Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([NH:4][C:5]1[N:6]=[C:7](Cl)[C:8]2[CH:13]=[CH:12][N:11]([CH3:14])[C:9]=2[N:10]=1)[CH2:2][CH3:3].C(O)CCC.C(=O)([O-])[O-].[K+].[K+].Cl.[NH:28]1[CH2:33][CH2:32][CH:31]([OH:34])[CH2:30][CH2:29]1>O>[CH2:1]([NH:4][C:5]1[N:6]=[C:7]([N:28]2[CH2:33][CH2:32][CH:31]([OH:34])[CH2:30][CH2:29]2)[C:8]2[CH:13]=[CH:12][N:11]([CH3:14])[C:9]=2[N:10]=1)[CH2:2][CH3:3]
Reactant: CCCNc1nc(Cl)c2ccn(C)c2n1
Reactant: OC1CCNCC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCCCO
Product: CCCNc1nc(N2CCC(O)CC2)c2ccn(C)c2n1
Temperature: 25 °C
Yield: 58.4 %

Procedure:
2-(n-Propyl)amino-4-chloro-7-methyl-pyrrolo[2,3-d]pyrimidine (CXXIV) (1.6 g, 7.1 mmol) was added to n-butanol (10 mL) followed by potassium carbonate (4.9 g, 35.5 mmol) and piperidin-4-ol hydrochloride (632 mg, 10.7 mmol). The mixture was stirred in an autoclave equipped with a stirrer at 130° C. for 16 h. After cooling to room temperature, water was added (20 mL), and the mixture was extracted with EtOAc (3×50 mL). The combined organic layers were washed with water and then with a brine solution, and dried over anhydrous Na2SO4. The solvents were removed in vacuo and the residue was purified by flash column chromatography (pet ether/EtOAc=3/1) to yield 2-(n-propyl)amino-4-(4-hydroxypiperidin-1-yl)-7-methyl-pyrrolo[2,3-d]pyrimidine (1.2 g, 75%) as a yellow solid. LCMS (ESI) m/z=290 (M+H)+.
Reaction SMILES: [C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]/[C:4]([OH:6])=[O:5].[S:9]1[CH:13]=[CH:12][C:11]2[C:14]([N:18]3[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][CH2:26][O:27]C4CC5C(=CC=CC=5)C(=O)N4C)[CH2:20][CH2:19]3)=[CH:15][CH:16]=[CH:17][C:10]1=2>C(O)C>[C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]/[C:4]([OH:6])=[O:5].[C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]/[C:4]([OH:6])=[O:5].[S:9]1[CH:13]=[CH:12][C:11]2[C:14]([N:18]3[CH2:23][CH2:22][N:21]([CH2:24][CH2:25][CH2:26][O:27][C:1]4[CH:2]=[C:3]5[C:10]([CH2:11][CH2:14][N:18]([CH3:19])[C:4]5=[O:6])=[CH:17][CH:16]=4)[CH2:20][CH2:19]3)=[CH:15][CH:16]=[CH:17][C:10]1=2
Reactant: CN1C(=O)c2ccccc2CC1OCCCN1CCN(c2cccc3sccc23)CC1
Agent: O=C(O)/C=C/C(=O)O
Solvent: CCO
Product: CN1CCc2ccc(OCCCN3CCN(c4cccc5sccc45)CC3)cc2C1=O

Procedure:
Fumaric acid was added to an ethanol solution of 7-[(3-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)propoxy]-2-methyl-3,4-dihydro-2H-isoquinolin-1-one and the solvent was evaporated under reduced pressure. The residue was recrystallized from 90% ethanol and thereby 7-[3-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)propoxy]-2-methyl-3,4-dihydro-2H-isoquinolin-1-one difumarate was obtained in the form of white prism crystal.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:11])[CH3:10].C([O:14][C:15]([C:17]1[C:24]([CH3:25])=[CH:23][C:20]([CH:21]=O)=[C:19]([O:26][CH3:27])[C:18]=1[CH3:28])=[O:16])C>>[OH:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9](=[O:11])[CH:10]=[CH:21][C:20]1[CH:23]=[C:24]([CH3:25])[C:17]([C:15]([OH:16])=[O:14])=[C:18]([CH3:28])[C:19]=1[O:26][CH3:27]
Reactant: CCOC(=O)c1c(C)cc(C=O)c(OC)c1C
Reactant: CC(=O)c1ccc(Cl)cc1O
Product: COc1c(C=CC(=O)c2ccc(Cl)cc2O)cc(C)c(C(=O)O)c1C

Procedure:
This compound was synthesized from 2′-hydroxy-4′-chloroacetophenone and 4-ethyloxycarbonyldimethylmethyloxybenzaldehyde (starting material 9) according to general method 2 described earlier.
Reaction SMILES: [CH3:1][N:2](S(C1C=CC(C)=CC=1)(=O)=O)[N:3]=[C:4](Cl)[C:5]1[C:10]([F:11])=[CH:9][CH:8]=[CH:7][C:6]=1[Cl:12].[Cl:24][C:25]1[CH:32]=[C:31]([N+:33]([O-:35])=[O:34])[CH:30]=[CH:29][C:26]=1[C:27]#[N:28].ClC1C=CC=CC=1Cl>C(Cl)(Cl)Cl.[Fe](Cl)(Cl)Cl>[Cl:12][C:6]1[CH:7]=[CH:8][CH:9]=[C:10]([F:11])[C:5]=1[C:4]1[N:28]=[C:27]([C:26]2[CH:29]=[CH:30][C:31]([N+:33]([O-:35])=[O:34])=[CH:32][C:25]=2[Cl:24])[N:2]([CH3:1])[N:3]=1
Reactant: N#Cc1ccc([N+](=O)[O-])cc1Cl
Reactant: Cc1ccc(S(=O)(=O)N(C)N=C(Cl)c2c(F)cccc2Cl)cc1
Agent: Cl[Fe](Cl)Cl
Solvent: ClC(Cl)Cl
Solvent: Clc1ccccc1Cl
Product: Cn1nc(-c2c(F)cccc2Cl)nc1-c1ccc([N+](=O)[O-])cc1Cl
Temperature: 140 °C
Reaction time: 1 h
Yield: 118.3 %

Procedure:
A mixture of N-methyl-N-(p-toluenesulfonyl)-2-chloro-6-fluorobenzohydrazonoyl chloride (1.90 g), 2-chloro-4-nitrobenzonitrile (1.80 g), anhydrous iron (III) chloride (1.60 g) and o-dichlorobenzene (5 ml) is stirred at an oil bath temperature of 140° C. for 1 hour. After cooling, the reaction mixture is dissolved in chloroform (100 ml), washed with dilute hydrochloric acid, dilute aqueous solution of sodium hydroxide and saline in this order, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate is purified by silica gel column chromatography using mixed solvent of hexane-ethyl acetate as eluent to give 2.20 g of desired compound (melting point: 144.0°-148.0° C.).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]([C:24]#N)[C:12]2[S:16][C:15]([NH:17][C:18]([NH:20][CH2:21][CH3:22])=[O:19])=[N:14][C:13]=2[CH:23]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)=[O:27]>O.[Al].[Ni]>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]([CH:24]=[O:27])[C:12]2[S:16][C:15]([NH:17][C:18]([NH:20][CH2:21][CH3:22])=[O:19])=[N:14][C:13]=2[CH:23]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=CO
Reactant: CCNC(=O)Nc1nc2cc(OCc3ccccc3)cc(C#N)c2s1
Agent: [Ni]
Agent: [Al]
Solvent: O
Product: CCNC(=O)Nc1nc2cc(OCc3ccccc3)cc(C=O)c2s1
Temperature: 95 °C
Reaction time: 5 h

Procedure:
1-(5-(Benzyloxy)-7-cyanobenzo[d]thiazol-2-yl)-3-ethylurea (1.00 g, 2.84 mmol) was stirred in formic acid (75 ml) and water (20 ml). Aluminum Nickel alloy (5.5 g, 64.7 mmol) was added and the reaction was stirred at 95° C. for 5 h under N2. LCMS indicated 60% conversion to the desired aldehyde. The reaction was allowed to cool then the volatiles were removed under reduced pressure. The resulting concentrated solution was neutralized to pH9 with a 2M aqueous solution of sodium hydroxide then extracted with EtOAc, the combined extracts concentrated and the resulting residue purified by column chromatography eluting with EtOAc 50 to 100% in petroleum-ether to afford the aldehyde as a yellow solid (200 mg, 99% purity by LC-MS) (20%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:12]=[CH:11][C:10]2[NH:9][C:8](=[O:13])[C:7]3[S:14][CH:15]=[CH:16][C:6]=3[C:5]=2[C:4]=1[C:17]1[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][C:25]#[N:26])=[CH:19][CH:18]=1.B>>[NH2:26][CH2:25][CH2:24][CH2:23][C:20]1[CH:19]=[CH:18][C:17]([C:4]2[C:5]3[C:6]4[CH:16]=[CH:15][S:14][C:7]=4[C:8](=[O:13])[NH:9][C:10]=3[CH:11]=[CH:12][C:3]=2[O:2][CH3:1])=[CH:22][CH:21]=1
Reactant: COc1ccc2[nH]c(=O)c3sccc3c2c1-c1ccc(CCC#N)cc1
Agent: B
Product: COc1ccc2[nH]c(=O)c3sccc3c2c1-c1ccc(CCCN)cc1
Yield: 59.6 %

Procedure:
Following the procedure outlined for Example 265, 3-[4-(8-methoxy-4-oxo-4,5-dihydrothieno[2,3-c]quinolin-9-yl)phenyl]propanenitrile (250 mg, 0.69 mmol) was reacted with borane (1.0 M in THF, 10 mL, 10 mmol) to afford the desired product (150 mg, 60%) as a brown oil: ESI MS m/z 365 [C21H20N2O2S+H]+.
Reaction SMILES: [C:1]([NH:9][C:10]1[CH:11]=[C:12]([NH:17][C:18](=[O:26])[C:19]2[CH:24]=[CH:23][C:22](Cl)=[N:21][CH:20]=2)[CH:13]=[CH:14][C:15]=1[Cl:16])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:27]([N:30]1[CH2:35][CH2:34][NH:33][CH2:32][CH2:31]1)(=[O:29])[CH3:28]>>[C:27]([N:30]1[CH2:35][CH2:34][N:33]([C:22]2[CH:23]=[CH:24][C:19]([C:18]([NH:17][C:12]3[CH:13]=[CH:14][C:15]([Cl:16])=[C:10]([NH:9][C:1](=[O:8])[C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[CH:11]=3)=[O:26])=[CH:20][N:21]=2)[CH2:32][CH2:31]1)(=[O:29])[CH3:28]
Reactant: CC(=O)N1CCNCC1
Reactant: O=C(Nc1ccc(Cl)c(NC(=O)c2ccccc2)c1)c1ccc(Cl)nc1
Product: CC(=O)N1CCN(c2ccc(C(=O)Nc3ccc(Cl)c(NC(=O)c4ccccc4)c3)cn2)CC1

Procedure:
N-(3-benzamido-4-chlorophenyl)-6-chloronicotinamide (0.15 mmol) was used in general procedure 3 with 1-acetylpiperazine (0.77 mmol). The product was purified by RP-HPLC to give 6-(4-acetylpiperazin-1-yl)-N-(3-benzamido-4-chlorophenyl)nicotinamide. MS (Q1) 478.0 (M)+
Reaction SMILES: C([O:3][C:4](=[O:31])[CH2:5][CH2:6][C@H:7]([C@@H:9]1[C@:26]2([CH3:27])[C:12]([C:13]3[CH2:14][CH2:15][C@@H:16]4[C@:21]([C:23]=3[CH2:24][CH2:25]2)([CH3:22])[CH2:20][CH2:19][C@H:18]([OH:28])[C:17]4([CH3:30])[CH3:29])=[CH:11][CH2:10]1)[CH3:8])C>C(O)C.[OH-].[Na+]>[OH:28][C@H:18]1[CH2:19][CH2:20][C@@:21]2([CH3:22])[C@@H:16]([CH2:15][CH2:14][C:13]3[C:12]4[C@:26]([CH3:27])([CH2:25][CH2:24][C:23]=32)[C@@H:9]([C@H:7]([CH3:8])[CH2:6][CH2:5][C:4]([OH:31])=[O:3])[CH2:10][CH:11]=4)[C:17]1([CH3:29])[CH3:30]
Reactant: CCOC(=O)CC[C@@H](C)[C@H]1CC=C2C3=C(CC[C@@]21C)[C@@]1(C)CC[C@H](O)C(C)(C)[C@@H]1CC3
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: C[C@H](CCC(=O)O)[C@H]1CC=C2C3=C(CC[C@@]21C)[C@@]1(C)CC[C@H](O)C(C)(C)[C@@H]1CC3
Temperature: 25 °C
Reaction time: 3.5 h
Yield: 83.3 %

Procedure:
3β-Hydroxy-4,4-dimethyl-5α-chola-8,14-dien-24-oic acid ethyl ester (1.9 g) is suspended in a mixture of 190 ml of 96% ethanol and 63 ml of 1M sodiumhydroxide. The mixture is stirred for 3.5 h at room temperature. After aqueous work-up and crystallization from ethanol/water, the title compound (1.48 g) is isolated. 1H-NMR (CDCl3, 400 MHz): δ=5.36 (1H, s); 3.22 (1H, m); 1.03 (3H, s). 1.01 (3H, s); 0.97 (3H, d); 0.83 (3H, s); 0.81 (3H, s). MS: Calculated: 400.6. Found 400.3.
Reaction SMILES: [CH3:1][O:2][CH:3]([CH2:8][CH3:9])[C:4]([O:6]C)=[O:5].O.[OH-].[Li+:12]>CO.O>[CH3:1][O:2][CH:3]([CH2:8][CH3:9])[C:4]([O-:6])=[O:5].[Li+:12]
Reactant: CCC(OC)C(=O)OC
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: CCC(OC)C(=O)[O-]
Reaction time: 8 h

Procedure:
In a 15-mL RBF was dissolved methyl 2-methoxybutanoate (0.027 g, 0.20 mmol) in methanol (0.75 mL). A solution of lithium hydroxide monohydrate (0.0086 g, 0.20 mmol) in water (0.75 mL) was added, and the mixture was stirred overnight. The mixture was concentrated to afford the title compound.
Reaction SMILES: [F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](/[CH:11]=[CH:12]/[C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=3)=[N:7][NH:8]2)=[CH:4][C:3]=1[C:20]#[N:21].S(=O)(=O)(O)[OH:23]>C(O)(=O)C.O>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6](/[CH:11]=[CH:12]/[C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[CH:14]=3)=[N:7][NH:8]2)=[CH:4][C:3]=1[C:20]([NH2:21])=[O:23]
Reactant: O=S(=O)(O)O
Reactant: N#Cc1cc2c(/C=C/c3cccc(F)c3)n[nH]c2cc1F
Solvent: CC(=O)O
Solvent: O
Product: NC(=O)c1cc2c(/C=C/c3cccc(F)c3)n[nH]c2cc1F
Temperature: 110 °C
Reaction time: 0.83 h

Procedure:
To a suspension of 89 mg of 6-fluoro-3-[(E)-2-(3-fluorophenyl)-vinyl]-1H-indazole-5-carbonitrile obtained by Example 100 in 0.4 mL of acetic acid and 0.4 mL of water was added 1.2 mL of concentrated sulfuric acid, and stirred at 110° C. for 50 minutes. After allowing to cool, ice was added, and extracted with a mixed solvent of 20 mL of ethyl acetate and 10 mL of tetrahydrofuran. The organic layer was washed successively with water, saturated aqueous sodium hydrogen carbonate and saturated brine, and dried over anhydrous magnesium sulfate. After making the organic layer pass through an alumina pad (2.5 diameter ×2 cm), the solvent was evaporated, to afford 76 mg of the title compound as pale yellow crystals.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][C:12]([CH:21]3[CH2:23][CH2:22]3)([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[C:16]=[C:15]=3)O)[C:6]3[CH2:24][CH2:25][N:26]([CH3:28])[CH2:27][C:5]=3[C:4]=2[CH:3]=1.S(=O)(=O)(O)[OH:30]>O>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11]/[C:12](/[C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)=[CH:21]\[CH2:22][CH2:23][OH:30])[C:6]3[CH2:24][CH2:25][N:26]([CH3:28])[CH2:27][C:5]=3[C:4]=2[CH:3]=1
Reactant: CN1CCc2c(c3cc(Cl)ccc3n2CC(O)(C2=C=C=C(F)C=C2)C2CC2)C1
Reactant: O=S(=O)(O)O
Solvent: O
Product: CN1CCc2c(c3cc(Cl)ccc3n2C/C(=C\CCO)c2ccc(F)cc2)C1
Temperature: 110 °C

Procedure:
2-(8-Chloro-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-1-cyclopropyl-1-(4-fluorocyclohexa-1,2,3,5-tetraenyl)ethanol (1 g, 25 mmol) was dissolved in 10 mL 25% sulfuric acid and heated at 110° C. for 4 h. The reaction mixture was cooled to RT, diluted with water and the resultant solid was filtered, washed with water, and diethylether. The solid was purified by reverse phase HPLC, and separated from the regioisomeric Compound No. 349. 1H NMR (CD3OD, HCl salt) δ (ppm): 7.50 (m, 1H), 7.38 (d, 1H), 7.15 (m, 3H), 7.0 (m, 1H), 6.80 (m, 2H), 5.80 (m, 1H), 5.22 (m, 2H), 4.60 (m, 1H), 4.25 (m, 1H), 3.80 (m, 2H), 3.45 (m, 2H), 3.15 (m, 2H), 3.0 (s, 3H), 2.65 (m, 2H).
Reaction SMILES: [O:1]1[CH2:19][CH:2]1[CH2:3][O:4][C:5]1[CH:6]=[C:7]([C:12]2[CH2:13][CH2:14][C:15](=[O:18])[NH:16][N:17]=2)[CH:8]=[CH:9][C:10]=1[CH3:11].[C:20]([NH2:24])([CH3:23])([CH3:22])[CH3:21]>CCOCC>[C:20]([NH:24][CH2:19][CH:2]([OH:1])[CH2:3][O:4][C:5]1[CH:6]=[C:7]([C:12]2[CH2:13][CH2:14][C:15](=[O:18])[NH:16][N:17]=2)[CH:8]=[CH:9][C:10]=1[CH3:11])([CH3:23])([CH3:22])[CH3:21]
Reactant: Cc1ccc(C2=NNC(=O)CC2)cc1OCC1CO1
Reactant: CC(C)(C)N
Solvent: CCOCC
Product: Cc1ccc(C2=NNC(=O)CC2)cc1OCC(O)CNC(C)(C)C

Procedure:
A stirred mixture of 6-[3-(2,3-epoxypropoxy)-4-methylphenyl]-4,5-dihydro-3(2H)-pyridazinone (3.3 g, 0.013 mole) methanol (33 ml) and t-butylamine (8 ml, 0.076 mole) was heated under reflux for 75 minutes. Evaporation of the solution under reduced pressure gave a gum which when treated with ether, solidified 4.27 g, 100%, m.p. 153°-158°C. 6-[3-(3-t-Butylamino-2-hydroxypropoxy)-4-methylphenyl]-4,5-dihydro-3(2H)-pyridazinone was purified as its hemisulphate m.p. 274°-276°C (decomposition), which recrystallised from aqueous ethanol had m.p. 275°-277°C (decomposition).
Reaction SMILES: [Cl-].[CH3:2][C:3]([NH3+:7])([CH3:6])[CH2:4]Cl.[CH3:8][C:9]1[CH:14]=[C:13]([N+:15]([O-:17])=[O:16])[CH:12]=[CH:11][C:10]=1[N:18]=[C:19]=[S:20]>>[CH3:8][C:9]1[CH:14]=[C:13]([N+:15]([O-:17])=[O:16])[CH:12]=[CH:11][C:10]=1[N:18]=[C:19]1[NH:7][C:3]([CH3:6])([CH3:2])[CH2:4][S:20]1
Reactant: Cc1cc([N+](=O)[O-])ccc1N=C=S
Reactant: CC(C)([NH3+])CCl
Agent: [Cl-]
Product: Cc1cc([N+](=O)[O-])ccc1N=C1NC(C)(C)CS1

Procedure:
1,1-Dimethyl-2-hydroxyamine was converted to 1,1-dimethyl-2-chloroethylammonium chloride according to Method B7a. 2-Methyl-4-nitrophenyl isothiocyanate was reacted with 1,1-dimethyl-2-chloroethylammonium chloride according to Method C1a to give 2-(2-methyl-4-nitrophenylimino)-4,4-dimethyl-1,3-thiazolidine. The thiazolidine was reacted with 2-methylprop-2-en-1-yl bromide according to Method D2g to afford 2-(2-methyl-4-nitrophenylimino)-4,4-dimethyl-3-(2-methylprop-2-en-1-yl)-1,3-thiazolidine HBr salt.
Reaction SMILES: C1C(=O)N([Br:8])C(=O)C1.[F:9][C:10]1[CH:18]=[CH:17][C:16]([C:19]([OH:21])=[O:20])=[C:15]2[C:11]=1[CH2:12][CH2:13][NH:14]2>C(Cl)Cl.CO>[Br:8][C:18]1[C:10]([F:9])=[C:11]2[C:15](=[C:16]([C:19]([OH:21])=[O:20])[CH:17]=1)[NH:14][CH2:13][CH2:12]2
Reactant: O=C1CCC(=O)N1Br
Reactant: O=C(O)c1ccc(F)c2c1NCC2
Solvent: ClCCl
Solvent: CO
Product: O=C(O)c1cc(Br)c(F)c2c1NCC2
Temperature: 25 °C
Reaction time: 8 h

Procedure:
NBS (40 mg, 0.23 mmol) was added to a solution of 4-fluoro-2,3-dihydro-1H-indole-7-carboxylic acid (36 mg, 0.14 mmol) in DCM (3 mL) and MeOH (1 mL). The reaction was stirred at room temperature overnight and filtered. The filtrate was evaporated, and the residue was purified by flash chromatography, giving the title compound.
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[OH:8][C:9]1[C:17]2[N:16]=[C:15]([CH2:18][O:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[N:14]([CH2:27][CH2:28][CH2:29][CH:30]3[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][CH2:31]3)[C:13]=2[CH:12]=[CH:11][CH:10]=1.[H-].[Na+].[CH:45]1(Br)[CH2:47][CH2:46]1>CN(C)C=O>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH:3]1([O:8][C:9]2[C:17]3[N:16]=[C:15]([CH2:18][O:19][C:20]4[CH:21]=[CH:22][C:23]([Cl:26])=[CH:24][CH:25]=4)[N:14]([CH2:27][CH2:28][CH2:29][CH:30]4[CH2:31][CH2:32][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:34][CH2:35]4)[C:13]=3[CH:12]=[CH:11][CH:10]=2)[CH2:2][CH2:47][CH2:45][CH2:46]1
Reactant: CC(C)(C)OC(=O)N1CCC(CCCn2c(COc3ccc(Cl)cc3)nc3c(O)cccc32)CC1
Reactant: BrC1CC1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O=C(O)C(F)(F)F
Product: CC(C)(C)OC(=O)N1CCC(CCCn2c(COc3ccc(Cl)cc3)nc3c(OC4CCCC4)cccc32)CC1
Temperature: 25 °C
Yield: 50 %

Procedure:
A solution of 4-hydroxy-2-[(4-chlorophenoxy)methyl]-1-[3-[1-(t-butoxycarbonyl)piperidin-4-yl]propyl]benzimidazole trifluoroacetate (300 mg, 0.6 mmol, 1 eq) in anhydrous N,N-dimethylformamide (3 m) was treated with sodium hydride (60% in mineral oil, 26 mg, 0.66 mmol, 1.1 eq). The resulting mixture was stirred for thirty minutes at room temperature. Cyclopropyl bromide (0.66 mmol, 1 eq) was added to the reaction and the resulting mixture was stirred for two hours at room temperature. The reaction was quenched with the addition of water (5 ml). The aqueous fraction was extracted with ethyl acetate (3×10 ml). The organic fractions were combined, washed with water (2×10 ml), then brine (1×10 ml), and then dried over sodium sulfate. The solvents were removed in vacuo. The residue was further purified by flash column chromatography to yield the title product as a crystalline product in 50% yield.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([CH3:9])[CH:3]=1.ClC1C=CC=C(C(OO)=[O:18])C=1>C(Cl)Cl>[Br:1][C:2]1[CH:7]=[C:6]([CH3:8])[N+:5]([O-:18])=[C:4]([CH3:9])[CH:3]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: Cc1cc(Br)cc(C)n1
Solvent: ClCCl
Product: Cc1cc(Br)cc(C)[n+]1[O-]
Temperature: 0 °C
Reaction time: 5 h

Procedure:
4-Bromo-2,6-dimethylpyridine (0.5 g, 2.69 mmol) was dissolved in DCM (10 ml), cooled to 0° C. and combined with a solution of m-chloroperbenzoic acid in DCM (75%, 0.928 g, 4.03 mmol in 5 ml). The resulting mixture was stirred at 0° C. for 15 minutes and for 5 hours at room temperature. The mixture was washed with saturated sodium bicarbonate solution, the phases were separated with a phase separator, the organic phase was evaporated under reduced pressure. The residue was purified by column chromatography (silica, gradient of 0.5 to 10% methanol in DCM). 475 of a yellow solid was obtained (2.35 mmol, 88%). MS (ESI) m/z=204.0 [M+1]+.
Reaction SMILES: O[C:2]1[CH:17]=[C:16]([OH:18])[CH:15]=[CH:14][C:3]=1[C:4]([C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][C:7]=1[OH:13])=[O:5]>O>[OH:18][C:16]1[CH:17]=[CH:2][C:3]2[C:4](=[O:5])[C:6]3[C:7]([O:13][C:14]=2[CH:15]=1)=[CH:8][C:9]([OH:12])=[CH:10][CH:11]=3
Reactant: O=C(c1ccc(O)cc1O)c1ccc(O)cc1O
Solvent: O
Product: O=c1c2ccc(O)cc2oc2cc(O)ccc12
Yield: 92.8 %

Procedure:
2,2',4,4'-Tetrahydroxybenzophenone (2.5 g, 10.15 mmol.) was heated in 20 ml of water at 195°-200° C. for 4 hours (Aldrich pressure tube). After cooling, the crude product was filtered off and mixed with 25 ml of water. The resulting suspension was refluxed for 25 min. and filtered at about 60° C. Pure product 3,6-dihydroxyxanthone 2.15 g was obtained in 90.4% yield. It did not melt below 330° C. HNMR (DMSO): 10.780 (s,2H), 7.983 (d,2H,J=8.6 Hz), 6,822 (m,4H). MS: 228,220, 1717, 115, 100, 69, 63.
Reaction SMILES: [F:1][CH:2](P(=O)(C1C=CC=CC=1)C1C=CC=CC=1)[F:3].C([N-]C(C)C)(C)C.[Li+].[O:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]1[O:32][C:33]1[CH:50]=[CH:49][C:48]2[C@@H:47]3[C:38]([C@H:39]4[C@@:43]([CH2:45][CH2:46]3)([CH3:44])[C:42](=O)[CH2:41][CH2:40]4)=[CH:37][CH2:36][C:35]=2[CH:34]=1>O1CCCC1.C(OCC)(=O)C.O>[F:1][C:2]([F:3])=[C:42]1[CH2:41][CH2:40][C@H:39]2[C:38]3[C@H:47]([CH2:46][CH2:45][C@:43]12[CH3:44])[C:48]1[CH:35]=[CH:34][C:33]([O:32][CH:27]2[CH2:28][CH2:29][CH2:30][CH2:31][O:26]2)=[CH:50][C:49]=1[CH2:36][CH:37]=3
Reactant: C[C@]12CC[C@H]3C(=CCc4cc(OC5CCCCO5)ccc43)[C@@H]1CCC2=O
Reactant: O=P(c1ccccc1)(c1ccccc1)C(F)F
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: C[C@]12CC[C@H]3C(=CCc4cc(OC5CCCCO5)ccc43)[C@@H]1CCC2=C(F)F
Reaction time: 1 h
Yield: 53.6 %

Procedure:
A solution of 3 g of difluoromethyldiphenylphosphine oxide in 85 ml of tetrahydrofuran is slowly mixed with 6 ml of 2 M lithium diisopropylamide solution at a bath temperature of -50° C., and it is stirred for 1 hour. Then, a solution of 1.7 g of 3-tetrahydropyranyloxy-estra-1,3,5(10),7-tetraen-17-one in 42 ml of tetrahydrofuran is slowly added, stirred for 15 minutes, slowly heated at a bath temperature of from -50° C. to 100° C. and refluxed for 2.5 hours. For working-up, it is diluted with ethyl acetate and water, suctioned off on Celite, rewashed with ethyl acetate, washed with water as well as with saturated sodium chloride solution, dried on sodium sulfate, concentrated by evaporation in a vacuum and chromatographed on silica gel with hexane/ethyl acetate/triethylamine. 1.0 g of 17-difluoromethylene-3-tetrahydropyranyloxy-estra-1,3,5(10),7-tetraene is obtained as colorless crystals with a melting point of 83-84° C., [α]D 22 =+139.6° (c=0.5% in pyridine).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:14])[CH2:9][C:10]([O:12][CH3:13])=[O:11])=[CH:4][CH:3]=1.[CH3:15][O:16]/[N:17]=[C:18](/[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)\[CH2:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27]O)=[CH:23][CH:22]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C1(C)C=CC=CC=1>[CH3:15][O:16]/[N:17]=[C:18](/[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)\[CH2:19][O:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][O:1][C:2]2[CH:3]=[CH:4][C:5]([C:8](=[O:14])[CH2:9][C:10]([O:12][CH3:13])=[O:11])=[CH:6][CH:7]=2)=[CH:23][CH:22]=1
Reactant: CO/N=C(\COc1ccc(CO)cc1)c1ccccc1
Reactant: COC(=O)CC(=O)c1ccc(O)cc1
Agent: CCCCP(CCCC)CCCC
Agent: O=C(N=NC(=O)N1CCCCC1)N1CCCCC1
Solvent: Cc1ccccc1
Product: CO/N=C(\COc1ccc(COc2ccc(C(=O)CC(=O)OC)cc2)cc1)c1ccccc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 14 %

Procedure:
To a 50 mL RB flask fitted with magnetic stirrer was charged 10 mL of Toluene. to the stirred solvent was added methyl 3-(4-hydroxyphenyl)-3-oxopropanoate (0.2 g, 1.036 mmol) and (4-{[(2Z)-2-(methoxyimino)-2-phenylethyl]oxy}phenyl)methanol (0.22 g, 0.82 mmol) was added Tributyl phosphine (0.271 g, 1.324 mmol) and 1,1′-(Azodicarbonyl)di-Piperidine portion wise at 0° C. (0.339 g, 1.346 mmol). Then the reaction mixture was stirred at RT for 12 h. After completion of the reaction (reaction monitored by TLC), reaction mixture was concentrated and extracted with ethyl acetate. Then the organic layer was dried over anhydrous Na2SO4. Solvent was removed under reduced pressure, and the resulting crude compound was purified by column chromatography on silica gel using petroleum ether and ethyl acetate as eluent (0.05 g Yield: 14%) MS (ESI, 120 eV): m/z=448.1 (M+H)+.
Reaction SMILES: [CH2:1]([Cl:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:9](O)[CH3:10]>CN(C=O)C>[CH:9]([CH:1]([Cl:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[CH2:10]
Reactant: ClCc1ccccc1
Reactant: CCO
Solvent: CN(C)C=O
Product: C=CC(Cl)c1ccccc1
Reaction time: 1 h

Procedure:
Vinyl benzyl chloride grafted film was synthesized by immersing an argon plasma pretreated LDPE film into a degassed monomer solution of 5 vol % using ethanol as solvent, and exposing the setup to near UV-irradiation for 2 h. The grafted film was subjected to prolonged washing with DMF before it was reacted with 0.024 M 4,4′-bipyridine in a water bath at 70° C. for 20 h, followed by 0.4 M benzyl chloride, again in a water bath at 70° C. for 20 h. Both reaction steps were carried out using DMF as solvent. The film was washed with DMF after both reaction steps to remove unreacted reactants. The viologen grafted film was finally immersed into a reaction mixture containing 0.10 M aniline and 0.025 M ammonium persulfate in 0.5 M HClO4 for 2 h. The green polyaniline (in the emeraldine state) was undoped in 0.5M NaOH for 1 h, washed in deionized water and dried under reduced pressure. The base film was exposed to near UV-light emitted from a 1 kW mercury lamp for 1 h. The sheet resistance of the film decreased from 1010 Ω/sq. (before irradiation) to 105 Ω/sq.(after irradiation). The change in Rs with respect to irradiation time is shown in FIG. 1.