Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9](=[NH:12])SC)[CH:5]=[C:4]([Cl:13])[C:3]=1[CH3:14].[NH2:15][NH2:16].O>C(O)C>[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]([NH2:12])=[N:15][NH2:16])[CH:5]=[C:4]([Cl:13])[C:3]=1[CH3:14]
Reactant: CSC(=N)Nc1cc(Cl)c(C)c(Cl)c1
Reactant: NN
Solvent: O
Solvent: CCO
Product: Cc1c(Cl)cc(NC(N)=NN)cc1Cl

Procedure:
To 7.18 g of 1-(2,6-dichloro-4-tolyl)-2-methylisothiourea.HJ (C), suspended in 26 ml of ethanol, 1.3 ml of hydrazine.hydrate is added after which the mixture is refluxed for 20 hours. The precipitate formed is filtered off and the filtrate evaporated to dryness. Yield: 6.35 g. Melting point HJ salt: 203°-205°C; melting point HCl salt: 149°-150°C.
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)[N:5]=[C:4]([N:14]2[CH2:20][CH:19]3[O:21][CH:16]([CH2:17][CH2:18]3)[CH2:15]2)[N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[NH2:28][C:29]1[CH:34]=[CH:33][C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][CH:30]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC>[N:8]1([C:6]2[N:5]=[C:4]([N:14]3[CH2:20][CH:19]4[O:21][CH:16]([CH2:17][CH2:18]4)[CH2:15]3)[N:3]=[C:2]([C:32]3[CH:33]=[CH:34][C:29]([NH2:28])=[CH:30][CH:31]=3)[N:7]=2)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1
Reactant: Clc1nc(N2CCOCC2)nc(N2CC3CCC(C2)O3)n1
Reactant: CC1(C)OB(c2ccc(N)cc2)OC1(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: Nc1ccc(-c2nc(N3CCOCC3)nc(N3CC4CCC(C3)O4)n2)cc1
Yield: 59 %

Procedure:
A mixture of 3-(4-chloro-6-morpholin-4-yl-1,3,5-triazin-2-yl)-8-oxa-3-azabicyclo[3.2.1]octane (2.0 g, 6.4 mmol), tetrakis(triphenylphosphine)palladium (0) in catalytic amount (100 mg), sodium carbonate solution 2 M (5 mL), 4-aminophenylboronic acid pinacol ester (1.5 g, 6.43 mmoles), DME (200 mL) was refluxed for 24 hours. The solvent was evaporated and the residue was dissolved in methylene chloride and filtered though Celite™. The organic layer was washed with water (200 mL) and dried over magnesium sulfate. It was filtered and the solvent was evaporated. The residue was chromatographed on silica gel column using Ethyl acetate/hexanes (1:1) as an eluent, to give 1.4 g, (59% yield) of the titled product. mp. 154; (M+H) 369.4.
Reaction SMILES: [CH3:1][C:2]([OH:6])([C:4]#[CH:5])[CH3:3].[CH3:7][O:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=[O:14])=[CH:11][CH:10]=1>C1COCC1>[CH3:7][O:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]([OH:14])[C:5]#[C:4][C:2]([CH3:3])([OH:6])[CH3:1])=[CH:11][CH:10]=1
Reactant: C#CC(C)(C)O
Reactant: COc1ccc(C=O)cc1
Solvent: C1CCOC1
Product: COc1ccc(C(O)C#CC(C)(C)O)cc1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 77.3 %

Procedure:
To a pre-cooled, −78° C. stirred solution of 2-methylbut-3-yn-2-ol (4.3 g, 0.04 mol) in dry THF (150 mL) n-BuLi (39.9 mL, 0.03 mol, 1.6 M in hexane) was added dropwise over 10 minutes under an inert atmosphere. The mixture was stirred for 30 min at −78° C., and then a solution of 4-methoxy-benzaldehyde (5 g, 0.037 mol) in dry THF (30 mL) was added to reaction mixture and stirring was continued for an additional 40 min at −78° C. The reaction mixture was then quenched with a saturated NH4Cl solution and extracted with EtOAc (2×100 mL). The combined organic layers were washed with water (100 mL) and brine (100 mL), dried over Na2SO4, filtered and concentrated in vacuo to obtain crude material. The crude material was purified via silica gel column chromatography eluting with 5% EtOAc in hexanes to afford 1-(4-methoxyphenyl)-4-methylpent-2-yne-1,4-diol (6.3 g, 78%) as an oil.
Reaction SMILES: [NH2:1][C:2]1[C:3]([O:17][CH3:18])=[C:4]([C:15]#[N:16])[CH:5]=[C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:7]=1[F:8].[Br:19]N1C(=O)CCC1=O>C(O)(=O)C>[NH2:1][C:2]1[C:3]([O:17][CH3:18])=[C:4]([C:15]#[N:16])[C:5]([Br:19])=[C:6]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:7]=1[F:8]
Reactant: COc1c(C#N)cc(-c2ccccc2)c(F)c1N
Reactant: O=C1CCC(=O)N1Br
Solvent: CC(=O)O
Product: COc1c(N)c(F)c(-c2ccccc2)c(Br)c1C#N
Temperature: 25 °C
Reaction time: 1 h
Yield: 89.5 %

Procedure:
5-Amino-6-fluoro-4-methoxybiphenyl-3-carbonitrile (I-234) (500 mg, 2.06 mmol) was dissolved in acetic acid (9.5 ml), and at room temperature, N-bromosuccinimide (441 mg, 2.48 mmol) was gradually added. After stirring under nitrogen atmosphere at room temperature for 1 hour, the solvent was evaporated away under reduced pressure. The residue was fractionated with ethyl acetate and aqueous 1M sodium hydroxide solution. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated away, and the resulting residue was purified by middle-pressure liquid chromatography (eluent, hexane:ethyl acetate=3:1) to obtain the entitled compound (592 mg, 89%) as a pale brown solid.
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-:10])=[O:9])[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[NH:17]1[CH:21]=[CH:20][N:19]=[CH:18]1.C>C1(C)C=CC=CC=1.[Cu].O>[N+:8]([C:4]1[CH:3]=[C:2]([N:17]2[CH:21]=[CH:20][N:19]=[CH:18]2)[CH:7]=[CH:6][CH:5]=1)([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1cccc(I)c1
Reactant: c1c[nH]cn1
Agent: [Cu]
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: O
Product: O=[N+]([O-])c1cccc(-n2ccnc2)c1
Temperature: 200 °C
Reaction time: 16 h
Yield: 71.4 %

Procedure:
An intimate mixture of 1-iodo-3-nitrobenzene (24.9 g, 0.1 mol), copper bronze (320 mg, 5 mmol), potassium carbonate (15.2 g, 0.11 mol) and imidazole (15.0 g, 0.22 mol) was heated under a stream of nitrogen at 200° C. for 90 minutes. The reaction was cooled to 100° C., carefully treated with water (750 ml) and the resulting suspension stirred to ambient temperature over 16 hours. Filtration gave a grey-coloured solid which was dissolved in hot toluene (125 ml) and treated with decolourising charcoal (2 g). Filtration and cooling afforded 1-(3-nitrophenyl)-1H-imidazole as pale green needles (13.5 g, 71%). δH (360 MHz, CDCl3) 7.29 (1H, br s), 7.38 (1H, br s), 7.68-7.78 (2H, m), 7.97 (1H, br s), 8.23-8.29 (2H, m).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]2[CH2:13][N:14]([C:16]3[CH:17]=[N:18][CH:19]=[C:20]([CH:24]=3)[C:21](O)=[O:22])[CH2:15][C@H:10]2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:25][C:26]1[CH:27]=[C:28]([CH:30]=[C:31]([CH3:33])[CH:32]=1)[NH2:29]>>[CH3:25][C:26]1[CH:27]=[C:28]([NH:29][C:21]([C:20]2[CH:24]=[C:16]([N:14]3[CH2:15][C@@H:10]4[CH2:9][N:8]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:12][C@@H:11]4[CH2:13]3)[CH:17]=[N:18][CH:19]=2)=[O:22])[CH:30]=[C:31]([CH3:33])[CH:32]=1
Reactant: Cc1cc(C)cc(N)c1
Reactant: CC(C)(C)OC(=O)N1C[C@@H]2CN(c3cncc(C(=O)O)c3)C[C@@H]2C1
Product: Cc1cc(C)cc(NC(=O)c2cncc(N3C[C@H]4CN(C(=O)OC(C)(C)C)C[C@H]4C3)c2)c1

Procedure:
The product from Example 33B and 3,5-dimethylaniline were processed as described in Example 33C to provide the title compound. MS (APCI) m/z 337 (M+H)+.
Reaction SMILES: ClC1C=C(Cl)C=CC=1C1N=C(CC)C(N[C@H]2[C@@H](OCC)CNC2)=NC=1CC.[Cl:28][C:29]1[CH:34]=[C:33]([Cl:35])[CH:32]=[CH:31][C:30]=1[C:36]1[N:37]=[C:38]([CH2:64][CH3:65])[C:39]([NH:44][C@H:45]2[C@@H:49]([O:50][CH2:51][CH2:52][F:53])[CH2:48][N:47](C(OCC3C=CC=CC=3)=O)[CH2:46]2)=[N:40][C:41]=1[CH2:42][CH3:43]>>[Cl:28][C:29]1[CH:34]=[C:33]([Cl:35])[CH:32]=[CH:31][C:30]=1[C:36]1[N:37]=[C:38]([CH2:64][CH3:65])[C:39]([NH:44][C@H:45]2[C@@H:49]([O:50][CH2:51][CH2:52][F:53])[CH2:48][NH:47][CH2:46]2)=[N:40][C:41]=1[CH2:42][CH3:43]
Reactant: CCc1nc(-c2ccc(Cl)cc2Cl)c(CC)nc1N[C@@H]1CN(C(=O)OCc2ccccc2)C[C@@H]1OCCF
Agent: CCO[C@H]1CNC[C@H]1Nc1nc(CC)c(-c2ccc(Cl)cc2Cl)nc1CC
Product: CCc1nc(-c2ccc(Cl)cc2Cl)c(CC)nc1N[C@@H]1CNC[C@@H]1OCCF

Procedure:
Following the procedure for the preparation of 5-(2,4-dichlorophenyl)-N-[(cis)-4-ethoxypyrrolidin-3-yl]-3,6-diethylpyrazin-2-amine but substituting benzyl (3R,4S)-3-{[5-(2,4-dichlorophenyl)-3,6-diethylpyrazin-2-yl]amino}-4-(2-fluoroethoxy)pyrrolidine-1-carboxylate and making non-critical variations provided the title compound as an oil: 1H NMR (400 MHz, CDCl3) δ) 7.49, 7.35-7.26, 5.38, 4.68-4.53, 4.11, 3.88, 3.80, 3.74, 3.46, 3.24-3.16, 2.93, 2.70, 2.62, 2.29, 2.00, 1.33-1.24, 1.15; IR (liq.) 2971 (s), 2936 (s), 2874, 2359 (w), 2342 (w), 1566 (s), 1552 (s), 1500 (s), 1470 (s), 1396 (s), 1200 (s), 1129 (s), 1102 (s), 1046 (s), 868, cm−1; HRMS (FAB) calcd for C20H25Cl2FN4O+H 427.1468, found 427.1474.
Reaction SMILES: C(O[C:6]([C:8]1[N:9]=[CH:10][C:11]2[C:16]([C:17]=1[OH:18])=[CH:15][CH:14]=[C:13]([S:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH:12]=2)=[O:7])CCC.[NH2:26][CH2:27][CH2:28][CH2:29][C:30]([OH:32])=[O:31].C[O-].[Na+]>>[OH:18][C:17]1[C:16]2[C:11](=[CH:12][C:13]([S:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:14][CH:15]=2)[CH:10]=[N:9][C:8]=1[C:6]([NH:26][CH2:27][CH2:28][CH2:29][C:30]([OH:32])=[O:31])=[O:7]
Reactant: NCCCC(=O)O
Reactant: CCCCOC(=O)c1ncc2cc(Sc3ccccc3)ccc2c1O
Agent: C[O-]
Agent: [Na+]
Product: O=C(O)CCCNC(=O)c1ncc2cc(Sc3ccccc3)ccc2c1O
Yield: 91.5 %

Procedure:
A mixture of 4-hydroxy-7-phenylsulfanyl-isoquinoline-3-carboxylic acid butyl ester (50 mg, 0.14 mmol) (prepared according to WO 2004108681), 4-aminobutyric acid (730 mg, 7.08 mmol) and NaOMe (11 mL, 5.31 mmol, 0.5 M in MeOH) was refluxed for 3 days, then partitioned between EtOAc and water. 1 M HCl was added with stirring until pH was ˜1. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by column chromatography (0-60% EtOAc/hexanes+2% AcOH) to give 49 mg of the title compound. MS: (+) m/z 383.09 (M+1).
Reaction SMILES: [F:1][C:2]([F:27])([F:26])[CH2:3][N:4]1[CH:8]=[C:7]([C:9]2[N:14]=[CH:13][C:12]3[CH:15]=[N:16][N:17](COCC[Si](C)(C)C)[C:11]=3[CH:10]=2)[CH:6]=[N:5]1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[F:27][C:2]([F:1])([F:26])[CH2:3][N:4]1[CH:8]=[C:7]([C:9]2[N:14]=[CH:13][C:12]3[CH:15]=[N:16][NH:17][C:11]=3[CH:10]=2)[CH:6]=[N:5]1
Reactant: C[Si](C)(C)CCOCn1ncc2cnc(-c3cnn(CC(F)(F)F)c3)cc21
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: FC(F)(F)Cn1cc(-c2cc3[nH]ncc3cn2)cn1
Temperature: 25 °C
Reaction time: 20 h
Yield: 99.9 %

Procedure:
A mixture of 6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1-((2-(trimethylsilyl)ethoxy)-methyl)-1H-pyrazolo[4,3-c]pyridine (800 mg, 2.02 mmol) and TFA (5 mL) in DCM (10 mL) was stirred at ambient temperature for 20 hours. The reaction mixture was concentrated under reduced pressure to afford 6-(1-(2,2,2-trifluoroethyl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-c]-pyridine as a yellow oil (539 mg, 100%). MS (ESI) m/z: 268 [M+H]+.
Reaction SMILES: CCCC[Sn]([O:14][Sn:15]([CH2:24][CH2:25][CH2:26][CH3:27])([CH2:20][CH2:21][CH2:22][CH3:23])[CH2:16][CH2:17][CH2:18][CH3:19])(CCCC)CCCC.[CH3:28][N:29]([CH3:34])[CH2:30][CH2:31][CH2:32]O.O>C1C=CC=CC=1>[CH2:24]([Sn:15]([O:14][CH2:32][CH2:31][CH2:30][N:29]([CH3:34])[CH3:28])([CH2:16][CH2:17][CH2:18][CH3:19])[CH2:20][CH2:21][CH2:22][CH3:23])[CH2:25][CH2:26][CH3:27]
Reactant: CN(C)CCCO
Reactant: CCCC[Sn](CCCC)(CCCC)O[Sn](CCCC)(CCCC)CCCC
Solvent: c1ccccc1
Solvent: O
Product: CCCC[Sn](CCCC)(CCCC)OCCCN(C)C

Procedure:
3-Dimethylamino-1-Propyl Tributylstannyl Ether is prepared from 59.6 gm (0.1 mole) bis(tributyltin) oxide and 20.6 gm (0.2 mole) 3-dimethylamino-1-propanol in 200 ml benzene. This is stirred and heated to reflux in a system that contains a Dean-Starke tube. After 30 minutes refluxing water began to collect in the Dean-Starke tube and after refluxing for 22 hours a total of 1.9 ml of water (theory 1.8 ml) had collected. The benzene is stripped off on a rotating evaporator to provide 77.1 gm of straw colored liquid. This is fractionated at reduced pressure, with 53.0 gm water-white liquid (Percent yield - 67.6) being collected at 135°-139° C. at 0.7 mm. Infrared spectral analysis shows this to be the desired ether.
Reaction SMILES: [C:1]([NH:4][C:5]1[C:6]([I:35])=[C:7]([C:24]([NH:26][CH2:27][CH:28]([CH2:30][CH:31]([OH:34])[CH2:32][OH:33])[OH:29])=[O:25])[C:8]([I:23])=[C:9]([C:21]=1[I:22])[C:10]([NH:12][CH2:13][CH:14]([CH2:16][CH:17]([OH:20])[CH2:18][OH:19])[OH:15])=[O:11])(=[O:3])[CH3:2].[CH3:36][O:37][CH2:38][CH2:39]Br>>[OH:34][CH:31]([CH2:32][OH:33])[CH2:30][CH:28]([OH:29])[CH2:27][NH:26][C:24](=[O:25])[C:7]1[C:6]([I:35])=[C:5]([N:4]([CH2:39][CH2:38][O:37][CH3:36])[C:1](=[O:3])[CH3:2])[C:21]([I:22])=[C:9]([C:10]([NH:12][CH2:13][CH:14]([CH2:16][CH:17]([OH:20])[CH2:18][OH:19])[OH:15])=[O:11])[C:8]=1[I:23]
Reactant: CC(=O)Nc1c(I)c(C(=O)NCC(O)CC(O)CO)c(I)c(C(=O)NCC(O)CC(O)CO)c1I
Reactant: COCCBr
Product: COCCN(C(C)=O)c1c(I)c(C(=O)NCC(O)CC(O)CO)c(I)c(C(=O)NCC(O)CC(O)CO)c1I

Procedure:
This compound is prepared from 5-acetamido-N,N'-bis[(2,3-dihydroxypropyl)-2-hydroxyethyl]-2,4,6-triiodoisophthalamide, prepared as in Example 2, Step B, with 2-bromoethyl methyl ether (BrCH2CH2OCH3) in the same manner as described in Example 8.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]3=[N:16][CH:17]=[C:18](I)[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].O1CCOCC1.[CH3:26][O:27][C:28]1[CH:29]=[C:30](B(O)O)[CH:31]=[CH:32][C:33]=1[O:34][CH3:35].C([O-])([O-])=O.[K+].[K+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[S:15][C:14]3=[N:16][CH:17]=[C:18]([C:31]4[CH:30]=[CH:29][C:28]([O:27][CH3:26])=[C:33]([O:34][CH3:35])[CH:32]=4)[N:13]3[N:12]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: COc1ccc(-c2nn3c(I)cnc3s2)cc1OC
Reactant: COc1ccc(B(O)O)cc1OC
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: COc1ccc(-c2nn3c(-c4ccc(OC)c(OC)c4)cnc3s2)cc1OC
Temperature: 120 °C
Yield: 21.8 %

Procedure:
A mixture of 2-(3,4-dimethoxy-phenyl)-5-iodo-imidazo[2,1-b][1,3,4]thiadiazole (0.10 g, 0.3 mmol, 1 eq), dioxane (5 mL), 3,4-dimethoxyphenylboronic acid (0.12 g, 0.6 mmol, 2.5 eq), Pd(Ph3P)2Cl2 (0.018 g, 0.1 eq), K2CO3 (0.178 g, 1.3 mmol, 5 eq) and water (2 mL) was heated in the microwave oven (120° C., 30 min). The reaction mixture was concentrated, and the residue was purified by column chromatography (SiO2, cyclohexane/5-100% EtOAc). The obtained product was triturated with MeOH/Et2O to give the desired product (yellow solid, 0.026 g, 26%). HPLC-MS: (5-100% B in 10 min, 0.6 mL/min, 50° C.): tR=7.24 min, [M+H]+ m/z 398.1; 1H NMR (300 MHz, DMSO) δ/ppm 7.74 (s, 1H), 7.70 (d, J=2.0, 1H), 7.61 (dd, J=2.0, 8.4, 1H), 7.57-7.50 (m, 2H), 7.17 (d, J=8.2, 1H), 7.09 (d, J=8.5, 1H), 3.88 (s, 6H), 3.86 (s, 3H), 3.81 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:23]=[CH:22][C:11]([O:12][C:13]([CH3:21])([C:17]([F:20])([F:19])[F:18])[C:14](O)=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.S(Cl)([Cl:26])=O.CN(C)C=O>C1C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:23]=[CH:22][C:11]([O:12][C:13]([CH3:21])([C:17]([F:20])([F:19])[F:18])[C:14]([Cl:26])=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1
Reactant: O=S(Cl)Cl
Reactant: CC(Oc1ccc(-c2ccc(Cl)cc2)cc1)(C(=O)O)C(F)(F)F
Solvent: CN(C)C=O
Solvent: c1ccccc1
Product: CC(Oc1ccc(-c2ccc(Cl)cc2)cc1)(C(=O)Cl)C(F)(F)F
Yield: 91.9 %

Procedure:
A solution of (±)-2-[4-(4-chlorophenyl)phenoxy]-3,3,3-trifluoro-2-methylpropionic acid (414 mg.), thionyl chloride (1.0 g.) and dimethylformamide (0.05 g.) in benzene (10 ml.) is heated under reflux for 1 hour. The solvent is evaporated in vacuo, and light petroleum (10 ml., b.p. 60°-80° C.) is added, and the mixture is re-evaporated. A further 10 ml. of light petroleum are added, and the mixture re-evaporated. The residue is dissolved in light petroleum, and the solution is filtered and evaporated to give (±)-2-[4-(4-chlorophenyl)-phenoxy]-3,3,3-trifluoro-2-methylpropionyl chloride (401 mg.).
Reaction SMILES: [CH2:1]([C:13]1[C:21]2[S:22][CH:23]=[CH:24][C:20]=2[C:19]([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])=[C:15]2[S:16][CH:17]=[CH:18][C:14]=12)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].C([Li])CCC.[CH3:42][Sn:43](Cl)([CH3:45])[CH3:44].O>O1CCCC1>[CH2:1]([C:13]1[C:21]2[S:22][C:23]([Sn:43]([CH3:45])([CH3:44])[CH3:42])=[CH:24][C:20]=2[C:19]([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH3:36])=[C:15]2[S:16][C:17]([Sn:43]([CH3:45])([CH3:44])[CH3:42])=[CH:18][C:14]=12)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: C[Sn](C)(C)Cl
Reactant: CCCCCCCCCCCCc1c2ccsc2c(CCCCCCCCCCCC)c2ccsc12
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Product: CCCCCCCCCCCCc1c2cc([Sn](C)(C)C)sc2c(CCCCCCCCCCCC)c2cc([Sn](C)(C)C)sc12
Temperature: 25 °C
Reaction time: 1 h
Yield: 58.5 %

Procedure:
Preparation of 4,8-didodecyl-2,6-Bis-trimethylstannylbenzo[1, 2-1):4,5-b′]dithiophene. To a solution of 4,8-didodecylbenzo[1,2-b:4,5-b′]dithiophene (553 mg, 1.05 mmol) in dry tetrahydrofuran (16 mL) was added n-butyllithium (2.5 M in hexane, 0.92 mL, 2.31 mmol) at −78° C. After 1 hour, trimethyltin chloride (488 mg, 2.45 mmol) was added in one portion. The mixture was stirred at room temperature for 2 hours, poured into water and extracted with ether three times. The organic layer was washed with brine and dried over anhydrous MgSO4. Upon evaporating the solvent, a pale yellow oil was obtained which is recrystallized from EtOH to give a white solid (524 mg, yield 58%). 1H NMR (CDCl3, 500 MHz) δ=7.51 (s, 2H), 3.22 (t, J=8.0 Hz, 4H), 1.76-1.91 (m, 4H), 1.36-1.42 (m, 4H), 1.22-1.42 (bs, 32H), 0.91 (t, J=7.0 Hz, 6H), 0.47 (s, 18 H). See also, Chem. Mater. 2006, 18, 3237.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[C:4]([NH2:9])[CH:3]=1.[C:10]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:15]=[CH:14][C:13]([CH:16]2[CH2:22][C:21](=O)[O:20][C:18](=[O:19])[CH2:17]2)=[CH:12][CH:11]=1.Cl>ClCCl.O1CCOCC1>[ClH:1].[C:10]1([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:15]=[CH:14][C:13]([CH:16]([CH2:22][C:21]2[NH:9][C:4]3[CH:3]=[C:2]([Cl:1])[CH:7]=[CH:6][C:5]=3[N:8]=2)[CH2:17][C:18]([OH:20])=[O:19])=[CH:12][CH:11]=1
Reactant: O=C1CC(c2ccc(-c3ccccc3)cc2)CC(=O)O1
Reactant: Nc1ccc(Cl)cc1N
Agent: Cl
Solvent: ClCCl
Solvent: C1COCCO1
Product: O=C(O)CC(Cc1nc2ccc(Cl)cc2[nH]1)c1ccc(-c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 84.2 %

Procedure:
Commercial 4-chloro-1,2-phenylenediamine (214 mg) and 3-(biphenyl-4-yl)glutaric anhydride (399 mg) were dissolved in dichloromethane (5 ml) with heating. The dark solution was stirred at rt for 1 h. The precipitate formed was collected by suction filtration, washed with dichloromethane, and dried in vacuo to give a mixture of regioisomeric amides (0.48 g) as light brown solid. This solid was dissolved in 1,4-dioxane (1 ml) with heating. 4M HCl in 1,4-dioxane (3 ml) was added and the solution was heated to reflux for 1.5 h. The precipitate formed is isolated by suction filtration and washed with 1,4-dioxane and diethyl ether. The crude (0.4 g) is crystallised from acetic acid to provide 3-(biphenyl-4-yl)-4-(5-chloro-2-benzimidazolyl)butanoic acid HCl (0.27 g) as light brown crystals.
Reaction SMILES: Cl.[CH3:2][NH:3][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[NH:11][C:10]([C:13]1[S:14][CH:15]=[CH:16][N:17]=1)=[CH:9]2.[Cl:18][C:19]1[C:24]([S:25](Cl)(=[O:27])=[O:26])=[CH:23][CH:22]=[CH:21][N:20]=1>N1C=CC=CC=1>[Cl:18][C:19]1[C:24]([S:25]([N:3]([CH3:2])[C:4]2[CH:5]=[CH:6][CH:7]=[C:8]3[C:12]=2[NH:11][C:10]([C:13]2[S:14][CH:15]=[CH:16][N:17]=2)=[CH:9]3)(=[O:27])=[O:26])=[CH:23][CH:22]=[CH:21][N:20]=1
Reactant: O=S(=O)(Cl)c1cccnc1Cl
Reactant: CNc1cccc2cc(-c3nccs3)[nH]c12
Agent: Cl
Solvent: c1ccncc1
Product: CN(c1cccc2cc(-c3nccs3)[nH]c12)S(=O)(=O)c1cccnc1Cl
Temperature: 25 °C
Reaction time: 2 h
Yield: 62.7 %

Procedure:
To a solution of N-methyl-2-(1,3-thiazol-2-yl)-1H-indole-7-amine monohydrochloride (132 mg) in pyridine (3 mL) was added 2-chloropyridine-3-sulfonyl chloride (120 mg) at 0° C., and the mixture was stirred at room temperature for 2 hr. The reaction mixture was concentrated, water was added, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to silica gel column chromatography (ethyl acetate:hexane=1:1) to give the title compound (126 mg, yield 62%) as pale-yellow crystals. melting point 203° C.
Reaction SMILES: [CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[N+:8]([C:11]1[CH:12]=[C:13]([CH:22]=[CH:23][C:24]=1Cl)[C:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:15])([O-:10])=[O:9]>>[N+:8]([C:11]1[CH:12]=[C:13]([CH:22]=[CH:23][C:24]=1[N:5]1[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]1)[C:14]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:15])([O-:10])=[O:9]
Reactant: CN1CCNCC1
Reactant: O=C(c1ccccc1)c1ccc(Cl)c([N+](=O)[O-])c1
Product: CN1CCN(c2ccc(C(=O)c3ccccc3)cc2[N+](=O)[O-])CC1
Yield: 90 %

Procedure:
N-methyl-piperazine is reacted with 3-nitro-4-chloro-benzophenone as described in Example 7 or 8 to obtain 3-nitro-4-(N-methyl-piperazino)-benzophenone (compound B11, supra with a yield of 90%. The product melts at 94°C. Analysis for C18H19N3O3 : Calculated: C 66.44% H 5.89% N 12.92% Found: C 66.28% H 5.83% N 12.79%
Reaction SMILES: [C:1]([N:8]([CH3:40])[CH:9]1[CH2:14][CH2:13][CH:12]([N:15]([CH2:28][C:29]2[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][C:34]=2[O:35][CH3:36])[C:16]([C:18]2[S:22][C:21]3[CH:23]=[CH:24][CH:25]=[CH:26][C:20]=3[C:19]=2[Cl:27])=[O:17])[CH2:11][CH2:10]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Br[C:42]1[CH:47]=[CH:46][C:45]([N:48]([CH3:52])[C:49](=[O:51])[CH3:50])=[CH:44][CH:43]=1>>[C:49]([N:48]([CH3:52])[C:45]1[CH:46]=[CH:47][C:42]([C:31]2[CH:32]=[CH:33][C:34]([O:35][CH3:36])=[C:29]([CH2:28][N:15]([C:16]([C:18]3[S:22][C:21]4[CH:23]=[CH:24][CH:25]=[CH:26][C:20]=4[C:19]=3[Cl:27])=[O:17])[CH:12]3[CH2:11][CH2:10][CH:9]([N:8]([CH3:40])[C:1](=[O:2])[O:3][C:4]([CH3:6])([CH3:7])[CH3:5])[CH2:14][CH2:13]3)[CH:30]=2)=[CH:43][CH:44]=1)(=[O:51])[CH3:50]
Reactant: CC(=O)N(C)c1ccc(Br)cc1
Reactant: COc1ccc(B(O)O)cc1CN(C(=O)c1sc2ccccc2c1Cl)C1CCC(N(C)C(=O)OC(C)(C)C)CC1
Product: COc1ccc(-c2ccc(N(C)C(C)=O)cc2)cc1CN(C(=O)c1sc2ccccc2c1Cl)C1CCC(N(C)C(=O)OC(C)(C)C)CC1

Procedure:
Boronic acid 5 (200 mg, 0.34 mmol) is coupled to aryl bromide 62 (93 mg, 0.41 mmol) using Method B to give the title compound.
Reaction SMILES: [C:1]1([C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:10]=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N+:17]([O-])(O)=O>C(O)(=O)C>[NH2:17][C:4]1[CH:5]=[CH:6][C:1]([C:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:10]=[CH:9][CH:8]=2)=[CH:2][CH:3]=1
Reactant: O=[N+]([O-])O
Reactant: c1ccc(-c2cccc3ccccc23)cc1
Solvent: CC(=O)O
Product: Nc1ccc(-c2cccc3ccccc23)cc1
Yield: 39 %

Procedure:
204 g of 1-phenylnaphthalene was nitrated in 1 l of acetic acid using nitric acid. The product was reduced using a reduced iron to obtain 1-(4-aminophenyl)naphthalene (yield: 39%).