9]>C1COCC1>[NH2:1][C:6]1[C:13]([N+:14]([O-:16])=[O:15])=[CH:12][CH:11]=[C:10]([F:17])[C:7]=1[C:8]#[N:9]
Reactant: N#Cc1c(F)ccc([N+](=O)[O-])c1F
Reactant: N
Solvent: C1CCOC1
Solvent: CCO
Product: N#Cc1c(F)ccc([N+](=O)[O-])c1N
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A solution of NH3 in EtOH (19 mL, 8.6 M, 160 mmol) was added dropwise to a solution of 2,6-difluoro-3-nitrobenzonitrile (10 g, 54 mmol) in THF (50 mL) at 0° C. under Ar and the resulting mixture was stirred at 0° C. for 1 h. The mixture was concentrated and the residue washed with brine and extracted with EtOAc. The organic layer was dried over Na2SO4, filtered and concentrated.
Reaction SMILES: C(N(CC)C(C1C=CC=CC=1[S:12]([C:15]1[C@H:16]([CH3:46])[C@@H:17]2[C@@H:34]([C@H:35]([O:37][Si:38]([C:41]([CH3:44])([CH3:43])[CH3:42])([CH3:40])[CH3:39])[CH3:36])[C:33](=[O:45])[N:18]2[C:19]=1[C:20]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][C:27]([N+:30]([O-:32])=[O:31])=[CH:26][CH:25]=1)=[O:21])(=O)=O)=O)C.[N+:49]([C:52]1[CH:65]=[CH:64][C:55]([CH2:56][O:57][C:58]([NH:60][CH2:61][CH2:62]S)=[O:59])=[CH:54][CH:53]=1)([O-:51])=[O:50]>>[Si:38]([O:37][C@@H:35]([C@H:34]1[C:33](=[O:45])[N:18]2[C:19]([C:20]([O:22][CH2:23][C:24]3[CH:25]=[CH:26][C:27]([N+:30]([O-:32])=[O:31])=[CH:28][CH:29]=3)=[O:21])=[C:15]([S:12][CH2:62][CH2:61][NH:60][C:58]([O:57][CH2:56][C:55]3[CH:64]=[CH:65][C:52]([N+:49]([O-:51])=[O:50])=[CH:53][CH:54]=3)=[O:59])[C@H:16]([CH3:46])[C@H:17]12)[CH3:36])([C:41]([CH3:43])([CH3:44])[CH3:42])([CH3:39])[CH3:40]
Reactant: O=C(NCCS)OCc1ccc([N+](=O)[O-])cc1
Reactant: CCN(CC)C(=O)c1ccccc1S(=O)(=O)C1=C(C(=O)OCc2ccc([N+](=O)[O-])cc2)N2C(=O)[C@H]([C@@H](C)O[Si](C)(C)C(C)(C)C)[C@H]2[C@H]1C
Product: C[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]1C(=O)N2C(C(=O)OCc3ccc([N+](=O)[O-])cc3)=C(SCCNC(=O)OCc3ccc([N+](=O)[O-])cc3)[C@H](C)[C@H]12
Yield: 87 %

Procedure:
Following a procedure similar to that described in Example 19(c), but using 4-nitrobenzyl (1R,5S,6S)-2-(2-diethylcarbamoylphenylsulfonyl)-1-methyl-6-[1(R)-t-butyldimethylsilyloxyethyl]-1-carbapen-2-em-3-carboxylate (prepared as described in Example 42) and 2-(4-nitrobenzyloxycarbonyl)aminoethylmercaptan as starting materials, in relative proportions similar to those used in that Example, the title compound was obtained in a yield of 87%.
Reaction SMILES: C(O[C:4](=[O:10])[C:5]([O:7][CH2:8]C)=[O:6])C.[NH2:11][CH:12]1[CH2:17][C:16]([CH3:19])([CH3:18])[NH:15][C:14]([CH3:21])([CH3:20])[CH2:13]1>CO>[CH3:20][C:14]1([CH3:21])[CH2:13][CH:12]([NH:11][C:4](=[O:10])[C:5]([O:7][CH3:8])=[O:6])[CH2:17][C:16]([CH3:19])([CH3:18])[NH:15]1
Reactant: CCOC(=O)C(=O)OCC
Reactant: CC1(C)CC(N)CC(C)(C)N1
Solvent: CO
Product: COC(=O)C(=O)NC1CC(C)(C)NC(C)(C)C1

Procedure:
Methyl N-(2,2,6,6-tetramethyl-4piperidinyl)oxamate was prepared from diethyloxalate and 4-amino-2,2,6,6-tetramethylpiperidine according to the first step in Example III, Method B. The ethyl ester undergoes ester interchange in methanol to form the methyl ester.
Reaction SMILES: [CH3:1][C:2]1[N:3]([C:8]2[C:9]([C:20]([OH:22])=O)=[N:10][C:11]([O:18][CH3:19])=[C:12]([C:14]([F:17])([F:16])[F:15])[CH:13]=2)[C:4]([CH3:7])=[CH:5][CH:6]=1.[NH2:23][CH2:24][CH:25]([OH:30])[C:26]([F:29])([F:28])[F:27]>>[F:27][C:26]([F:29])([F:28])[CH:25]([OH:30])[CH2:24][NH:23][C:20]([C:9]1[C:8]([N:3]2[C:4]([CH3:7])=[CH:5][CH:6]=[C:2]2[CH3:1])=[CH:13][C:12]([C:14]([F:17])([F:15])[F:16])=[C:11]([O:18][CH3:19])[N:10]=1)=[O:22]
Reactant: NCC(O)C(F)(F)F
Reactant: COc1nc(C(=O)O)c(-n2c(C)ccc2C)cc1C(F)(F)F
Product: COc1nc(C(=O)NCC(O)C(F)(F)F)c(-n2c(C)ccc2C)cc1C(F)(F)F

Procedure:
This compound was prepared from 3-(2,5-Dimethyl-pyrrol-1-yl)-6-methoxy-5-trifluoromethyl-pyridine-2-carboxylic acid (Intermediate D2) and 3-amino-1,1,1-trifluoropropan-2-ol analogously to Example 1; LC-MS Rt=1.50 mins [M+H]+ 426 (Method 2minLC_v002).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:9]=1[CH2:10][C:11](=[O:17])[NH:12]2.[N:18]1([CH2:23][CH2:24][NH:25][C:26]([C:28]2[CH:32]=[C:31]([CH3:33])[NH:30][C:29]=2[CH:34]=O)=[O:27])[CH2:22][CH2:21][CH2:20][CH2:19]1>C(O)C.N1CCCCC1>[N:18]1([CH2:23][CH2:24][NH:25][C:26]([C:28]2[CH:32]=[C:31]([CH3:33])[NH:30][C:29]=2[CH:34]=[C:10]2[C:9]3[C:13](=[CH:14][CH:15]=[CH:16][C:8]=3[C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[F:1])[NH:12][C:11]2=[O:17])=[O:27])[CH2:22][CH2:21][CH2:20][CH2:19]1
Reactant: Cc1cc(C(=O)NCCN2CCCC2)c(C=O)[nH]1
Reactant: O=C1Cc2c(cccc2-c2ccccc2F)N1
Solvent: C1CCNCC1
Solvent: CCO
Product: Cc1cc(C(=O)NCCN2CCCC2)c(C=C2C(=O)Nc3cccc(-c4ccccc4F)c32)[nH]1
Temperature: 25 °C
Reaction time: 72 h
Yield: 50.9 %

Procedure:
To a solution of 4-(2-fluoro-phenyl)-1,3-dihydro-indol-2-one (56.8 mg, 0.25 mmol) and 2-formyl-5-methyl-1H-pyrrole-3-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide (64.8 mg, 0.26 mmol) in ethanol (2 mL) was added piperidine (3 drops). The reaction mixture was stirred at room temperature for three days. A yellow solid product was precipitated out, filtered, washed by ethanol for three times, and dried under high vacuum to provide pure product 2-[4-(2-fluoro-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidenemethyl]-5-methyl-1H-pyrrole-3-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide as a yellow solid (58.4 mg, 51%).
Reaction SMILES: C([CH2:4][N:5]1[C:9](=[O:10])[CH2:8][S:7][C:6]1=[S:11])(O)=O.[NH2:12][C:13]1[CH:22]=[CH:21][C:16]2[N:17]=[C:18]([SH:20])[NH:19][C:15]=2[CH:14]=1.C1(N=C=NC2CCCCC2)CCCCC1.CN(C)C=[O:41]>O1CCCC1>[SH:20][C:18]1[NH:19][C:15]2[CH:14]=[C:13]([NH:12][C:4]([N:5]3[C:9](=[O:10])[CH2:8][S:7][C:6]3=[S:11])=[O:41])[CH:22]=[CH:21][C:16]=2[N:17]=1
Reactant: O=C(O)CN1C(=O)CSC1=S
Reactant: CN(C)C=O
Reactant: Nc1ccc2nc(S)[nH]c2c1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: C1CCOC1
Product: O=C1CSC(=S)N1C(=O)Nc1ccc2nc(S)[nH]c2c1
Temperature: 25 °C
Reaction time: 5 h

Procedure:
1.15 g of 3-carboxymethyl rhodanine and 1 g of 5-amino-2-mercaptobenzimidazole were dissolved in 25 ml of tetrahydrofuran. A solution of 1.2 g of dicyclohexyl carbodiimide in 5 ml of tetrahydrofuran was added to the solution. The mixture was then stirred at room temperature for 5 hours. The resulting precipitate was filtered off to obtain 2 g of semiopaque powder. 20 ml of N,N-dimethylformamide was added to the powder. The mixture was then stirred. Insoluble matters were filtered out. 200 ml of water was added to the filtrate. The resulting precipitate was filtered off, washed with water and then dried to obtain 1.1 g of 3-[N-(2-mercaptobenzimidazole-5-yl)carbamoyl]rhodanine in the form of semiopaque powder;
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2[CH:16]=[CH:15][C:14](Cl)=[CH:13][CH:12]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.C(O)(=O)C[SH:20].[OH-].[K+].[CH3:25][CH:26]([OH:28])C>CN(C)C=O.O>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([C:11]2[CH:16]=[CH:15][C:14]([CH2:25][C:26]([OH:28])=[S:20])=[CH:13][CH:12]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: Cc1ccc(S(=O)(=O)c2ccc(Cl)cc2)cc1
Reactant: O=C(O)CS
Reactant: CC(C)O
Agent: [K+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1ccc(S(=O)(=O)c2ccc(CC(O)=S)cc2)cc1
Temperature: 120 °C
Reaction time: 6 h

Procedure:
In 250 ml of N,N-dimethylformamide, 140 g of 4-methyl-4'-chlorodiphenylsulfone was dissolved, and further 77 g of thioglycolic acid and 71 g of 85% potassium hydroxide pellet were added and stirred for 6 hours at 120° C. The reaction mixture was poured into 2-propanol and filtered off to obtain a precipitate. After the precipitate obtained was dissolved in water and then the insoluble matter was filtered off, 150 ml of concentrated chloric acid and 500 g of ice were added therein. The formed white crystal was filtered off and washed with water and further recrystallized with a mixed solvent of n-hexane and ethylacetate to obtain 110 g of the intended 4-(4-methylphenylsulfonyl)phenylthio acetic acid.
Reaction SMILES: [C:1]([C:5]1[CH:6]=[C:7]([C:12]2[N:16]([CH2:17][CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]3)[C:15]([CH3:24])=[C:14]([S:25]([NH2:28])(=[O:27])=[O:26])[CH:13]=2)[CH:8]=[C:9]([OH:11])[CH:10]=1)([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:36][CH2:37][CH2:38][C:39]([O:41][CH3:42])=[O:40].O>CN(C=O)C>[C:1]([C:5]1[CH:10]=[C:9]([CH:8]=[C:7]([C:12]2[N:16]([CH2:17][CH:18]3[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]3)[C:15]([CH3:24])=[C:14]([S:25](=[O:27])(=[O:26])[NH2:28])[CH:13]=2)[CH:6]=1)[O:11][CH2:36][CH2:37][CH2:38][C:39]([O:41][CH3:42])=[O:40])([CH3:4])([CH3:2])[CH3:3]
Reactant: Cc1c(S(N)(=O)=O)cc(-c2cc(O)cc(C(C)(C)C)c2)n1CC1CCCCC1
Reactant: COC(=O)CCCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)CCCOc1cc(-c2cc(S(N)(=O)=O)c(C)n2CC2CCCCC2)cc(C(C)(C)C)c1
Temperature: 40 °C
Reaction time: 4 h
Yield: 69.7 %

Procedure:
To a solution of compound 14 (202 mg, 0.5 mmol) in DMF (20 mL) were added Cs2CO3 (325 mg, 1 mmol) and methyl 4-bromobutanoate (99 mg, 0.55 mmol). The reaction mixture was stirred for 4 h at 40° C., then water (30 mL) was added and the reaction mixture was extracted with EA (150 mL). The organic layer was washed with brine and dried over Na2SO4, concentrated and purified by CC (hexane/EA=3/1) to give compound 15 (176 mg, 70%).
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[NH:10][CH:11]([O:22][C:23](=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:12]([O:14]CC1C=CC=CC=1)=[O:13].[H][H]>C(OCC)(=O)C.[Pd]>[Cl:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[NH:10][CH:11]([O:22][C:23](=[O:30])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[C:12]([OH:14])=[O:13]
Reactant: [H][H]
Reactant: Cc1ccc(Cl)c(NC(OC(=O)c2ccccc2)C(=O)OCc2ccccc2)c1Cl
Agent: [Pd]
Solvent: CCOC(C)=O
Product: Cc1ccc(Cl)c(NC(OC(=O)c2ccccc2)C(=O)O)c1Cl

Procedure:
20 grams of ester IV (0.045 mol) obtained as in Example 1 were dissolved in 200 ml of ethyl acetate and, after adding 2 g of 10% palladium on carbon, were treated with hydrogen at ambient temperature and pressure. At the end of the reaction the catalyst was filtered on Celite, washing the filter with a little ethyl acetate, and the solvent was then evaporated in vacuo and the residue was recrystallized from ethyl acetate and hexane.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([Si:8]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)([CH3:15])[CH2:9][N:10]2[CH:14]=[N:13][CH:12]=[N:11]2)=[CH:4][CH:3]=1.C([Li])CCC.[CH3:28][S:29]SC>C1COCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([Si:8]([C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)([CH3:15])[CH2:9][N:10]2[C:14]([S:29][CH3:28])=[N:13][CH:12]=[N:11]2)=[CH:6][CH:7]=1
Reactant: C[Si](Cn1cncn1)(c1ccc(F)cc1)c1ccc(F)cc1
Reactant: CSSC
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CSc1ncnn1C[Si](C)(c1ccc(F)cc1)c1ccc(F)cc1
Reaction time: 0.5 h
Yield: 77.5 %

Procedure:
A solution of 1.5 g (0.005 mol) of bis(4-fluorophenyl)methyl(1H-1,2,4-triazol-1-ylmethyl)silane in 10 mL of THF was treated with n-butyllithium as described in Example 1. To this solution was added 0.63 mL (0.007 mol) of dimethyl disulfide. The reaction mixture was allowed to warm to 0°, stirred 30 minutes, then poured into 1:1 ether/hexanes, washed with 7% aqueous NaHCO3 and brine, dried over Na2SO4, filtered and evaporated. The crude product was flash chromatographed (5% ether/methylene chloride) to give 1.4 g of the title compound as a clear oil: nD 1.5750; ir (neat) 3030 (w), 2935 (w), 1587, 1496, 1230, 1160, 1106, 1035, 822 cm-1 ; nmr (CDCl3) δ 0.7 (3H, s), 2.6 (3H, s), 4.0 (2H, s), 7.1 (4H, m), 7.5 (4H, m), 7.8 (1 H, s).
Reaction SMILES: [CH2:1]([CH:3]([CH2:6][CH2:7][CH2:8][CH3:9])[CH2:4][OH:5])[CH3:2].[CH2:10]([O:14][CH2:15][CH:16]1[O:18][CH2:17]1)[CH2:11][CH2:12][CH3:13].Cl(O)(=O)(=O)=O>CCOCC>[CH2:10]([O:14][CH2:15][CH:16]([OH:18])[CH2:17][O:5][CH2:4][CH:3]([CH2:1][CH3:2])[CH2:6][CH2:7][CH2:8][CH3:9])[CH2:11][CH2:12][CH3:13]
Reactant: CCCCOCC1CO1
Reactant: CCCCC(CC)CO
Agent: [O-][Cl+3]([O-])([O-])O
Solvent: CCOCC
Product: CCCCOCC(O)COCC(CC)CCCC
Temperature: 100 °C

Procedure:
260 g (2 mol) of 2-ethylhexanol and 130 g (1 mol) of 1-butoxy-2,3-epoxypropane were stirred together and 0.25 ml of 70% aqueous perchloric acid was added thereto. The mixture was heated for 4 h at 100° C. and then cooled. Next, 1 l of ether was added. The mixture was rinsed twice with water and dried over potassium carbonate. After filtration and concentration by evaporation the crude product was fractionated under reduced pressure. The excess 2-ethylhexanol was removed. Yield: 151 g of oil-former 10 (58.2%) boiling at 146° C./12 mm Hg.
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[C:11]#[C:12][CH2:13][OH:14])[CH:4]=[CH:3][N:2]=1>C(O)C.CO.[Pd]>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[CH2:11][CH2:12][CH2:13][OH:14])[CH:4]=[CH:3][N:2]=1
Reactant: OCC#Cc1cccc2ccncc12
Agent: [Pd]
Solvent: CCO
Solvent: CO
Product: OCCCc1cccc2ccncc12
Reaction time: 22 h
Yield: 33.3 %

Procedure:
A solution of 0.4 g of 3-(8-isoquinolinyl)-2-propyn-1-ol in a mixture of 10 mL of ethanol and 5 mL of methanol was hydrogenated over 0.06 g 10% Pd/C at room temperature and atmospheric pressure for 22 hours and then at 50 psi for 20 hours. After the catalyst was removed by filtration and the filtrate was concentrated, the residual oil was purified by HPLC (methanol-chloroform; 1:19) and crystallized from ethyl acetate-hexane to yield 0.136 g of 8-isoquinolinepropanol, mp 66°-69° C.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:7])[CH:5]=[CH2:6])[CH3:2].[CH3:8][O:9][C:10](=[O:14])[C:11]([CH3:13])=[CH2:12].[CH2:15](OC(=O)C(C)=C)[CH:16]1[O:18][CH2:17]1.[C:25]([OH:30])(=[O:29])[C:26]([CH3:28])=[CH2:27]>>[CH2:1]([O:3][C:4](=[O:7])[CH:5]=[CH2:6])[CH3:2].[C:10]([O:9][CH3:8])(=[O:14])[C:11]([CH3:13])=[CH2:12].[CH2:15]([CH:27]=[C:26]([CH3:28])[C:25]([OH:30])=[O:29])[CH:16]1[O:18][CH2:17]1
Reactant: C=C(C)C(=O)O
Reactant: C=C(C)C(=O)OCC1CO1
Agent: C=C(C)C(=O)OC
Agent: C=CC(=O)OCC
Product: CC(=CCC1CO1)C(=O)O

Procedure:
The procedure of Example 1 was repeated, a mixture of monomers containing 250 g of ethylacrylate, 185 g of methylmethacrylate, 100 g of glycidylmethacrylate, 25 g of methacrylic acid was employed.
Reaction SMILES: [C:1]([O:9]C)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.[CH2:11]1[CH2:16]OC(=O)[CH2:12]1.C[O-].[Na+].[ClH:20].C(=O)(O)[O-].[Na+]>O1CCOCC1>[Cl:20][CH2:12][CH2:11][CH2:16][C:1]([C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1)=[O:9]
Reactant: Cl
Reactant: COC(=O)c1cccnc1
Reactant: O=C1CCCO1
Agent: C[O-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Product: O=C(CCCCl)c1cccnc1

Procedure:
A solution of methyl nicotinate (59 g, 0.43 mol), 4-hydroxybutyric acid lactone (51.8 g, 0.602 mol), and sodium methoxide (70 g, 1.29 mol) in dioxane (500 mL) is refluxed for 1 hour and then cooled. Concentrated hydrochloric acid (650 mL) is added, and the reaction mixture refluxed for 12 hours. The resulting solution is neutralized with solid sodium bicarbonate and extracted with chloroform. The organic phase is dried (sodium sulfate), and the solvent evaporated in vacuo. The residue is taken up in 2-propanol (50 mL) and treated with a saturated solution of hydrogen chloride in 2-propanol. The hydrochloride salt of 4-chloro-1-(3-pyridinyl)-1-butanone is obtained as a white solid (30 g); mp 73-76° C.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][S:16]([CH3:19])(=[O:18])=[O:17])[CH:10]=2)[N:3]=1.[CH2:20]([O:27][C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1B(O)O)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>>[CH2:20]([O:27][C:28]1[CH:33]=[C:32]([F:34])[CH:31]=[CH:30][C:29]=1[C:2]1[N:7]=[CH:6][N:5]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][S:16]([CH3:19])(=[O:18])=[O:17])[CH:10]=2)[N:3]=1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1
Reactant: CS(=O)(=O)Cc1cccc(Nc2ncnc(Cl)n2)c1
Reactant: OB(O)c1ccc(F)cc1OCc1ccccc1
Product: CS(=O)(=O)Cc1cccc(Nc2ncnc(-c3ccc(F)cc3OCc3ccccc3)n2)c1

Procedure:
Example 4 was prepared under similar conditions as described in the preparation of Example 1 using crude 4-chloro-N-{3-[(methylsulfonyl)methyl]phenyl}-1,3,5-triazin-2-amine and [2-(benzyloxy)-4-fluorophenyl]boronic acid (ABCR GmbH & CO. KG). The batch was purified by preparative HPLC: