Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([C:3]1[N:4]=[C:5]2[C:10]([CH3:11])=[CH:9][C:8]([CH3:12])=[N:7][N:6]2[C:13]=1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:33]=[CH:32][CH:31]=[CH:30][C:22]=2[C:23]([O:25]C(C)(C)C)=[O:24])=[CH:17][CH:16]=1)[CH3:2].C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O>C(Cl)Cl>[C:23]([C:22]1[CH:30]=[CH:31][CH:32]=[CH:33][C:21]=1[C:18]1[CH:17]=[CH:16][C:15]([CH2:14][C:13]2[N:6]3[N:7]=[C:8]([CH3:12])[CH:9]=[C:10]([CH3:11])[C:5]3=[N:4][C:3]=2[CH2:1][CH3:2])=[CH:20][CH:19]=1)([OH:25])=[O:24]
Reactant: CCc1nc2c(C)cc(C)nn2c1Cc1ccc(-c2ccccc2C(=O)OC(C)(C)C)cc1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Solvent: COc1ccccc1
Product: CCc1nc2c(C)cc(C)nn2c1Cc1ccc(-c2ccccc2C(=O)O)cc1
Temperature: 25 °C
Reaction time: 14 h
Yield: 86.1 %

Procedure:
To a solution of 0.111 g (0.25 mmol) of the product of Step H and 0.055 g (0.51 mmol) of anisole dissolved in 0.25 mL of methylene chloride was added 0.4 mL of trifluoroacetic acid and the reaction mixture was stirred under a nitrogen atmosphere at room temperature for 14 hours. The reaction mixture was then evaporated in vacuo and purified on a silica gel flash chromatography column eluted with CHCl3 -MeOH-NH4OH (80:15:1). Evaporation of the purified fractions and drying in vacuo afforded 0.083 g (86%) of the title compound as a white amorphous solid.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][N:13](C(OC(C)(C)C)=O)[CH2:12][CH2:11]2)[CH:2]=1.[ClH:23].O1CCOCC1>CO>[ClH:23].[ClH:23].[ClH:23].[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[CH:2]=1
Reactant: CC(C)(C)OC(=O)N1CCN(CCCc2cccnc2)CC1
Agent: Cl
Solvent: C1COCCO1
Solvent: CO
Product: c1cncc(CCCN2CCNCC2)c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a solution of 420 mg of tert-butyl 4-[3-(pyridin-3-yl)propyl]piperazine-1-carboxylate in 6 mL of methanol was added 2 mL of a 4 M hydrogen chloride-dioxane solution, followed by stirring at room temperature for 16 hours. The solvent was evaporated under reduced pressure to obtain 395 mg of 1-[3-(pyridin-3-yl)propyl]piperazine trihydrochloride.
Reaction SMILES: [CH:1](=O)[CH2:2][CH3:3].[O:5]=[C:6]([CH3:19])[CH2:7][C:8]([O:10][CH2:11][CH2:12][O:13][C:14](=[O:18])[C:15]([CH3:17])=[CH2:16])=[O:9].N1CCCCC1.Cl>O>[C:6]([C:7](=[CH:1][CH2:2][CH3:3])[C:8]([O:10][CH2:11][CH2:12][O:13][C:14](=[O:18])[C:15]([CH3:17])=[CH2:16])=[O:9])(=[O:5])[CH3:19]
Reactant: C=C(C)C(=O)OCCOC(=O)CC(C)=O
Reactant: CCC=O
Agent: Cl
Solvent: O
Solvent: C1CCNCC1
Product: C=C(C)C(=O)OCCOC(=O)C(=CCC)C(C)=O
Temperature: 0 °C
Reaction time: 0.02 h

Procedure:
To a magnetically stirred, 1000 mL, round bottom flask were added 200 mL of propionaldehyde and 587 mL 2-(methacryloyloxy)ethyl 3-oxobutanoate. The reaction mixture was cooled to 0° C., in an ice bath, and then 3 to 5 mL of piperidine was added dropwise over one minute. The mixture was stirred at 0° C., for 2 hours, and then allowed to warm to room temperature over the course of 2-2.5 hours. To the reaction mixture was slowly added 30 mL of 3N HCl, over about one minute, to neutralize the piperdine. The mixture was poured into a separatory funnel, and then 150 mL of deionized water was added. The mixture was shaken, and then the aqueous layer was separated and disposed of. The reaction mixture was washed three more times with 150 mL of deionized water, each time, and then dried over MgSO4. The reaction mixture was filtered, and then stabilized with 10 mass ppm of 4-hydroxy-TEMPO. The dried reaction mixture was used without further purification.
Reaction SMILES: C(=O)(O)[O-].[Na+].Cl.[NH2:7][OH:8].[CH2:9]([C:12]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:13]=1[CH:14]=O)[CH:10]=[CH2:11]>O.CO>[CH2:9]([C:12]1[CH:19]=[CH:18][CH:17]=[C:16]([Cl:20])[C:13]=1[CH:14]=[N:7][OH:8])[CH:10]=[CH2:11]
Reactant: C=CCc1cccc(Cl)c1C=O
Reactant: NO
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: O
Product: C=CCc1cccc(Cl)c1C=NO
Temperature: 0 °C
Reaction time: 8 h

Procedure:
5.58 g of sodium bicarbonate were added to a solution of 4.62 g of hydroxylamine hydrochloride in 50 ml of water, and the mixture was cooled to 0° C. A solution of 9.7 g (44.32 mmol) of 2-allyl-6-chlorobenzaldehyde in 50 ml of methanol was added, and the mixture was stirred at room temperature overnight. The methanol was subsequently removed under reduced pressure and the residue was added with stirring to 300 ml of water. The aqueous phase was extracted with diethyl ether, the combined organic phases were washed with saturated ammonium chloride solution and dried and the solvent was removed. This gave 8.7 g (quantitative) of 2-allyl-6-chlorobenzaldehyde oxime in the form of a viscous oil.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:20]2([O:26][CH3:27])[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[CH:5]=[C:6]([S:8][C:9]2[CH:18]=[C:17]3[C:12]([C:13](=O)[CH2:14][CH2:15][O:16]3)=[CH:11][CH:10]=2)[CH:7]=1.Cl.[NH2:29][OH:30]>N1C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4]([C:20]2([O:26][CH3:27])[CH2:25][CH2:24][O:23][CH2:22][CH2:21]2)[CH:5]=[C:6]([S:8][C:9]2[CH:18]=[C:17]3[C:12]([C:13](=[N:29][OH:30])[CH2:14][CH2:15][O:16]3)=[CH:11][CH:10]=2)[CH:7]=1
Reactant: NO
Reactant: COC1(c2cc(F)cc(Sc3ccc4c(c3)OCCC4=O)c2)CCOCC1
Agent: Cl
Solvent: c1ccncc1
Product: COC1(c2cc(F)cc(Sc3ccc4c(c3)OCCC4=NO)c2)CCOCC1
Temperature: 80 °C
Yield: 62.7 %

Procedure:
A mixture of 7-[5-fluoro-3-(4-methoxytetrahydropyran-4-yl)phenylthio]chroman-4-one (0.172 g), hydroxylamine hydrochloride (0.04 g) and pyridine (3 ml) was stirred and heated to 80° C. for 2 hours. The mixture was cooled to ambient temperature and partitioned between ethyl acetate and dilute aqueous hydrochloric acid. The organic phase was washed with brine, dried (MgSO4) and evaporated. The product was purified by column chromatography using a 4:1 mixture of petroleum ether and ethyl acetate as eluent. There was thus obtained, as a mixture of (E)- and (Z)-isomers, 7-[5-fluoro-3-(4-methoxytetrahydropyran-4-yl)phenylthio]chroman-4-one oxime (0.112 g, 63%), m.p. 173°-174° C.;
Reaction SMILES: [C:1]([C:3]1[CH:4]=[CH:5][C:6]2[CH:12]=[CH:11][C:10]3[CH:13]=[CH:14][CH:15]=[CH:16][C:9]=3[S:8](=[O:18])(=[O:17])[C:7]=2[CH:19]=1)#N.N1C=CC=CC=1.C(O)(=[O:28])C.[PH2]([O-])=O.[Na+]>[Ni].O>[CH:5]1[C:6]2[CH:12]=[CH:11][C:10]3[CH:13]=[CH:14][CH:15]=[CH:16][C:9]=3[S:8](=[O:18])(=[O:17])[C:7]=2[CH:19]=[C:3]([CH:1]=[O:28])[CH:4]=1
Reactant: N#Cc1ccc2c(c1)S(=O)(=O)c1ccccc1C=C2
Reactant: CC(=O)O
Agent: [Ni]
Agent: O=[PH2][O-]
Agent: [Na+]
Solvent: O
Solvent: c1ccncc1
Product: O=Cc1ccc2c(c1)S(=O)(=O)c1ccccc1C=C2
Temperature: 25 °C
Reaction time: 24 h

Procedure:
Mix 267 mg (1 mmole) of 3-cyano-dibenzo[b,f]thiepin-5,5-dioxide, 10 ml pyridine, 5 ml acetic acid, and 5 ml water. Add 0.5 g sodium hypophosphite and approximately 0.1 g Raney nickel. Stir at 25° C. for 24 hours and then at 45°-50° C. for 2 hours. Filter the reaction mixture to remove the catalyst and wash any product from the catalyst using 10 ml ethyl acetate. Add 10 ml 6N hydrochloric acid and separate the organic layer containing the product. Evaporate the organic layer to obtain a solid residue comprising the title product, m.p., 175°-177° C. Swishing with methanol and drying the residue gives product melting at 177°-178° C.
Reaction SMILES: C[O:2][C:3]1[C:12]([CH3:13])=[CH:11][CH:10]=[C:9]2[C:4]=1[CH2:5][C@@H:6]([CH:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)[O:7][C@H:8]2[CH2:14][NH:15][CH:16]=[O:17].Br[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33].C(N(C(C)C)CC)(C)C>C(#N)C>[CH2:35]([O:34][C:32](=[O:33])[CH:31]([N:21]1[CH2:20][CH2:19][CH:18]([C@@H:6]2[CH2:5][C:4]3[C:9](=[CH:10][CH:11]=[C:12]([CH3:13])[C:3]=3[OH:2])[C@H:8]([CH2:14][NH:15][CH:16]=[O:17])[O:7]2)[CH2:23][CH2:22]1)[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:25]=1)[CH3:36]
Reactant: COc1c(C)ccc2c1C[C@@H](C1CCNCC1)O[C@H]2CNC=O
Reactant: CCOC(=O)Cc1ccccc1Br
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)C(c1ccccc1)N1CCC([C@@H]2Cc3c(ccc(C)c3O)[C@H](CNC=O)O2)CC1

Procedure:
Stir a solution of N-((1R,3S)-5-methoxy-6-methyl-3-(4-piperidinyl)-1-isochromanyl-methyl)formamide (200 mg, 0.58 mmole), ethyl 2-bromophenylacetate (229 mg, 0.94 mmole) and diisopropylethylamine (243 mg, 1.88 mmole) in acetonitrile overnight at room temperature. Add ethyl acetate and water (2 mL each), then separate the organic phase and dry over Na2SO4. Purify the crude product on a 4 g silica gel column (eluting with ethyl acetate:heptane 3:1). Collect the appropriate fractions and concentrate to obtain the title compound. It was used without further purification in the next step.
Reaction SMILES: Cl.Cl.[NH2:3][C:4]1[CH:5]=[C:6]([NH:10][C:11](=[O:26])[CH2:12][N:13]2[CH2:18][CH2:17][CH:16]([CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:15][CH2:14]2)[CH:7]=[CH:8][CH:9]=1.N1C=CC=CC=1.[Cl:33]CCl.[CH3:36][S:37]([Cl:40])(=[O:39])=[O:38]>C(=O)([O-])O.[Na+]>[ClH:33].[ClH:40].[CH2:19]([CH:16]1[CH2:17][CH2:18][N:13]([CH2:12][C:11]([NH:10][C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([NH:3][S:37]([CH3:36])(=[O:39])=[O:38])[CH:5]=2)=[O:26])[CH2:14][CH2:15]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: Nc1cccc(NC(=O)CN2CCC(Cc3ccccc3)CC2)c1
Reactant: CS(=O)(=O)Cl
Reactant: ClCCl
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccncc1
Product: CS(=O)(=O)Nc1cccc(NC(=O)CN2CCC(Cc3ccccc3)CC2)c1
Temperature: 25 °C
Reaction time: 10 h
Yield: 73 %

Procedure:
To a stirred solution of 0.36 g (1 mmol) of N-(3-amino-phenyl)-2-(4-benzyl-piperidin-1-yl)-acetamide dihydrochloride (Example 175) and 0.24 ml (3 mmol) of pyridine in 10 ml of dichloromethane 0.16 ml (2 mmol) of methanesulfonyl chloride in 5 ml of dichloromethene is added dropwise below 10° C., and the reaction mixture is stirred at room temperature for 10 hours. Then 20 ml of 8% sodium hydrogencarbonate solution is added to the mixture, the organic layer is separated and the water phase is extracted three times with 10 ml of dichloromethane. The combined organic layers are washed with 20 ml of water and dried over sodium sulfate, concentrated, the residue is treated with diethylether and 2.5 N hydrochloric acid in ethyl acetate and the precipitated crystals are filtered off to yield 0.32 g (73%) of the title compound. Melting Point: 110-114° C. (diethylether-ethyl acetate)
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[O:24][C:25]1[C:29]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][CH2:40][NH2:41])=[CH:33][CH:32]=2)=[C:28]([CH:42]([CH3:44])[CH3:43])[NH:27][N:26]=1)(=[O:3])[CH3:2].C(N(CC)CC)C.Cl[C:53](OC1C=CC([N+]([O-])=O)=CC=1)=[O:54].[NH2:65][CH2:66][CH2:67][N:68]1[CH2:73][CH2:72][O:71][CH2:70][CH2:69]1>ClCCl.O>[C:1]([O:4][C@@H:5]1[C@@H:10]([O:11][C:12](=[O:14])[CH3:13])[C@H:9]([O:15][C:16](=[O:18])[CH3:17])[C@@H:8]([CH2:19][O:20][C:21](=[O:23])[CH3:22])[O:7][C@H:6]1[O:24][C:25]1[C:29]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH2:38][CH2:39][CH2:40][NH:41][C:53]([NH:65][CH2:66][CH2:67][N:68]3[CH2:73][CH2:72][O:71][CH2:70][CH2:69]3)=[O:54])=[CH:33][CH:32]=2)=[C:28]([CH:42]([CH3:44])[CH3:43])[NH:27][N:26]=1)(=[O:3])[CH3:2]
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Reactant: CC(=O)OC[C@H]1O[C@@H](Oc2n[nH]c(C(C)C)c2Cc2ccc(OCCCN)cc2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Reactant: NCCN1CCOCC1
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: CC(=O)OC[C@H]1O[C@@H](Oc2n[nH]c(C(C)C)c2Cc2ccc(OCCCNC(=O)NCCN3CCOCC3)cc2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: 25 °C
Reaction time: 1 h
Yield: 47.8 %

Procedure:
To a solution of 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-{[4-(3-aminopropoxy)phenyl]methyl}-5-isopropyl-1H-pyrazole (97 mg) in dichloromethane (3 mL) were added triethylamine (0.035 mL) and 4-nitrophenyl chloroformate (35 mg), and the mixture was stirred at room temperature for 1 hour. To the reaction mixture was added 4-(2-aminoethyl)morpholine (41 mg), and the mixture was stirred at room temperature overnight. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with water, a saturated aqueous sodium hydrogen carbonate solution, water and brine successively, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate-dichloromethane/methanol=10/1-5/1) to give 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-5-isopropyl-4-{[4-(3-{3-[2-(morpholin-4-yl)ethyl]ureido}propoxy)phenyl]-methyl}-1H-pyrazole (58 mg). This material was dissolved in methanol (3 mL). To the solution was added sodium methoxide (28% methanol solution, 0.03 mL), and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, and the residue was purified by solid phase extraction on ODS (washing solvent: distilled water, eluent: methanol) to give the title compound (39 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].F[C:22]1[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][C:23]=1[C:24]([OH:26])=[O:25].Cl>C1COCC1.CCCCCC.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]2[CH:15]=[CH:16][C:17]([NH:20][C:22]3[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][C:23]=3[C:24]([OH:26])=[O:25])=[CH:18][CH:19]=2)[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: Nc1ccc(CCCCCc2ccc(Cl)c(Cl)c2)cc1
Reactant: O=C(O)c1cc([N+](=O)[O-])ccc1F
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: C1CCOC1
Product: O=C(O)c1cc([N+](=O)[O-])ccc1Nc1ccc(CCCCCc2ccc(Cl)c(Cl)c2)cc1
Temperature: -78 °C
Reaction time: 0.17 h
Yield: 74.7 %

Procedure:
To a cooled (−78° C.) solution of 4-[5-(3,4-dichlorophenyl)pentyl]-phenylamine (0.231 g, 0.75 mmol) in THF (2 mL), LHDMS (2.25 mL, 1 M in hexane, 2.25 mmol) was added dropwise. The reaction mixture was allowed to stir at −78° C. for 10 minutes. A solution of 2-fluoro-5-nitrobenzoic acid (0.139 g, 0.75 mmol) in THF (2 mL) was added dropwise, and this solution was stirred for 30 minutes at −78° C. The reaction mixture was allowed to gradually warm to room temperature and stir for 2 hours under N2 atmosphere. The reaction mixture was diluted with EtOAc, and acidified with 1N HCl (pH 3). The organic layer was dried (Na2SO4), filtered and concentrated in vacuo to yield a brown residue. Purification by flash chromatography (silica gel, 2% MeOH/CH2Cl2) then recrystallization with MeOH yielded 265 mg (0.56 mmol, 75%) of the desired product. mp 147-148° C.
Reaction SMILES: [N:1]1[CH:6]=[C:5]([CH2:7][C:8]2[C:9](=[O:15])[NH:10][C:11](=[S:14])[NH:12][CH:13]=2)[CH:4]=[N:3][CH:2]=1.[CH3:16]CN(C(C)C)C(C)C.Cl[CH2:26][C:27]1[CH:28]=[CH:29][C:30]([O:35][C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([C:42]([F:45])([F:44])[F:43])[CH:37]=2)=[C:31]([CH:34]=1)[C:32]#[N:33].CI>C(Cl)Cl.[Zn+2].[Br-].[Br-].CN1C(=O)CCC1>[CH3:16][N:12]1[CH:13]=[C:8]([CH2:7][C:5]2[CH:6]=[N:1][CH:2]=[N:3][CH:4]=2)[C:9](=[O:15])[N:10]=[C:11]1[S:14][CH2:26][C:27]1[CH:28]=[CH:29][C:30]([O:35][C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([C:42]([F:45])([F:44])[F:43])[CH:37]=2)=[C:31]([CH:34]=1)[C:32]#[N:33]
Reactant: CCN(C(C)C)C(C)C
Reactant: N#Cc1cc(CCl)ccc1Oc1cccc(C(F)(F)F)c1
Reactant: O=c1[nH]c(=S)[nH]cc1Cc1cncnc1
Agent: [Br-]
Agent: [Zn+2]
Solvent: ClCCl
Solvent: CI
Solvent: CN1CCCC1=O
Product: Cn1cc(Cc2cncnc2)c(=O)nc1SCc1ccc(Oc2cccc(C(F)(F)F)c2)c(C#N)c1
Temperature: 60 °C
Reaction time: 0.17 h
Yield: 9.8 %

Procedure:
To a solution of 5-(5-pyrimidinylmethyl)-2-thioxo-2,3-dihydro-4(1H)-pyrimidinone (70.7 mg, 0.321 mmol) and DIPEA (0.084 ml, 0.481 mmol) in DCM (2 ml) was added 5-(chloromethyl)-2-{[3-(trifluoromethyl)phenyl]oxy}benzonitrile (100 mg, 0.321 mmol). The reaction mixture was heated at 60° C. overnight. After removing the solvent by nitrogen, the residue was dissolved in MeCN (4 ml), and NMP (1.5 ml), and ZnBr2 (107 mg, 0.477 mmol) and DIPEA (0.083 ml, 0.477 mmol) were added. The mixture was then stirred at 60° C. for 10 min. And MeI (0.022 mL, 0.353 mmol) was added dropwise, then stirred at 60° C. for 1.5 h. Purification via MDAP then afforded the title compound (16 mg, 8.01% yield). LCMS: rt=2.96 min, [M+H+]=510
Reaction SMILES: [CH2:1]([OH:8])[C@@H:2]([OH:7])[CH2:3][CH2:4][C:5]#[CH:6].C(N([CH2:14][CH3:15])CC)C.[C:16]1(C)[C:17]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:19]=C[CH:21]=1>C(Cl)Cl.C([Sn](=O)CCCC)CCC>[OH:7][C@@H:2]([CH2:3][CH2:4][C:5]#[CH:6])[CH2:1][O:8][S:22]([C:17]1[CH:18]=[CH:19][C:14]([CH3:15])=[CH:21][CH:16]=1)(=[O:24])=[O:23]
Reactant: Cc1ccccc1S(=O)(=O)Cl
Reactant: C#CCC[C@H](O)CO
Reactant: CCN(CC)CC
Agent: CCCC[Sn](=O)CCCC
Solvent: ClCCl
Product: C#CCC[C@H](O)COS(=O)(=O)c1ccc(C)cc1
Temperature: 0 °C
Reaction time: 22 h
Yield: 80.4 %

Procedure:
Diol (1) (1.560 g, 13.667 mmol) was dissolved in DCM (140 mL) cooled to 0° C. and dibutyltin oxide (67.9 mg, 0.2728 mmol), triethylamine (2.08 mL, 1.518 g, 15.005 mmol) and toluenesulfonyl chloride (2.864 g, 15.022 mmol) were added. After 10 minutes the icebath was removed and the reaction mixture was stirred for 22 hours. Then it was filtrated and the filtrate concentrated in vacuo. Purification by chromatography (hexane/EtOAc 4/1) provided 2.950 g of compound (2a) as clear colourless oil with 80% yield.
Reaction SMILES: [Cl:1][C:2]1[C:11]([S:12]([NH2:15])(=[O:14])=[O:13])=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.C1(C)C=CC=CC=1.C[Al](C)C.C[O:28][C:29](=O)[NH:30][C:31]1[N:36]=[C:35]([O:37][CH3:38])[N:34]=[C:33]([O:39][CH3:40])[N:32]=1>C(Cl)Cl>[Cl:1][C:2]1[C:11]([S:12]([NH:15][C:29]([NH:30][C:31]2[N:32]=[C:33]([O:39][CH3:40])[N:34]=[C:35]([O:37][CH3:38])[N:36]=2)=[O:28])(=[O:14])=[O:13])=[C:10]2[C:5]([CH:6]=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1
Reactant: COC(=O)Nc1nc(OC)nc(OC)n1
Reactant: NS(=O)(=O)c1c(Cl)ccc2cccnc12
Agent: C[Al](C)C
Solvent: ClCCl
Solvent: Cc1ccccc1
Product: COc1nc(NC(=O)NS(=O)(=O)c2c(Cl)ccc3cccnc23)nc(OC)n1
Reaction time: 0.75 h
Yield: 27.5 %

Procedure:
To a stirred mixture of 7-chloro-8-quinolinesulfonamide (1.5 g) in 75 ml methylene chloride is added a 2 M toluene solution of trimethyl aluminum (4.7 ml). The resulting solution is stirred under N2 for 45 min. Solid methyl(4,6-dimethoxy-1,3,5-triazin-2-yl)carbamate (1.1 g) is added and the mixture is heated at reflux for 60 h. The reaction is quenched sequentially with acetic acid (1 ml), 6 N HCl (2.5 ml) and water (13 ml). The organic solution is retained, dried with MgSO4, and is concentrated to an oil-solid mixture. Filtration afforded 0.6 g yellow solid m.p. 169°-191° C. (dec). The infrared spectrum showed characteristic absorption bands at 3300 and 1700 cm-1.
Reaction SMILES: Br[CH:2]1[CH2:7][CH2:6][O:5][C:3]1=[O:4].[C:8]([OH:13])(=[O:12])[C:9]([CH3:11])=[CH2:10].C(N(CC)CC)C>C(C(C)=O)C(C)C>[C:8]([O:13][CH:2]1[CH2:7][CH2:6][O:5][C:3]1=[O:4])(=[O:12])[C:9]([CH3:11])=[CH2:10]
Reactant: C=C(C)C(=O)O
Reactant: O=C1OCCC1Br
Solvent: CCN(CC)CC
Solvent: CC(=O)CC(C)C
Product: C=C(C)C(=O)OC1CCOC1=O
Temperature: 25 °C
Reaction time: 10 h
Yield: 85 %

Procedure:
100 g of α-bromo-γ-butyrolactone and 104.4 g of methacrylic acid (2.0 mole times with respect to α-bromo-γ-butyrolactone) were charged, and methyl isobutyl ketone was added thereto in an amount of 3 weight times that of α-bromo-γ-butyrolactone to prepare a solution. Then, 183.6 g of triethylamine (3.0 mole times with respect to α-bromo-γ-butyrolactone) was added dropwise thereto, followed by stirring at room temperature for about 10 hours. After filtration, an organic layer was washed with 5% by weight aqueous solution of sodium bicarbonate, followed by washing with water for 2 times. The organic layer was concentrated to obtain α-methacryloyloxy-γ-butyrolactone represented by the following formula in a 85% yield.
Reaction SMILES: [OH:1][CH:2]([CH:4]([CH2:8][CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:5]([OH:7])=O)[CH3:3].ON1C2C=CC=CC=2N=N1.CN1CCOCC1.Cl.CN(C)CCCN=C=NCC.[NH2:46][CH:47]([C:49]1[C:50](=[O:64])[NH:51][C:52]([CH2:55][C:56]2[CH:61]=[CH:60][C:59]([O:62][CH3:63])=[CH:58][CH:57]=2)=[N:53][N:54]=1)[CH3:48]>>[OH:1][CH:2]([CH:4]([CH2:8][CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:5]([NH:46][CH:47]([C:49]1[C:50](=[O:64])[NH:51][C:52]([CH2:55][C:56]2[CH:61]=[CH:60][C:59]([O:62][CH3:63])=[CH:58][CH:57]=2)=[N:53][N:54]=1)[CH3:48])=[O:7])[CH3:3]
Reactant: COc1ccc(Cc2nnc(C(C)N)c(=O)[nH]2)cc1
Reactant: CC(O)C(CCCc1ccccc1)C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CN1CCOCC1
Product: COc1ccc(Cc2nnc(C(C)NC(=O)C(CCCc3ccccc3)C(C)O)c(=O)[nH]2)cc1

Procedure:
1.02 g (4.61 mmol) of 2-(1-hydroxyethyl)-5-phenylpentanoic acid are reacted analogously to Example 39A with 620 mg (4.61 mmol) of 1-hydroxy-1H-benzotriazole, 930 mg (9.22 mmol) of 4-methylmorpholine, 880 mg (4.61 mmol) of N′-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride and 1.00 g (3.84 mmol) of 6-(1-aminoethyl)-3-(4-methoxybenzyl)-1,2,4-triazin-5(4H)-one to give 2-(1-hydroxyethyl)-N-{1-[3-(4-methoxybenzyl)-5-oxo-4,5-dihydro-1,2,4-triazin-6-yl]ethyl}-5-phenylpentanamide.
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)([O-])[O-].[K+].[K+].[O:14]([CH2:32][C:33]1[CH:38]=[CH:37][C:36]([CH2:39]OS(C)(=O)=O)=[CH:35][C:34]=1[Cl:45])[Si:15]([C:28]([CH3:31])([CH3:30])[CH3:29])([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.O>CN(C)C=O>[O:14]([CH2:32][C:33]1[CH:38]=[CH:37][C:36]([CH2:39][O:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:35][C:34]=1[Cl:45])[Si:15]([C:28]([CH3:29])([CH3:30])[CH3:31])([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1
Reactant: CC(C)(C)[Si](OCc1ccc(COS(C)(=O)=O)cc1Cl)(c1ccccc1)c1ccccc1
Reactant: Oc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)[Si](OCc1ccc(COc2ccccc2)cc1Cl)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 78.5 %

Procedure:
To a solution of phenol (969 mg) in N,N-dimethylformamide (27 ml) was added potassium carbonate powder (1.92 g) and the mixture was stirred at room temperature for 5 min. 1-((tert-Butyldiphenylsiloxy)methyl)-2-chloro-4-((methanesulfonyloxy) methyl)benzene (3.39 g) was added and the mixture was stirred at 100° C. for 3 hr. The reaction mixture was allowed to cool to room temperature. Water was added and the mixture was extracted twice with hexane. The organic layers were combined, washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was purified by column chromatography (silica gel, hexane/ethyl acetate=50/1) to give 1-((tert-butyldiphenylsiloxy)-methyl)-2-chloro-4-(phenoxymethyl)benzene (2.65 g) as a colorless oil.