Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][CH:6]=1)=[O:4].[NH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.CCN=C=NCCCN(C)C.C(N(CC)CC)C>O.C1COCC1>[NH:14]([C:9]([C:8]1[CH:7]=[CH:6][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:13][CH:12]=1)=[O:11])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: COC(=O)c1ccc(C(=O)O)cc1
Reactant: Nc1ccccc1
Agent: CCN=C=NCCCN(C)C
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Solvent: O
Product: COC(=O)c1ccc(C(=O)Nc2ccccc2)cc1
Temperature: 25 °C
Reaction time: 20 h

Procedure:
4-Methoxycarbonyl benzoic acid (540 mg), aniline (0.27 ml), WSC (863 mg) and triethylamine (0.84 ml) were added to THF (20 ml). After the reaction mixture was stirred at room temperature for 20 hours, the reaction mixture was placed in water, and extraction was conducted using ethyl acetate-THF (1:1). The organic layer was washed with water, saturated sodium bicarbonate solution, and saturated aqueous sodium chloride solution, dried, and then concentrated. The resulting crude crystals were recrystallized from ethyl acetate-hexane to give the titled compound (659 mg).
Reaction SMILES: [CH3:1][C:2]1[C:12]2[S:11][CH2:10][CH2:9][C:8](=O)[NH:7][C:6]=2[CH:5]=[CH:4][CH:3]=1.COCCO[AlH2-]OCCOC.[Na+].[OH-].[Na+].[C@H](O)(C([O-])=O)[C@@H](O)C([O-])=O.[Na+].[K+]>C1(C)C=CC=CC=1.C(Cl)(Cl)Cl>[CH3:1][C:2]1[C:12]2[S:11][CH2:10][CH2:9][CH2:8][NH:7][C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: Cc1cccc2c1SCCC(=O)N2
Agent: COCCO[AlH2-]OCCOC
Agent: O=C([O-])[C@H](O)[C@@H](O)C(=O)[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: ClC(Cl)Cl
Product: Cc1cccc2c1SCCCN2
Temperature: 85 °C
Reaction time: 1 h
Yield: 107.3 %

Procedure:
To a suspension of 9-methyl-2,3-dihydro-1,5-benzothiazepin-4(5H)-one (4:1 regioisomers, 500 mg, 2.6 mmol) in toluene (10 mL) was added dropwise over 3 min Red-Al (65% w. in toluene, 1.6 mL). This solution was heated at 85° C. for 1.5 h. After it was allowed to cool to 23° C., aqueous 1N NaOH solution (2 mL) was added cautiously. Then, CHCl3 (50 mL) and aqueous saturated Rochelle salt solution (50 mL) were added sequentially. This two-phase mixture was stirred vigorously at 23° C. for 1 h. The layers were separated, and the aqueous layer was back-extracted with CHCl3 (2×50 mL). The extracts were combined, dried (MgSO4) and concentrated in vacuo. to give 9-methyl-2,3,4,5-tetrahydro-1,5-benzothiazepine (500 mg, >100%) as a yellow oil. 1H NMR (CDCl3, 300 MHz): δ6.92 (t, 1H, J=7.3 Hz), 6.75 (d, 1H, J=7.4 Hz), 6.58 (d, 1H, J=8.1 Hz), 3.34 (t, 1H, J=5.2 Hz), 2.92 (t, 2H, J=5.8 Hz), 2.48 (s, 3H), 2.25 (s, 3H), 2.04 (quintet, 2H, J=3.0 Hz) ppm.
Reaction SMILES: [C:1]([OH:20])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].[CH2:21](O)[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH3:38].C1(C)C(S(O)(=O)=O)=CC=CC=1.O>C1(C)C=CC=C(C)C=1>[C:1]([O:20][CH2:38][CH2:37][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH3:21])(=[O:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CCCCCCCCCCCCCCCCCCO
Reactant: CCCCCCCCCCCCCCCCCC(=O)O
Agent: Cc1ccccc1S(=O)(=O)O
Solvent: Cc1cccc(C)c1
Solvent: O
Product: CCCCCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCCCC
Yield: 112.5 %

Procedure:
71.1 grams (0.25 mole) of purified stearic acid (melting point 70° C.) and 101.5 grams (0.375 mole) of 1-octadecanol were added to 5.5 grams of toluenesulfonic acid in 100 ml of m-xylene and charged into a Dean-Stark equipped 1-liter round bottom flask. After 4 hours of reflux under nitrogen at a pot temperature of 180° C., 6 ml of water was collected. The solvent and any excess alcohol were stripped under 29 inches of mercury vacuum at 130° C. to give 151 grams of a solid having a melting point of 58° C. The acid number of the product was 3.0. Infrared spectroscopic analysis showed formation of the ester function.
Reaction SMILES: [C:1]1([C:7]#[C:8][C:9]2[CH:10]=[N:11][NH:12][C:13]=2[NH:14]C(=O)C)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:18]([O:20][CH:21]=[CH2:22])[CH3:19]>C(Cl)Cl.O1CCOCC1>[CH2:18]([O:20][CH:21]([N:12]1[C:13]([NH2:14])=[C:9]([C:8]#[C:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:10]=[N:11]1)[CH3:22])[CH3:19]
Reactant: CC(=O)Nc1[nH]ncc1C#Cc1ccccc1
Reactant: C=COCC
Solvent: C1COCCO1
Solvent: ClCCl
Product: CCOC(C)n1ncc(C#Cc2ccccc2)c1N
Temperature: 75 °C
Yield: 80.3 %

Procedure:
A solution of N-(4-(phenylethynyl)-1H-pyrazol-5-yl)acetamide (17.6 g, 78 mmol), ethoxyethene (11.2 mL, 117 mmol) and HO in 1,4-dioxane (1 mL, 4 mmol) in CH2Cl2 (520 mL) was stirred at room temperature for 1 h and concentrated in vacuo. The residue was dissolved in ethanol (260 mL) and 25% aq. NaOH solution (260 mL) and the reaction mixture was heated to 75° C. for 4 h and cooled to room temperature. The ethanol was partly concentrated in vacuo and the resulting solid collected by filtration, washed with water and minimum cold ethanol and dried in vacuo to provide the title compound as a solid (16 g).
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]([NH:13][CH:14]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=3)[C:15]([F:18])([F:17])[F:16])=[O:12])[NH:8]2)=[CH:4][C:3]=1[C:29]([NH:31][C:32]1([C:35]#[N:36])[CH2:34][CH2:33]1)=[O:30].[H-].[Na+].[CH2:39](Br)[C:40]#[CH:41].O>CN(C)C=O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]([NH:13][CH:14]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:26])([F:28])[F:27])[CH:20]=3)[C:15]([F:16])([F:18])[F:17])=[O:12])[N:8]2[CH2:41][C:40]#[CH:39])=[CH:4][C:3]=1[C:29]([NH:31][C:32]1([C:35]#[N:36])[CH2:34][CH2:33]1)=[O:30]
Reactant: N#CC1(NC(=O)c2cc3cc(C(=O)NC(c4cccc(C(F)(F)F)c4)C(F)(F)F)[nH]c3cc2Cl)CC1
Reactant: C#CCBr
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: C#CCn1c(C(=O)NC(c2cccc(C(F)(F)F)c2)C(F)(F)F)cc2cc(C(=O)NC3(C#N)CC3)c(Cl)cc21
Yield: 50.9 %

Procedure:
6-Chloro-N5-(1-cyanocyclopropyl)-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide (0.14 g, 0.26 mmol) was dissolved under argon at 0° C. in N,N-dimethylformamide (1 ml). Sodium hydride (60%; 0.079 g, 1.97 mmol) was added and the mixture was stirred while cooling with ice for 1.5 h. Subsequently, propargyl bromide (0.04 mg, 0.26 mmol) was added dropwise. The reaction mixture was thawed while stirring within 16 h. Water and ethyl acetate were added and the phases were separated. The organic phase was washed with saturated sodium chloride solution and dried over magnesium sulphate, and the solvent was removed under reduced pressure. The residue is purified by means of preparative HPLC (Kromasil100, C18 250×20; eluent: acetonitrile in water, gradient: 10-100%) to obtain 0.075 g (50% of theory) of 6-chloro-N5-(1-cyanocyclopropyl)-1-(prop-2-yn-1-yl)-N2-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}-1H-indole-2,5-dicarboxamide.
Reaction SMILES: [NH2:1][S:2]([N:5]1[CH2:9][CH2:8][C@H:7]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:6]1)(=[O:4])=[O:3].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:59]1[CH:64]=[C:63]([O:65][CH3:66])[N:62]=[C:61]([S:67][CH2:68][C:69]2[CH:74]=[CH:73][CH:72]=[C:71]([F:75])[C:70]=2[F:76])[N:60]=1>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[F:76][C:70]1[C:71]([F:75])=[CH:72][CH:73]=[CH:74][C:69]=1[CH2:68][S:67][C:61]1[N:60]=[C:59]([NH:1][S:2]([N:5]2[CH2:9][CH2:8][C@H:7]([NH:10][C:11](=[O:17])[O:12][C:13]([CH3:14])([CH3:16])[CH3:15])[CH2:6]2)(=[O:4])=[O:3])[CH:64]=[C:63]([O:65][CH3:66])[N:62]=1
Reactant: COc1cc(Cl)nc(SCc2cccc(F)c2F)n1
Reactant: CC(C)(C)OC(=O)N[C@H]1CCN(S(N)(=O)=O)C1
Agent: [Pd]
Agent: CC(C)c1cc(C(C)C)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c(C(C)C)c1
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: C1COCCO1
Product: COc1cc(NS(=O)(=O)N2CC[C@H](NC(=O)OC(C)(C)C)C2)nc(SCc2cccc(F)c2F)n1
Temperature: 100 °C

Procedure:
A mixture of tert-butyl [(3S)-1-(aminosulfonyl)pyrrolidin-3-yl]carbamate (the product from step i), 0.525 g), tris(dibenzylideneacetone)dipalladium (0) (50 mg), 2-dicyclohexylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (XPHOS) (50 mg), cesium carbonate (0.429 g) and 4-Chloro-2-[[(2,3-difluorophenyl)methyl]thio]-6-methoxypyrimidine ((the product from example 35 step i), 0.400 g) in dioxane (20 ml) was heated at reflux in a microwave at 100° C., 300 W, open vessel with cooling for 40 mins. The reaction mixture was then reduced in vacuo and the residue separated between DCM (150 ml) and H2O (150 ml). The organics were separated and the aqueous layer was re-extracted with DCM (2×150 ml). Organics were combined, dried (MgSO4) and reduced in vacuo to give the subtitle compound as a yellow solid. Yield: 0.75 g
Reaction SMILES: O=P12OP3(OP(OP(O3)(O1)=O)(=O)O2)=O.CS(O)(=O)=O.CO[CH:22]([O:40]C)[CH2:23][NH:24][C:25]([C:27]1[CH:28]=[C:29]([CH3:39])[C:30]2[NH:34][C:33]([CH2:35][CH2:36][CH3:37])=[N:32][C:31]=2[CH:38]=1)=O.C(=O)([O-])O.[Na+]>C(OCC)(=O)C>[CH3:39][C:29]1[C:30]2[NH:34][C:33]([CH2:35][CH2:36][CH3:37])=[N:32][C:31]=2[CH:38]=[C:27]([C:25]2[O:40][CH:22]=[CH:23][N:24]=2)[CH:28]=1
Reactant: CCCc1nc2cc(C(=O)NCC(OC)OC)cc(C)c2[nH]1
Agent: CS(=O)(=O)O
Agent: O=C([O-])O
Agent: O=P12OP3(=O)OP(=O)(O1)OP(=O)(O2)O3
Solvent: CCOC(C)=O
Product: CCCc1nc2cc(-c3ncco3)cc(C)c2[nH]1
Temperature: 130 °C
Reaction time: 7 h
Yield: 65.5 %

Procedure:
[step 2] To 7.7% phosphorus pentaoxide-methanesulfonic acid (Eaton's reagent; 10 mL) was added 6-(2,2-dimethoxyethylcarbamoyl)-4-methyl-2-propylbenzimidazole (400 mg, 1.31 mmol) obtained in step 1, and the mixture was stirred at 130° C. for 7 hr. The reaction solution was added to ice-cooled aqueous solution (100 mL), and the mixture was stirred for 30 min. After stirring, saturated aqueous sodium hydrogen carbonate solution (80 mL) and ethyl acetate (200 mL) were added to the mixture. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate=20/80 to 0/100) to give the title compound (207 mg, 66%).
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([O:10][CH2:11][CH3:12])[N:5]=[C:4]([C:13]([OH:15])=O)[CH:3]=1.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[NH2:48][CH2:49][C:50]1([CH3:63])[CH2:55][CH2:54][N:53]([C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])[CH2:52][CH2:51]1>CN(C)C=O.O>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([O:10][CH2:11][CH3:12])[N:5]=[C:4]([C:13]([NH:48][CH2:49][C:50]2([CH3:63])[CH2:55][CH2:54][N:53]([C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])[CH2:52][CH2:51]2)=[O:15])[CH:3]=1
Reactant: CC1(CN)CCN(C(=O)OC(C)(C)C)CC1
Reactant: CCOc1nc(C(=O)O)cc(N)c1C#N
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CCOc1nc(C(=O)NCC2(C)CCN(C(=O)OC(C)(C)C)CC2)cc(N)c1C#N
Reaction time: 0.25 h

Procedure:
A solution of 4-amino-5-cyano-6-ethoxypicolinic acid (0.100 g) in N,N-dimethylformamide (2.5 mL) was treated with 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (0.102 g), 1-hyroxybenzotriazole hydrate (0.0813 g), followed by diisopropylethylamine (0.252 mL) at room temperature. After stirring for 15 minutes, the compound prepared in Example 416 (0.116 g) was added. Stirring was continued overnight, the mixture diluted with water, organic layer separated and washed with brine, dried, evaporated in vacuo to a beige paste that was triturated in ether and solids collected by filtration (0.584 g) with the following physical data.
Reaction SMILES: ClC(Cl)C(O)=O.CO.COC1C=CC(C([O:30][CH2:31][CH2:32][O:33][CH2:34][CH2:35][O:36][CH2:37][CH2:38][O:39][CH2:40][CH2:41][O:42][N:43]2[C:47](=[O:48])[C:46]3=[CH:49][CH:50]=[CH:51][CH:52]=[C:45]3[C:44]2=[O:53])(C2C=CC=CC=2)C2C=CC(OC)=CC=2)=CC=1>C(Cl)Cl>[C:44]1(=[O:53])[N:43]([O:42][CH2:41][CH2:40][O:39][CH2:38][CH2:37][O:36][CH2:35][CH2:34][O:33][CH2:32][CH2:31][OH:30])[C:47](=[O:48])[C:46]2=[CH:49][CH:50]=[CH:51][CH:52]=[C:45]12
Reactant: COc1ccc(C(OCCOCCOCCOCCON2C(=O)c3ccccc3C2=O)(c2ccccc2)c2ccc(OC)cc2)cc1
Agent: O=C(O)C(Cl)Cl
Solvent: CO
Solvent: ClCCl
Product: O=C1c2ccccc2C(=O)N1OCCOCCOCCOCCO
Reaction time: 18 h
Yield: 72 %

Procedure:
A solution of dichloroacetic acid in CH2Cl2 (100 mL, 3:97, v/v) and methanol (20 mL) was added to N-[11-(4,4′-dimethoxytrityloxy)-3,6,9-trioxaundecanyloxy]phthalimide (2.3 g, 3.6 mmol), and the reaction mixture was stirred for 18 hours. All volatile material was evaporated in vacuo and the residue was dissolved in CH2Cl2 (10 mL). Silica gel column purification using an eluent system with a stepwise gradient of acetic acid in CH2Cl2 (0-4%) gave 0.88 g (72%) of 11-(phthalimidooxy)-3,6,9-trioxaundecan-1-ol after coevaporation of the pooled fractions with water and pyridine.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[NH:7][N:8]=[C:9]([CH3:12])[C:10]=1[Cl:11])=[O:5])[CH3:2].C([O-])([O-])=O.[K+].[K+].Cl[CH2:20][C:21]([N:23]1[CH2:28][CH2:27][N:26]([C:29]2[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=2)[CH2:25][CH2:24]1)=[O:22].CN(C=O)C>CCCCCC.C(OCC)(=O)C>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH2:20][C:21]([N:23]2[CH2:24][CH2:25][N:26]([C:29]3[CH:34]=[CH:33][C:32]([F:35])=[CH:31][CH:30]=3)[CH2:27][CH2:28]2)=[O:22])[N:8]=[C:9]([CH3:12])[C:10]=1[Cl:11])=[O:5])[CH3:2]
Reactant: O=C(CCl)N1CCN(c2ccc(F)cc2)CC1
Reactant: CCOC(=O)c1[nH]nc(C)c1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCCCCC
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCOC(=O)c1c(Cl)c(C)nn1CC(=O)N1CCN(c2ccc(F)cc2)CC1

Procedure:
Protocol T was followed using 4-Chloro-5-methyl-2H-pyrazole-3-carboxylic acid ethyl ester, K2CO3, 2-Chloro-1-[4-(4-fluoro-phenyl)-piperazin-1-yl]-ethanone and DMF. Column chromatography using a solvent mixture (hexane/ethyl acetate=2/3) afforded the title compound as a white solid. 1H NMR (400 MHz, CDCl3): 6.94-7.1 (m, 2H), 6.84-6.88 (dd, 2H), 5.04 (s, 2H), 4.38-4.44 (q, 2H), 3.62-3.80 (m, 4H), 3.02-3.14 (m, 4H), 2.3 (s, 3H), 1.36-1.42 (t, 3H). 13C NMR (400 MHz, CDCl3): 182, 165, 119, 116.2, 116, 61.4, 52.3, 51, 50.8, 45.8, 42.6, 14.4, 10.
Reaction SMILES: [CH3:1][S:2][C:3]1[CH:18]=[CH:17][C:6]2[N:7]([OH:16])[C:8]([C:10]3[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=3)=[N:9][C:5]=2[CH:4]=1.[CH2:19]1COCC1.CI>>[CH3:19][O:16][N:7]1[C:6]2[CH:17]=[CH:18][C:3]([S:2][CH3:1])=[CH:4][C:5]=2[N:9]=[C:8]1[C:10]1[CH:11]=[N:12][CH:13]=[CH:14][CH:15]=1
Reactant: C1CCOC1
Reactant: CSc1ccc2c(c1)nc(-c1cccnc1)n2O
Solvent: CI
Product: COn1c(-c2cccnc2)nc2cc(SC)ccc21
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a stirred solution of 5-(methyl-thio)-2-(pyridin-3-yl)-1H-benzo[d]imidazol-1-ol (0.36 g, 0.001 mol) in THF (20 ml) NaH (60% suspension in mineral oil), (0.14 g, 0.003 mol) was added. After stirring for the next 20 min at room temperature methyl iodide (0.39 g, 0.002 mol) was added drop wise. The resulting solution was continued to stir at room temperature for the next 3 h. The reaction was quenched with ice cold water and extracted with ethyl acetate (3×100 ml). The combined organic layers were washed with brine dried over Na2SO4 and concentrated under vacuum to afford to afford the crude compound which was purified by chromatography to obtain title compound 1-methoxy-5-(methyl-thio)-2-(pyridin-3-yl)-1H-benzo[ ]imidazole as a stick brown solid. 1H NMR (400 MHz, DMSO-d6), δ 9.47 (s, 1H), 8.74-8.73 (m, 1H), 8.53-8.50 (m, 1H), 7.71 (s, 1H), 7.49-7.33 (m, 3H), 4.05 (s, 3H) 2.58 (s, 3H). MS (M+1): 272.
Reaction SMILES: [O:1]([C:8]1[CH:9]=[C:10]([C:18](OC)=[O:19])[CH:11]=[C:12]([CH:17]=1)[C:13](OC)=[O:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCNCC1>C1(C)C=CC=CC=1.C1COCC1>[O:1]([C:8]1[CH:9]=[C:10]([CH:18]=[O:19])[CH:11]=[C:12]([CH:17]=1)[CH:13]=[O:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC(=O)c1cc(Oc2ccccc2)cc(C(=O)OC)c1
Agent: CN1CCNCC1
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: O=Cc1cc(C=O)cc(Oc2ccccc2)c1
Reaction time: 2 h
Yield: 83.1 %

Procedure:
To a solution of dimethyl 5-phenoxyisophthalate (0.143 g, 0.50 mmol) in toluene (12 mL) was added drop-wise a solution of Red-A1 (60% in toluene, 0.673 mL, 2.0 mmol) and 1-methylpiperazine (0.243 mL, 2.2 mmol) in THF at 5° C., and the resulting mixture was stirred for 2 h. The reaction was quenched with H2O (4 mL), and then extracted with EtOAc (20 mL). The organic layer was washed with H2O (10 mL), dried over anhydrous Na2SO4, and then concentrated under reduced pressure. Purification by flash column chromatography (10% EtOAc/hexanes) afforded the desired product (0.094 g, 83%) as a white solid. 1H NMR (300 MHz, CDCl3) δ ppm 10.04 (s, 2H), 8.08 (s, 1H), 7.72 (t, J=1.5 Hz, 2H), 7.46-7.40 (m, 2H), 7.28-7.24 (m, 1H), 7.09-7.06 (m, 2H).
Reaction SMILES: [SH:1][CH2:2][CH2:3][C:4]([N:6]1[C@@H:13]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([O:22][CH3:23])[CH:15]=2)[CH2:12][CH2:11][C@H:7]1[C:8](O)=[O:9])=[O:5].C(=O)=O.CC(C)=O.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl.CN(C)C1C=CN=CC=1>[CH3:23][O:22][C:16]1[CH:15]=[C:14]([C@H:13]2[N:6]3[C@@H:7]([C:8](=[O:9])[S:1][CH2:2][CH2:3][C:4]3=[O:5])[CH2:11][CH2:12]2)[CH:19]=[CH:18][C:17]=1[O:20][CH3:21]
Reactant: COc1ccc([C@H]2CC[C@@H](C(=O)O)N2C(=O)CCS)cc1OC
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Agent: O=C=O
Solvent: ClCCl
Solvent: CC(C)=O
Product: COc1ccc([C@@H]2CC[C@@H]3C(=O)SCCC(=O)N32)cc1OC
Reaction time: 0.08 h

Procedure:
The compound produced in Example 2 is dissolved in about 500 milliliters methylene chloride and the solution is chilled under nitrogen to 15° C. in a dry ice-acetone mixture. 4-Dimethylaminopyridine is added and the mixture is stirred for five minutes. A slight excess of dicyclohexylcarbodiimide dissolved in methylene chloride is added with stirring. The chilled source is removed after 15 minutes and the solution is stirred overnight at room temperature. The volume of the reaction mixture is reduced on a rotary evaporator under reduced pressure to about 100 milliliters. A precipitate is removed by filtration and the filter residue is washed several times with methylene chloride. The filtrate and combined washings are washed successively with 1 N HCl, saturated aqueous NaHCO3, water and saline and the solution is dried over MgSO4. Evaporation of the methylene chloride with a rotary evaporator under reduced pressure yields the title compound.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:7][C:8]1[CH:16]=[C:15]([Cl:17])[CH:14]=[C:13]([Cl:18])[C:9]=1[C:10](Cl)=[O:11].O.[OH-].[Na+]>C1COCC1>[Cl:7][C:8]1[CH:16]=[C:15]([Cl:17])[CH:14]=[C:13]([Cl:18])[C:9]=1[CH2:10][OH:11]
Reactant: O=C(Cl)c1c(Cl)cc(Cl)cc1Cl
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: OCc1c(Cl)cc(Cl)cc1Cl
Reaction time: 1 h
Yield: 69.9 %

Procedure:
A solution of lithium aluminium hydride (1M in THF, 18 mmol, 18 ml) was added slowly to a solution of 2,4,6-trichlorobenzoyl chloride (4.35 g, 17.8 mmol) in THF (70 ml) at 0°. After 1 h water (685 μl) was added, followed by aqueous sodium hydroxide (3M, 685 μl) and more water (2.06 ml). The suspension was stirred vigorously for 1 h, the precipitate filtered off and the filtrate evaporated in vacuo to give a slightly yellow solid. Recrystallisation from diisopropylether gave the title compound as white needles (2.63 g, 70%), m.p. 100-101°δH (CDCl3) 7.35 (2H, s, ArH), 4.91 (2H, br s, CH2CH) and 2.07 (1H, br s, CH); m/z (ES, 60V) 193 (M--OH).
Reaction SMILES: [NH:1](C(OC(C)(C)C)=O)[CH2:2][C:3]([NH:5][C@H:6]([C:14]([NH:16][C@H:17]([C:22]([OH:24])=[O:23])[CH2:18][CH:19]([CH3:21])[CH3:20])=[O:15])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4].N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C>[NH2:1][CH2:2][C:3]([NH:5][C@H:6]([C:14]([NH:16][C@H:17]([C:22]([OH:24])=[O:23])[CH2:18][CH:19]([CH3:20])[CH3:21])=[O:15])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)=[O:4]
Reactant: CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)OC(C)(C)C)C(=O)O
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC(C)C[C@H](NC(=O)[C@H](Cc1ccccc1)NC(=O)CN)C(=O)O
Reaction time: 3.75 h

Procedure:
Boc-Gly-L-Phe-L-Leu-OH (44 mg, 0.1 mmol), benzotriazol-1-yloxytris(dimethylamino)phosphonium hexaflurophsophate (14 mg, 0.104 mmol) are dissolved in dry DMF (1 mL). DIEA (20 μL, 0.115 mmol) is added and about 0.5-1.0 mL of this solution is transferred to a test tube containing amino derivatized ELAMS™. The tube is sealed, vortexed for about 3.5-4 hours and the ELAMS™ pelleted and washed with DMF (3×) and methylene chloride (2×). The ELAMS™ are then deprotected with a solution of 50% trifluoroacetic acid (TFA) in methylene chloride for 30 min., washed with methylene chloride (2×), ethanol (2×) and methylene chloride (2×), and dried at 55° C. for about 1 hour. The identifier tag from each ELAMS™ is detected and recorded.
Reaction SMILES: Cl[C:2]1[CH:3]=[C:4]([N:11]([C:16]2[C:35]([CH:36]3[CH2:38][CH2:37]3)=[CH:34][C:19]3[C:20]([C:30]([NH:32][CH3:33])=[O:31])=[C:21]([C:23]4[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=4)[O:22][C:18]=3[CH:17]=2)[S:12]([CH3:15])(=[O:14])=[O:13])[CH:5]=[CH:6][C:7]=1[N+:8]([O-:10])=[O:9].[CH3:39][Al](C)C.C[Al](C)C.C1N2CCN(CC2)C1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:36]1([C:35]2[C:16]([N:11]([C:4]3[CH:5]=[CH:6][C:7]([N+:8]([O-:10])=[O:9])=[C:2]([CH3:39])[CH:3]=3)[S:12]([CH3:15])(=[O:13])=[O:14])=[CH:17][C:18]3[O:22][C:21]([C:23]4[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=4)=[C:20]([C:30]([NH:32][CH3:33])=[O:31])[C:19]=3[CH:34]=2)[CH2:38][CH2:37]1
Reactant: C[Al](C)C
Reactant: CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(c3ccc([N+](=O)[O-])c(Cl)c3)S(C)(=O)=O)c(C3CC3)cc12
Agent: [Pd]
Agent: C1CN2CCN1CC2
Agent: CC1(C)c2cccc(P(c3ccccc3)c3ccccc3)c2Oc2c(P(c3ccccc3)c3ccccc3)cccc21
Solvent: C1CCOC1
Product: CNC(=O)c1c(-c2ccc(F)cc2)oc2cc(N(c3ccc([N+](=O)[O-])c(C)c3)S(C)(=O)=O)c(C3CC3)cc12
Temperature: 100 °C
Yield: 82 %

Procedure:
To the mixture of 6-(N-(3-chloro-4-nitrophenyl)methylsulfonamido)-5-cyclopropyl-2-(4-fluorophenyl)-N-methylbenzofuran-3-carboxamide (2.5 g, 4.48 mmol) and DABAL-Me3 (1.366 g, 5.38 mmol) in dry Tetrahydrofuran (10 mL) under nitrogen atmosphere was added Pd2(dba)3 (0.041 g, 0.045 mmol) and Xantphos (0.052 g, 0.090 mmol) and the reaction was refluxed at 100° C. for 0.5 h. Reaction mixture was filtered through Celite and washed with methanol (50 mL). After evaporation of the solvent, the crude was redissolved in DCM and washed with water. DCM was dried over anhydrous Na2SO4 and evaporated to give the title compound as a yellow solid in 82% yield. 1H NMR (400 MHz, DMSO-d6) δ ppm: 8.02 (d, J=9.2 Hz, 1H), 7.86-7.93 (m, 2H), 7.55 (d, J=1.8 Hz, 2H), 7.17-7.27 (m, 4H), 5.80 (d, J=4.5 Hz, 1H), 3.22-3.44 (m, 3H), 3.02 (d, J=4.9 Hz, 3H), 2.47-2.66 (m, 3H), 1.88-2.11 (m, 1H), 1.03 (br. s., 1H), 0.89 (d, J=7.2 Hz, 2H), 0.62 (br. s., 1H). LCMS (m/z, ES+)=538 (M+H+).