Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:18](=O)[C:19]#[CH:20])=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[N:10]=2)[CH:7]=1.Cl.[CH:23]1([NH:28][C:29]([NH2:31])=[NH:30])[CH2:27][CH2:26][CH2:25][CH2:24]1.C(=O)([O-])[O-]>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:18]3[CH:19]=[CH:20][N:31]=[C:29]([NH:28][CH:23]4[CH2:27][CH2:26][CH2:25][CH2:24]4)[N:30]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=3)[N:10]=2)[CH:7]=1
Reactant: N=C(N)NC1CCCC1
Reactant: C#CC(=O)c1c(-c2ccc(F)cc2)nc2ccc(Br)cn12
Agent: Cl
Agent: O=C([O-])[O-]
Product: Fc1ccc(-c2nc3ccc(Br)cn3c2-c2ccnc(NC3CCCC3)n2)cc1
Yield: 61 %

Procedure:
In a similar manner as described in Example 2 from 1-[6-bromo-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl]-2-propyn-1-one (1.0 g, 2.9 mmol), cyclopentylguanidine hydrochloride (0.71 g, 4.4 mmol) and anhydrous carbonate (0.6 g, 4.4 mmol), was obtained N-{4-[6-bromo-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-3-yl]-2-pyrimidinyl}-N-cyclopentylamine (0.8 g, 61%) as a solid. 1H NMR (CDCl3) δ 10.0 (broad s, 1H), 8.13 (d, 1H), 7.65 (m, 3H), 7.44 (dd, 1H), 7.17 (t, 2H), 6.45 (s, 1H), 5.30 (d, 1H), 4.40 (m, 1H), 2.1 (m, 2H), 1.4–2.0 (m, 6H); 19F NMR (CDCl3) δ −112.8; MS m/z 452 (M+1).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:4]=[C:5]([C:11](=O)[CH2:12][CH3:13])[CH:6]=[C:7]([I:10])[C:8]=1[OH:9].Cl.[CH3:16][O:17][NH2:18].C>N1C=CC=CC=1.C(O)C>[CH3:16][O:17][N:18]=[C:11]([C:5]1[CH:6]=[C:7]([I:10])[C:8]([OH:9])=[C:3]([CH2:2][NH2:1])[CH:4]=1)[CH2:12][CH3:13]
Reactant: CON
Reactant: CCC(=O)c1cc(I)c(O)c(CN)c1
Agent: Cl
Solvent: CCO
Solvent: c1ccncc1
Product: CCC(=NOC)c1cc(I)c(O)c(CN)c1
Yield: 54.8 %

Procedure:
To a solution of 2.0 g of 3'-aminomethyl-4'-hydroxy5'-iodopropiophenone in 15 ml of pyridine and 7 ml of ethanol is added 1.4 g of O-methylhydroxylamine hydrochloride, and the mixture is refluxed with heating for 45 minutes. The reaction mixture is treated with activated charcoal and filtered. The filtrate is concentrated under reduced pressure and to the residue is added ice-cold water. To the mixture is added 1.4 g of sodium hydrogencarbonate and stirred. The precipitated crystals are collected by filtration, washed with water and then recrystallized from methanol to give 1.2 g of 3'-aminomethyl-4'-hydroxy-5'-iodopropiophenone O-methyloxime, melting at 156°-157° C. with decomposition.
Reaction SMILES: [C:1]([NH:9][CH:10]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([NH:23][S:24]([C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([N+:33]([O-])=O)[CH:28]=2)(=[O:26])=[O:25])[CH:18]=1)[CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Sn](Cl)Cl>>[NH2:33][C:29]1[CH:28]=[C:27]([S:24]([NH:23][C:19]2[CH:18]=[C:17]([CH:10]([NH:9][C:1](=[O:8])[C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:22]=[CH:21][CH:20]=2)(=[O:25])=[O:26])[CH:32]=[CH:31][CH:30]=1
Reactant: CCOC(=O)CC(NC(=O)c1ccccc1)c1cccc(NS(=O)(=O)c2cccc([N+](=O)[O-])c2)c1
Agent: Cl[Sn]Cl
Product: CCOC(=O)CC(NC(=O)c1ccccc1)c1cccc(NS(=O)(=O)c2cccc(N)c2)c1

Procedure:
Corresponding to Example 3d, 1.76 g of (4c) were treated with tin-(II) chloride. A yellowish solid was obtained (yield: 779 mg).
Reaction SMILES: [F:1][C:2]1([F:24])[CH2:8][O:7][C:6]2[CH:9]=[CH:10][C:11](I)=[CH:12][C:5]=2[N:4]2[N:14]=[C:15]([C:21]([NH2:23])=[O:22])[C:16]([C:17]([F:20])([F:19])[F:18])=[C:3]12.[C:25]([C@:27]1([OH:34])[CH2:31][CH2:30][N:29]([CH3:32])[C:28]1=[O:33])#[CH:26]>>[F:1][C:2]1([F:24])[CH2:8][O:7][C:6]2[CH:9]=[CH:10][C:11]([C:26]#[C:25][C@:27]3([OH:34])[CH2:31][CH2:30][N:29]([CH3:32])[C:28]3=[O:33])=[CH:12][C:5]=2[N:4]2[N:14]=[C:15]([C:21]([NH2:23])=[O:22])[C:16]([C:17]([F:20])([F:19])[F:18])=[C:3]12
Reactant: C#C[C@]1(O)CCN(C)C1=O
Reactant: NC(=O)c1nn2c(c1C(F)(F)F)C(F)(F)COc1ccc(I)cc1-2
Product: CN1CC[C@@](O)(C#Cc2ccc3c(c2)-n2nc(C(N)=O)c(C(F)(F)F)c2C(F)(F)CO3)C1=O

Procedure:
Similar to as described in General Procedure G, 4,4-difluoro-9-iodo-3-(trifluoromethyl)-4,5-dihydrobenzo[b]pyrazolo[1,5-d][1,4]oxazepine-2-carboxamide was reacted with (R)-3-ethynyl-3-hydroxy-1-methylpyrrolidin-2-one to give a titled compound after purification by HPLC.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:32]=[CH:33][C:34]=1[Cl:35])[CH2:5][NH:6][C:7]([C:9]1[N:10]=[C:11]2[N:19]([CH2:20][CH2:21][N:22]3[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]3)[C:18]3[CH:28]=[CH:29][CH:30]=[CH:31][C:17]=3[N:12]2[C:13](=[O:16])[C:14]=1[OH:15])=[O:8].C(N(CC)CC)C.[S:43](Cl)([CH3:46])(=[O:45])=[O:44]>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([CH:32]=[CH:33][C:34]=1[Cl:35])[CH2:5][NH:6][C:7]([C:9]1[N:10]=[C:11]2[N:19]([CH2:20][CH2:21][N:22]3[CH2:23][CH2:24][N:25]([S:43]([CH3:46])(=[O:45])=[O:44])[CH2:26][CH2:27]3)[C:18]3[CH:28]=[CH:29][CH:30]=[CH:31][C:17]=3[N:12]2[C:13](=[O:16])[C:14]=1[O:15][S:43]([CH3:46])(=[O:45])=[O:44])=[O:8]
Reactant: CS(=O)(=O)Cl
Reactant: O=C(NCc1ccc(Cl)c(Cl)c1)c1nc2n(CCN3CCNCC3)c3ccccc3n2c(=O)c1O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)Oc1c(C(=O)NCc2ccc(Cl)c(Cl)c2)nc2n(CCN3CCN(S(C)(=O)=O)CC3)c3ccccc3n2c1=O
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 66.3 %

Procedure:
3-Hydroxy-4-oxo-10-(2-piperazin-1-yl-ethyl)-4,10-dihydro-benzo[4,5]imidazo[1,2-a]pyrimidine-2-carboxylic acid, 3,4-dichloro-benzylamide (Example 15.5) (75 mg, 0.146 mmol) and triethylamine (60 μL, 0.31 mmol) were dissolved in dichloromethane (1 mL) and to this was added mesyl chloride (18 μL, 0.31 mmol). The reaction was stirred at room temperature for 15 minutes after which time the solvents were concentrated in vacuo and the residue purified by column chromatography (95:4.5:0.5 dichloromethane:methanol:aqueous ammonia) to afford the desired product (65 mg, 76%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:11])=[C:6]([CH:10]=1)[C:7]([OH:9])=O.CN(C=O)C.C(Cl)(=O)C(Cl)=O.[CH:23]1([NH2:26])[CH2:25][CH2:24]1.CCN(C(C)C)C(C)C>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:11])=[C:6]([CH:10]=1)[C:7]([NH:26][CH:23]1[CH2:25][CH2:24]1)=[O:9]
Reactant: NC1CC1
Reactant: O=C(O)c1cc(Br)ccc1Cl
Agent: O=C(Cl)C(=O)Cl
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(NC1CC1)c1cc(Br)ccc1Cl
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a toluene solution (1 M) of 5-bromo-2-chlorobenzoic acid (1 eq.) and DMF (1.2 eq.) was added at 0° C. oxalyl chloride (1.2 eq.) dropwise over 1 h. The resulting solution was stirred at 0° C. for 2 h before the volatiles were removed in vacuo. The resulting residue was taken up in dichloromethane (1 M), cooled to 0° C. and added sequentially cyclopropylamine (1.5 eq.) and Hunig's base (2 eq.) dropwise over 1 h. The resulting suspension was stirred at RT for 18 h. The reaction was quenched with 1 N HCl and extracted with dichloromethane. The combined organic extracts were dried over MgSO4, filtered and the filtrate concentrated in vacuo to ˜⅓ in volume. The resulting white suspension was added an equivalent volume of hexanes and the title compound was isolated via vacuum filtration.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:22])[C:9]([N:19]([CH3:21])[CH3:20])([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:10][CH3:11])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH3:29][NH:30][CH3:31]>CN(C)C=O>[CH3:29][N:30]([CH3:31])[C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:22])[C:9]([N:19]([CH3:21])[CH3:20])([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:10][CH3:11])=[CH:4][CH:3]=1
Reactant: CNC
Reactant: CCC(Cc1ccccc1)(C(=O)c1ccc(F)cc1)N(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCC(Cc1ccccc1)(C(=O)c1ccc(N(C)C)cc1)N(C)C
Reaction time: 24 h

Procedure:
A stirred autoclave is filled with 50 g (0.167 mol) of 1-(4-fluorophenyl)-2-dimethylamino-2-benzylbutan-1-one (crude product from B), 300 ml of dimethylformamide and 23.1 g (0.167 mol) of potassium carbonate. 22.6 g (0.5 mol) of dimethylamine are then added under pressure (3-4 bar). The mixture is heated to 100° and stirred at this temperature for 24 hours.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[O:17][C:18]4[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=4[N:20]=3)=[CH:12][C:11]=2[N+:25]([O-])=O)=[CH:5][CH:4]=1.[H][H].[C:30](Cl)(=O)[CH3:31].C(=O)([O-])O.[Na+]>[C].[Pd].O1CCCC1>[O:17]1[C:18]2[CH:24]=[CH:23][CH:22]=[CH:21][C:19]=2[N:20]=[C:16]1[C:13]1[CH:14]=[CH:15][C:10]2[N:9]([C:6]3[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[C:30]([CH3:31])=[N:25][C:11]=2[CH:12]=1
Reactant: COc1ccc(Nc2ccc(-c3nc4ccccc4o3)cc2[N+](=O)[O-])cc1
Reactant: CC(=O)Cl
Reactant: [H][H]
Agent: [Pd]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1ccc(-n2c(C)nc3cc(-c4nc5ccccc5o4)ccc32)cc1
Temperature: 25 °C
Reaction time: 3 h
Yield: 31.9 %

Procedure:
2-(4-(4-methoxyphenylamino)-3-nitrophenyl)benzoxazole (Working Example 15-3) (150 mg, 0.415 mmol) was added to a tetrahydrofuran (5 mL) solution containing 10% palladium-carbon (50 mg), and a hydrogen atmosphere was substituted in the flask and this was stirred at room temperature for 3 hours. After the reaction was complete, this was filtered through Celite and the filtrate was concentrated. To a solution of the oil obtained in toluene (5 mL) was added acetyl chloride (70.8 mg, 0.902 mmol), and this was heated to reflux with stirring for 2.5 hours. After the reaction was complete, this was cooled to room temperature, saturated aqueous sodium hydrogen carbonate solution was added, and this was extracted with ethyl acetate. The organic layer obtained was dried over anhydrous sodium sulfate, filtered, and concentrated to give crystals that were purified by silica gel column chromatography to yield the title compound (47 mg, 32% yield) as dark brown crystals.
Reaction SMILES: C(OC([N:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1)=O)(C)(C)C.CN([CH:16]=[O:17])C.[H-].[Na+].[Cl:20][C:21]1[CH:26]=[CH:25][CH:24]=[C:23](F)[C:22]=1[Cl:28]>>[Cl:20][C:21]1[C:22]([Cl:28])=[CH:23][CH:24]=[CH:25][C:26]=1[O:17][C@@H:16]([C@H:11]1[CH2:10][CH2:9][NH:8][CH2:12]1)[CH:21]([CH2:26][CH3:25])[CH2:22][CH3:23]
Reactant: CN(C)C=O
Reactant: CC(C)(C)OC(=O)N1CCCC1
Reactant: Fc1cccc(Cl)c1Cl
Agent: [H-]
Agent: [Na+]
Product: CCC(CC)[C@@H](Oc1cccc(Cl)c1Cl)[C@H]1CCNC1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
(S)-3-(R)-2-Ethyl-1-hydroxybutyl)pyrrolidine-1-carboxylic acid t-butyl ester (28 mg, 0.1 mmol) was dissolved in DMF (380 μL, 4.9 mmol). 60% Sodium hydride in oil (0.4:0.6, sodium hydride:mineral oil, 18.6 mg, 310 μmmol) was slowly added, and the resulting mixture was stirred at room temperature for 15 minutes. 1,2-Dichloro-3-fluorobenzene (23.8 μL, 206 μmmol) was added and the mixture was stirred at 70° C. for 3 hours. The mixture was concentrated, treated with 1.25M HCl in EtOH (578 μL, 722 μmmol), then stirred overnight at room temperature. The product was concentrated under vacuum, redissolved in 1:1AcOH:H2O, filtered, and purified by preparative HPLC to yield the title compound as a mono-TFA salt (5.3 mg, 97% purity). MS m/z: [M+H]+ calcd for C16H23Cl2NO, 316.12; found 316.3.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17](=[S:19])[NH2:18])=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Br[CH2:21][C:22](=O)[C:23]([O:25][CH2:26][CH3:27])=[O:24]>CCO>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([C:17]3[S:19][CH:21]=[C:22]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[N:18]=3)=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CCOC(=O)C(=O)CBr
Reactant: CC(C)(C)OC(=O)n1ccc2cc(C(N)=S)ccc21
Solvent: CCO
Product: CCOC(=O)c1csc(-c2ccc3c(ccn3C(=O)OC(C)(C)C)c2)n1
Temperature: 60 °C
Reaction time: 1.5 h

Procedure:
To a solution of 5-thiocarbamoyl-indole-1-carboxylic acid tert-butyl ester (13.16 g, 47.6 mmol) and 250 mL of EtOH was added ethyl bromopyruvate (6.05 mL, 48.2 mmol). The resulting solution was stirred at 60° C. for 1.5 h, then concentrated in vacuo. The resulting solid was purified by flash chromatography on silica gel using 5% EtOAc/hexane→80% EtOAc/hexane→CH2Cl2 as the eluant to give a white solid. MS m/z: 373 (M+1). Calc'd for C19H20N2O4S-372.44.
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][C:11](=[O:14])[CH:10]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[Cl:21])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Br:22]Br>C(Cl)(Cl)Cl>[BrH:22].[Br:22][CH:12]1[CH2:13][N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:9][CH:10]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[Cl:21])[C:11]1=[O:14]
Reactant: O=C1CCN(Cc2ccccc2)CC1c1ccccc1Cl
Reactant: BrBr
Solvent: ClC(Cl)Cl
Product: Br
Product: O=C1C(Br)CN(Cc2ccccc2)CC1c1ccccc1Cl
Temperature: 50 °C
Reaction time: 1 h
Yield: 202.7 %

Procedure:
Benzyl-3-(2-chloro-phenyl)-piperidin-4-one (100 mg, 0.33 mmol) was dissolved in chloroform (1 mL). To this solution bromine (66 mg, 0.35 mmol) in chloroform (0.5 mL) was added drop wise at −11° C. The reaction was stirred for 1½ hours at 5° C., for 1 hour at room temperature and for 1 hours at 50° C. The solvent was removed under reduced pressure to yield the crude title compound (163 mg) which was used directly in the next step without further purification.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)(=[O:3])[CH3:2].[NH:10]([CH3:12])[CH3:11].Cl.[CH3:14]CO>>[CH3:11][N:10]([CH3:14])[CH2:12][CH2:2][C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[O:3]
Reactant: CC(=O)c1ccccc1
Reactant: CNC
Reactant: CCO
Agent: Cl
Product: CN(C)CCC(=O)c1ccccc1
Yield: 40 %

Procedure:
The solution of acetophenone (30 g, 0.25 mol) and Me2NH.HCl (0.28 mol) in EtOH (400 mL) was heated at 70° C. overnight. The resulting mixture was concentrated and the residue was washed with EtOAc to give 3-(dimethylamino)-1-phenylpropan-1-one (17.7 g, 40%). 1H NMR (400 MHz, CDCl3): δ=2.36 (m, 6H), 2.74 (m, 2H), 3.14 (m, 2H), 7.43 (m, 2H), 7.52 (m, 1H), 7.94 (m, 2H).
Reaction SMILES: [NH:1]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:2][CH2:3][C:4](CCl)=[O:5].[Na+].[I-].O.[SH:18][C:19]1[N:27]=[CH:26][N:25]=[C:24]2[C:20]=1[NH:21][CH:22]=[N:23]2.C([O-])([O-])=[O:29].[Ca+2]>CC(C)=O.CN(C=O)C>[NH:1]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:2][CH2:3][C:4]([OH:5])=[O:29].[CH:22]1[NH:21][C:20]2[C:19]([N:27]=[CH:26][NH:25][C:24]=2[N:23]=1)=[S:18]
Reactant: O=C([O-])[O-]
Reactant: Sc1ncnc2nc[nH]c12
Reactant: CC(C)(C)OC(=O)NCCC(=O)CCl
Agent: [Ca+2]
Agent: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)NCCC(=O)O
Product: S=c1nc[nH]c2nc[nH]c12
Temperature: 25 °C
Reaction time: 1 h
Yield: 28.5 %

Procedure:
A suspension of (13) (1.0 g, 4.2 mmol) and NaI (0.755 g, 5.04 mmol) in acetone (15 mL) was stirred for 1 hour at room temperature, followed by addition of a solution of (1) (0.595 g, 3.5 mmol) and CaCO3 (1.738 g, 17.4 mmol) in DMF (15 mL). The mixture was stirred at room temperature overnight, followed by filtration. The filtrate was concentrated in vacuo and the residue dissolved in EtOAc (100 mL), washed with water (100 mL), brine (100 mL), and dried over anhydrous MgSO4. The solvent was removed in vacuo and the residue purified by silica gel column chromatography (0 to 5% MeOH in CHCl3, v/v) to give 340 mg (28.6%) of product (14): 13C NMR (CDCl3+CD3OD) δ 28.429 (3×CH3 of Boc), 34.868 (CH2C(═O)O), 36.109 (NHCH2CH2), 61.223 (OCH2S), 81.537 (C(CH3)3), 142.901 (Ar—C), 145.640 (Ar—C), 148.623 (Ar—C), 149.749 (Ar—C), 152.181 (Ar—C), 156.738 (NHC(═O)O), 172.431 (C(═O)O).
Reaction SMILES: Cl.FC1[CH:4]=[C:5]([C:9]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25](F)[CH:24]=2)=[CH:10][O:11][CH2:12][CH2:13][N:14]2[CH2:19][CH2:18][CH:17]=[C:16]([C:20]([OH:22])=[O:21])[CH2:15]2)[CH:6]=[CH:7][CH:8]=1.[OH-].[Na+].Cl.[Cl:33][CH2:34][Cl:35].[CH2:36](O)C>>[ClH:33].[Cl:35][C:34]1[CH:4]=[C:5](/[C:9](/[C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][C:28]=2[CH3:36])=[CH:10]/[O:11][CH2:12][CH2:13][N:14]2[CH2:19][CH2:18][CH:17]=[C:16]([C:20]([OH:22])=[O:21])[CH2:15]2)[CH:6]=[CH:7][CH:8]=1
Reactant: O=C(O)C1=CCCN(CCOC=C(c2cccc(F)c2)c2cccc(F)c2)C1
Reactant: CCO
Reactant: ClCCl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Product: Cc1ccccc1/C(=C\OCCN1CCC=C(C(=O)O)C1)c1cccc(Cl)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 30 %

Procedure:
E or Z-1-[2-[[2-(3-Chlorophenyl)-2-(2-methylphenyl)ethenyl]oxy]ethyl]-1,2, 5,6-tetrahydro-3-pyridine carboxylic acid methyl ester (0.55 g, 0.0013 mol) (prepared as described in Method D) was dissolved in ethanol (5 ml) and 12 N sodium hydroxide solution (0.33 ml) was introduced. After stirring the solution at room temperature for 3 h, 37% hydrochloric acid solution was added until the pH was measured as ca. 1. Dichloromethane (200 ml) was introduced, and the mixture was dried (Na2SO4), filtered and evaporated to a residue, which was co-evaporated twice with acetone. Recrystallization from acetone/ethyl acetate provided the title compound (0.17 g, 30%) as a white solid, m.p. 214°-215°.
Reaction SMILES: [C:1]1(/[CH:7]=[CH:8]/[C:9]2[O:10][CH:11]=[C:12]([CH2:14][O:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[CH2:22][CH2:23][CH2:24][OH:25])[N:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:26][S:27](Cl)(=[O:29])=[O:28]>>[CH3:26][S:27]([O:25][CH2:24][CH2:23][CH2:22][C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][C:16]=1[O:15][CH2:14][C:12]1[N:13]=[C:9](/[CH:8]=[CH:7]/[C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[O:10][CH:11]=1)(=[O:29])=[O:28]
Reactant: OCCCc1ccccc1OCc1coc(/C=C/c2ccccc2)n1
Reactant: CS(=O)(=O)Cl
Product: CS(=O)(=O)OCCCc1ccccc1OCc1coc(/C=C/c2ccccc2)n1
Yield: 95 %

Procedure:
In substantially the same manner as in Reference Example 12, 3-[2-[2-[(E)-2-phenylethenyl]-4-oxazolylmethoxy]phenyl]propanol was allowed to react with methanesulfonyl chloride to give 3-[2-[2-[(E)-2-phenylethenyl]-4-oxazolylmethoxy]phenyl]propyl methanesulfonate. The yield was 95%. Recrystallization from ethyl acetate-hexane gave colorless prisms, mp 93-94° C.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].[NH2:12][CH2:13][CH2:14][CH2:15][OH:16]>C(O)CCC>[CH3:8][C:5]1[CH:6]=[CH:7][C:2]([NH:12][CH2:13][CH2:14][CH2:15][OH:16])=[C:3]([N+:9]([O-:11])=[O:10])[CH:4]=1
Reactant: NCCCO
Reactant: Cc1ccc(Cl)c([N+](=O)[O-])c1
Solvent: CCCCO
Product: Cc1ccc(NCCCO)c([N+](=O)[O-])c1
Yield: 33 %

Procedure:
A mixture of 171 parts of 1-chloro-4-methyl-2-nitrobenzene, 150 parts of 3-amino-1-propanol and 400 parts of butanol is stirred and refluxed for 30 hours. The reaction mixture is evaporated and the residue is poured onto water. The product is extracted with methylbenzene. The extract is washed with water and with a hydrochloric acid solution 2N, dried, filtered and evaporated. The residue is purified by columnchromatography over silica gel using a mixture of trichloromethane and 5% of methanol as eluent. The pure fractions are collected and the eluent is evaporated, yielding 70 parts (33%) of 3-[(4-methyl-2-nitrophenyl)amino]-1-propanol as a residue.
Reaction SMILES: [Cl:1][C:2]1[C:15]2[C:14](=O)[C:13]3[C:8](=[C:9]([Cl:17])[CH:10]=[CH:11][CH:12]=3)[C:7](=O)[C:6]=2[CH:5]=[CH:4][CH:3]=1.I.O.CO>C(O)(=O)C>[Cl:1][C:2]1[C:15]2[CH2:14][C:13]3[C:8](=[C:9]([Cl:17])[CH:10]=[CH:11][CH:12]=3)[CH2:7][C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: O=C1c2cccc(Cl)c2C(=O)c2cccc(Cl)c21
Agent: I
Solvent: O
Solvent: CO
Solvent: CC(=O)O
Product: Clc1cccc2c1Cc1cccc(Cl)c1C2
Temperature: 25 °C

Procedure:
A mixture of 1,5-dichloro anthraquinone (49, 10 g, 36 mmol), red phosphorous (4.5 g, 145 mmol) and hydroiodic acid (47+%, 70 ml) in 470 ml of glacial acetic acid was refluxed under N2 for 4 days. The resulting mixture was cooled to room temperature and poured into 1 L of water to precipitate a violet colored solid. The solid was collected by filtration, dissolved in 800 ml of CH2Cl2, and filtered again. The filtrate was washed once with 100 ml of H2O, dried over Na2SO4 and concentrated under vacuum to yield the yellow colored, crude solid product. Methanol (100 ml) was added to this solid product and filtered again to collect white needles of the desired product (7.2 g, 80%). 1H NMR (300 MHz, CDCl3): δ 4.10 (s, 4H), 7.12-7.25 (m, 6H). 13C NMR (300 MHz, CDCl3): δ 32.93, 126.50, 127.13, 127.20, 133.15, 137.16.
Reaction SMILES: [C:1]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17](O)=[O:18])=[CH:13][C:12]=1[N+:20]([O-:22])=[O:21])(=[O:8])[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.S(Cl)([Cl:25])=O>CN(C)C=O>[ClH:25].[C:1]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([Cl:25])=[O:18])=[CH:13][C:12]=1[N+:20]([O-:22])=[O:21])(=[O:8])[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1
Reactant: O=S(Cl)Cl
Reactant: O=C(O)c1ccc(COC(=O)c2ccncc2)c([N+](=O)[O-])c1
Solvent: CN(C)C=O
Product: Cl
Product: O=C(Cl)c1ccc(COC(=O)c2ccncc2)c([N+](=O)[O-])c1

Procedure:
The 4-carboxy-2-nitrobenzyl isonicotinate (C) was treated with excess thionyl chloride and a few drops of dimethylformamide at room temperature for 45 minutes, followed by rotary evaporation to remove thionyl chloride and azeotropic removal of thionyl chloride by 3 additions of toluene followed by rotary evaporation to give 4-chlorocarbonyl-2-nitrobenzyl isonicotinate hydrochloride (D). The 4-chlorocarbonyl-2-nitrobenzyl isonicotinate hydrochloride (D) and excess triethylamine were dissolved in chloroform and cooled in an ice/acetone bath. A chloroform solution of 3-aminopropyltriethoxysilane was added dropwise and the reaction was allowed to warm to room temperature and stirred for 4 hours. The solvents were removed by rotary evaporation. The resultant mixture was treated with ether and filtered to remove salts. The filtrate was rotary evaporated and purified by flash chromatography on silica gel using ethyl acetate as the eluent to yield 4-[N-(3-triethoxysilyl)propyl]carbamoyl-2-nitrobenzyl isonicotinate.
Reaction SMILES: FC(F)(F)C1C=CC=C(C(F)(F)F)C=1.[Br:15][C:16]1[CH:17]=[C:18]([CH:22]=[CH:23][C:24]=1[O:25][C:26]([F:29])([F:28])[F:27])[C:19](Cl)=[O:20].[H][H]>O>[Br:15][C:16]1[CH:17]=[C:18]([CH:22]=[CH:23][C:24]=1[O:25][C:26]([F:27])([F:28])[F:29])[CH:19]=[O:20]
Reactant: [H][H]
Reactant: O=C(Cl)c1ccc(OC(F)(F)F)c(Br)c1
Agent: FC(F)(F)c1cccc(C(F)(F)F)c1
Solvent: O
Product: O=Cc1ccc(OC(F)(F)F)c(Br)c1
Temperature: 105 °C
Yield: 74 %

Procedure:
0.5 g of 5% palladium on barium sulfate (recovered from Example 1) and 48 g of 3-bromo-4-trifluoromethoxybenzoyl chloride were placed in a reaction vessel at room temperature with exclusion of water. A gentle stream of hydrogen gas was then introduced at atmospheric pressure. The mixture was subsequently heated to 100-110° C. and hydrogen gas was introduced continuously at atmospheric pressure. After liberation of acidic offgases had ceased (11 hours), the mixture was cooled to room temperature, the catalyst was removed by filtration and the filtrate was distilled at 25 mbar. At a boiling point of 112° C., 3-bromo-4-trifluoromethoxybenzaldehyde was obtained in a yield of 31.3 g. This corresponds to a yield of 74% of theory.
Reaction SMILES: C(Cl)Cl.[OH:4][CH2:5][C:6](=[O:8])[CH3:7].CCN(CC)CC.[CH3:16][C:17]([Si:20](Cl)([CH3:22])[CH3:21])([CH3:19])[CH3:18]>CN(C1C=CN=CC=1)C.O>[Si:20]([O:4][CH2:5][C:6](=[O:8])[CH3:7])([C:17]([CH3:19])([CH3:18])[CH3:16])([CH3:22])[CH3:21]
Reactant: CC(=O)CO
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: CN(C)c1ccncc1
Solvent: O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(=O)CO[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 74.2 %

Procedure:
To a DCM (5 mL) solution of 1-hydroxypropan-2-one (500 mg, 6.8 mmol), DMAP (41 mg, 0.34 mmol) and Et3N (1.2 mL, 8.16 mmol) was added TBSCl (1.133 g, 7.5 mmol) at 0° C. under nitrogen atmosphere. The mixture was stirred at r.t. for 2 h. Then the mixture was added water and extracted with EtOAc. The organic layer was purified by silica gel chromatography using PE/EA (10/1) to give the title compound (950 mg, 75%). EDI-MS (M+1): 189. 1H NMR (300 MHz, CDCl3) δ 4.057 (s, 2H), 2.080 (s, 3H), 0.832 (s, 9H), 0.001 (s, 6H).