Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:29])[CH2:10][NH:11][C:12](=[O:28])[C@H:13]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([N+:25]([O-])=O)=[CH:21][CH:20]=1)[NH:14][C:15](=[O:17])[CH3:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(Cl)Cl.CO.C(O)(=O)C>CO.[Pt](=O)=O>[CH2:1]([O:8][C:9](=[O:29])[CH2:10][NH:11][C:12](=[O:28])[C@H:13]([CH2:18][C:19]1[CH:24]=[CH:23][C:22]([NH2:25])=[CH:21][CH:20]=1)[NH:14][C:15](=[O:17])[CH3:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(=O)N[C@@H](Cc1ccc([N+](=O)[O-])cc1)C(=O)NCC(=O)OCc1ccccc1
Agent: O=[Pt]=O
Solvent: CO
Solvent: CC(=O)O
Solvent: ClC(Cl)Cl
Product: CC(=O)N[C@@H](Cc1ccc(N)cc1)C(=O)NCC(=O)OCc1ccccc1

Procedure:
Compound 14 (267 mg, 0.67 mmol) was dissolved in methanol (50 ml). Platinum dioxide (3% of weight of peptide) was added, and the mixture was hydrogenated at atmospheric pressure. After 4 hours TLC (chloroform/methanol/acetic acid: 85/10/5) showed a clean conversion to the amine. The catalyst was separated by decantation, and the solvent was removed under reduced pressure. Compound 15 was obtained in nearly quantitative yield as a glassy solid.
Reaction SMILES: [CH2:1]([N:3]([CH3:11])[C:4]([N:6]1[CH:10]=[CH:9][N:8]=[CH:7]1)=[O:5])[CH3:2].[S:12]([O:17]C)([O:15][CH3:16])(=[O:14])=[O:13]>C(#N)C>[CH3:16][O:15][S:12]([O-:17])(=[O:14])=[O:13].[CH2:1]([N:3]([C:4]([NH+:6]1[CH:10]=[CH:9][N:8]([CH3:16])[CH2:7]1)=[O:5])[CH3:11])[CH3:2]
Reactant: CCN(C)C(=O)n1ccnc1
Reactant: COS(=O)(=O)OC
Solvent: CC#N
Product: CCN(C)C(=O)[NH+]1C=CN(C)C1
Product: COS(=O)(=O)[O-]
Temperature: 25 °C
Reaction time: 8 h
Yield: 197.8 %

Procedure:
To the cooled solution of N-ethyl-N-methyl-1H-imidazole-1-carboxamide (5 g, 32.7 mmol) in acetonitrile (10 mL) was added slowly dimethyl sulfate (4.12 g, 32.7 mmol). The reaction mixture was stirred at room temperature overnight and then was evaporated under vacuum to yield 1-[[N-ethyl-(N-methyl)amino]carbonyl]-3-methyl-1H-imidazolium methyl sulfate (9.1 g). 1H NMR (CDCl3) δ 9.7 (s, 1H); 7.7 (s, 1H); 7.6 (s, 1H); 4.1 (s, 3H); 3.65 (s, 3H), 3.5 (q, J=7.2 Hz, 2H), 3.15 (s, 3H), 1.3 (t, J=7.2 Hz, 3H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[CH:3]=1.C([Li])CCC.[F:14][CH:15]([F:27])[O:16][C:17]1[CH:22]=[CH:21][C:20]([C:23](=O)[CH3:24])=[C:19]([CH3:26])[CH:18]=1.C1CCCCC1.C(OCC)(=O)C>O1CCCC1>[Br:8][C:4]1[CH:3]=[C:2]([C:23]([C:20]2[CH:21]=[CH:22][C:17]([O:16][CH:15]([F:14])[F:27])=[CH:18][C:19]=2[CH3:26])=[CH2:24])[CH:7]=[CH:6][CH:5]=1
Reactant: Brc1cccc(Br)c1
Reactant: CC(=O)c1ccc(OC(F)F)cc1C
Agent: [Li]CCCC
Solvent: CCOC(C)=O
Solvent: C1CCCCC1
Solvent: C1CCOC1
Product: C=C(c1cccc(Br)c1)c1ccc(OC(F)F)cc1C
Temperature: -78 °C
Reaction time: 1 h

Procedure:
To a solution of 1,3-dibromobenzene (7.6 g, 32.2 mmol, 1 eq) in 64 mL of dry tetrahydrofuran at −78° C. under N2 atmosphere, n-butyllithium (1.6 N in hexane, 20 mL, 1.1 eq) was added dropwise. The mixture was stirred at −78° C. for 1 h, then was added via cannula to a solution of 1-(4-difluoromethoxy-2-methyl-phenyl)-ethanone (6.5 g, 32.2 mmol, 1 eq) in dry tetrahydrofuran at −78° C. The mixture was allowed to warm to room temperature. The reaction mixture was examined after 1 h by TLC (cyclohexane/ethyl acetate 9:1) which showed complete conversion to the desired product. Sat. aqueous ammonium chloride (30 mL) was added, the tetrahydrofuran layer was separated aqueous phase was extracted with dichloromethane (30 mL). The organic fractions were collected, dried over sodium sulfate and evaporated. The crude was dissolved in acetic acid (65 mL) and cone. sulfuric acid (13 mL) was added and mixture was stirred at room temperature for 2 h. A solution of 15% NaOH was added to the mixture until pH 6-5, then extracted with dichloromethane (50 mL). The organic phases were collected, dried and evaporated. The crude was purified by flash chromatography eluting with cyclohexane. 6.10 g of clean product was obtained as colorless oil (yield: 55%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@@:9]([OH:31])([CH2:25][N:26]1[CH:30]=[N:29][CH:28]=[N:27]1)[C@H:10]([C:12]1[S:13][CH:14]=[C:15]([C:17]2[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][CH:18]=2)[N:16]=1)[CH3:11].C(OC(C1C(C)=CC(C([Br:50])(C)OC(=O)CN)=CC=1C)=O)(C)(C)C>CC#N>[Br-:50].[C:21]([C:20]1[CH:23]=[CH:24][C:17]([C:15]2[N:16]=[C:12]([C@H:10]([CH3:11])[C@:9]([C:3]3[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=3[F:1])([OH:31])[CH2:25][N:26]3[CH:30]=[NH+:29][CH:28]=[N:27]3)[S:13][CH:14]=2)=[CH:18][CH:19]=1)#[N:22]
Reactant: Cc1cc(C(C)(Br)OC(=O)CN)cc(C)c1C(=O)OC(C)(C)C
Reactant: C[C@@H](c1nc(-c2ccc(C#N)cc2)cs1)[C@](O)(Cn1cncn1)c1cc(F)ccc1F
Solvent: CC#N
Product: C[C@@H](c1nc(-c2ccc(C#N)cc2)cs1)[C@](O)(Cn1c[nH+]cn1)c1cc(F)ccc1F
Product: [Br-]
Yield: 133.8 %

Procedure:
A mixture of 22.7 mg of 4-{2-[(1R,2R)-2-(2,5-Difluoro-phenyl)-2-hydroxy-1-methyl -3-[1,2,4]triazol-1-yl-propyl]-thiazol-4-yl}-benzonitrile and 25.0 mg of 4-tert-butoxycarbonyl-methyl-aminoacetoxy-3,5-dimethyl-benzyl bromide in CH3CN(1.5 mL) was refluxed over 15 hrs. The solvent was evaporated in vacuo and the residue was chromatographed on silica gel (Wakogel C-200, solvent:CH2Cl2/MeOH=10/1) to give 4-{4-[(tert-Butoxycarbonyl-methyl-amino)-acetoxy]-3,5 -dimethyl-benzyl)}-1-[(2R,3R)-3-[4-(4-cyano-phenyl)-thiazol-2-yl]-2-(2,5-difluoro-phenyl)-2-hydroxy-butyl]-1H-[1,2,4]triazol-4-ium bromide (36.0 mg, 84% as colorless heavy syrup);
Reaction SMILES: [C:1]1(=[O:6])[O:5][CH2:4][CH2:3][CH2:2]1.[ClH:7].[CH2:8](O)[CH3:9].[OH-].[Na+]>C1(C)C=CC=CC=1>[CH2:4]([O:5][C:1](=[O:6])[CH2:2][CH2:9][CH2:8][Cl:7])[CH3:3]
Reactant: Cl
Reactant: CCO
Reactant: O=C1CCCO1
Agent: [Na+]
Agent: [OH-]
Solvent: Cc1ccccc1
Product: CCOC(=O)CCCCl
Temperature: 100 °C
Reaction time: 2 h
Yield: 85 %

Procedure:
51.7 kg (0.6 kmol) of gamma-butyrolactone (100 percent) was placed in an enamel pressure agitator. The closed system was heated to 100° C. with good agitation, and starting from 60° C. a total of about 26.5 kg (0.72 kmol) of HCl was pressed on. The temperature and pressure quickly rose, caused by the exothermia. The addition of HCl and heat output were regulated so that the reaction could be performed isothermally at 100° C. and isobarically at 11 bars of pressure. Addition was continued until no more HCl was absorbed (about 5 to 6 hours). Then it was cooled to 20° C. and the residual HCl was discharged. Then 62.3 kg (1.35 kmol) of ethanol was added to the reaction solution. Then 2 kg (0.055 kmol) of HCl was again pressed on. It was heated to 100° C. and kept at this temperature for 2 hours (pressure was 6 bars) and then cooled to 20 ° C. The solution was then mixed with 92 kg of toluene and made basic with 23 kg of aqueous NaOH (30 percent) (pH 8 to 8.5). The phases were separated and the organic phase was washed with 26 kg of water. The combined water phases were again extracted with 46 kg of toluene. The organic phase was distilled. Thus, toluene, ethanol and water were separated. 87 kg of crude gamma-chlorobutyric acid ethyl ester (content 88 percent) remained as still residue, which could be used directly in the following step. The yield was 85 percent, relative to the gamma-butyrolactone.
Reaction SMILES: [CH3:1][C:2]([N+:9]([O-])=O)([CH3:8])[CH2:3][NH:4][CH2:5][CH2:6][OH:7]>CO.[Ni].O>[NH2:9][C:2]([CH3:8])([CH3:1])[CH2:3][NH:4][CH2:5][CH2:6][OH:7]
Reactant: CC(C)(CNCCO)[N+](=O)[O-]
Agent: [Ni]
Solvent: CO
Solvent: O
Product: CC(C)(N)CNCCO
Reaction time: 19 h
Yield: 78 %

Procedure:
To a solution of 2-((2-methyl-2-nitropropyl)amino)ethanol (20.4 g, 126 mmol) in methanol (120 ml) was added a slurry of 50% Raney Nickel® in H2O (6 ml). The vessel was pressurized with H2 (450 psi) and the suspension stirred for 19 h. The mixture was filtered through Celite and concentrated in vacuo to give 20 g of a crude liquid, which was distilled under vacuum (<1 mbar, 100-125° C.) to give 13 g of a clear liquid, which was found to be partially purified and was used directly in the next step without purification. LRMS (ESI/APCI) m/z 133 [M+H]+.
Reaction SMILES: [N:1]1([S:7]([C:10]2[CH:15]=[CH:14][C:13]([C:16]3[NH:17][C:18](=[O:25])[C:19](=[CH:23][CH:24]=3)[C:20](O)=O)=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)[Cl:27].C[Si](Cl)(C)C.S(Cl)(Cl)=O>C(N(CC)CC)C>[N:1]1([S:7]([C:10]2[CH:15]=[CH:14][C:13]([C:16]3[NH:17][C:18](=[O:25])[C:19](=[CH:23][CH:24]=3)[CH2:20][Cl:27])=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: ClCCl
Reactant: O=C(O)c1ccc(-c2ccc(S(=O)(=O)N3CCCCC3)cc2)[nH]c1=O
Agent: C[Si](C)(C)Cl
Solvent: CCN(CC)CC
Solvent: O=S(Cl)Cl
Product: O=c1[nH]c(-c2ccc(S(=O)(=O)N3CCCCC3)cc2)ccc1CCl

Procedure:
From 5.0 g. of 6-[4-(1-piperidinylsulfonyl)phenyl]-1,2-dihydro-2-oxonicotinic acid in 150 ml. of methylene chloride, 2.0 ml. of triethylamine, 1.75 ml. of trimethylsilyl chloride and 2.0 ml. of thionyl chloride, following the procedure of a) above, there is obtained 6-[4-(1-piperidinylsulfonyl)phenyl]-1,2-dihydro-2-oxonicotinyl chloride.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:11]([O:12][CH3:13])=[CH:10][CH:9]=[CH:8][C:4]=1[CH2:5][CH2:6][OH:7].C(O[CH:17](OCC)[CH2:18][Cl:19])C.Cl>O>[Cl:19][CH2:18][CH:17]1[C:8]2[C:4](=[C:3]([O:2][CH3:1])[C:11]([O:12][CH3:13])=[CH:10][CH:9]=2)[CH2:5][CH2:6][O:7]1
Reactant: CCOC(CCl)OCC
Reactant: COc1cccc(CCO)c1OC
Agent: Cl
Solvent: O
Product: COc1ccc2c(c1OC)CCOC2CCl
Yield: 82.6 %

Procedure:
A mixture of 30 g of 2,3-dimethoxyphenethyl alcohol, 30 g of chloroacetaldehyde diethyl acetal and 50 ml of concentrated hydrochloric acid was heated at 60°-80° C for 1 hour and, after cooling, the reaction mixture was diluted with water. The resultant oily precipitate was extracted into ethyl acetate, rinsed with water, dehydrated and concentrated under reduced pressure. The residue was then recrystallized from petroleum ether. By the above procedure was obtained 33 g of 1-chloromethyl-5,6-dimethoxyisochroman as colorless needles, melting point: 63°-65° C.
Reaction SMILES: [C:1]([O:4]C(=O)C)(=[O:3])[CH3:2].[C:8](Cl)(=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11]C=1.[OH-:17].[Na+].N1C2C(=CC=CC=2)C=CC=1>N1C=CC=CC=1>[O:17]=[C:14]1[C@H:13]([O:4][C:1](=[O:3])[CH3:2])[C@H:12]([CH3:11])[O:15][CH:8]=[CH:9]1
Reactant: CC(=O)OC(C)=O
Reactant: [OH-]
Reactant: O=C(Cl)c1ccccc1
Agent: [Na+]
Solvent: c1ccncc1
Solvent: c1ccc2ncccc2c1
Product: CC(=O)O[C@H]1C(=O)C=CO[C@H]1C

Procedure:
Examples of suitable blocking groups which may be used throughout the present synthesis technique include acetyl ##STR23## and benzoyl ##STR24## groups. These groups may be introduced by reacting the compound of formula 5 with, respectively, such compounds as acetic anhydride or benzoyl chloride. The reaction is preferably conducted in a solvent which is a good acid receptor, such as pyridine, sodium hydroxide solution, or quinoline. Subsequent to the reaction, the solvent is removed under reduced pressure, and the residue is co-evaporated several times with toluene. The product is purified by distillation, recrystallization, and/or column chromatography. When the preferred reactant, acetic anhydride, is reacted with the compound of formula 5, 1,5-anhydro-3-oxo-4-O-acetyl-2,3,6-trideoxy-L-threo-hex-1-enitol is produced.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[N:6][C:7]([N:10]2[CH2:15][CH2:14][CH:13]([C:16]3[S:17][CH:18]=[C:19]([CH2:21][O:22][C:23]4[CH:28]=[CH:27][C:26]([N:29]5[CH:33]=[N:32][N:31]=[N:30]5)=[CH:25][CH:24]=4)[N:20]=3)[CH2:12][CH2:11]2)=[N:8][CH:9]=1)([O-])=O.[Cl-].[NH4+]>CCO.C1COCC1.O.[Fe]>[N:29]1([C:26]2[CH:27]=[CH:28][C:23]([O:22][CH2:21][C:19]3[N:20]=[C:16]([CH:13]4[CH2:12][CH2:11][N:10]([C:7]5[N:8]=[CH:9][C:4]([NH2:1])=[CH:5][N:6]=5)[CH2:15][CH2:14]4)[S:17][CH:18]=3)=[CH:24][CH:25]=2)[CH:33]=[N:32][N:31]=[N:30]1
Reactant: O=[N+]([O-])c1cnc(N2CCC(c3nc(COc4ccc(-n5cnnn5)cc4)cs3)CC2)nc1
Agent: [Fe]
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCO
Solvent: C1CCOC1
Solvent: O
Product: Nc1cnc(N2CCC(c3nc(COc4ccc(-n5cnnn5)cc4)cs3)CC2)nc1
Temperature: 100 °C

Procedure:
5-Nitro-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine (Example 192) (1.07 mmol), ammonium chloride (3 eq.) and iron powder (3 eq.) were suspended in EtOH:THF:H2O (40:20:10) and heated at 100° C. for 5 hours. The hot reaction mixture was filtered through a pad of celite and the filtrate was concentrated. The resulting oil was dissolved in DMF and water and extracted with ethylacetate. The organic layer was washed with water, brine and dried over sodium sulfate. The resulting filtrate was concentrated under reduced pressure. Purification using silica gel chromatography (DCM/MeOH 98:2) provided the expected product. 1H NMR (DMSO-d6): δ 9.96 (1H, s), 7.97 (2H, m), 7.90 (2H, m), 7.63 (1H, s), 5.19 (2H, s), 4.44 (2H, m), 3.73 (1H, m), 2.97 (2H, m), 2.20 (2H, m), 1.95 (2H, m).
Reaction SMILES: [CH:1]1([N:5]2[CH2:11][CH2:10][C:9]3[CH:12]=[CH:13][C:14]([O:16][C:17]4[CH:22]=[CH:21][C:20](I)=[CH:19][N:18]=4)=[CH:15][C:8]=3[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[NH:24]1[CH2:28][CH2:27][NH:26][C:25]1=[O:29]>>[CH:1]1([N:5]2[CH2:11][CH2:10][C:9]3[CH:12]=[CH:13][C:14]([O:16][C:17]4[N:18]=[CH:19][C:20]([N:24]5[CH2:28][CH2:27][NH:26][C:25]5=[O:29])=[CH:21][CH:22]=4)=[CH:15][C:8]=3[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1
Reactant: O=C1NCCN1
Reactant: Ic1ccc(Oc2ccc3c(c2)CCN(C2CCC2)CC3)nc1
Product: O=C1NCCN1c1ccc(Oc2ccc3c(c2)CCN(C2CCC2)CC3)nc1

Procedure:
The title compound was prepared from 3-cyclobutyl-7-[(5-iodo-2-pyridinyl)oxy]-2,3,4,5-tetrahydro-1H-3-benzazepine (E207) and 2-imidazolidinone using the method of Example 261; MS (ES+) m/e 379 [M+H]+.
Reaction SMILES: [CH:1]([C:4]1[CH:5]=[C:6]2[C:11](=[C:12]([C:14]3[CH:19]=[CH:18][CH:17]=[C:16]([CH:20]=[CH2:21])[CH:15]=3)[CH:13]=1)[N:10]=[CH:9][CH:8]=[CH:7]2)([CH3:3])[CH3:2].[N+](=[C:24]([C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=1)[C:25]1[CH:30]=[CH:29][C:28]([Cl:31])=[CH:27][CH:26]=1)=[N-]>C1C=CC=CC=1>[Cl:31][C:28]1[CH:29]=[CH:30][C:25]([C:24]2([C:32]3[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=3)[CH2:21][CH:20]2[C:16]2[CH:15]=[C:14]([C:12]3[CH:13]=[C:4]([CH:1]([CH3:2])[CH3:3])[CH:5]=[C:6]4[C:11]=3[N:10]=[CH:9][CH:8]=[CH:7]4)[CH:19]=[CH:18][CH:17]=2)=[CH:26][CH:27]=1
Reactant: [N-]=[N+]=C(c1ccc(Cl)cc1)c1ccc(Cl)cc1
Reactant: C=Cc1cccc(-c2cc(C(C)C)cc3cccnc23)c1
Solvent: c1ccccc1
Product: CC(C)c1cc(-c2cccc(C3CC3(c3ccc(Cl)cc3)c3ccc(Cl)cc3)c2)c2ncccc2c1
Temperature: 21 °C

Procedure:
A solution of the 6-isopropyl-8-(3-vinyl-phenyl)-quinoline from Step 3 (230 mg, 0.84 mmol) and the diazo bis-(4-chloro-phenyl)-methane from Step 2 (530 mg, 2.0 mmol) in benzene (10 mL) was heated to reflux for 18 h, cooled to 21° C., and purified by flash chromatography (eluting with hexane/ethyl acetate, 90:10) to provide the 8-{3-[2,2-bis-(4-chloro-phenyl)-cyclopropyl]-phenyl}-6-isopropyl-quinoline compound as a yellow foam.
Reaction SMILES: [Cl:1][C:2]1[CH:15]=[CH:14][C:5]([NH:6]C(OC(C)(C)C)=O)=[CH:4][CH:3]=1.[F:16][C:17]1[C:25]([F:26])=[CH:24][CH:23]=[CH:22][C:18]=1[C:19](Cl)=[O:20]>>[NH2:6][C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:15][C:14]=1[C:19]([C:18]1[CH:22]=[CH:23][CH:24]=[C:25]([F:26])[C:17]=1[F:16])=[O:20]
Reactant: CC(C)(C)OC(=O)Nc1ccc(Cl)cc1
Reactant: O=C(Cl)c1cccc(F)c1F
Product: Nc1ccc(Cl)cc1C(=O)c1cccc(F)c1F
Yield: 14 %

Procedure:
In a manner similar to that described above for compound 1aa, 4-Chloro-N-Boc-aniline and 2,3-difluoro-benzoyl chloride were converted to 1v (14% yield) MS m/z=268 (M+H).
Reaction SMILES: [C:1]([C:3](=[N:15][O:16][CH:17]([CH3:19])[CH3:18])[C:4]([N:10]1[CH:14]=[N:13][CH:12]=[N:11]1)=[N:5][O:6][CH:7]([CH3:9])[CH3:8])#[N:2].O.OO.C(=O)([O-])[O-:24].[K+].[K+]>CS(C)=O>[C:1]([C:3](=[N:15][O:16][CH:17]([CH3:19])[CH3:18])[C:4]([N:10]1[CH:14]=[N:13][CH:12]=[N:11]1)=[N:5][O:6][CH:7]([CH3:9])[CH3:8])(=[O:24])[NH2:2]
Reactant: CC(C)ON=C(C#N)C(=NOC(C)C)n1cncn1
Reactant: O=C([O-])[O-]
Agent: OO
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: CC(C)ON=C(C(N)=O)C(=NOC(C)C)n1cncn1
Temperature: 25 °C
Reaction time: 10 h
Yield: 76.9 %

Procedure:
To 2 ml of a dimethyl sulfoxide solution containing 4.0 g (15.1 mmol) of 1-(2-cyano-1,2-diisopropoxyiminoethyl)-1H-1,2,4-triazole were added, with ice-cooling, 3.5 ml of hydrogen peroxide water and 2.30 g (16.6 mmol) of potassium carbonate, followed by stirring at room temperature for 10 hours. The resulting crystal was washed with water and isopropyl ether in this order, to obtain 3.28 g (yield: 77%) of a title compound.
Reaction SMILES: C[Si](C)(C)[O:3][CH2:4][CH2:5][O:6][CH2:7][CH2:8][NH:9][C:10](=[O:13])[CH:11]=[CH2:12].CO.C(C1C=C(C)C=C(C(C)(C)C)C=1O)(C)(C)C>C(O)(=O)C>[OH:3][CH2:4][CH2:5][O:6][CH2:7][CH2:8][NH:9][C:10](=[O:13])[CH:11]=[CH2:12]
Reactant: C=CC(=O)NCCOCCO[Si](C)(C)C
Agent: Cc1cc(C(C)(C)C)c(O)c(C(C)(C)C)c1
Solvent: CO
Solvent: CC(=O)O
Product: C=CC(=O)NCCOCCO
Reaction time: 8 h

Procedure:
N-[2-(2-trimethylsiloxyethoxy)ethyl]acrylamide (73.5 g), methanol (400 g) and acetic acid (50 g) were introduced into a 1 L eggplant type flask and were mixed to a homogeneous state, after which the mixture was allowed to stand at room temperature overnight. 2,6-di-t-butyl-4-methylphenol (0.2 g) was added, after which the solvent was removed by means of a rotary vacuum evaporator (using a vacuum pump; bath temperature, 60 to 70° C.). The volatile components were removed by means of a vacuum pump under decreased pressure over a two-hour period at 70° C. and N-[2-(2-hydroxyethoxy)ethyl]acrylamide was obtained as a yellow transparent, viscous liquid.
Reaction SMILES: [NH2:1][C:2]12[CH2:9][CH2:8][C:5]([C:10]([O:12][CH2:13][CH3:14])=[O:11])([CH2:6][CH2:7]1)[CH2:4][CH2:3]2.C(N(C(C)C)CC)(C)C.Br[CH2:25][C:26]([N:28]1[CH2:32][CH2:31][CH2:30][C@H:29]1[C:33]#[N:34])=[O:27]>CN(C)C=O>[CH2:13]([O:12][C:10]([C:5]12[CH2:4][CH2:3][C:2]([NH:1][CH2:25][C:26]([N:28]3[CH2:32][CH2:31][CH2:30][C@H:29]3[C:33]#[N:34])=[O:27])([CH2:9][CH2:8]1)[CH2:7][CH2:6]2)=[O:11])[CH3:14]
Reactant: CCOC(=O)C12CCC(N)(CC1)CC2
Reactant: N#C[C@@H]1CCCN1C(=O)CBr
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CCOC(=O)C12CCC(NCC(=O)N3CCC[C@H]3C#N)(CC1)CC2
Temperature: 25 °C
Reaction time: 2 h
Yield: 51.6 %

Procedure:
Ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate (115 mg) was dissolved in N,N-dimethylformamide (1.5 mL) and diisopropylethylamine (100 μL) was added to the solution. (2S)-1-(2-Bromoacetyl)pyrrolidine-2-carbonitrile (120 mg) in N,N-dimethylformamide (1 mL) was then added dropwise at room temperature. The mixture was stirred for 2 hours at room temperature and was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluant:chloroform:methanol=10:1) to give (2S)-1-[[N-(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]pyrrolidine-2-carbonitrile (95.1 mg).
Reaction SMILES: O[C:2]1([CH2:18][CH2:19][NH:20][C:21](=[O:23])[CH3:22])[C:13]2[C:12]3[O:11][C:10]([CH3:14])=[N:9][C:8]=3[CH:7]=[CH:6][C:5]=2[CH2:4][CH:3]1[CH:15]([CH3:17])[CH3:16].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.S([O-])([O-])(=O)=O.[Mg+2]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH:15]([C:3]1[CH2:4][C:5]2[CH:6]=[CH:7][C:8]3[N:9]=[C:10]([CH3:14])[O:11][C:12]=3[C:13]=2[C:2]=1[CH2:18][CH2:19][NH:20][C:21](=[O:23])[CH3:22])([CH3:17])[CH3:16]
Reactant: CC(=O)NCCC1(O)c2c(ccc3nc(C)oc23)CC1C(C)C
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=S(=O)([O-])[O-]
Agent: [Mg+2]
Solvent: O
Solvent: CCOC(C)=O
Solvent: Cc1ccccc1
Product: CC(=O)NCCC1=C(C(C)C)Cc2ccc3nc(C)oc3c21
Temperature: 100 °C
Reaction time: 1 h
Yield: 61.2 %

Procedure:
To a solution of N-[2-(8-hydroxy-7-isopropyl-2-methyl-7,8-dihydro-6H-indeno[5,4-d][1,3]oxazol-8-yl)ethyl]acetamide (132 mg, 0.417 mmol) in toluene (4.2 mL) were added p-toluenesulfonic acid monohydrate (396 mg, 2.08 mmol) and magnesium sulfate (1 g), and the mixture was stirred at 100° C. for 1 hr. The reaction solution was diluted with ethyl acetate, washed with saturated aqueous sodium hydrogencarbonate solution and saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane=30/70→100/0) to give the title compound (76.1 mg, yield 61%).
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:9]([O:11][SiH:12]([O:16][CH2:17][CH3:18])[O:13][CH2:14][CH3:15])[CH3:10].C([Si](C=C)(C)O[Si](C)(C)C)=C>C1(C)C=CC=CC=1>[CH2:1]([Si:12]([O:16][CH2:17][CH3:18])([O:13][CH2:14][CH3:15])[O:11][CH2:9][CH3:10])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: C=Cc1ccccc1
Reactant: CCO[SiH](OCC)OCC
Agent: C=C[Si](C)(C=C)O[Si](C)(C)C
Solvent: Cc1ccccc1
Product: CCO[Si](CCc1ccccc1)(OCC)OCC
Temperature: 50 °C
Yield: 1.6 %

Procedure:
208 mg Of styrene, 328 mg of triethoxysilane, and 52 mg of toluene were placed in a glass reaction tube. Next, 0.002 ml of a toluene solution of a 0-valent platinum complex of divinyltetramethyldisiloxane (platinum content: 0.4 Wt. %) was added to this mixture. The reaction tube was sealed with a Teflon tape and heated for 1 hour in an oil bath at 50° C. When the tube contents were analyzed by GC-MS following cooling, the conversion rate of styrene was 7.4% and phenethyltriethoxysilane was produced at a yield of 1.6%. The yield of (α-methylbenzyl) triethoxysilane was 0.9%
Reaction SMILES: [C:1]([O:5][C:6](=[O:28])[CH:7]([NH:11][S:12]([C:15]1[CH:20]=[CH:19][C:18]([C:21]2[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=2)=[CH:17][CH:16]=1)(=[O:14])=[O:13])[CH:8]([CH3:10])[CH3:9])([CH3:4])([CH3:3])[CH3:2].[F:29][C:30]1[CH:35]=[CH:34][C:33]([N:36]=[C:37]=[O:38])=[CH:32][CH:31]=1.CCN(CC)CC>C(OCC)C>[C:1]([O:5][C:6](=[O:28])[CH:7]([NH:11][S:12]([C:15]1[CH:16]=[CH:17][C:18]([C:21]2[CH:22]=[CH:23][C:24]([O:27][C:37](=[O:38])[NH:36][C:33]3[CH:34]=[CH:35][C:30]([F:29])=[CH:31][CH:32]=3)=[CH:25][CH:26]=2)=[CH:19][CH:20]=1)(=[O:14])=[O:13])[CH:8]([CH3:10])[CH3:9])([CH3:3])([CH3:4])[CH3:2]
Reactant: O=C=Nc1ccc(F)cc1
Reactant: CC(C)C(NS(=O)(=O)c1ccc(-c2ccc(O)cc2)cc1)C(=O)OC(C)(C)C
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: CC(C)C(NS(=O)(=O)c1ccc(-c2ccc(OC(=O)Nc3ccc(F)cc3)cc2)cc1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 0.83 h
Yield: 57 %

Procedure:
2-(4′-Hydroxy-biphenyl-4-sulfonylamino)-3-methyl-butyric acid tert-butyl ester (300 mg, 0.74 mmol, 1 eqiv.) was dissolved in diethyl ether (7.5 mL), followed by the addition of 4-fluorophenylisocyanate (101 mg, 0.74 mmol, 1 equiv.) and Et3N (1 mL). The reaction mixture was stirred at room temperature for 50 min. Solid precipitated from the reaction mixture. Solid was collected by filtration and washed with ether to yield 2-[4′-(4-Fluoro-phenylcarbamoyloxy)-biphenyl-4-sulfonylamino]-3-methyl-butyric acid tert-butyl ester in 57% yield (228 mg).
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[N:3][C:2]=1[CH2:11][O:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=1)[CH2:16]O.CO.C(Cl)(Cl)[Cl:24]>O=S(Cl)Cl>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[N:3][C:2]=1[CH2:11][O:12][C:13]1[CH:14]=[C:15]([CH:18]=[CH:19][CH:20]=1)[CH2:16][Cl:24]
Reactant: ClC(Cl)Cl
Reactant: OCc1cccc(OCc2ncc3ccccc3n2)c1
Solvent: O=S(Cl)Cl
Solvent: CO
Product: ClCc1cccc(OCc2ncc3ccccc3n2)c1
Temperature: 25 °C
Reaction time: 15 h

Procedure:
To a solution of 1.00 g (3.76 mmol) of 3-(2-quinazolinylmethoxy)benzyl alcohol in 10 ml of CHCl3, 0.5 ml of SOCl2 was added, followed by stirring at room temperature for 15 hours. A small amount of MeOH was added to the reaction mixture and the solvents were distilled off under reduced pressure, whereby 1.08 g of 3-(2-quinazolinylmethoxy)benzyl chloride were obtained as white powder.