Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: O.[OH-].[Li+].C[O:5][C:6](=[O:36])[CH2:7][C:8]1[C:17]([CH3:18])=[C:16]([C:19]2[CH:24]=[CH:23][C:22]([S:25]([C:28]3[CH:33]=[CH:32][CH:31]=[C:30]([Cl:34])[CH:29]=3)(=[O:27])=[O:26])=[CH:21][CH:20]=2)[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([F:35])[CH:14]=2)[CH:9]=1>C1COCC1.O>[Cl:34][C:30]1[CH:29]=[C:28]([S:25]([C:22]2[CH:21]=[CH:20][C:19]([C:16]3[C:15]4[C:10](=[CH:11][CH:12]=[C:13]([F:35])[CH:14]=4)[CH:9]=[C:8]([CH2:7][C:6]([OH:36])=[O:5])[C:17]=3[CH3:18])=[CH:24][CH:23]=2)(=[O:27])=[O:26])[CH:33]=[CH:32][CH:31]=1
Reactant: COC(=O)Cc1cc2ccc(F)cc2c(-c2ccc(S(=O)(=O)c3cccc(Cl)c3)cc2)c1C
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: Cc1c(CC(=O)O)cc2ccc(F)cc2c1-c1ccc(S(=O)(=O)c2cccc(Cl)c2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 55.1 %

Procedure:
Lithium hydroxide monohydrate (0.022 g, 0.52 mmol) was added to a stirred solution of {4-[4-(3-chloro-benzenesulfonyl)-phenyl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid methyl ester (0.063 g, 0.12 mmol) in a 3:1 THF—H2O mixture (4 mL). The reaction mixture was stirred for 16 hours at room temperature. The THF was distilled off under reduced pressure, and the crude residue was diluted with water, acidified [pH˜2] via the drop-wise addition of an aqueous solution of hydrochloric acid (6.0 N). The mixture was extracted twice with ethyl acetate. The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the crude product. Trituration with hexanes afforded {4-[4-(3-chloro-benzenesulfonyl)-phenyl]-6-fluoro-3-methyl-naphthalen-2-yl}-acetic acid (0.031 g, 51%) as a solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 12.47 (br. s, 1 H) 8.19 (d, J=8.20 Hz, 2 H) 8.13 (t, J=2.10 Hz, 1 H) 8.05 (d, J=7.60 Hz, 1 H) 8.00 (dd, J=8.90, 5.80 Hz, 1 H) 7.91 (s, 1 H) 7.84 (d, J=7.60 Hz, 1 H) 7.72 (t, J=8.10 Hz, 1 H) 7.54 (d, J=8.10 Hz, 2 H) 7.38 (td, J=8.30, 2.60 Hz, 1 H) 6.64 (dd, J=10.90, 2.40 Hz, 1 H) 3.84 (s, 2 H) 2.03 (s, 3 H). MS calcd. for C25H18ClFO4S [(M−H)−] 467, obsd. 467.3.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[NH:8][CH:9]=[CH:10][C:3]=12.CN(C=O)C.[H-].[Na+].Cl.[N:19]1[CH:24]=[CH:23][C:22]([CH2:25]Cl)=[CH:21][CH:20]=1>C(OCC)(=O)C>[Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:25][C:22]3[CH:23]=[CH:24][N:19]=[CH:20][CH:21]=3)[CH:9]=[CH:10][C:3]=12
Reactant: Brc1ccnc2[nH]ccc12
Reactant: ClCc1ccncc1
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Brc1ccnc2c1ccn2Cc1ccncc1
Temperature: -15 °C
Reaction time: 0.42 h

Procedure:
A 250-mL argon-purged round-bottomed flask equipped with a magnetic stirrer is charged with 4-Bromo-1H-pyrrolo[2,3-b]pyridine (0.70 g, 3.55 mmol) and DMF (25 mL) and the solution is cooled to −15° C. A 60% dispersion of sodium hydride in mineral oil (183 mg, 4.58 mmol) is then added and the reaction stirred at −15° C. for 25 min. The reaction is then charged with 4-picolylchloride hydrochloride (376 mg, 2.29 mmol) and stirred at −15° C. for a further 5 min. After such time the cooling bath is removed and the reaction is stirred for 30 min at ambient temperature. Additional 4-picolylchloride hydrochloride (117 mg, 0.71 mmol) and a 60% dispersion of sodium hydride in mineral oil (28 mg, 0.71 mmol) are then added and the reaction is stirred at ambient temperature for a further 30 min. The reaction is then poured into ethyl acetate (100 mL) and the mixture is washed with 3% aqueous sodium bicarbonate (1×100 mL), water (2×100 mL) and brine (1×100 mL). The organic layer is separated, dried over sodium sulfate and concentrated in vacuo to provide a residue, which is then purified by flash chromatography to afford 1b as a yellow solid.
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:12]([NH2:18])[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2].[CH3:19][N:20]([CH3:32])[C:21]1[CH:31]=[CH:30][CH:29]=[C:23]2[C:24]([O:26][C:27](=O)[C:22]=12)=[O:25]>C(O)(=O)C>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([CH:12]([N:18]2[C:27](=[O:26])[C:22]3[C:23](=[CH:29][CH:30]=[CH:31][C:21]=3[N:20]([CH3:19])[CH3:32])[C:24]2=[O:25])[CH2:13][S:14]([CH3:17])(=[O:16])=[O:15])[CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH3:2]
Reactant: CCOc1cc(C(N)CS(C)(=O)=O)ccc1OC
Reactant: CN(C)c1cccc2c1C(=O)OC2=O
Solvent: CC(=O)O
Product: CCOc1cc(C(CS(C)(=O)=O)N2C(=O)c3cccc(N(C)C)c3C2=O)ccc1OC

Procedure:
2-[1-(3-Ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-dimethylaminoisoindoline-1,3-dione was prepared by the procedure of Example 8 from 1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethylamine (572 mg, 2.09 mmol) and 3-dimethylaminophthalic anhydride (400 mg, 2.09 mmol) in acetic acid (20 mL). The product was obtained as a yellow solid (740 mg, 80% yield): mp, 94.0-96.0° C.; 1H NMR (CDCl3) δ 1.46 (t, J=7.0 Hz, 3H, CH3), 2.82 (s, 3H, CH3), 3.08 (s, 6H, CH3), 3.76-3.84 (m, 1H, CHH), 3.82 (s, 3H, CH3), 4.11 (q, J=7.0 Hz, 2H, CH2), 4.54 (dd, J=9.9, 14.5 Hz, 1H, CHH), 5.88 (dd, J=4.8, 9.9 Hz, 1H, NCH), 6.81-6.84 (m, 1H, Ar), 7.04-7.15 (m, 3H, Ar), 7.23-7.27 (m, 1H, Ar), 7.48 (dd, J=7.3, 8.3 Hz, 1H, Ar); 13C NMR (CDCl3) δ 14.68, 41.47, 43.39, 48.74, 55.20, 55.92, 64.43, 111.34, 112.54, 113.78, 114.41, 120.47, 122.09, 129.97, 134.32, 134.81, 148.46, 149.44, 150.42, 167.06, 168.19; Anal Calcd for C22H26NO6S: C, 59.14; H, 5.91; N, 6.27. Found: C, 59.14; H, 5.91; N, 6.10.
Reaction SMILES: [K].[CH3:2][C:3]1([CH3:19])[CH:5]([CH:6]=[C:7]([Cl:15])[C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)[CH:4]1[C:16]([OH:18])=[O:17].[F:20][C:21]1[C:26]([CH2:27]Br)=[C:25]([F:29])[C:24]([F:30])=[C:23]([F:31])[C:22]=1[F:32]>CN(C)C=O>[CH3:2][C:3]1([CH3:19])[CH:5]([CH:6]=[C:7]([Cl:15])[C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][CH:9]=2)[CH:4]1[C:16]([O:18][CH2:27][C:26]1[C:25]([F:29])=[C:24]([F:30])[C:23]([F:31])=[C:22]([F:32])[C:21]=1[F:20])=[O:17]
Reactant: CC1(C)C(C=C(Cl)c2ccc(Cl)cc2)C1C(=O)O
Reactant: Fc1c(F)c(F)c(CBr)c(F)c1F
Agent: [K]
Solvent: CN(C)C=O
Product: CC1(C)C(C=C(Cl)c2ccc(Cl)cc2)C1C(=O)OCc1c(F)c(F)c(F)c(F)c1F
Yield: 74.4 %

Procedure:
10.7 g (0.033 mol) of the potassium salt of 2,2-dimethyl-3-(2-chloro-2-p-chlorophenyl-vinyl)-cyclopropanecarboxylic acid were dissolved in 100 ml of dimethylformamide and the solution was heated to 120° C., together with 6.8 g (0.026 mol) of pentafluorobenzyl bromide, for 3 hours. After the reaction had ended, the dimethylformamide was distilled off in vacuo and the residue which remained was taken up in 200 ml of methylene chloride. The methylene chloride solution was then extracted by shaking twice with 100 ml of water each time, the organic phase was dried over sodium sulphate and the solvent was stripped off in vacuo. Last residues of solvent were removed by brief incipient distillation at a bath temperature of 60° C./1 mm Hg. 9.0 g (74.4% of theory) of pentafluoro-benzyl 2,2-dimethyl-3-(2-chloro-2-p-chloro-phenyl-vinyl)-cyclopropanecarboxylate were obtained as a yellow oil with the refractive index nD25 :1.5382.
Reaction SMILES: [CH3:1][O-:2].[Na+].Cl[C:5]1[CH:6]=[CH:7][C:8]([N+:12]([O-:14])=[O:13])=[C:9]([CH:11]=1)[NH2:10]>O1CCOCC1>[CH3:1][O:2][C:5]1[CH:6]=[CH:7][C:8]([N+:12]([O-:14])=[O:13])=[C:9]([CH:11]=1)[NH2:10]
Reactant: C[O-]
Reactant: Nc1cc(Cl)ccc1[N+](=O)[O-]
Agent: [Na+]
Solvent: C1COCCO1
Product: COc1ccc([N+](=O)[O-])c(N)c1

Procedure:
70 ml of a 28% w/v methanolic solution of sodium methoxide were added at room temperature to a solution of 25 g of 5-chloro-2-nitroaniline in 500 ml of 1,4-dioxane, and the resulting mixture was heated under reflux for 4 hours, after which the solvent was removed by distillation under reduced pressure. The resulting residue was diluted with water, and the resulting aqueous mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, after which the solvent was removed by distillation under reduced pressure. The resulting residue was purified by column chromatography through silica gel using a gradient elution method, with mixtures of ethyl acetate and hexane in ratios ranging from 1:4 to 1:2 by volume as the eluent, to give 16.3 g of the title compound, melting at 124°-128° C.
Reaction SMILES: [NH:1]1[C:10](=O)[C:9]2[NH:8][CH:7]=[N:6][C:5]=2[NH:4][C:2]1=[S:3].P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=[S:13].[OH-].[Na+]>N1C=CC=CC=1>[NH:1]1[C:10](=[S:13])[C:9]2[NH:8][CH:7]=[N:6][C:5]=2[NH:4][C:2]1=[S:3]
Reactant: O=c1[nH]c(=S)[nH]c2nc[nH]c12
Reactant: S=P12SP3(=S)SP(=S)(S1)SP(=S)(S2)S3
Agent: [Na+]
Agent: [OH-]
Solvent: c1ccncc1
Product: S=c1[nH]c(=S)c2[nH]cnc2[nH]1
Yield: 258.8 %

Procedure:
13.22 g (50 mM) of 2-thioxanthine and 13.34 g (60 mM) of phosphorus pentasulfide were heated under reflux in 160 ml of pyridine for 3 days. At 5-10° C., 66 ml (132 mM) of 2N NaOH were added. The solvents were evaporated in vacuo, the residue treated with 200 ml of water and evaporated again. The residue was again suspended in 200 ml of water and collected. The crude product was dissolved in 120 ml of 1N NaOH, treated twice with 0.14 g of charcoal, filtered and acidified with 32 ml of SN HCl to pH 4.5. The solid was collected, washed and dried to give 14.31 g of crude dithioxanthine. This was dissolved in 300 ml of chloroform; some insoluble material was filtered off, and the solution passed through 71.5 g of silica gel in a column. Crystallization from isopropanol gave 12.17 g (86.8%) of 2,6-dithioxanthine with mp 196-200° C.
Reaction SMILES: [N:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][NH2:12])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[C:13]([C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[C:21]([CH2:24][CH2:25][NH:26][C:27](=[O:41])[C:28]3[CH:33]=[CH:32][C:31]([C:34]4[CH:39]=[CH:38][N:37]=[C:36](Cl)[N:35]=4)=[CH:30][CH:29]=3)[CH:22]=2)[NH:17][CH:16]=1)#[N:14]>>[C:13]([C:15]1[C:23]2[C:18](=[CH:19][CH:20]=[C:21]([CH2:24][CH2:25][NH:26][C:27](=[O:41])[C:28]3[CH:33]=[CH:32][C:31]([C:34]4[CH:39]=[CH:38][N:37]=[C:36]([NH:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][N:1]5[CH2:6][CH2:5][O:4][CH2:3][CH2:2]5)[N:35]=4)=[CH:30][CH:29]=3)[CH:22]=2)[NH:17][CH:16]=1)#[N:14]
Reactant: N#Cc1c[nH]c2ccc(CCNC(=O)c3ccc(-c4ccnc(Cl)n4)cc3)cc12
Reactant: NCCCCCN1CCOCC1
Product: N#Cc1c[nH]c2ccc(CCNC(=O)c3ccc(-c4ccnc(NCCCCCN5CCOCC5)n4)cc3)cc12

Procedure:
Using 5-(morpholin-4-yl)-pentylamine (reference example 93b) and and N-[2-(3-Cyano-1H-indol-5-yl)-ethyl]-4-[2-chloro-pyrimidin-4-yl]-benzamide (reference example 1az) as substrates. MS (ion spray) m/z 538 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:13]([CH3:14])[C:12]3[CH:15]=[C:16]([O:29][CH3:30])[C:17]([O:19][C:20]4([C:26](O)=O)[CH:25]=[CH:24][CH:23]=[CH:22][NH:21]4)=[CH:18][C:11]=3[N:10]=2)=[CH:4][C:3]=1[CH3:31].[N:32]1([CH2:37][CH2:38][NH2:39])[CH2:36][CH2:35]C[CH2:33]1.CN([C:43]([O:47]N1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>O1CCCC1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:13]([CH3:14])[C:12]3[CH:15]=[C:16]([O:29][CH3:30])[C:17]([O:19][C:20]4([CH:26]5[CH2:33][N:32]([CH2:37][CH2:38][NH:39][CH:43]=[O:47])[CH2:36][CH2:35]5)[CH:25]=[CH:24][CH:23]=[CH:22][NH:21]4)=[CH:18][C:11]=3[N:10]=2)=[CH:4][C:3]=1[CH3:31]
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Reactant: COc1cc2c(cc1OC1(C(=O)O)C=CC=CN1)nc(Nc1ccc(Br)c(C)c1)n2C
Reactant: NCCN1CCCC1
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: COc1cc2c(cc1OC1(C3CCN(CCNC=O)C3)C=CC=CN1)nc(Nc1ccc(Br)c(C)c1)n2C
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To 4-(2-{[4-bromo-3-methylpheylamino)-6-methoxy-1-methylbenzimidazol-5-yloxy)pyridine-2-carboxylic acid (1 eq) in tetrahydrofuran was added 2-pyrrolidinylethylamine (2 eq), HBTU (2 eq) and N,N-diisopropylethylamine (4 eq) and stir at ambient temperature for 16 h. The mixture was then concentrated and partitioned between ethyl acetate and water. The organic layer was concentrated and preparative chromatography yielded [4-(2-{[4-bromo-3-methylphenyl]amino-6-methoxy-1-methylbenzimidazol-5-yloxy)(2-pyridyl)]-N-(2-pyrrolidinylethyl)carboxamide. MS: MH+=579.
Reaction SMILES: Cl.N[C:3]1[CH:8]=[C:7]([O:9][C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]3[N:33]=[CH:32][CH:31]=[CH:30][C:18]=3[C:19]([NH:21][C:22]3[CH:27]=[CH:26][C:25](F)=[CH:24][C:23]=3F)=[O:20])=[CH:12][C:11]=2[F:34])[CH:6]=[CH:5][N:4]=1.Cl.N1C2=NC=CC(OC3C=CC(NC4C([C:59]([NH:61]C5C=CC(F)=CC=5F)=[O:60])=CN=CC=4)=CC=3F)=C2C=C1.[CH2:71](NC(=O)C1C=CC=NC=1Cl)C1C=CC=CC=1>>[CH2:22]([NH:21][C:19]([C:18]1[C:17]([NH:16][C:13]2[CH:14]=[CH:15][C:10]([O:9][C:7]3[CH:6]=[CH:5][N:4]=[C:3]([C:59]([NH2:61])=[O:60])[CH:8]=3)=[C:11]([F:34])[CH:12]=2)=[N:33][CH:32]=[CH:31][CH:30]=1)=[O:20])[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:71]=1
Reactant: O=C(NCc1ccccc1)c1cccnc1Cl
Reactant: O=C(Nc1ccc(F)cc1F)c1cnccc1Nc1ccc(Oc2ccnc3[nH]ccc23)c(F)c1
Reactant: Nc1cc(Oc2ccc(Nc3ncccc3C(=O)Nc3ccc(F)cc3F)cc2F)ccn1
Agent: Cl
Product: NC(=O)c1cc(Oc2ccc(Nc3ncccc3C(=O)NCc3ccccc3)cc2F)ccn1
Yield: 44 %

Procedure:
4-(4-Amino-2-fluorophenoxy)picolinamide (0.099 g, 0.40 mmol, Compound C of Example 3) was converted to the desired compound (0.080 g, 44%) in a manner similar to the preparation of 4-(4-(3-(2,4-difluorophenylcarbamoyl)pyridin-4-ylamino)-2-fluorophenoxy)picolinamide (Step D of Example 1), except that N-benzyl-2-chloronicotinamide (Maybridge, 0.099 g, 0.40 mmol) was used instead of 4-chloro-N-(2,4-difluorophenyl)nicotinamide. MS(ESI+) m/z 458 (M+H)+.
Reaction SMILES: [F:1][C:2]([F:21])([F:20])[C:3]([C:9]1[CH:16]=[CH:15][C:12]([CH:13]=[O:14])=[C:11]([CH2:17][CH2:18][CH3:19])[CH:10]=1)([OH:8])[C:4]([F:7])([F:6])[F:5].[BH4-].[Na+]>CO.ClCCl>[F:1][C:2]([F:20])([F:21])[C:3]([C:9]1[CH:16]=[CH:15][C:12]([CH2:13][OH:14])=[C:11]([CH2:17][CH2:18][CH3:19])[CH:10]=1)([OH:8])[C:4]([F:5])([F:7])[F:6]
Reactant: CCCc1cc(C(O)(C(F)(F)F)C(F)(F)F)ccc1C=O
Agent: [BH4-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: CCCc1cc(C(O)(C(F)(F)F)C(F)(F)F)ccc1CO
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 80 %

Procedure:
4-(1,1,1,3,3,3-Hexafluoro-2-hydroxypropan-2-yl)-2-propylbenzaldehyde (0.636 mmol, 200 mg) was dissolved in methanol (4 mL)/dichloromethane (1 mL) and sodium borohydride (1.909 mmol, 72.2 mg) was added. The mixture was stirred at room temperature for 90 minutes then was concentrated under reduced pressure. The residue was dissolved in dichloromethane (50 mL) and washed with a saturated solution of sodium bicarbonate (25 mL). The organic phase was filtered through a hydrophobic frit and concentrated to afford the title compound (161 mg).
Reaction SMILES: [CH:1]1([CH2:4][N:5]2[C:9]3[CH:10]=[CH:11][C:12]([C:16]4[CH:30]=[CH:29][C:19]([CH2:20][N:21]5[CH2:25][C:24](=[O:26])[N:23]([CH3:27])[C:22]5=[O:28])=[C:18]([F:31])[CH:17]=4)=[C:13]([S:14][CH3:15])[C:8]=3[N:7]=[N:6]2)[CH2:3][CH2:2]1.[OH-:32].[Ca+2].[OH-:34]>C(Cl)(Cl)Cl>[CH:1]1([CH2:4][N:5]2[C:9]3[CH:10]=[CH:11][C:12]([C:16]4[CH:30]=[CH:29][C:19]([CH2:20][N:21]5[CH2:25][C:24](=[O:26])[N:23]([CH3:27])[C:22]5=[O:28])=[C:18]([F:31])[CH:17]=4)=[C:13]([S:14]([CH3:15])(=[O:34])=[O:32])[C:8]=3[N:7]=[N:6]2)[CH2:3][CH2:2]1
Reactant: CSc1c(-c2ccc(CN3CC(=O)N(C)C3=O)c(F)c2)ccc2c1nnn2CC1CC1
Reactant: [OH-]
Agent: [Ca+2]
Solvent: ClC(Cl)Cl
Product: CN1C(=O)CN(Cc2ccc(-c3ccc4c(nnn4CC4CC4)c3S(C)(=O)=O)cc2F)C1=O
Temperature: 0 °C
Reaction time: 1.5 h

Procedure:
To a solution of 1-{4-[1-(cyclopropylmethyl)-4-(methylsulfanyl)-1H-benzotriazol-5-yl]-2-fluorobenzyl}-3-methylimidazolidine-2,4-dione (Example 15, 14 mg, 0.032 mmol) in chloroform (0.45 mL) at 0° C. was added meta-peroxychlorobenzoic acid (7.1 mg, 0.032 mmol). The mixture was stirred for 1.5 hours at 0° C. and then warmed to ambient temperature and stirred for an additional 14 hours. The mixture was cooled to 0° C. and treated with calcium hydroxide (3.3 mg, 0.045 mmol), stirred for 30 minutes and filtered. The filtrate was concentrated in vacuo and purified via preparative reversed-phase HPLC (5-95% MeCN/water+0.1% TFA) to provide the title compound: 1H NMR (400 MHz, CDCl3) 7.82 (d, 1H, J=8.0 Hz), 7.42 (d, 1H, J=8.8 Hz), 7.39 (t, 1H, J=7.6 Hz), 7.17-7.23 (m, 2H), 4.70 (s, 2H), 4.61 (d, 2H, J=7.2 Hz), 3.89 (s, 2H), 3.67 (s, 3H), 3.06 (s, 3H), 1.41-1.47 (m, 1H), 0.71-0.76 (m, 2H), 0.54-0.58 (m, 2H) ppm. LRMS m/z (M+H) 472.2 found, 472.1 required.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([CH:19]=[O:20])=[CH:11][C:12]3[NH:16][CH:15]=[N:14][C:13]=3[C:17]=2[F:18])=[C:4]([Cl:21])[CH:3]=1.C([Sn](CCCC)(CCCC)[CH2:27][O:28][CH2:29][O:30][CH3:31])CCC>>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([CH:19]([OH:20])[CH2:27][O:28][CH2:29][O:30][CH3:31])=[CH:11][C:12]3[NH:16][CH:15]=[N:14][C:13]=3[C:17]=2[F:18])=[C:4]([Cl:21])[CH:3]=1
Reactant: O=Cc1cc2[nH]cnc2c(F)c1Nc1ccc(Br)cc1Cl
Reactant: CCCC[Sn](CCCC)(CCCC)COCOC
Product: COCOCC(O)c1cc2[nH]cnc2c(F)c1Nc1ccc(Br)cc1Cl

Procedure:
6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carbaldehyde 10f is treated with tributyl-methoxymethoxymethyl-stannane according to the procedure described in Example 42, Step A to yield compound 10l. MS APCI (+) m/z 444, 446 (M+, Br pattern) detected.
Reaction SMILES: S[CH2:2][CH2:3][C:4]([OH:6])=O.C(C1C=C(C)C=C(C(C)(C)C)N=1)(C)(C)C.FC(F)(F)[S:24]([O-])(=O)=O.[F:30][C:31]([I+]C1C=CC=CC=1)([F:36])[C:32]([F:35])([F:34])[F:33]>C(Cl)Cl>[F:30][C:31]([F:36])([CH2:2][CH2:3][C:4]([OH:6])=[S:24])[C:32]([F:35])([F:34])[F:33]
Reactant: O=C(O)CCS
Reactant: O=S(=O)([O-])C(F)(F)F
Reactant: FC(F)(F)C(F)(F)[I+]c1ccccc1
Agent: Cc1cc(C(C)(C)C)nc(C(C)(C)C)c1
Solvent: ClCCl
Product: OC(=S)CCC(F)(F)C(F)(F)F
Temperature: 25 °C

Procedure:
2.0 ml of methylene chloride, 0.05 ml (0.58 mmol) of 3-mercaptopropionic acid and 120 mg (0.59 mmol) of 2,6-di-tert-butyl-4-methylpyridine were charged in a flask, and 261 mg (0.55 mmol) of pentafluoroethylphenyliodonium trifluoromethanesulfonate was added thereto in small portions while stirring at room temperature, followed by stirring the mixture at room temperature for 20 minutes. The resulting white precipitate was filtered, subjected to column chromatography of a small amount of silica gel and, after eluting iodobenzene with hexane, the desired product was eluted with diethyl ether. Diethyl ether was distilled off from the eluate to obtain 3-pentafluoroethylthiopropionic acid as a colorless liquid. A sample of the product was purified by gas chromatography. Yield, 83%.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[F:9])[NH2:5].[Cl:10][C:11]1[CH:18]=[CH:17][C:14]([CH:15]=O)=[CH:13][CH:12]=1.C([O:21][C:22](=O)[C:23](=[O:30])[CH2:24][C:25](=[O:29])[CH:26]([CH3:28])[CH3:27])C>C(#N)C>[Cl:10][C:11]1[CH:18]=[CH:17][C:14]([CH:15]2[N:5]([C:4]3[CH:6]=[CH:7][C:8]([F:9])=[C:2]([F:1])[CH:3]=3)[C:22](=[O:21])[C:23]([OH:30])=[C:24]2[C:25](=[O:29])[CH:26]([CH3:28])[CH3:27])=[CH:13][CH:12]=1
Reactant: Nc1ccc(F)c(F)c1
Reactant: CCOC(=O)C(=O)CC(=O)C(C)C
Reactant: O=Cc1ccc(Cl)cc1
Solvent: CC#N
Product: CC(C)C(=O)C1=C(O)C(=O)N(c2ccc(F)c(F)c2)C1c1ccc(Cl)cc1
Temperature: 25 °C
Yield: 55.7 %

Procedure:
A mixture of 3,4-difluoro-aniline (1.8 g, 14.2 mmol), 4-chloro-benzaldehyde (2.0 g, 14.2 mmol) and 5-methyl-2,4-dioxo-hexanoic acid ethyl ester (2.6 g, 14.2 mmol) acetic acid (10 mL) was refluxed overnight. The reaction mixture was allowed to cool to rt and diluted with acetonitrile. The resulting precipitate was collected by vacuum filtration and dried to afford 3.1 g of the title compound. tR: 5.89 min (HPLC 2); ESI-MS: 390 [M−H]− (LC-MS 2).
Reaction SMILES: [CH2:1]([NH2:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12].[N-:14]=[C:15]=[O:16].C([NH+](CC)CC)C>C(Cl)(Cl)Cl>[CH2:1]([NH:13][C:15]([NH2:14])=[O:16])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH3:12]
Reactant: CCCCCCCCCCCCN
Reactant: [N-]=C=O
Agent: CC[NH+](CC)CC
Solvent: ClC(Cl)Cl
Product: CCCCCCCCCCCCNC(N)=O
Temperature: 25 °C
Reaction time: 24 h

Procedure:
14.1 g of dodecylamine (0.076 mol) dissolved in 20 ml of chloroform were added dropwise at room temperature with stirring to 100 ml of a solution of 10 g of triethylammonium isocyanate (0.069 mol) in chloroform, prepared according to Example 1. After completion of the addition, the mixture was subsequently stirred at room temperature for 24 hours and heated to reflux for 1 hour. The solvent was evaporated and the residue was recrystallized from chloroform. 9.45 g, i.e. 60% of theory, of dodecylurea were obtained in this way.
Reaction SMILES: [O:1]1[C:5]([C:6]2[C:7]3[N:8]([C:16]([C:19](O)=[O:20])=[CH:17][N:18]=3)[CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=2)=[CH:4][N:3]=[CH:2]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[F:47][CH:48]1[CH2:51][NH:50][CH2:49]1.C(N(CC)C(C)C)(C)C>O.CN(C=O)C>[F:47][CH:48]1[CH2:51][N:50]([C:19]([C:16]2[N:8]3[CH:9]=[C:10]([C:12]([F:15])([F:14])[F:13])[CH:11]=[C:6]([C:5]4[O:1][CH:2]=[N:3][CH:4]=4)[C:7]3=[N:18][CH:17]=2)=[O:20])[CH2:49]1
Reactant: FC1CNC1
Reactant: O=C(O)c1cnc2c(-c3cnco3)cc(C(F)(F)F)cn12
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Solvent: O
Product: O=C(c1cnc2c(-c3cnco3)cc(C(F)(F)F)cn12)N1CC(F)C1
Temperature: 25 °C
Reaction time: 5 h
Yield: 92.3 %

Procedure:
A mixture of 8-(1,3-oxazol-5-yl)-6-(trifluoromethyl)imidazo[1,2-a]pyridine-3-carboxylic acid (100 mg), HATU (154 mg), 3-fluoroazetidine hydrochloride (45.0 mg), N,N-diisopropylethylamine (0.147 mL) and DMF (2 mL) was stirred at room temperature for 5 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/hexane), and recrystallized from ethyl acetate/hexane to give the title compound (110 mg).
Reaction SMILES: Cl.[NH2:2][C:3]1[CH:32]=[CH:31][C:6]2[NH:7][C:8]([C:13]3[C:14](=[O:30])[C:15]([CH3:29])([CH2:24][CH2:25][CH:26]([CH3:28])[CH3:27])[C:16]4[C:21]([C:22]=3[OH:23])=[CH:20][CH:19]=[CH:18][CH:17]=4)=[N:9][S:10](=[O:12])(=[O:11])[C:5]=2[CH:4]=1.[S:33](Cl)([CH3:36])(=[O:35])=[O:34].N1C=CC=CC=1>CC(C)=O>[OH:23][C:22]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:15]([CH3:29])([CH2:24][CH2:25][CH:26]([CH3:28])[CH3:27])[C:14](=[O:30])[C:13]=1[C:8]1[NH:7][C:6]2[CH:31]=[CH:32][C:3]([NH:2][S:33]([CH3:36])(=[O:35])=[O:34])=[CH:4][C:5]=2[S:10](=[O:12])(=[O:11])[N:9]=1
Reactant: CC(C)CCC1(C)C(=O)C(C2=NS(=O)(=O)c3cc(N)ccc3N2)=C(O)c2ccccc21
Reactant: CS(=O)(=O)Cl
Agent: Cl
Solvent: CC(C)=O
Solvent: c1ccncc1
Product: CC(C)CCC1(C)C(=O)C(C2=NS(=O)(=O)c3cc(NS(C)(=O)=O)ccc3N2)=C(O)c2ccccc21
Yield: 84.5 %

Procedure:
A solution of Example 34B (0.053 g, 0.112 mmol), mesyl chloride (0.035 mL, 0.447 mmol), and pyridine (0.073 mL, 0.893 mmol) in acetone (1.5 mL) was stirred at 25° C. for 18 hours. The solution was partitioned between ethyl acetate and dilute citric acid and the layers were separated. The ethyl acetate layer was dried with sodium sulfate, filtered, and concentrated in vacuo. The residue was chromatographed on silica gel eluting with methylene chloride and 2.5% methanol in methylene chloride to give the desired product (0.049 g, 84%). 1HNMR (300 MHz, DMSO-d6): δ ppm 0.43 (m, 1 H) 0.74 (m, 7 H) 1.34 (m, 1 H) 1.57 (m, 3 H) 2.15 (m, 2 H) 3.08 (m, 3 H) 7.56 (m, 3 H) 7.75 (m, 3 H) 8.16 (m, 1 H) 10.26 (m, 1 H) 13.76 (m, 1 H).