Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][N:3]=1.[CH2:11]([O:13][C:14]1[CH:20]=[CH:19][C:17]([NH2:18])=[C:16]([N+:21]([O-:23])=[O:22])[CH:15]=1)[CH3:12]>>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([C:6]([NH:18][C:17]2[CH:19]=[CH:20][C:14]([O:13][CH2:11][CH3:12])=[CH:15][C:16]=2[N+:21]([O-:23])=[O:22])=[O:7])=[CH:9][CH:10]=1
Reactant: O=C(Cl)c1ccc(Cl)nc1
Reactant: CCOc1ccc(N)c([N+](=O)[O-])c1
Product: CCOc1ccc(NC(=O)c2ccc(Cl)nc2)c([N+](=O)[O-])c1

Procedure:
The title compound was prepared from 6-chloronicotinoyl chloride and 4-ethoxy-2-nitroaniline and was obtained as a yellow solid as described in Example 1. 1H NMR (CDCl3): 11.13 (s, 1H), 9.01 (d, J=2.4, 1H), 8.82 (d, J=9.3, 1H), 8.24-8.20 (m, 1H), 7.74 (d, J=3.0, 1H), 7.51 (d, J=7.8, 1H), 7.34-7.30(m, 1H), 4.11 (q, J=6.9, 2H), 1.47 (t, J=6.9, 3H).
Reaction SMILES: [C:1]1([CH:7]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[N:8]2[CH2:11][CH:10]([OH:12])[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.F[C:20]1[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=1.O>C1COCC1>[C:13]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:8]2[CH2:11][CH:10]([O:12][C:20]3[CH:25]=[CH:24][C:23]([N+:26]([O-:28])=[O:27])=[CH:22][CH:21]=3)[CH2:9]2)[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: OC1CN(C(c2ccccc2)c2ccccc2)C1
Solvent: C1CCOC1
Solvent: O
Product: O=[N+]([O-])c1ccc(OC2CN(C(c3ccccc3)c3ccccc3)C2)cc1
Temperature: 23 °C
Reaction time: 1 h
Yield: 40 %

Procedure:
0.5 g (2 mmol) of 1-(diphenylmethyl)-3-hydroxyazetidine is added under an argon atmosphere to a suspension of 0.06 g (2.3 mmol) of Na in 20 ml of dry THF. After agitation for one hour at 23° C., a solution of 0.29 g (2.1 mmol) of 4-fluoronitrobenzene in 5 ml of dry THF is added dropwise to the reaction mixture. Agitation is maintained for another 2 hours at 23° C. and the whole is finally poured into 25 ml of water. The product is extracted twice with 25 ml of ethyl acetate, the organic phase is then washed twice with 25 ml of salt water, dried over magnesium sulphate, filtered and concentrated under vacuum. The product is purified on a silica column (eluant: 12% of ethyl acetate in heptane). The pure fractions are evaporated in order to produce a colourless oil with a yield of 40%.
Reaction SMILES: [C:1]([CH2:5][C:6](Cl)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Sn](CCCC)(CCCC)[C:14]1[S:15][CH:16]=[CH:17][CH:18]=1)CCC>C1(C)C=CC=CC=1.CCOCC.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>[CH3:2][C:1]([CH3:4])([CH3:3])[CH2:5][C:6]([C:14]1[S:15][CH:16]=[CH:17][CH:18]=1)=[O:7]
Reactant: CC(C)(C)CC(=O)Cl
Reactant: CCCC[Sn](CCCC)(CCCC)c1cccs1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CCOCC
Solvent: Cc1ccccc1
Product: CC(C)(C)CC(=O)c1cccs1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 61.7 %

Procedure:
A mixture of t-butylacetyl chloride (1 ml, 7.2 mmol), 2-(tributylstannyl)thiophene (2.4 ml, 7.56 mmol) and PdCl2(PPh3)2 (98 mg, 0.14 mmol) in toluene (50 ml) was heated at reflux until the starting material disappeared. After cooling at room temperature, the brown-black solution was diluted with ether and washed with a 0.1 N aqueous HCl solution. The organic phase was separated and stirred vigorously with a 10% w/v aqueous KF solution for 30 minutes. After filtration, the layers were separated and the organic one washed with water, brine, dried over MgSO4 and concentrated. The residual brown oil was chromatographied on silica gel (hexane/AcOEt 97/3) to give 3,3-dimethyl-1-(2-thienyl)-1-butanone 10 as a colorless oil (810 mg, 62%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[C:7]([Cl:11])[C:8]=1[O:9][CH3:10])[NH2:5].CCN(C1C=CC=CC=1)CC.Cl[C:24]([O:26][CH:27]([CH3:29])[CH3:28])=[O:25]>C1C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:5][C:24](=[O:25])[O:26][CH:27]([CH3:29])[CH3:28])[CH:6]=[C:7]([Cl:11])[C:8]=1[O:9][CH3:10]
Reactant: CC(C)OC(=O)Cl
Reactant: COc1c(Cl)cc(N)cc1Cl
Solvent: CCN(CC)c1ccccc1
Solvent: c1ccccc1
Product: COc1c(Cl)cc(NC(=O)OC(C)C)cc1Cl
Temperature: 0 °C
Reaction time: 12 h
Yield: 92.1 %

Procedure:
3,5-Dichloro-4-methoxyaniline (1.8 g) and diethylaniline (1.5 g) were dissolved in benzene (20 ml). To the resultant solution was dropwise added isopropyl chloroformate (1.2 g) in 5 minutes under ice-cooling. After being allowed to stand at room temperature for 12 hours, the reaction mixture was poured into ice-water and extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel chromatography using a mixture of benzene and tetrahydrofuran as the eluent to give isopropyl N-(3,5-dichloro-4-methoxyphenyl)carbamate (Compound No. 2) (2.4 g) in a yield of 91.8%. M.P., 107.5°-108° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:12]([NH:13][C:14](=[S:22])OC2C=CC=CC=2)=[N:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.[CH3:23][O:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[N:31]1[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]1.C1CCN2C(=NCCC2)CC1>O1CCCC1>[CH3:1][O:2][C:3]1[C:12]([NH:13][C:14]([N:34]2[CH2:33][CH2:32][N:31]([C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][C:25]=3[O:24][CH3:23])[CH2:36][CH2:35]2)=[S:22])=[N:11][C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1
Reactant: COc1ccccc1N1CCNCC1
Reactant: COc1nc2ccccc2nc1NC(=S)Oc1ccccc1
Solvent: C1CCOC1
Solvent: C1CCC2=NCCCN2CC1
Product: COc1ccccc1N1CCN(C(=S)Nc2nc3ccccc3nc2OC)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 62.4 %

Procedure:
Phenyl N-(2-methoxyquinoxalin-3-yl)thiocarbamate (215 mg, 0.69 mmol) and 1-(2-methoxyphenyl)piperazine (154 mg, 0.69 mmol) were dissolved in anhydrous tetrahydrofuran (25 ml) and thereto DBU (105 mg, 0.69 mmol) was added. The mixture was stirred at room temperature for 2 hours, concentrated under the reduced pressure to remove the solvent and purified by column chromatography to obtain the titled compound.
Reaction SMILES: [C:1](O)(=O)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][C:12]([OH:14])=[O:13].[C:17](O)(=O)CCCCC(O)=O>>[C:12]([O:14][CH3:17])(=[O:13])[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][CH3:1]
Reactant: O=C(O)CCCCC(=O)O
Reactant: O=C(O)CCCCCCCCCCC(=O)O
Product: CCCCCCCCCCCC(=O)OC

Procedure:
Fermentation of dodecane with strain H534 under the standard fermentation conditions (Example 20) produced approximately 139 g/l within 233 hrs with a substrate conversion efficiency of 32.1%. The final production rate was 0.58 g/l/hr. The product was 82.7% dodecanedioic acid. The remaining product was predominantly adipic acid. With methyl laurate as the substrate, H534 produced 115.3 g/l dicarboxylic acid within 223 hrs with a substrate conversion efficiency of 34.6%. The production rate was 0.49 g/l/hr. The product was 89.1% dodecanedioic acid. The remaining product was predominantly adipic acid.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([OH:9])=[C:4]([CH3:10])[CH:3]=1.[CH2:11](Br)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Br:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:4]([CH3:10])[CH:3]=1
Reactant: BrCc1ccccc1
Reactant: Cc1cc(Br)cc(Cl)c1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: Cc1cc(Br)cc(Cl)c1OCc1ccccc1
Reaction time: 12 h
Yield: 89.6 %

Procedure:
A solution of 50 g of 4-bromo-6-chloro-2-methylphenol and 42.5 g of benzyl bromide dissolved in 200 ml of N,N-dimethylformamide was stirred at room temperature, to which 37.4 g of potassium carbonate was added, and the mixture was stirred for 12 hours. After completion of the reaction, the solvent was removed by distillation under reduced pressure, and the residue was added to 400 ml of diethyl ether, washed with water, dried with anhydrous magnesium sulfate, and concentrated to obtain a crude product. The crude product was subjected to silica gel chromatography, which afforded 63 g of 4-bromo-6-chloro-2-methyl-1-benzyloxybenzene (90% yield).
Reaction SMILES: [C:1](=[O:23])([O:3][CH2:4][CH:5]1[C:17]2([OH:19])[O:18][N:12]([CH2:13][CH:14]3[CH:16]2[NH:15]3)[C:11]2[C:6]1=[C:7]([OH:22])[CH:8]=[C:9]([CH2:20][OH:21])[CH:10]=2)[NH2:2].C(O[C:28](=[O:30])[CH3:29])(=O)C>N1C=CC=CC=1>[C:4]([O:22][C:7]1[CH:8]=[C:9]([CH2:20][O:21][C:28](=[O:30])[CH3:29])[CH:10]=[C:11]2[C:6]=1[CH:5]([CH2:4][O:3][C:1](=[O:23])[NH2:2])[C:17]1([OH:19])[O:18][N:12]2[CH2:13][CH:14]2[CH:16]1[N:15]2[C:17](=[O:18])[CH3:16])(=[O:3])[CH3:5]
Reactant: NC(=O)OCC1c2c(O)cc(CO)cc2N2CC3NC3C1(O)O2
Reactant: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CC(=O)OCc1cc(OC(C)=O)c2c(c1)N1CC3C(N3C(C)=O)C(O)(O1)C2COC(N)=O
Reaction time: 8 h

Procedure:
To a solution of 6.9-dihydroxy-4-hydroxymethyl-14-oxa-1,11-diazatetracyclo[7.4.1.02,7.010,12 ]tetradeca-2,4,6-trien-8-ylmethyl carbamate (21 mg) in pyridine (1 ml) was added acetic anhydride (34 μl), and the mixture was allowed to stand at room temperature overnight. The reaction mixture was evaporated to dryness in vacuo, and the residual oil was subjected to preparative thin layer chromatography, which was developed with a mixture of methanol and chloroform (5:95, v/v) to give 4-acetoxymethyl-11-acetyl-8-carbamoyloxymethyl-9-hydroxy-14-oxa-1,11-diazatetracyclo[7.4.1.02,7.010,12 ]tetradeca-2,4,6-trien-6-yl acetate (24 mg).
Reaction SMILES: [BH4-].[Na+].[CH:3]([C:5]1[CH:22]=[CH:21][CH:20]=[CH:19][C:6]=1[CH:7]=[CH:8][CH2:9][C:10]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:11]=1[OH:18])=[O:4]>CO>[OH:4][CH2:3][C:5]1[CH:22]=[CH:21][CH:20]=[CH:19][C:6]=1[CH:7]=[CH:8][CH2:9][C:10]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:11]=1[OH:18]
Reactant: COc1ccc(O)c(CC=Cc2ccccc2C=O)c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: COc1ccc(O)c(CC=Cc2ccccc2CO)c1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Sodium borohydride (35 mg) was added in one portion to a solution of 2-(o-formylcinnamyl)-4-methoxyphenol (240 mg; 0.89 mM) in 5 ml of methanol. The reaction was stirred at room temperature for 2 hours and then the solvent was removed in vacuo. The residue was taken up in 2N aqueous hydrochloric acid and extracted with ether. The ethereal phase was washed with water, dried over magnesium sulfate, stripped of solvent, and filtered through 11/2" of silica gel in a 30 ml fritted funnel with 50% ethyl acetate/hexane providing 240 mg (99%) of pure 2-(o-hydroxymethylcinnamyl)-4-methoxyphenol.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([I:12])=[CH:9][CH:10]=2)[N:5]=[C:4]([CH3:13])[CH:3]=1.[NH:14]1[CH2:18][CH2:17][CH2:16][CH2:15]1.N1C=CC=CC=1.[I-].[K+]>C(O)C>[I:12][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([N:14]3[CH2:18][CH2:17][CH2:16][CH2:15]3)=[CH:3][C:4]([CH3:13])=[N:5]2)=[CH:10][CH:9]=1
Reactant: Cc1cc(Cl)c2ccc(I)cc2n1
Reactant: C1CCNC1
Agent: [I-]
Agent: [K+]
Solvent: c1ccncc1
Solvent: CCO
Product: Cc1cc(N2CCCC2)c2ccc(I)cc2n1
Yield: 87 %

Procedure:
A suspension of 2 g of 4-chloro-7-iodo-2-methyl-quinoline (European patent application EP 0497371, CA 143946-47-8) in 20 ml absolute ethanol is treated successively with 1.09 ml pyrrolidine, 0.2 ml pyridine and 50 mg potassium iodide under argon. The resulting mixture is refluxed for 24 h. The solvent is then distilled off. The residue is taken up in 50 ml water and basified to pH 12 with a 2N solution of sodium hydroxyde. The solid is filtered upon precipitation and washed with 20 ml of water and 20 ml of diethylether. The final product is dried under vacuum yielding 1.95 g (87%) of 7-iodo-2-methyl-4-pyrrolidin-1-yl-quinoline as an off-white solid. Mp: 99-102° C. MS (EI): peaks at m/e: 338(M+, 100%), 296 (5%), 183(9%).
Reaction SMILES: [CH3:1][C:2](O)([CH3:28])[CH2:3][N:4]1[CH2:9][CH2:8][CH:7]([CH2:10][O:11][C:12]2[CH:13]=[N:14][C:15]([C:18]3[CH2:19][CH2:20][N:21]([S:24]([CH3:27])(=[O:26])=[O:25])[CH2:22][CH:23]=3)=[CH:16][CH:17]=2)[CH2:6][CH2:5]1.COCCN(S(F)(F)[F:40])CCOC.C(=O)(O)[O-].[Na+]>ClCCl>[F:40][C:2]([CH3:28])([CH3:1])[CH2:3][N:4]1[CH2:9][CH2:8][CH:7]([CH2:10][O:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]3[CH2:19][CH2:20][N:21]([S:24]([CH3:27])(=[O:26])=[O:25])[CH2:22][CH:23]=3)=[N:14][CH:13]=2)[CH2:6][CH2:5]1
Reactant: COCCN(CCOC)S(F)(F)F
Reactant: CC(C)(O)CN1CCC(COc2ccc(C3=CCN(S(C)(=O)=O)CC3)nc2)CC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: CC(C)(F)CN1CCC(COc2ccc(C3=CCN(S(C)(=O)=O)CC3)nc2)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 72.4 %

Procedure:
To a solution of 2-methyl-1-[4-[[6-(1-methylsulfonyl-3,6-dihydro-2H-pyridin-4-yl)-3-pyridyl]oxymethyl]-1-piperidyl]propan-2-ol (33 g; 77.91 mmoles) in dichloromethane (155 mL) is added bis(2-methoxyethyl)aminosulfur trifluoride (16.63 mL; 85.70 mmoles) at an internal temperature of 22-23° C. The reaction is stirred at 25° C. for 2 h. Aqueous saturated solution of sodium bicarbonate is added to pH 7. Layers are separated, the aqueous layer is extracted with dichloromethane (2×500 mL), the combined organic layers are dried over magnesium sulphate, filtered and concentrated. The crude material is purified by silica gel chromatography eluting with 98:2 dichloromethane:methanol. The solid is triturated with 500 mL of methyl t-butyl ether and filtered. The solid is dried in an oven at 40° C. for 3 days to obtain 24 g of the title compound as a white solid. MS (m/z) 426 (M+1).
Reaction SMILES: [O-:1][O-:2].[Na+].[Na+].Cl[C:6]([O:8][C:9]([C:12]#[N:13])([CH3:11])[CH3:10])=[O:7]>O>[C:6]([O:1][O:2][C:6]([O:8][C:9]([C:12]#[N:13])([CH3:11])[CH3:10])=[O:7])([O:8][C:9]([C:12]#[N:13])([CH3:11])[CH3:10])=[O:7]
Reactant: [O-][O-]
Reactant: CC(C)(C#N)OC(=O)Cl
Agent: [Na+]
Solvent: O
Product: CC(C)(C#N)OC(=O)OOC(=O)OC(C)(C)C#N
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 63 %

Procedure:
Into a 500 ml round bottom flask equipped with a thermometer, a dropping funnel and a Teflon blade stirrer were added a solution of 50 weight percent sodium hydroxide (41.9 grams, 0.52 mole) and 84 grams of distilled water. The solution was cooled to 15° C. by an ice bath and 50% hydrogen peroxide (18.4 grams, 0.27 mole) was added slowly through the dropping funnel. A sodium peroxide slurry formed immediately. The sodium peroxide slurry was transferred slowly into a 500 ml four-necked round bottom reactor flask containing 82.1 grams (0.5 mole) of the 1-cyano-1-methylethyl chloroformate of Example 1. The reactor flask was equipped with a Teflon blade stirrer, a bottom stopcock, a vent, a sodium peroxide slurry inlet and a thermometer. The temperature within the reactor flask was maintained at about 15° C. or less by spraying ice water on the outside of the flask. On completing the addition of the sodium peroxide slurry, 50 ml of distilled water was added to the reactor flask with stirring and a solid material precipitated immediately. The stirring was continued for 90 minutes. Thereafter, the solid precipitate (43.5 grams, 63% yield) was recovered by filtration, washed twice with distilled water and once with 2-propanol. The product was a white solid having a melting point of 58°-59° C. Identification of the product as di(1-cyano-1-methylethyl)peroxydicarbonate was confirmed by infrared and NMR spectroscopy. Iodometric titration of the product gave a percarbonate assay of 93%.
Reaction SMILES: [C:1]([C:5]1[CH:11]=[CH:10][C:8]([NH2:9])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[C:12]([C:16]1[CH:31]=[CH:30][CH:29]=[CH:28][C:17]=1[O:18][C:19]1[C:24]([N:25]=[C:26]=[S:27])=[CH:23][CH:22]=[CH:21][N:20]=1)([CH3:15])([CH3:14])[CH3:13]>ClCCCl>[C:12]([C:16]1[CH:31]=[CH:30][CH:29]=[CH:28][C:17]=1[O:18][C:19]1[C:24]([NH:25][C:26]([NH:9][C:8]2[CH:7]=[CH:6][C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])=[CH:11][CH:10]=2)=[S:27])=[CH:23][CH:22]=[CH:21][N:20]=1)([CH3:15])([CH3:13])[CH3:14]
Reactant: CC(C)(C)c1ccccc1Oc1ncccc1N=C=S
Reactant: CC(C)(C)c1ccc(N)cc1
Solvent: ClCCCl
Product: CC(C)(C)c1ccc(NC(=S)Nc2cccnc2Oc2ccccc2C(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 48 h
Yield: 54.3 %

Procedure:
To a solution of 4-tert-butyl aniline (30 mg, 0.20 mmol) in DCE (2 mL) was slowly added 1c (50 mg, 0.17 mmol). The reaction was stirred 48 h at rt and concentrated. 96a was crystallized from methanol to afford 40 mg (52% yield) of white crystals. [M+H]+=434.04.
Reaction SMILES: [CH2:1]([C@H:8]1[CH2:12][O:11][C:10]([CH3:14])([CH3:13])[N:9]1[C:15](=[O:35])[C:16]([C:18]1[CH:22]=[CH:21][N:20]([C:23]2[CH:28]=[CH:27][C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:25][CH:24]=2)[CH:19]=1)=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[BH4-].[Na+]>CCOC(C)=O.CO>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10]([CH3:14])([CH3:13])[N:9]1[C:15](=[O:35])[CH:16]([C:18]1[CH:22]=[CH:21][N:20]([C:23]2[CH:24]=[CH:25][C:26]([C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)=[CH:27][CH:28]=2)[CH:19]=1)[OH:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC1(C)OC[C@H](Cc2ccccc2)N1C(=O)C(=O)c1ccn(-c2ccc(-c3ccccc3)cc2)c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Solvent: CCOC(C)=O
Product: CC1(C)OC[C@H](Cc2ccccc2)N1C(=O)C(O)c1ccn(-c2ccc(-c3ccccc3)cc2)c1
Reaction time: 2.75 h
Yield: 99.2 %

Procedure:
To a solution of 1-(4(S)-benzyl-2,2-dimethyl-oxazolidin-3-yl)-2-[1-(biphenyl-4-yl)-1H-pyrrol-3-yl)ethane-1,2-dione (250 mg, 0.54 mmol) in EtOAc (6 mL) and MeOH (2 mL) at 0° C. was added NaBH4 (20 mg, 0.54 mmol). After 2.75 hours at 0° C., more NaBH4 (20 mg, 0.54 mmol) was added. After 1.25 hours at 0° C., the reaction was quenched with HOAc (few drops) and H2O (2 mL). The pH was adjusted to 5 (by pH paper) with HOAc and partitioned between H2O (25 mL) and EtOAc (25 mL). The organic layers were dried over Na2SO4 and concentrated to provide 0.25 g (99%) of 1-(4(S)-benzyl-2,2-dimethyl-oxazolidin-3-yl)-2-[1-(biphenyl-4-yl)1H-pyrrol-3-yl]-2-hydroxy-ethanone as a crisp foam. 1H NMR: δ 7.65 (d, 2H, J=8.5 Hz), 7.59 (d, 2H, J=7.4 Hz), 7.48-7.19 (m, 10H), 7.14 (t, 1H, J=2.0 Hz), 7.06 (t, 1H, J=2.6 Hz), 6.31 (t, 1H, J=2.4Hz), 5.11 (d, 1H, J=7.4 Hz), 4.29 (d, 1H, J=6.6 Hz), 3.99-3.95 (m, 1H), 3.76 (d, 1H, J=9.2 Hz), 3.60 (dd, 1H, J=5.0, 8.6 Hz), 3.08-3.02 (m, 1H), 2.90 (dd, 1H, J=10.5, 13.4 Hz), 1.82 (s, 3H), 1.60 (s, 3H). Anal. Calculated for C30H30N2O3•0.4 H2O: C, 76.05; H, 6.55; N, 5.91. Found: C, 76.17; H, 6.66; N, 5.74.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:16])=[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=2)[CH:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1C=CC(S(O[CH2:34][C:35]([F:38])([F:37])[F:36])(=O)=O)=CC=1>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl:16])=[C:6]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:34][C:35]([F:38])([F:37])[F:36])=[CH:11][CH:10]=2)[CH:7]=1
Reactant: Oc1ccc(Cc2cc(Br)ccc2Cl)cc1
Reactant: Cc1ccc(S(=O)(=O)OCC(F)(F)F)cc1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: FC(F)(F)COc1ccc(Cc2cc(Br)ccc2Cl)cc1
Reaction time: 0.17 h

Procedure:
4-[(5-bromo-2-chloro-phenyl)methyl]phenol 7c (14.5 g, 48.7 mmol, prepared according to the method in WO2009026537) was dissolved in 300 mL DMF, followed by addition of cesium carbonate (31.7 g, 97.5 mmol). The reaction mixture was stirred for 10 minutes. The reaction mixture was stirred for 8 hours at 80° C. after 2,2,2-trifluoroethyl-4-methylbenzenesulfonate 7b (12.4 g, 48.7 mmol) was added. Thereafter, the reaction mixture was filtered and washed with a small amount of ethyl acetate before the filtrate was concentrated under reduced pressure. The resulting residue was partitioned after 100 mL water and 50 mL saturated sodium chloride solution were added. The aqueous phase was extracted with ethyl acetate (100 mL×3) and the organic extract was washed with saturated sodium chloride solution (100 mL), combined and concentrated. The resulting residue was purified by silica gel chromatography with elution system B to obtain the title compound 4-bromo-1-chloro-2-[[4-(2,2,2-trifluoroethoxy)phenyl]methyl]benzene 7d (7.26 g, white solid), yield: 39.2%. 1H NMR (400 MHz, CDCl3): δ 7.32 (s, 1H), 7.30-7.24 (m, 2H), 7.21-7.14 (m, 2H), 6.98-6.87 (m, 2H), 4.38 (d, 2H), 4.06 (s, 2H).
Reaction SMILES: C[O:2][C:3]([C@@H:5]1[O:9][C:8](=[O:10])[N:7]([C:11]2[CH:24]=[CH:23][C:14]3[N:15]([CH3:22])[C:16](=[O:21])[C:17]([F:20])([F:19])[O:18][C:13]=3[CH:12]=2)[CH2:6]1)=O.[CH3:25][NH2:26]>CO>[CH3:25][NH:26][C:3]([C@@H:5]1[O:9][C:8](=[O:10])[N:7]([C:11]2[CH:24]=[CH:23][C:14]3[N:15]([CH3:22])[C:16](=[O:21])[C:17]([F:20])([F:19])[O:18][C:13]=3[CH:12]=2)[CH2:6]1)=[O:2]
Reactant: CN
Reactant: COC(=O)[C@H]1CN(c2ccc3c(c2)OC(F)(F)C(=O)N3C)C(=O)O1
Solvent: CO
Product: CNC(=O)[C@H]1CN(c2ccc3c(c2)OC(F)(F)C(=O)N3C)C(=O)O1
Reaction time: 16 h
Yield: 50 %

Procedure:
To a stirred solution of (5R)-3-(2,2-Difluoro-4-methyl-3-oxo-3,4-dihydro-2H -1,4-benzoxazin-7-yl)-2-oxo-5-oxazolidinecarboxylic acid methyl ester (EXAMPLE 80, Step 3, 50 mg, 0.14 mmol) in MeOH (1 mL) is added 2M MeNH2 in MeOH (2 mL, 4 mmol). The resulting mixture is stirred for 16 h at which time a precipitate forms. The mixture is heated until it becomes clear, and the product is allowed to crystallize at room temperature in the form of white needles. The crystals are separated, washed with ether and dried under high vacuum at 50° C. to give the title compound (25 mg, 50%), 1H NMR (300 MHz, DMSO) δ 8.38 (br d, 1H), 7.60 (d, 1H), 7.51-7.41 (m, 2H), 5.06 (dd, 1H), 4.29 (t, 1H), 4.03 (dd, 1H), 3.41 (s, 3H), 2.65 (d, 2H); MS for C14H13F2N3O5 m/z 342.5 (M+H)+.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:21])[C:5]([NH:7][C:8]1[C:17]([N+:18]([O-:20])=[O:19])=[CH:16][CH:15]=[C:14]2[C:9]=1[CH2:10][CH2:11][CH2:12][NH:13]2)=[O:6])[CH3:2].CI.[C:24](=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C>[CH2:1]([O:3][C:4](=[O:21])[C:5]([N:7]([CH3:24])[C:8]1[C:17]([N+:18]([O-:20])=[O:19])=[CH:16][CH:15]=[C:14]2[C:9]=1[CH2:10][CH2:11][CH2:12][NH:13]2)=[O:6])[CH3:2]
Reactant: O=C([O-])[O-]
Reactant: CCOC(=O)C(=O)Nc1c([N+](=O)[O-])ccc2c1CCCN2
Agent: [Cs+]
Solvent: CI
Solvent: CC#N
Product: CCOC(=O)C(=O)N(C)c1c([N+](=O)[O-])ccc2c1CCCN2
Temperature: 25 °C
Reaction time: 2 h
Yield: 93 %

Procedure:
A mixture of the product from Example 87 (0.87 g, 3 mmol), methyl iodide (0.51 g, 3.6 mmol) and cesium carbonate (1.17 g, 3.6 mmol) in 15 mL of acetonitrile was stirred at room temperature for 2 hours. The inorganic salts were removed by filtration and the filtrate evaporated. The residue was dissolved in methylene chloride, filtered and evaporated. The product was then used without further purification (0.86 g, 93% yield).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([CH3:17])=[CH:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1.[Br:18]Br>C(O)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[N:10]=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([CH2:17][Br:18])=[CH:13][CH:12]=3)[NH:8][C:5]2=[N:6][CH:7]=1
Reactant: Cc1ccc(-c2nc3cc(Br)cnc3[nH]2)cc1
Reactant: BrBr
Solvent: CC(=O)O
Product: BrCc1ccc(-c2nc3cc(Br)cnc3[nH]2)cc1

Procedure:
The title compound was prepared by refluxing 6-bromo-2-(4-methylphenyl)-3H-imidazo[4,5-b]pyridine with a large excess of bromine in acetic acid overnight. APCI-MS m/z: 366/368/370 [MH+].
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH2:12][CH2:13][C:14]([OH:16])=O)=[O:5])[CH3:2].[CH:17]1([C:21]2[N:22]=[C:23](/[CH:26]=[CH:27]/[C:28]3[CH:29]=[C:30]([NH2:34])[CH:31]=[CH:32][CH:33]=3)[S:24][CH:25]=2)[CH2:20][CH2:19][CH2:18]1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:5])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=1[CH2:12][CH2:13][C:14]([NH:34][C:30]1[CH:31]=[CH:32][CH:33]=[C:28](/[CH:27]=[CH:26]/[C:23]2[S:24][CH:25]=[C:21]([CH:17]3[CH2:20][CH2:19][CH2:18]3)[N:22]=2)[CH:29]=1)=[O:16])[CH3:2]
Reactant: CCOC(=O)c1ccccc1CCC(=O)O
Reactant: Nc1cccc(/C=C/c2nc(C3CCC3)cs2)c1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CCOC(=O)c1ccccc1CCC(=O)Nc1cccc(/C=C/c2nc(C3CCC3)cs2)c1
Reaction time: 16 h
Yield: 95.4 %

Procedure:
A solution composed of 0.44 g of 2-(ethoxycarbonyl)benzenepropanoic acid and 25 ml of methylene chloride was added to a solution composed of 0.51 g of (E)-3-[2-[4-(cyclobutyl)-2-thiazolyl]ethenyl]benzeneamine, 0.4 g of N-ethyl-N-(dimethylaminopropyl)carbodiimide, 1.0 g of 4-dimethylaminopyridine and 25 ml of methylene chloride at 0° C. After 16 hr., the reaction mixture was washed with 30 ml of water, dried (MgSO4) and the solvents removed by rotary evaporation. The residual materials were recrystallized from ethyl ether to yield 0.87 g of (E)-2-[3-[3-[2-[4-(cyclobutyl)-2-thiazolyl]ethenyl]phenylamino]-3-oxopropyl]benzoic acid ethyl ester; m.p.110°14 111° C.