Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[NH2:10])[C:5]#[N:6].[C:11](N1C=CN=C1)(N1C=CN=C1)=[O:12]>C1COCC1.CCOC(C)=O>[C:5]([C:4]1[CH:7]=[CH:8][C:9]2[NH:10][C:11](=[O:12])[NH:1][C:2]=2[CH:3]=1)#[N:6]
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: N#Cc1ccc(N)c(N)c1
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: N#Cc1ccc2[nH]c(=O)[nH]c2c1
Yield: 79.6 %

Procedure:
After 4-amino-3-nitrobenzonitrile (3.26 g, 20 mmol) was treated with hydrogen in MeOH (300 mL) in the presence of 5% palladium on active carbon (1 g) at room temperature for 16 hours, the reaction mixture was filtered and the filtrate was concentrated to give 3,4-diaminobenzonitrile (2.4 g, 90% yield). A solution of 3,4-diaminobenzonitrile (2 g, 15 mmol) in THF (100 mL) was treated with carbonyldiimidazole (CDI, 3.2 g, 19 mmol) at room temperature for 18 hours. The mixture was diluted with EtOAc (150 mL), washed with 1N HCl (30 mL) and brine, and dried over MgSO4. Filtration and concentration gave 5-cyanobenzimidazolinone (1.9 g, 80%). 1H NMR (CD3OD) δ 7.40 (dd, J=8.1 Hz, J=1.5 Hz, 1H), 7.34 (d, J=1.5 Hz, 1H), 7.15 (d, J=8.1 Hz, 1H); MS: 160.1 (M+H)+.
Reaction SMILES: [NH2:1][CH2:2][C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].[C:10]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)(=O)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[C:11]1([C:10](=[N:1][CH2:2][C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4])[C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: O=C(c1ccccc1)c1ccccc1
Reactant: CC(C)(C)OC(=O)CN
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)CN=C(c1ccccc1)c1ccccc1
Temperature: 15 °C
Yield: 48.8 %

Procedure:
A solution of t-butyl 2-aminoacetate (113.7 g, 866.8 mmol, 1.0 equiv) in toluene (1000 mL) was combined with benzophenone (157.9 g, 866.5 mmol, 1.0 equiv) and 4-methylbenzenesulfonic acid (14.9 g, 86.5 mmol, 0.1 equiv). The resulting solution was heated to reflux overnight. The mixture was then concentrated in vacuo to 600 mL. The mixture was cooled to 15° C. with a water/ice bath. The product precipitated and the solids were collected by filtration. The solids was washed with petroleum ether (5×150 mL) to yield t-butyl 2-(diphenylmethyleneamino)acetate (125 g) as a white solid.
Reaction SMILES: [CH:1]([C:3]1[C:19]2[CH:18]=[C:17](C(OCC)=O)[O:16][C:15]=2[C:14]2[CH:13]=[CH:12][C:11]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=3[C:5]=2[CH:4]=1)=[O:2].C1COCC1.Cl>O>[CH:18]1[C:19]2[C:3]([CH:1]=[O:2])=[CH:4][C:5]3[C:6]4[CH:7]=[CH:8][CH:9]=[CH:10][C:11]=4[CH:12]=[CH:13][C:14]=3[C:15]=2[O:16][CH:17]=1
Reactant: CCOC(=O)c1cc2c(C=O)cc3c4ccccc4ccc3c2o1
Agent: Cl
Solvent: O
Solvent: C1CCOC1
Product: O=Cc1cc2c3ccccc3ccc2c2occc12
Yield: 37 %

Procedure:
To a RB flask equipped with a magnetic stirring bar, condenser, and N2 inlet line with bubbler was added ethyl 11-formyl-phenanthro[1,2-b]furan-2-carboxylate (15A, 2.5 g, 7.8 mmol), 1NaOH solution (25 mL), THF (50 mL) and H2O (25 mL). The mixture was refluxed for 2 h until it became homogeneous. The mixture was acidified with 1N HCl and the solvent removed by rotary evaporaton. The crude solid was then heated to 150° with copper powder (0.9 g) and quinoline and (Aldrich, 25 mL) for 1 h. The reaction mixture was cooled and the quinoline removed under vacuum to give a crude dark green solid. After chromatography and cyrstallization (CH2Cl2 /hexane) 0.71 g (37% yield) of phenanthro[1,2-b]furan-11-carbaldehyde, mp 145°-150°, (C,H).
Reaction SMILES: [N:1]1([C:7]2[CH:8]=[CH:9][C:10]3[N:11]([C:13]([C:16]([F:19])([F:18])[F:17])=[N:14][N:15]=3)[CH:12]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[F:20][CH:21]([F:49])[C:22]1[CH:47]=[CH:46][C:45]([F:48])=[CH:44][C:23]=1[CH2:24]N1CCN(C2C=CC3N(C(C(F)(F)F)=NN=3)N=2)CC1>>[F:49][CH:21]([F:20])[C:22]1[CH:47]=[CH:46][C:45]([F:48])=[CH:44][C:23]=1[CH2:24][N:4]1[CH2:3][CH2:2][N:1]([C:7]2[CH:8]=[CH:9][C:10]3[N:11]([C:13]([C:16]([F:18])([F:17])[F:19])=[N:14][N:15]=3)[CH:12]=2)[CH2:6][CH2:5]1
Reactant: FC(F)(F)c1nnc2ccc(N3CCNCC3)cn12
Reactant: Fc1ccc(C(F)F)c(CN2CCN(c3ccc4nnc(C(F)(F)F)n4n3)CC2)c1
Product: Fc1ccc(C(F)F)c(CN2CCN(c3ccc4nnc(C(F)(F)F)n4c3)CC2)c1
Yield: 39 %

Procedure:
Obtained in 39% yield by General Synthetic Method 9, starting from 6-(piperazin-1-yl)-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine and 2-difluoromethyl-5-fluorobenzaldehyde (obtained as described in Example 779, preparation of starting materials).
Reaction SMILES: Br[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[NH:8]([C:12]1[CH:18]=[CH:17][C:15]([OH:16])=[CH:14][CH:13]=1)[C:9]([CH3:11])=[O:10].C([O-])([O-])=O.[K+].[K+]>CC(C)=O>[CH2:6]([O:5][C:3](=[O:4])[CH2:2][O:16][C:15]1[CH:14]=[CH:13][C:12]([NH:8][C:9](=[O:10])[CH3:11])=[CH:18][CH:17]=1)[CH3:7]
Reactant: CC(=O)Nc1ccc(O)cc1
Reactant: CCOC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOC(=O)COc1ccc(NC(C)=O)cc1
Yield: 80.1 %

Procedure:
Ethyl bromoacetate (452 g, 2.7 mol.) was added to a mixture of paracetamol (300 g, 1.984 mol) and anhydrous K2CO3 (1.80 kg, 7.814 mmol) in anhydrous acetone (3 L) and refluxed for 16 hours. Acetone was distilled and water (5 L) was added. Crude I was filtered, dried and recrystallised from a mixture of toluene:hexane (1:5) to give pure 1 (377 grams, 80%) as a white shining powder. The melting point was found to be 104.2-106.2° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]2[CH:28]=[CH:27][C:26]([NH:29]C(=O)C)=[CH:25][CH:24]=2)[C:6]2[C:11]([C:12]=1[O:13][CH3:14])=[CH:10][CH:9]=[CH:8][CH:7]=2.Cl>CO>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]2[CH:24]=[CH:25][C:26]([NH2:29])=[CH:27][CH:28]=2)[C:6]2[C:11]([C:12]=1[O:13][CH3:14])=[CH:10][CH:9]=[CH:8][CH:7]=2
Reactant: COc1cc(CCCCCCCCc2ccc(NC(C)=O)cc2)c2ccccc2c1OC
Agent: Cl
Solvent: CO
Product: COc1cc(CCCCCCCCc2ccc(N)cc2)c2ccccc2c1OC
Yield: 74.7 %

Procedure:
A solution of 554.6 mg (1.28 mmol) of 1-(3,4-dimethoxy-1-naphthyl)-8-(4-acetamidophenyl)-octane in 20 mL of MeOH was mixed with 21 mL of 2N HCl. The reaction mixture was refluxed for 23 hr. Then the reaction mixture was partitioned between 75 mL of CH2Cl2 and 21 mL of 2N NaOH. The aqueous phase was extracted with CH2Cl2 (5×40 mL). The CH2Cl2 extracts were combined, dried with MgSO4, and evaporated to dryness. Column chromatography on silica gel with 1% MeOH in CH2Cl2 gave 374.6 mg (75%) of aniline 37: 1H NMR (250 MHz, CDCl3, TMS) δ 8.14 (d, J=8 Hz, 1H), 7.94 (d, J=8 Hz, 1H), 7.47 (t, J=8 Hz, 1H), 7.37 (t, J=8 Hz, 1H), 7.12 (s, 1H), 6.96 (d, J=8 Hz, 2H), 6.62 (d, J=8 Hz, 2H), 3.99 (s, 3H), 3.97 (s, 3H), 3.1-3.0 (m, 2H), 2.5-2.4 (m, 2H), 1.8-1.3 (m 12H).
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([O:12][CH3:13])=[O:11])=[CH:4][CH:3]=1.[C:14]1([C:20]#[CH:21])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1>>[C:14]1([C:20]#[C:21][C:2]2[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([O:12][CH3:13])=[O:11])=[CH:4][CH:3]=2)[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: COC(=O)CCc1ccc(I)cc1
Reactant: C#Cc1ccccc1
Product: COC(=O)CCc1ccc(C#Cc2ccccc2)cc1

Procedure:
The title compound was prepared from methyl 3-(4-iodophenyl)propanoate (100 mg, 0.34 mmol) and phenylacetylene (0.04 mL, 0.36 mmol) according to the general procedure IA to give 66 mg (72%) of a brown oil after purification by flash chromatography (SiO2, EtOAc/hexanes, 1:10). Rf: 0.31 (EtOAc:hexanes, 1:5); 1HNMR (CDCl3) δ 7.53-7.50 (m, 2H), 7.47-7.44 (m, 2H), 7.34-7.32 (m, 3H), 7.19-7.16 (m, 2H), 3.66 (s, 3H), 2.98-2.93 (t, 2H, J=7.5 Hz), 2.66-2.61 (t, 2H, J=7.5 Hz); 13CNMR (CDCl3) δ 173.1, 140.8, 131.7, 131.5, 128.3, 128.3, 128.1, 123.3, 121.2, 89.3, 89.1, 51.6, 35.4, 30.8; ESI-MS m/z 287.1 (MNa+).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[O:10][C:11]([C:18]([OH:20])=O)=[C:12]([C:14]([F:17])([F:16])[F:15])[N:13]=1.[CH3:21][O:22][CH2:23][CH2:24][N:25]([CH3:33])[C:26]1[N:31]=[CH:30][C:29]([NH2:32])=[CH:28][N:27]=1>>[CH3:21][O:22][CH2:23][CH2:24][N:25]([CH3:33])[C:26]1[N:27]=[CH:28][C:29]([NH:32][C:18]([C:11]2[O:10][C:9]([C:4]3[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=3[O:2][CH3:1])=[N:13][C:12]=2[C:14]([F:15])([F:16])[F:17])=[O:20])=[CH:30][N:31]=1
Reactant: COc1ccccc1-c1nc(C(F)(F)F)c(C(=O)O)o1
Reactant: COCCN(C)c1ncc(N)cn1
Product: COCCN(C)c1ncc(NC(=O)c2oc(-c3ccccc3OC)nc2C(F)(F)F)cn1

Procedure:
With a procedure similar to example 1 above, 2-(2-methoxy-phenyl)-4-trifluoromethyl-oxazole-5-carboxylic acid {2-[(2-methoxy-ethyl)-methyl-amino]-pyrimidin-5-yl}-amide was prepared from 2-(2-methoxy-phenyl)-4-trifluoromethyl-oxazole-5-carboxylic acid and N-(2-methoxy-ethyl)-N-methyl-pyrimidine-2,5-diamine. LCMS calcd for C20H20F3N5O4 (m/e) 451, obsd 452 (M+H).
Reaction SMILES: [OH:1][C:2]1[C:11]2[N:10]=[CH:9][CH:8]=[CH:7][C:6]=2[C:5]([C:12]([O:14][CH3:15])=[O:13])=[N:4][C:3]=1[C:16]([O:18]C)=O.[F:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][NH2:28])=[C:23]([S:29][CH3:30])[CH:22]=1.CN(C=O)C>C1(C)C=CC=CC=1>[F:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][NH:28][C:16]([C:3]2[N:4]=[C:5]([C:12]([O:14][CH3:15])=[O:13])[C:6]3[CH:7]=[CH:8][CH:9]=[N:10][C:11]=3[C:2]=2[OH:1])=[O:18])=[C:23]([S:29][CH3:30])[CH:22]=1
Reactant: CSc1cc(F)ccc1CN
Reactant: COC(=O)c1nc(C(=O)OC)c2cccnc2c1O
Solvent: CN(C)C=O
Solvent: Cc1ccccc1
Product: COC(=O)c1nc(C(=O)NCc2ccc(F)cc2SC)c(O)c2ncccc12
Temperature: 110 °C
Reaction time: 18 h

Procedure:
A slurry of dimethyl 8-hydroxy-1,6-naphthyridine-5,7-dicarboxylate (0.25 g, 0.953 mmol), 1-[4-fluoro-2-(methylthio)phenyl]methanamine (0.326 g, 1.91 mmol) and N,N,N-diisopropylethylamine (170 uL, 0.953 mmol) in toluene (4.0 mL) were heated in a pressure tube at 110 degrees C. for 18 hrs. The reaction was incomplete by LCMS analysis and solids remained undissolved. DMF (1 mL) was added to solubilize the reagents and the reaction was again heated in a pressure tube at 110 degrees C. for 18 hrs. Upon cooling to room temperature, the resulting solution was transferred to a round bottom flask and reduced to a small volume. The residue was partitioned between methylene chloride and water. The organic layer was dried with Na2SO4, filtered and reduced in vacuo. The material was crystallized with a small amount of chloroform. The solid was filtered and dried in vacuo to afford the desired compound as a white solid.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C(Cl)(=O)C(Cl)=O.[CH:17]1([CH2:20][NH2:21])[CH2:19][CH2:18]1.C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C>[Br:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([NH:21][CH2:20][CH:17]1[CH2:19][CH2:18]1)=[O:9]
Reactant: NCC1CC1
Reactant: O=C(O)c1cncc(Br)c1
Agent: O=C(Cl)C(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClCCl
Product: O=C(NCC1CC1)c1cncc(Br)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 71.1 %

Procedure:
To a solution of 5-bromonicotinic acid (XVI) (1.01 g, 5 mmol) in dry DCM (10 mL) under nitrogen was added oxalyl chloride (0.654 mL, 7.5 mmol) followed by dry DMF (0.1 mL) The solution was stirred at r.t. for 30 min. The solvent was evaporated under vacuum before adding dry pyridine (10 mL) followed by cyclopropylmethanamine (0.39 mL, 4.5 mmol). The solution was stirred at r.t. under nitrogen for 2 h. The solution was poured into ice water, basified with sat. aq. NaHCO3 and extracted with DCM. The combined organic phases were dried over MgSO4, concentrated and dried under vacuum to yield 5-bromo-N-(cyclopropylmethyl)nicotinamide (XVII) as an off-white solid (0.82 g, 3.2 mmol, 71% yield). 1H NMR (DMSO-d6) δ ppm −0.07-0.07 (m, 2H), 0.15-0.29 (m, 2H), 0.68-0.88 (m, 1H), 2.93 (t, J=6.22 Hz, 2H), 8.20 (t, J=1.88 Hz, 1H), 8.62 (d, J=1.70 Hz, 2H), 8.75 (s, 1H); ESIMS found C10H11BrN2O m/z 254, 256 (M+, M+2).
Reaction SMILES: [Mg].Br[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[O:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH:10]1[O:15][CH2:16][CH2:17][CH:18]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)=[O:20].[Cl-].[NH4+]>O1CCCC1>[O:9]1[CH2:14][CH2:13][CH2:12][CH2:11][CH:10]1[O:15][CH2:16][CH2:17][CH:18]([C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[C:19]([C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)[OH:20]
Reactant: Brc1ccccc1
Reactant: O=C(c1ccccc1)C(CCOC1CCCCO1)c1ccccc1
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: C1CCOC1
Product: OC(c1ccccc1)(c1ccccc1)C(CCOC1CCCCO1)c1ccccc1

Procedure:
First a Grignard complex is prepared under dry conditions by allowing 3.6 g of magnesium turnings in 25 ml of dry tetrahydrofuran to react with 23.6 g of bromobenzene in 50 ml of dry tetrahydrofuran. Then the evaporation residue obtained in step (a) in 75 ml of dry tetrahydrofuran is added. The reaction mixture is refluxed for 2 h. The cooled mixture is poured into a saturated solution of ammonium chloride. After shaking, the organic layer is separated. The extraction is repeated with ether. Then the organic layers are combined and dried over sodium sulfate. Finally the solvent is evaporated.
Reaction SMILES: [NH2:1][CH:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[O:11][CH3:12])[CH2:3]1.Cl[C:14]1[C:15]2[C:22]([CH3:23])=[CH:21][S:20][C:16]=2[N:17]=[CH:18][N:19]=1.C(N(CC)CC)C>C(O)C>[CH3:12][O:11][C:8]1[CH:7]=[CH:6][CH:5]=[C:4]2[C:9]=1[CH2:10][CH:2]([NH:1][C:14]1[C:15]3[C:22]([CH3:23])=[CH:21][S:20][C:16]=3[N:17]=[CH:18][N:19]=1)[CH2:3]2
Reactant: COc1cccc2c1CC(N)C2
Reactant: Cc1csc2ncnc(Cl)c12
Solvent: CCO
Solvent: CCN(CC)CC
Product: COc1cccc2c1CC(Nc1ncnc3scc(C)c13)C2
Yield: 94.1 %

Procedure:
Using 2-amino-4-methoxyindan (27 mg, 0.17 mmol) synthesized in the above b) in Preparation Example 5, 4-chloro-5-methylthieno[2,3-d]pyrimidine (31 mg, 0.17 mmol), triethylamine (71 μl, 0.51 mmol), and ethanol (1.5 ml), a similar procedure to b) in Example 19 was carried out. The product obtained was purified by silica gel chromatography (hexane:ethyl acetate=2:1) to obtain the title compound (50 mg, 0.16 mmol) having the following physical properties:
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C(=O)N([Br:28])C(=O)C1>CC#N>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[C:16]([Br:28])[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: O=C1CCC(=O)N1Br
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(N)cc2)CC1
Solvent: CC#N
Product: CC(C)(C)OC(=O)N1CCC(c2ccc(N)c(Br)c2)CC1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 97 %

Procedure:
A solution of 2.00 g (7.24 mmol) 4-(4-amino-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (as prepared in the previous step) in 40 mL of CH3CN was treated with solid 1.25 g (7.02 mmol) NBS and stirred at RT for 15 min. The solvents were evaporated in vacuo, the residue was taken up in EtOAc (70 mL) and washed with saturated aqueous NaHCO3 (2×50 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. Silica gel chromatography of the residue with 10-25% EtOAc-hexanes afforded 3.12 g (97%) of the title compound as a tan solid: Mass spectrum (ESI, m/z): Calcd. for C12H16N2O2Br, 299.0 (M−C4H9+2H), found 299.1/301.1.
Reaction SMILES: [C:1]([O:5][C@@H:6]1[CH2:11][NH:10][C@H:9]([C:12]([OH:14])=O)[C@@H:8]([C:15]([O:17][CH3:18])=[O:16])[CH2:7]1)([CH3:4])([CH3:3])[CH3:2].[C:19]1([N:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CN(C)C=O.C(N(CC)C(C)C)(C)C>>[C:1]([O:5][C@@H:6]1[CH2:11][NH:10][C@H:9]([C:12]([N:28]2[CH2:29][CH2:30][N:25]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:26][CH2:27]2)=[O:14])[C@@H:8]([C:15]([O:17][CH3:18])=[O:16])[CH2:7]1)([CH3:2])([CH3:3])[CH3:4]
Reactant: c1ccc(N2CCNCC2)cc1
Reactant: COC(=O)[C@H]1C[C@H](OC(C)(C)C)CN[C@@H]1C(=O)O
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: COC(=O)[C@H]1C[C@H](OC(C)(C)C)CN[C@@H]1C(=O)N1CCN(c2ccccc2)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a mixture of (2S,3S,5S)-5-tert-butoxy-3-(methoxycarbonyl)piperidine-2-carboxylic acid (43.0 mg, 0.000166 mol), 1-phenyl-piperazine (0.03166 mL, 0.0002073 mol) and benzotriazol-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (0.09168 g, 0.0002073 mol) in N,N-dimethylformamide (0.40 mL, 0.0052 mol) was added N,N-diisopropylethylamine (0.03611 mL, 0.0002073 mol). The reaction was stirred at rt for 2 h, then quenched with water. The mixture was extracted with ethyl acetate. The combined organic layers were washed with brine, dried and concentrated to dry. The residue was used directly in next step. MS (ESI): (M+H)+=404.2.
Reaction SMILES: [I:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]3[CH:16]=[C:15]([O:17][CH3:18])[C:14]([O:19][CH3:20])=[C:13]([O:21][CH3:22])[CH:12]=3)[N:9]=2)[NH:4][CH:3]=1.[H-].[Na+].[CH3:25][C:26]1[CH:31]=[CH:30][C:29]([S:32](Cl)(=[O:34])=[O:33])=[CH:28][CH:27]=1>C1COCC1>[I:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[C:8]([C:11]3[CH:16]=[C:15]([O:17][CH3:18])[C:14]([O:19][CH3:20])=[C:13]([O:21][CH3:22])[CH:12]=3)[N:9]=2)[N:4]([S:32]([C:29]2[CH:30]=[CH:31][C:26]([CH3:25])=[CH:27][CH:28]=2)(=[O:34])=[O:33])[CH:3]=1
Reactant: COc1cc(-c2cnc3[nH]cc(I)c3n2)cc(OC)c1OC
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COc1cc(-c2cnc3c(n2)c(I)cn3S(=O)(=O)c2ccc(C)cc2)cc(OC)c1OC
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 94.3 %

Procedure:
7-Iodo-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine (371 mg, 0.9 mmol) was suspended in 5 ml of THF and cooled to 0° C. in an ice bath. Sodium hydride, 60% dispersion in mineral oil (43 mg, 1.08 mmol) was added and the suspension was stirred for 20 minutes. 4-Methyl-benzenesulfonyl chloride (189 mg, 0.99 mmol) was added, the ice bath was removed, and the reaction was stirred at room temperature for 3 hours. The solvent was evaporated on a rotary evaporator. The residue was triturated with 1M potassium hydroxide. The solid was filtered, washed with water, and dried to yield 480 mg of 7-iodo-5-(toluene-4-sulfonyl)-2-(3,4,5-trimethoxy-phenyl)-5H-pyrrolo[2,3-b]pyrazine which was used without further purification.
Reaction SMILES: N(C(OCC)=O)=NC(OCC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:32]([O:36][C:37]([N:39]1[CH2:43][CH2:42][C@@H:41]([OH:44])[CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33].O[C:46]1[CH:47]=[N:48][CH:49]=[CH:50][CH:51]=1>O1CCCC1.C(Cl)Cl>[C:32]([O:36][C:37]([N:39]1[CH2:43][CH2:42][C@H:41]([O:44][C:46]2[CH:47]=[N:48][CH:49]=[CH:50][CH:51]=2)[CH2:40]1)=[O:38])([CH3:35])([CH3:33])[CH3:34]
Reactant: CC(C)(C)OC(=O)N1CC[C@@H](O)C1
Reactant: Oc1cccnc1
Agent: CCOC(=O)N=NC(=O)OCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CC[C@H](Oc2cccnc2)C1
Temperature: 2.5 °C
Reaction time: 0.25 h
Yield: 70.8 %

Procedure:
Under a nitrogen atmosphere, diethyl azodicarboxylate (4.65 g, 26.70 mmol) was added to a cold (0-5° C.), stirring solution of triphenylphosphine (7.00 g, 26.70 mmol) in dry tetrahydrofuran (60 mL, distilled from sodium and benzophenone). The mixture was stirred at 0-5° C. for 15 min. The resulting yellow solution was treated drop-wise at 0-5° C. with a solution of (3R)-N-(tert-butoxycarbonyl)-3-hydroxypyrrolidine (2.50 g, 13.35 mmol) in dry THF (20 mL) producing a thick yellow mixture. At 0-5° C., 3-hydroxypyridine (2.54 g, 26.70 mmol) was added in one portion. The resulting yellow solution was allowed to stir and warm to ambient temperature over 24 h. The solution was diluted with CH2Cl2 (150 mL) and washed with saturated K2CO3 solution (2×100 mL). The combined CH2Cl2 extracts were dried (Na2SO4), filtered, concentrated by rotary evaporation and briefly dried under high vacuum to give a viscous, light-yellow gel. The crude product was purified by column chromatography on silica gel (302 g), eluting with CHCl3—CH3OH (95:5, v/v). Selected fractions containing the product (Rf 0.44) were combined and concentrated to afford 2.50 g of a light-yellow oil, that contained solids. Impure fractions were combined and concentrated to give 16 g of solids. The solids were triturated with pentane (4×75 mL) in an ultrasonic bath, and the pentane filtrate was concentrated to give 3.40 g of an oil. The oil was chromatographed on silica gel (180 g), eluting with CHCl3-acetone (4:1, v/v). Selected fractions containing the product (Rf 0.29) were combined and concentrated to afford 1.23 g of a light-yellow oil. The 2.50 g lot was triturated with pentane (2×50 mL) in an ultrasonic bath and the pentane filtrate was concentrated. The resulting oil was purified by column chromatography on silica gel (50 g), eluting with CHCl3-acetone (4:1, v/v). Selected fractions containing the product were combined and concentrated to give 0.58 g of a light-yellow oil. Impure fractions from the latter column were combined and concentrated, and the residue was chromatographed on silica gel (50 g) to give 0.28 g of a light-yellow oil. All purified materials were combined, concentrated and dried under high vacuum to yield 1.83 g (51.9%) of a light-yellow oil.
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: CCO
Reactant: ClCc1ccccc1
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.