Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[CH2:10][N:9]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[CH2:8]2)=[O:4].[Li+].[OH-]>C1COCC1>[CH2:17]([O:16][C:14]([N:9]1[CH2:8][C:7]2[C:11](=[CH:12][CH:13]=[C:5]([C:3]([OH:4])=[O:2])[CH:6]=2)[CH2:10]1)=[O:15])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: COC(=O)c1ccc2c(c1)CN(C(=O)OCc1ccccc1)C2
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Product: O=C(O)c1ccc2c(c1)CN(C(=O)OCc1ccccc1)C2
Temperature: 25 °C
Reaction time: 14 h
Yield: 95.4 %

Procedure:
1,3-Dihydro-isoindole-2,5-dicarboxylic acid 2-benzyl ester 5-methyl ester (2.25 g) is suspended in THF (8 mL) and treated with an aqueous 2N LiOH solution. (5.51 mL) and stirred 14 h at ambient temperature. After evaporation, the residue is partitioned between dichloromethane and water. The organic phase is dried and evaporated. 2.05 g of the title compound are obtained with MP 197-199° C.
Reaction SMILES: B(Br)(Br)Br.[Br:5][C:6]1[CH:7]=[C:8]([C:20]([O:23]C)=[CH:21][N:22]=1)[C:9]([NH:11][CH2:12][C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)=[O:10].CO>C(Cl)Cl>[Br:5][C:6]1[CH:7]=[C:8]([C:20]([OH:23])=[CH:21][N:22]=1)[C:9]([NH:11][CH2:12][C:13]1[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=1)=[O:10]
Reactant: COc1cnc(Br)cc1C(=O)NCc1ccc(F)cc1
Agent: BrB(Br)Br
Solvent: CO
Solvent: ClCCl
Product: O=C(NCc1ccc(F)cc1)c1cc(Br)ncc1O
Temperature: 25 °C
Reaction time: 10 h
Yield: 93.8 %

Procedure:
BBr3 (20 mL) was added dropwise to a mixture of 2-bromo-N-(4-fluorobenzyl)-5-methoxyisonicotinamide (2.0 g, 5.9 mmol) in DCM (10 mL) at −78° C. The mixture was stirred at RT for 10 h, and then MeOH (20 mL) was added to quench the reaction. The mixture was concentrated in vacuum to give the product of compound 2-bromo-N-(4-fluorobenzyl)-5-hydroxyisonicotinamide (1.8 g, yield: 95%). 1H-NMR (DMSO-d6, 400 MHz) δ 11.9 (s, 1H), 9.35 (s, 1H), 8.16 (s, 1H), 7.90 (s, 1H), 7.38 (t, J=6.0 Hz, 2H), 7.16 (d, J=8.8 Hz, 2H), 4.78 (s, 2H). MS (M+H)+: 325/327.
Reaction SMILES: [CH2:1]([N:4]1[C:12](=[O:13])[C:11]2[N:10]=[C:9]([CH:14]([CH3:27])[CH2:15][C:16]3[CH:21]=[CH:20][C:19]([NH:22][CH2:23][C:24]([OH:26])=[O:25])=[CH:18][CH:17]=3)[NH:8][C:7]=2[N:6]([CH2:28][CH2:29][CH3:30])[C:5]1=[O:31])[CH2:2][CH3:3].S(=O)(=O)(O)O.[CH3:37]O>C(OCC)C>[CH2:1]([N:4]1[C:12](=[O:13])[C:11]2[N:10]=[C:9]([CH:14]([CH3:27])[CH2:15][C:16]3[CH:21]=[CH:20][C:19]([NH:22][CH2:23][C:24]([O:26][CH3:37])=[O:25])=[CH:18][CH:17]=3)[NH:8][C:7]=2[N:6]([CH2:28][CH2:29][CH3:30])[C:5]1=[O:31])[CH2:2][CH3:3]
Reactant: CCCn1c(=O)c2nc(C(C)Cc3ccc(NCC(=O)O)cc3)[nH]c2n(CCC)c1=O
Reactant: CO
Agent: O=S(=O)(O)O
Solvent: CCOCC
Product: CCCn1c(=O)c2nc(C(C)Cc3ccc(NCC(=O)OC)cc3)[nH]c2n(CCC)c1=O
Temperature: 60 °C

Procedure:
Dissolve 2-[4-[2-(2,3,6,9-tetrahydro-1,3-dipropyl-2,6-dioxo-1H-purin-8-yl)propyl]phenylamino]acetic acid (85.4 g, 0.2 mol) in methanol (500 mL) and treat with concentrated sulfuric acid (0.5 mL). Heat to 60° C. for 16 hours, cool and reduce the solvent by 50% in vacuo. Dilute with ethyl ether (500 mL), wash with saturated sodium hydrogen carbonate, then brine. Dry (MgSO4) and evaporate the solvent in vacuo to give the title compound.
Reaction SMILES: Cl[Sn](Cl)(Cl)Cl.[S:6]1[CH:10]=[CH:9][CH:8]=[C:7]1[CH2:11][C:12](Cl)=[O:13]>C(Cl)Cl>[S:6]1[CH:10]=[CH:9][CH:8]=[C:7]1[C:12](=[O:13])[CH2:11][C:7]1[S:6][CH:10]=[CH:9][CH:8]=1
Reactant: O=C(Cl)Cc1cccs1
Agent: Cl[Sn](Cl)(Cl)Cl
Solvent: ClCCl
Product: O=C(Cc1cccs1)c1cccs1
Yield: 80.4 %

Procedure:
SnCl4 (1.01 g, 3.94 mmol) in CH2Cl2 (5 ml) was added to 2-thiophenylacetyl chloride (6.33 g, 39.4 mmol) and thiopene (3.32 g, 39.4 mmol) in CH2Cl2 (300 ml) at room temperature. The reaction was complete (by TLC) after 3 hours. The solution was poured over a 10% aqueous HCl/ice slurry. The organic layer was separated, washed twice with H2O and dried over MgSO4. The solvent was removed under reduced pressure. The crude oil was chromatographed on SiO2 (300 g), eluting with Hexane/CH2Cl2, 1/1 to afford 30 (3.3 g, 40.5%).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[CH:6][C:7]2[O:11][C:10]([C:12]([OH:14])=O)=[CH:9][C:8]=2[CH:15]=1)([O-:3])=[O:2].Cl.Cl.[NH2:18][C@H:19]1[CH:24]2[CH2:25][CH2:26][N:21]([CH2:22][CH2:23]2)[CH2:20]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CN(C=O)C>[N:21]12[CH2:26][CH2:25][CH:24]([CH2:23][CH2:22]1)[C@H:19]([NH:18][C:12]([C:10]1[O:11][C:7]3[CH:6]=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:15][C:8]=3[CH:9]=1)=[O:14])[CH2:20]2
Reactant: O=C(O)c1cc2cc([N+](=O)[O-])ccc2o1
Reactant: N[C@@H]1CN2CCC1CC2
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(N[C@@H]1CN2CCC1CC2)c1cc2cc([N+](=O)[O-])ccc2o1

Procedure:
187 mg (0.90 mmol) of 5-nitrobenzofuran-2-carboxylic acid, 150 mg (0.75 mmol) of (S)-3-aminoquinuclidine dihydrochloride, 343.7 mg (0.90 mmol) of HATU, 350.5 mg (3.71 mmol) of N,N-diisopropylethylamine and 5 ml of DMF are reacted according to the general procedure (variant B). 169.1 mg (70% of theory) of the title compound are obtained. The analytical data correspond to those of the enantiomeric compound from example 30.
Reaction SMILES: [N:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]([NH:12][NH2:13])=O)=[CH:9][C:4]=2[NH:3][CH:2]=1.[CH2:14]([N:21]=[C:22]=[O:23])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>>[NH:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]3[N:21]([CH2:14][C:15]4[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=4)[C:22](=[O:23])[NH:13][N:12]=3)=[CH:9][C:4]=2[N:3]=[CH:2]1
Reactant: O=C=NCc1ccccc1
Reactant: NNC(=O)c1ccc2nc[nH]c2c1
Product: O=c1[nH]nc(-c2ccc3[nH]cnc3c2)n1Cc1ccccc1

Procedure:
The compound was synthesized starting from benzimidazol-5-carbohydrazide (176 mg; 1 mmol) and benzylisocyanate (0.133 g; 0.123 ml; 1 mmol); Yield: 0.077 (26%); MS m/z: 292.4 [M+H]+; 1H-NMR (DMSO d6, 400 MHz): δ 4.92 (s, 2H); 7.02-7.04 (m, 2H); 7.23-7.27 (m, 3H); 7.52 (dd, 1H, 4J=1.7 Hz, 3J=8.7 Hz); 7.76 (d, 1H, 3J=8.7 Hz); 7.81 (m, 1H); 8.99 (s, 1H), 12.08 (s, 1H); HPLC (METHOD [A]): rt 8.28 min (100%)
Reaction SMILES: [O-]CC.[Na+].CCO.[O:8]=[C:9]([NH:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[CH2:10][C:11]([O:13]CC)=[O:12].CO/[CH:25]=[CH:26]/[C:27](=O)[CH3:28]>>[CH3:25][C:26]1[N:16]([C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[C:9](=[O:8])[C:10]([C:11]([OH:13])=[O:12])=[CH:28][CH:27]=1
Reactant: CO/C=C/C(C)=O
Reactant: CCOC(=O)CC(=O)Nc1ccccc1
Agent: CC[O-]
Agent: [Na+]
Solvent: CCO
Product: Cc1ccc(C(=O)O)c(=O)n1-c1ccccc1
Yield: 27.1 %

Procedure:
To a solution of sodium ethoxide in EtOH (prepared from sodium (0.5 g, 21.75 mmol) dissolved in EtOH (40 mL)) is added ethyl 3-oxo-3-(phenylamino)propanoate (4 g, 19.30 mmol) and trans-4-methoxy-3-buten-2-one (2 g, 19.98 mmol). After the reaction is stirred at reflux overnight, the mixture is concentrated. The residue is partitioned between H2O (50 mL) and EtOAc (50 mL). The aqueous layer is acidified with concentrated HCl to a pH 3˜4 and then it is extracted with EtOAc. The organic extracts are dried and concentrated. The residue is purified by silica gel column chromatography eluting with DCM:MeOH (25:1) to give the product (1.20 g, 27% yield). MS (m/z): 230.0 (M+H).
Reaction SMILES: CO[C:3]([C:5]1[S:34][C:8]2[N:9]=[CH:10][N:11]=[C:12]([NH:13][C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][C:15]=3[O:21][C@H:22]3[CH2:27][CH2:26][CH2:25][N:24](C(=O)C(F)(F)F)[CH2:23]3)[C:7]=2[C:6]=1[CH3:35])=[O:4].[NH3:36]>CO>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([NH:13][C:12]2[C:7]3[C:6]([CH3:35])=[C:5]([C:3]([NH2:36])=[O:4])[S:34][C:8]=3[N:9]=[CH:10][N:11]=2)=[C:15]([O:21][C@H:22]2[CH2:27][CH2:26][CH2:25][NH:24][CH2:23]2)[CH:16]=1
Reactant: COC(=O)c1sc2ncnc(Nc3ccc(Cl)cc3O[C@H]3CCCN(C(=O)C(F)(F)F)C3)c2c1C
Reactant: N
Solvent: CO
Product: Cc1c(C(N)=O)sc2ncnc(Nc3ccc(Cl)cc3O[C@H]3CCCNC3)c12
Temperature: 100 °C

Procedure:
4-{4-Chloro-2-[(S)-1-(2,2,2-trifluoro-acetyl)-piperidin-3-yloxy]-phenylamino}-5-methyl-thieno[2,3-d]pyrimidine-6-carboxylic acid methyl ester (150 mg) and ammonia in methanol (7M; 5 ml) were combined and heated at 100° C. in sealed tube. The reaction heated under these conditions for 48 h. The residue was purified by chromatography tho give the inteded product.
Reaction SMILES: [NH2:1][C:2]1[N:7]([CH3:8])[C:6](=[O:9])[N:5]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[C:4](=[O:19])[C:3]=1[N:20]=O.S(S([O-])=O)([O-])=O.[Na+].[Na+]>[OH-].[NH4+].O>[NH2:20][C:3]1[C:4](=[O:19])[N:5]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[C:6](=[O:9])[N:7]([CH3:8])[C:2]=1[NH2:1]
Reactant: COc1ccc(Cn2c(=O)c(N=O)c(N)n(C)c2=O)cc1
Agent: O=S([O-])S(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: O
Product: COc1ccc(Cn2c(=O)c(N)c(N)n(C)c2=O)cc1
Reaction time: 4 h
Yield: 89.8 %

Procedure:
To a solution of 6-amino-3-(4-methoxybenzyl)-1-methyl-5-nitrosopyrimidine-2,4(1H,3H)-dione (4.1 g, 14.1 mmol) in ammonium hydroxide (100 mL, 14% wt/wt) was added sodium dithionite (4.9 g, 28.2 mmol) in small portions at 60° C., and the mixture was stirred at this temperature for 4 h. The reaction was cooled and was diluted with water. The solids were collected, rinsed with water and dried under vacuum to give 5,6-diamino-3-(4-methoxybenzyl)-1-methylpyrimidine-2,4(1H,3H)-dione (3.5 g, 89.8% yield) as a light yellow solid. LCMS retention time 0.404 min; LCMS MH+ 277.
Reaction SMILES: C([N:8]1[CH2:13][CH2:12][O:11][C@H:10]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][CH:23]3[CH2:25][CH2:24]3)=[C:17]([Cl:26])[CH:16]=2)[CH2:9]1)C1C=CC=CC=1>ClCCCl>[Cl:26][C:17]1[CH:16]=[C:15]([CH:20]=[CH:19][C:18]=1[O:21][CH2:22][CH:23]1[CH2:25][CH2:24]1)[CH2:14][C@H:10]1[O:11][CH2:12][CH2:13][NH:8][CH2:9]1
Reactant: Clc1cc(C[C@@H]2CN(Cc3ccccc3)CCO2)ccc1OCC1CC1
Solvent: ClCCCl
Product: Clc1cc(C[C@@H]2CNCCO2)ccc1OCC1CC1
Temperature: 85 °C

Procedure:
Sodium hydride (50 mg, 1.25 mmol) was washed twice with isohexane and then suspended in anhydrous N,N-dimethyl formamide (0.5 mL), under an atmosphere of nitrogen and cooled to 0° C. Then cyclopropylmethanol (90 mg, 1.25 mmol) was added. When effervescence had finished intermediate (a), N-Benzyl-(R)-2-(3-chloro-4-fluorobenzyl)morpholine (0.10 g, 0.31 mmol) was added as a solution in N,N-dimethyl formamide (1.0 mL). The reaction was then warmed to 100° C. (bath temperature) for 6 hrs and cooled to room temperature. The mixture was poured into water (25 mL) and extracted with ethyl acetate (25 mL). The organic layer was washed with brine (10 mL×2), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by column chromatography (silica; 20% ethyl acetate/isohexane) to give a residue that was added to an SCX-2 column (10 g) as a solution in dichloromethane, washed with dichloromethane (6 mL×2) and methanol (6 mL×2). The SCX-2 column was then washed with ammonia (2N in methanol, 3×6 mL). Combined ammonia washes were concentrated in vacuo to yield the desired product as colorless oil (85 mg). N-Benzyl-(R)-2-(4-cyclopropylmethoxy-3-chlorobenzyl)morpholine (82 mg, 0.22 mmol) was then dissolved in 1,2-dichloroethane (3 mL) and treated with 1-chloro-ethyl-chloroformate (94 mg, 0.66 mmol) and heated at 85° C. for 3 hrs. The reaction mixture was then concentrated in vacuo. The residue was dissolved in methanol (7 mL) and heated at 75° C. for 2.5 hrs. The reaction mixture was then concentrated in vacuo. The crude residue was dissolved in dichloromethane (1 mL) and the solution poured onto a SCX-2 column (2 g), eluting with dichloromethane (2 ml×2) and methanol (2 mL×2). The column was then washed with ammonia (2N in methanol, 2 mL×2). The ammonia washes were concentrated in vacuo. The crude residue was purified by preparative chiral HPLC to yield the desired morpholine example 27 as a yellow oil (10 mg).
Reaction SMILES: [CH:1]([O:4][CH:5]([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([CH2:20][NH:21][C:22](=[O:38])[C:23]2[CH:28]=[CH:27][C:26](B3OC(C)(C)C(C)(C)O3)=[CH:25][CH:24]=2)[CH:13]=1)[C:6]([O:8]CC)=[O:7])([CH3:3])[CH3:2].Br[C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=1>>[CH:1]([O:4][CH:5]([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([CH2:20][NH:21][C:22](=[O:38])[C:23]2[CH:24]=[CH:25][C:26]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][N:41]=3)=[CH:27][CH:28]=2)[CH:13]=1)[C:6]([OH:8])=[O:7])([CH3:3])[CH3:2]
Reactant: Brc1ccccn1
Reactant: CCOC(=O)C(Cc1ccc(OC)c(CNC(=O)c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)c1)OC(C)C
Product: COc1ccc(CC(OC(C)C)C(=O)O)cc1CNC(=O)c1ccc(-c2ccccn2)cc1

Procedure:
Using ethyl 2-isopropoxy-3-[4-methoxy-3-([4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)benzoyl]aminomethyl)phenyl]propanoate and 2-bromopyridine, 2-isopropoxy-3-[4-methoxy-3-[([4-(2-pyridyl)benzoyl]amino)methyl]phenyl)propanoic acid was obtained in the same method as in Example 285).
Reaction SMILES: N1C=CC=CC=1.C(N(C(C)C)C(C)C)C.[Cl:16][CH:17]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:18](Cl)=[O:19].[CH3:27][C:28]([NH:38][CH2:39][CH:40]=[CH2:41])([C:30]1[CH:35]=[C:34]([Cl:36])[CH:33]=[C:32]([Cl:37])[CH:31]=1)[CH3:29]>ClCCl.O>[CH3:29][C:28]([N:38]([CH2:39][CH:40]=[CH2:41])[C:18](=[O:19])[CH:17]([Cl:16])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)([C:30]1[CH:31]=[C:32]([Cl:37])[CH:33]=[C:34]([Cl:36])[CH:35]=1)[CH3:27]
Reactant: C=CCNC(C)(C)c1cc(Cl)cc(Cl)c1
Reactant: O=C(Cl)C(Cl)c1ccccc1
Solvent: O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: C=CCN(C(=O)C(Cl)c1ccccc1)C(C)(C)c1cc(Cl)cc(Cl)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 73.9 %

Procedure:
In 15 ml of dichloromethane containing 1.3 g of pyridine and 0.53 g of N-ethyldiisopropylamine, 2 ml of a dichloromethane solution containing 0.93 g of 2-chloro-2-phenylacetyl chloride were added dropwise to 1.0 g of N-[1-methyl-1-(3,5-dichlorophenyl)ethyl]-2-propenylamine at ice subzero temperature. Afterward, the solution was stirred at room temperature for 1 hour, and then poured into water, followed by extraction with ethyl acetate. The resultant extract was washed with a saturated aqueous sodium bicarbonate solution, and then dried over anhydrous magnesium sulfate. After concentration, column chromatography was done to obtain 1.2 g of the desired N-[1-methyl-1-(3,5dichlorophenyl)ethyl]-N-(2-propenyl)-2-chloro-2-phenylacetamide.
Reaction SMILES: [C:1]1([CH:7]([CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][C:18]2=[O:23])[CH2:8][C:9](=O)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(O)(=O)C.Cl>O>[C:10]1([C:9]2[CH:19]3[C:18](=[O:23])[CH:17]([CH:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[CH:8]=2)[CH2:22][CH2:21][CH2:20]3)[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: O=C(CC(c1ccccc1)C1CCCCC1=O)c1ccccc1
Agent: Cl
Solvent: CC(=O)O
Solvent: O
Product: O=C1C2CCCC1C(c1ccccc1)C=C2c1ccccc1
Temperature: 25 °C

Procedure:
Into a 1 L round bottom flask fifteen parts of 2-(α-phenyl-β-benzoylethyl)-cyclohexanone, 500 ml acetic acid and 100 mL of concentrated hydrochloric acid was added. Reaction mixture was heated under reflux for 45 hours. The hot reaction mixture was diluted with 250 ml of water (reaction mixture was cloudy). The reaction mixture was cool to room temperature to give a white solid which was filtered and dried under vacuum, to yield 11.75 g of product. The reaction proceeded as follows:
Reaction SMILES: C[O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]2[C:14](=[O:15])[NH:13][C:12](=[O:16])[NH:11][C:10]2=[O:17])=[CH:5][CH:4]=1.B(Br)(Br)Br.[OH-].[Na+]>C(Cl)Cl>[OH:2][C:3]1[CH:4]=[CH:5][C:6]([CH:9]2[C:10](=[O:17])[NH:11][C:12](=[O:16])[NH:13][C:14]2=[O:15])=[CH:7][CH:8]=1
Reactant: COc1ccc(C2C(=O)NC(=O)NC2=O)cc1
Agent: BrB(Br)Br
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: O=C1NC(=O)C(c2ccc(O)cc2)C(=O)N1
Temperature: 0 °C
Reaction time: 2 h
Yield: 103 %

Procedure:
To a suspension of 5-(4-Methoxyphenyl)barbituric Acid (222 mg) in 5 ml of methylene chloride, kept at −5/−10° C. and under nitrogen atmosphere, is dropped a solution of boron tribromide (473 μl) in 2 ml of methylene chloride. The stirring is continued for additional 2 hours at −5° C., then the temperature is brought to room temperature and stirring is continued for further 20 hours. The reaction mixture is again cooled to 0° C. with an ice bath and it is basified to pH=9-10 by adding dropwise 5% sodium hydroxide. The aqueous phase is separated, filtered through a celite plug, cooled with ice bath and acidified to pH=1 with 37% hydrochloric acid. A white solid separates which after 1 hour is separated by filtration and dried under vacuum at 60° C. to give 215 mg of the product.
Reaction SMILES: COC[O:4][C:5]1[CH:12]=[CH:11][CH:10]=[CH:9][C:6]=1[CH:7]=[O:8].C[C:14]1[CH:21]=[CH:20][CH:19]=[C:18](C)[C:15]=1[CH:16]=O.Cl>O1CCCC1>[C:5]1([C:16]([C:15]2[CH:14]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[CH:16][C:15]2[CH:18]=[CH:19][C:20]([C:7]([C:6]3[CH:9]=[CH:10][CH:11]=[CH:12][C:5]=3[OH:4])=[O:8])=[CH:21][CH:14]=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:6]=1
Reactant: Cc1cccc(C)c1C=O
Reactant: COCOc1ccccc1C=O
Agent: Cl
Solvent: C1CCOC1
Product: O=C(c1ccc(C=C(c2ccccc2)c2ccccc2)cc1)c1ccccc1O
Temperature: 25 °C
Reaction time: 12 h
Yield: 208.4 %

Procedure:
A tetrahydrofuran solution (30 mL) of the intermediate compound was prepared by the same method described in Example 6 except that 2-methoxymethoxybenzaldehyde (1.2 g) synthesized in the above-described Synthesis Example 2 was used instead of 2,6-dimethylbenzaldehyde (0.65 g). A 6 N hydrochloric acid solution (1 mL) was added to the tetrahydrofuran solution, and the mixture was stirred at 25° C. for 12 hours. After confirmation of the degree of reaction progress by TLC, the reaction was quenched with an aqueous solution of sodium hydrogen carbonate, and the organic phase was extracted with ethyl acetate. The resulting organic phase was dried over anhydrous magnesium sulfate, concentrated, and recrystallized to obtain 1.9 g (yield: 84%) of [4-(2,2-diphenylvinyl)phenyl]-(2-hydroxyphenyl)methanone (10) as yellow crystals. The structure of Product 10 was confirmed by 1H-NMR. Table 1 shows optical characteristics and practical utility of Product 10.
Reaction SMILES: [F-:1].[K+].Cl[C:4]1[C:13]2[C:8](=[C:9]([C:15]([NH:17][CH2:18][CH2:19][N:20]([CH2:23][CH3:24])[CH2:21][CH3:22])=[O:16])[CH:10]=[C:11]([I:14])[CH:12]=2)[N:7]=[CH:6][CH:5]=1>CS(C)=O>[CH2:21]([N:20]([CH2:23][CH3:24])[CH2:19][CH2:18][NH:17][C:15]([C:9]1[CH:10]=[C:11]([I:14])[CH:12]=[C:13]2[C:8]=1[N:7]=[CH:6][CH:5]=[C:4]2[F:1])=[O:16])[CH3:22]
Reactant: CCN(CC)CCNC(=O)c1cc(I)cc2c(Cl)ccnc12
Reactant: [F-]
Agent: [K+]
Solvent: CS(C)=O
Product: CCN(CC)CCNC(=O)c1cc(I)cc2c(F)ccnc12
Temperature: 200 °C
Reaction time: 3 h
Yield: 85.3 %

Procedure:
Potassium fluoride (725 mg, 12.5 mmol) was dried under vacuum and stirring, at 200° C. for 3 h. After cooling to room temperature, a solution of compound 101 (1.00 g, 2.32 mmol) in anhydrous dimethylsulfoxide (20 mL) was added. The mixture was then heated at 130° C., under argon, for 3 h. After cooling to room temperature, the solvent was evaporated under vacuum and the residue was chromatographed (Al2O3, AcOEt/cyclohexane, 9/1, v/v) to give compound 102 (821 mg, 1.98 mmol) as a yellow solid. Yield 85%; Rf (Al2O3, AcOEt/cyclohexane, 9/1, v/v) 0.42; mp 79-81° C.; IR (KBr) ν 1529, 1667, 2798, 2966, 3200-3300 cm−1; 1H NMR (200 MHz, CDCl3) δ 1.04 (t, 6H, J=7.1 Hz), 2.59 (q, 4H, J=7.1 Hz), 2.70 (t, 2H, J=6.4 Hz), 3.61 (q, 2H, J=6.4 Hz), 7.15 (dd, 1H, 3JH-F=9.2 Hz, J=5.1 Hz), 8.53 (d, 1H, J=2.1 Hz), 8.83 (dd, 1H, 4JH-F=8.4 Hz, J=5.1 Hz), 9.05 (d, 1H, J=2.1 Hz), 11.04 (m, 1H); MS m/z 415 (M+, 1), 342 (1), 299 (4), 271 (1), 173 (2), 145 (6), 118 (2), 99 (8), 86 (100), 58 (9).
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[CH:4][C:3]=1[C:11]([F:14])([F:13])[F:12]>[Ni].CO>[NH2:8][C:5]1[CH:4]=[C:3]([C:11]([F:14])([F:12])[F:13])[C:2]([I:1])=[CH:7][CH:6]=1
Reactant: O=[N+]([O-])c1ccc(I)c(C(F)(F)F)c1
Agent: [Ni]
Solvent: CO
Product: Nc1ccc(I)c(C(F)(F)F)c1

Procedure:
In the presence of 1.7 g of Raney nickel, 8.6 g (27 mmol) of 4-iodo-3-trifluoromethyl-nitro-benzene are hydrogenated in 170 ml of methanol. The reaction mixture is filtered over Celite. Concentration of the filtrate by evaporation yields the oily title compound, which slowly crystallises when left to stand: 1H NMR (CDCl3) 7.63 (d, 1H), 6.98 (d, 1H), 6.54 (dd, 1H), 5.75 (s, H2N); FAB-MS (M+H)+=288.
Reaction SMILES: NC1N(C(OC(C)(C)C)=O)N=C(C2C=CC(O[CH2:19][C:20]3[CH:25]=[CH:24][C:23]([C:26]4[S:30][C:29]([N:31]5[CH2:40][CH2:39][C:38]6[C:33](=[C:34]([C:41](=[O:60])[N:42]([C:51]7[S:52][C:53]8[CH:59]=[CH:58][CH:57]=[CH:56][C:54]=8[N:55]=7)[CH2:43][O:44][CH2:45][CH2:46][Si:47]([CH3:50])([CH3:49])[CH3:48])[CH:35]=[CH:36][CH:37]=6)[CH2:32]5)=[N:28][C:27]=4[C:61]([O:63][CH2:64][CH3:65])=[O:62])=[CH:22][CH:21]=3)=CC=2)C=1C#N.[NH2:70][C:71]1[N:75]([C:76]([O:78][C:79]([CH3:82])([CH3:81])[CH3:80])=[O:77])[N:74]=[C:73]([C:83]2[CH:88]=[CH:87][CH:86]=[C:85]([OH:89])[CH:84]=2)[C:72]=1[C:90]#[N:91]>>[NH2:70][C:71]1[N:75]([C:76]([O:78][C:79]([CH3:82])([CH3:81])[CH3:80])=[O:77])[N:74]=[C:73]([C:83]2[CH:84]=[C:85]([CH:86]=[CH:87][CH:88]=2)[O:89][CH2:19][C:20]2[CH:21]=[CH:22][C:23]([C:26]3[S:30][C:29]([N:31]4[CH2:40][CH2:39][C:38]5[C:33](=[C:34]([C:41](=[O:60])[N:42]([C:51]6[S:52][C:53]7[CH:59]=[CH:58][CH:57]=[CH:56][C:54]=7[N:55]=6)[CH2:43][O:44][CH2:45][CH2:46][Si:47]([CH3:48])([CH3:49])[CH3:50])[CH:35]=[CH:36][CH:37]=5)[CH2:32]4)=[N:28][C:27]=3[C:61]([O:63][CH2:64][CH3:65])=[O:62])=[CH:24][CH:25]=2)[C:72]=1[C:90]#[N:91]
Reactant: CC(C)(C)OC(=O)n1nc(-c2cccc(O)c2)c(C#N)c1N
Reactant: CCOC(=O)c1nc(N2CCc3cccc(C(=O)N(COCC[Si](C)(C)C)c4nc5ccccc5s4)c3C2)sc1-c1ccc(COc2ccc(-c3nn(C(=O)OC(C)(C)C)c(N)c3C#N)cc2)cc1
Product: CCOC(=O)c1nc(N2CCc3cccc(C(=O)N(COCC[Si](C)(C)C)c4nc5ccccc5s4)c3C2)sc1-c1ccc(COc2cccc(-c3nn(C(=O)OC(C)(C)C)c(N)c3C#N)c2)cc1

Procedure:
The title compound 37A was prepared in a similar manner to the synthesis of compound 35A by substituting compound 31F with compound 36A as a mixture of two inseparable isomers: MS (ESI(+)): m/z 984 (M+H).
Reaction SMILES: C(=O)C1C=CC=CC=1.[O:9]1[C:13]2([CH2:18][CH2:17][N:16]([C:19]3[CH:26]=[CH:25][C:22]([CH:23]=O)=[CH:21][CH:20]=3)[CH2:15][CH2:14]2)[O:12][CH2:11][CH2:10]1.COC1C=CC(/C=[C:42]2/[C:43]([NH:45][C:46]([S:48]/2)=[NH:47])=[O:44])=CC=1OC1CCCC1>>[O:9]1[C:13]2([CH2:18][CH2:17][N:16]([C:19]3[CH:26]=[CH:25][C:22]([CH:23]=[C:42]4[S:48][C:46](=[NH:47])[NH:45][C:43]4=[O:44])=[CH:21][CH:20]=3)[CH2:15][CH2:14]2)[O:12][CH2:11][CH2:10]1
Reactant: COc1ccc(/C=C2\SC(=N)NC2=O)cc1OC1CCCC1
Reactant: O=Cc1ccc(N2CCC3(CC2)OCCO3)cc1
Solvent: O=Cc1ccccc1
Product: N=C1NC(=O)C(=Cc2ccc(N3CCC4(CC3)OCCO4)cc2)S1

Procedure:
The title compound was prepared from 4-(1,4-dioxa-8-aza-spiro[4.5]dec-8-yl)-benzaldehyde benzaldehyde (Taylor, E. C., Strotnicki, J. S. Synthesis, 1981, 606) and pseudothiohydantoin according to the procedure of Example 35 as an orange solid; 1H NMR (300 MHz, DMSO-d6) δ 1.68 (t, J=5.6 Hz, 4 H), 3.43 (t, J=5.6 Hz, 4 H), 3.91 (s, 4 H), 7.06 (d, J=8.9 Hz, 2 H), 7.41 (d, J=8.9 Hz, 2 H), 7.48 (s, 1 H), 8.99 (brs, 1 H), 9.33 (brs, 1 H); MS (ES) m/z: 345.9 (MH+); HRMS Calcd. for C17H20N3O3S (MH+): 346.1226. Found: 346.1205. Anal. Calcd. for C17H19N3O3S: C, 59.11; H, 5.54; N, 12.16. Found: C, 58.80; H, 5.71; N, 12.38.
Reaction SMILES: [C:1]([O:7][CH2:8][CH:9]=[CH2:10])(=[O:6])[CH2:2][CH2:3][CH2:4][CH3:5].[CH3:11][O:12][SiH:13]([O:16][CH3:17])[O:14][CH3:15]>[Pt]>[C:1]([O:7][CH2:8][CH2:9][CH2:10][Si:13]([O:16][CH3:17])([O:14][CH3:15])[O:12][CH3:11])(=[O:6])[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: CO[SiH](OC)OC
Reactant: C=CCOC(=O)CCCC
Agent: [Pt]
Product: CCCCC(=O)OCCC[Si](OC)(OC)OC
Yield: 76.8 %

Procedure:
A stirrer bar was put into a 50 ml two-mouth eggplant flask equipped with a thermometer and a calcium chloride tube. The flask was charged with 5.13 g (40 mmol) of allyl valerate (manufactured by Aldrich Co.) and 0.2 g of a platinum catalyst (“BY 24-835” manufactured by a Toray-Dow Corning Co.). Then, 4.89 g (40 mmol) of trimethoxysilane (manufactured by Tokyo Kasei Kogyo Co., Ltd.) was added while stirring and controlling the temperature at 50° C. or less. After further addition of 0.2 g of the platinum catalyst, the mixture was reacted at room temperature for six hours. After completion of the reaction, the reaction mixture was distilled under reduced pressure using a Kugelrohr distillation apparatus to obtain 8.12 g of 3-trimethoxysilylpropyl valerate of the silane compound (1).