Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([CH3:22])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]#[C:13][C:14]3[CH:19]=[CH:18][C:17]([CH2:20][OH:21])=[CH:16][N:15]=3)[CH:10]=2)[O:5][CH2:4][CH2:3]1.[C:23](O)(=[O:25])[CH3:24].C1(N=C=NC2CCCCC2)CCCCC1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH3:1][C:2]1([CH3:22])[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]#[C:13][C:14]3[CH:19]=[CH:18][C:17]([CH2:20][O:21][C:23](=[O:25])[CH3:24])=[CH:16][N:15]=3)[CH:10]=2)[O:5][CH2:4][CH2:3]1
Reactant: CC1(C)CCOc2ccc(C#Cc3ccc(CO)cn3)cc21
Reactant: CC(=O)O
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CC(=O)OCc1ccc(C#Cc2ccc3c(c2)C(C)(C)CCO3)nc1

Procedure:
A solution of 2.81 g (10 mmol) of 2-[2-(4,4-dimethylchroman-6-yl)ethynyl]-5-hydroxymethylpyridine, 600 mg (10 mmol) of glacial acetic acid, 2.06 g (10 mmol) of dicyclohexylcarbodiimide and 460 mg (3.765 mmol) of 4-dimethylaminopyridine in 150 ml methylene chloride is stirred at room temperature for 48 hours. The reaction mixture is then filtered and the residue washed with 50 ml of methylene chloride. The filtrate is then concentrated in vacuo and the residue is purified by chromatography followed by recrystallization to give the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](I)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[CH3:12][O:13][CH2:14][CH2:15][O:16][CH2:17][C:18](=[CH2:26])[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20].C(N(CC)CC)C>ClCCl.O>[CH3:12][O:13][CH2:14][CH2:15][O:16][CH2:17]/[C:18](=[CH:26]\[S:8]([C:5]1[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=1)(=[O:10])=[O:9])/[C:19]([O:21][C:22]([CH3:24])([CH3:23])[CH3:25])=[O:20]
Reactant: C=C(COCCOC)C(=O)OC(C)(C)C
Reactant: O=S(=O)(I)c1ccc(Br)cc1
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClCCl
Product: COCCOC/C(=C\S(=O)(=O)c1ccc(Br)cc1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 2.5 h
Yield: 96.3 %

Procedure:
To a solution of 4-bromobenzenesulphonyl iodide (1.06 g, 3.15 mmol) in dichloromethane (4.5 mL) at room temperature was added tert-butyl 2-(2-methoxyethoxymethyl)acrylate (0.45 g, 2.1 mmol). The mixture was stirred at room temperature for 2.5 hours, cooled to 0° C. and triethylamine (0.58 mL, 4.2 mmol) added dropwise. The reaction was stirred at 0° C. for 0.5 hours and at room temperature for 1.0 hour, diluted with distilled water (20 mL) and dichloromethane (15 mL) and the layers separated. The aqueous layer was further extracted with dichloromethane (2×5 mL) and the combined organic extracts were washed with 1.0M aqueous hydrochloric acid solution (20 mL), 5% aqueous sodium thiosulphate solution (20 mL) and distilled water (20 mL). The dichloromethane phase was dried (MgSO4), filtered and concentrated under reduced pressure to give a brown oil (0.88 g). The crude product was purified by chromatography on silica by gradient elution with hexane/ethyl acetate mixtures to give, after combination and evaporation of appropriate fractions, the title compound as a yellow oil (0.75 g, 83%), Rf =0.39 (silica; hexane/ethyl acetate, 2:1).
Reaction SMILES: [CH3:1][O:2][C:3]1[N:8]=[C:7]2[CH:9]=[CH:10][N:11]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C:6]2=[CH:5][CH:4]=1.[Li]C(C)(C)C.[B:24](OC(C)C)([O:29]C(C)C)[O:25]C(C)C>C1COCC1>[C:15]([O:14][C:12]([N:11]1[C:6]2[C:7](=[N:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[CH:9]=[C:10]1[B:24]([OH:29])[OH:25])=[O:13])([CH3:18])([CH3:17])[CH3:16]
Reactant: COc1ccc2c(ccn2C(=O)OC(C)(C)C)n1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: [Li]C(C)(C)C
Solvent: C1CCOC1
Product: COc1ccc2c(cc(B(O)O)n2C(=O)OC(C)(C)C)n1
Temperature: -78 °C
Reaction time: 1 h
Yield: 36.8 %

Procedure:
To a solution of tert-butyl 5-methoxy-1H-pyrrolo[3,2-b]pyridine-1-carboxylate (3 g, 12.08 mmol) in 40 mL of dry THF was added dropwise t-BuLi (1.16 g, 18.12 mmol) at −78° C. Then the solution was stirred at −78° C. for 1 hour. Then triisopropyl borate (4.55 g, 24.17 mmol) was added dropwise to the solution still at −78° C. The mixture was stirred at −78° C. for 2 hours and quenched the reaction with 1 M of HCl at low temperature to pH=3˜4. After it was extracted with EtOAc, the combined organic phase was washed with brine, dried over Na2SO4. After concentrated, the resulting residue was purified using column (petroleum ether:ethyl acetate=3:1) to provide (1-(tert-butoxycarbonyl)-5-methoxy-1H-pyrrolo[3,2-b]pyridin-2-yl)boronic acid (1.3 g, yield: 37%). 1H-NMR (CDCl3, 400 MHz) δ 8.10 (d, J=9.2 Hz, 1H), 7.46 (s, 1H), 6.88˜6.84 (m, 2H), 6.70 (d, J=9.2 Hz, 1H), 3.98 (s, 3H), 1.71 (s, 9H). MS (M+H)+: 293.
Reaction SMILES: [OH:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]1[CH:11]=[C:10]([N+]([O-])=O)[CH:9]=[CH:8][N+:7]=1[O-:15].C[O-].[Na+].CO.C[C:22](O)=[O:23]>>[OH:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]1[CH:11]=[C:10]([O:23][CH3:22])[CH:9]=[CH:8][N+:7]=1[O-:15]
Reactant: O=[N+]([O-])c1cc[n+]([O-])c(NCCCO)c1
Reactant: CC(=O)O
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: COc1cc[n+]([O-])c(NCCCO)c1
Yield: 116 %

Procedure:
A solution of 2-[(3-hydroxy-1-propyl)amino]-4-nitropyridine-N-oxide (0.275 g, 1 mmol) and 0.5 M NaOMe in MeOH (16 mL, 8 mmol) was heated at reflux under argon for 3 hr. The reaction was then allowed to cool, and glacial AcOH (0.5 mL, 8 mmol) was added. The solution was concentrated to dryness and the residue was triturated with CH2Cl2. The insoluble materials were removed by filtration and the filtrate was concentrated. Silica gel chromatography (5-15% MeOH/CH2Cl2) gave the title compound (0.23 g, 90%) as a colorless oil: MS (ES) m/e 199.0 (M+H)+.
Reaction SMILES: Br[C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5]([Cl:11])=[CH:4][N:3]=1.[F:12][C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:11][C:5]1[CH:6]=[C:7]([N+:8]([O-:10])=[O:9])[C:2]([O:19][C:16]2[CH:17]=[CH:18][C:13]([F:12])=[CH:14][CH:15]=2)=[N:3][CH:4]=1
Reactant: O=[N+]([O-])c1cc(Cl)cnc1Br
Reactant: Oc1ccc(F)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1cc(Cl)cnc1Oc1ccc(F)cc1

Procedure:
The title compound was prepared according to general procedure A using 2-bromo-5-chloro-3-nitro-pyridine (750 mg, 3.17 mmol), 4-fluorophenol (463 mmol, 4.13 mmol), K2CO3 (437 mg, 4.75 mmol) and DMF (5 mL). MS m/z: 269.0 (M+H).
Reaction SMILES: Br[CH2:2][CH2:3][CH:4]1[O:8][CH2:7][CH2:6][O:5]1.[C:9]1([CH2:15][NH:16][CH2:17][C@@H:18]2[CH2:23][CH2:22][NH:21][CH2:20][C@H:19]2[OH:24])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C([O-])([O-])=O.[Na+].[Na+]>>[O:5]1[CH2:6][CH2:7][O:8][CH:4]1[CH2:3][CH2:2][N:21]1[CH2:22][CH2:23][C@@H:18]([CH2:17][NH:16][CH2:15][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C@H:19]([OH:24])[CH2:20]1
Reactant: O[C@@H]1CNCC[C@H]1CNCc1ccccc1
Reactant: BrCCC1OCCO1
Agent: O=C([O-])[O-]
Agent: [Na+]
Product: O[C@@H]1CN(CCC2OCCO2)CC[C@H]1CNCc1ccccc1
Yield: 46.8 %

Procedure:
A mixture of 2-(2-bromoethyl)-1,3-dioxolane (0.04 mol), intermediate (6) (0.04 mol) and Na2CO3 (10%, 0.08 mol) in MIK (400 ml) was stirred and refluxed for 20 hours and then cooled. The solvent was evaporated. The residue was taken up in DCM and water. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/(CH3OH/NH3) 96/4). The pure fractions were collected and the solvent was evaporated. Toluene was added and evaporated again, yielding 6 g of (trans)-1-[2-(1,3-dioxolan-2-yl)ethyl]4-[[(phenylmethyl)amino]methyl]-3-piperidinol (intermediate 7).
Reaction SMILES: [C:1]([C:3]1[N:4]=[C:5]([C:18]2[C:23]([F:24])=[CH:22][CH:21]=[CH:20][C:19]=2[F:25])[O:6][C:7]=1[NH:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=1)#[N:2].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[NH:59]1[CH2:64][CH2:63][O:62][CH2:61][CH2:60]1>CCOC(C)=O>[F:25][C:19]1[CH:20]=[CH:21][CH:22]=[C:23]([F:24])[C:18]=1[C:5]1[O:6][C:7]([NH:8][C:9]2[CH:17]=[CH:16][C:12]([C:13]([N:59]3[CH2:64][CH2:63][O:62][CH2:61][CH2:60]3)=[O:15])=[CH:11][CH:10]=2)=[C:3]([C:1]#[N:2])[N:4]=1
Reactant: C1COCCN1
Reactant: N#Cc1nc(-c2c(F)cccc2F)oc1Nc1ccc(C(=O)O)cc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCOC(C)=O
Solvent: CCN(C(C)C)C(C)C
Product: N#Cc1nc(-c2c(F)cccc2F)oc1Nc1ccc(C(=O)N2CCOCC2)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 37.3 %

Procedure:
To a solution of 4-(4-cyano-2-(2,6-difluorophenyl)oxazol-5-ylamino)benzoic acid (0.020 g, 0.059 mmol), O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.022 g, 0.059 mmol), and diisopropylethylamine (0.020 mL, 0.117 mmol) in N,N-dimethylformide (2 mL) was added morpholine (0.005 mL, 0.059 mmol) and the reaction mixture stirred at room temperature for 16 hours. The reaction was then diluted with EtOAc washed with 1M HCl, water and brine. The organic phase was dried over MgSO4 and the solvent removed in vacuo. The residue was purified by preparative HPLC to afford 2-(2,6-difluorophenyl)-5-(4-(morpholine-4-carbonyl)phenylamino)oxazole-4-carbonitrile (0.009 g, 0.022 mmol, 37%) as a yellow solid. LCMS (2) Rt: 2.38 min; m/z (ES+) 411.
Reaction SMILES: [Cl:1][CH2:2]C(CCl)=O.[C:7]([NH:17][C@H:18]([C:23]([OH:25])=O)[CH2:19][CH:20]([CH3:22])[CH3:21])([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8].[BH4-].[Na+]>CO>[CH2:19]([C@H:18]([NH:17][C:7]([O:9][CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)=[O:8])[C@H:23]([OH:25])[CH2:2][Cl:1])[CH:20]([CH3:21])[CH3:22]
Reactant: CC(C)C[C@H](NC(=O)OCc1ccccc1)C(=O)O
Reactant: O=C(CCl)CCl
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CC(C)C[C@H](NC(=O)OCc1ccccc1)[C@H](O)CCl
Yield: 117.8 %

Procedure:
To a solution of N-Cbz-leucine chloromethyl ketone (2.0 g) in 20 mL of methanol was added, at 0° C., 1.0 g of sodium borohydride and the mixture was stirred at ambient temperature for 24 h. The solution was concentrated under reduced pressure and the residue partitioned between 20 mL of saturated aqueous NH4Cl and 500 ml of diethyl ether. The organic fraction was separated, dried over MgSO4 and concentrated in vacuo and the residue purified by silica gel chromatography to yield 1.8 g of white solid.
Reaction SMILES: [Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][N:3]=1.C1C=C(Cl)C=C(C(OO)=[O:20])C=1>C(Cl)Cl>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][N+:3]=1[O-:20]
Reactant: Clc1nccc2ccccc12
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: [O-][n+]1ccc2ccccc2c1Cl
Temperature: 25 °C
Reaction time: 48 h
Yield: 37.1 %

Procedure:
To a solution of 1-chloroisoquinoline (3.0 g, 18 mmol) in DCM (50 mL) was added m-CPBA (9.5 g, 55 mmol). The mixture was stirred at room temperature for 48 h. The mixture was diluted with DCM, and then washed with brine, dried over Na2SO4, filtered, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel flash column chromatography eluting with a gradient of petroleum ether: EtOAc (5:1 to 0:1) to afford the title compound (1.2 g, 36%) as a yellow solid.
Reaction SMILES: [F:1][C:2]([F:39])([F:38])[C:3]1[CH:33]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:31]=[CH:30][C:4]=1[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11](/[CH:15]=[C:16]3/[C:17](=[O:29])[N:18]([C@@H:22]4[CH2:27][CH2:26][NH:25][CH2:24][C@H:23]4[OH:28])[C:19](=[O:21])[S:20]/3)=[CH:12][CH:13]=2)[CH:8]=[N:7]1.[CH2:40]=O>>[F:39][C:2]([F:38])([F:1])[C:3]1[CH:33]=[C:32]([C:34]([F:35])([F:36])[F:37])[CH:31]=[CH:30][C:4]=1[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11](/[CH:15]=[C:16]3/[C:17](=[O:29])[N:18]([C@@H:22]4[CH2:27][CH2:26][N:25]([CH3:40])[CH2:24][C@H:23]4[OH:28])[C:19](=[O:21])[S:20]/3)=[CH:12][CH:13]=2)[CH:8]=[N:7]1
Reactant: O=C1S/C(=C\c2ccc3c(cnn3Cc3ccc(C(F)(F)F)cc3C(F)(F)F)c2)C(=O)N1[C@@H]1CCNC[C@H]1O
Reactant: C=O
Product: CN1CC[C@@H](N2C(=O)S/C(=C\c3ccc4c(cnn4Cc4ccc(C(F)(F)F)cc4C(F)(F)F)c3)C2=O)[C@H](O)C1

Procedure:
(5Z)-5-({1-[2,4-Bis(trifluoromethyl)benzyl]-1H-indazol-5-yl}methylidene)-3-[trans-3-hydroxy-1-methyl piperidin-4-yl]-1,3-thiazolidine-2,4-dione was prepared from (5Z)-5-({1-[2,4-bis(trifluoromethyl)benzyl]-1H-indazol-5-yl}methylidene)-3-[trans-3-hydroxypiperidin-4-yl]-1,3-thiazolidine-2,4-dione (Example 271) and formaldehyde following General Procedure R.
Reaction SMILES: [O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]([O:14]C)=[O:13])=[CH:4][NH:3]1.[H][H].O=C1C2C(=CC=CC=2)C(C(OC)=O)CN1.[OH-].[Na+]>[Pd].O1CCCC1>[O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12]([OH:14])=[O:13])=[CH:4][NH:3]1
Reactant: [H][H]
Reactant: COC(=O)c1c[nH]c(=O)c2ccccc12
Agent: [Pd]
Agent: COC(=O)C1CNC(=O)c2ccccc21
Agent: [Na+]
Solvent: C1CCOC1
Product: O=C(O)c1c[nH]c(=O)c2ccccc12
Temperature: 25 °C
Reaction time: 8 h
Yield: 91.1 %

Procedure:
2.50 g (12.30 mmol) of methyl 1-oxo-1,2-dihydroisoquinoline-4-carboxylate and 1.30 g of 10% strength palladium on carbon were suspended in an autoclave, and the mixture was hydrogenated at 70° C. and 20 bar of hydrogen for 4 h. The autoclave was vented, after which the catalyst was filtered off and the solvent was removed under reduced pressure, and the crude product was purified by chromatography (ethyl acetate: n-heptane 2:1). This gave 2.28 g (88%) of the desired methyl 1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate. 1H-NMR (400 MHz, CDCl3 δ, ppm) 8.10 (d, 1H), 7.52 (t, 1H), 7.44 (t, 1H), 7.31 (d, 1H), 6.17 (br. s, 1H), 3.98 (dt, 1H), 3.88 (m, 1H), 3.29 (dd, 1H), 3.71 (s, 3H). 2.28 g (11.11 mmol) of methyl 1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate were dissolved in 20 ml of tetrahydrofuran, and 20 ml of 1 N aqueous sodium hydroxide solution were added. The solution was stirred at room temperature for 8 h, the solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate and 1 N hydrochloric acid. The phases were separated, the organic phase was dried over magnesium sulphate and the solvent was removed under reduced pressure. In this manner, 2.12 g (94% of theory) of the desired 1-oxo-1,2-dihydroisoquinoline-4-carboxylic acid were obtained. 1H-NMR (400 MHz, d6-DMSO δ, ppm) 12.65 (br. s, 1H), 7.94 (d, 1H), 7.83 (d, 1H), 7.51 (t, 1H), 7.41-7.35 (m, 2H), 3.89 (t, 1H), 3.68-3.54 (m, 2H). 0.200 g (1.046 mmol) of 1-oxo-1,2-dihydroisoquinoline-4-carboxylic acid were dissolved in 10 ml of acetonitrile, and 0.109 ml (1.569 mmol) of cyclopropylamine, 0.170 g (1.255 mmol) of 1-hydroxy-1H-benzotriazole and 0.221 g (1.151 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride were added. The solution was stirred at room temperature for 8 h, diluted with ethyl acetate and the organic phase was extracted initially with saturated sodium bicarbonate solution and then with 1 N hydrochloric acid.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[C:6]([CH3:17])=[C:7]2[C:12](Cl)=[C:11]([C:14]#[N:15])[CH:10]=[N:9][N:8]2[CH:16]=1)=[O:4].[C:18]([O:22][C:23](=[O:42])[C:24]([O:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[O:34][C:35]1[CH:40]=[CH:39][C:38]([NH2:41])=[CH:37][CH:36]=1)([CH3:26])[CH3:25])([CH3:21])([CH3:20])[CH3:19].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[CH3:1][O:2][C:3]([C:5]1[C:6]([CH3:17])=[C:7]2[C:12]([NH:41][C:38]3[CH:39]=[CH:40][C:35]([O:34][C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=4[O:27][C:24]([C:23]([O:22][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:42])([CH3:26])[CH3:25])=[CH:36][CH:37]=3)=[C:11]([C:14]#[N:15])[CH:10]=[N:9][N:8]2[CH:16]=1)=[O:4]
Reactant: CC(C)(C)OC(=O)C(C)(C)Oc1ccccc1Oc1ccc(N)cc1
Reactant: COC(=O)c1cn2ncc(C#N)c(Cl)c2c1C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)c1cn2ncc(C#N)c(Nc3ccc(Oc4ccccc4OC(C)(C)C(=O)OC(C)(C)C)cc3)c2c1C
Temperature: 25 °C
Reaction time: 16 h
Yield: 91 %

Procedure:
A mixture of 4-chloro-3-cyano-5-methyl-pyrrolo[1,2-b]pyridazine-6-carboxylic acid methyl ester (prepared using the procedure of Example 1D) (320 mg, 1.28 mmol), aniline 388C (440 mg, 1.28 mmol) and K2CO3 (1.77 g, 12.8 mmol) in anhydrous DMF (8 ml) was stirred at rt for 16 h. After regular workup, the residue was purified by silica gel flash column chromatography to afford 388D (651 mg, 91%) as a faintly yellow solid (0%-4% EtOAc—CH2Cl2). LCMS Found: (M+H)+=556.8; (M−tBu+2H)+=500.9
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8](=O)[CH2:9][CH2:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][CH:16]([C:19]3[CH:20]=[C:21]([NH:25][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[CH:22]=[CH:23][CH:24]=3)[CH2:15][CH2:14]2)[CH:5]=[CH:6][CH:7]=1.Cl.[C:33]1([N:39]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)N)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:39]([C:41]3[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=3)[C:33]3[C:34]([C:9]=2[CH2:10][CH2:11][CH2:12][N:13]2[CH2:18][CH2:17][CH:16]([C:19]4[CH:20]=[C:21]([NH:25][C:26](=[O:30])[CH:27]([CH3:29])[CH3:28])[CH:22]=[CH:23][CH:24]=4)[CH2:15][CH2:14]2)=[CH:35][CH:36]=[CH:37][CH:38]=3)[CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)C(=O)Nc1cccc(C2CCN(CCCCC(=O)c3cccc(Cl)c3)CC2)c1
Reactant: NN(c1ccccc1)c1ccccc1
Agent: Cl
Product: CC(C)C(=O)Nc1cccc(C2CCN(CCCc3c(-c4cccc(Cl)c4)n(-c4ccccc4)c4ccccc34)CC2)c1

Procedure:
Prepared by Procedure E and Scheme M using N-(3-{1-[5-(3-chlorophenyl)-5-oxopentyl]-4-piperidinyl}phenyl)-2-methylpropanamide and 1,1-diphenylhydrazine hydrochloride: ESMS m/e: 590.3 (M+H)+.
Reaction SMILES: [NH:1]([C:3]1[S:4][C:5]2[CH:11]=[CH:10][CH:9]=[CH:8][C:6]=2[N:7]=1)[NH2:2].[CH:12]([O-])([O-])OCC.C1(C)C(C)=CC=CC=1>C(O)C>[N:1]1[N:2]=[CH:12][N:7]2[C:6]3[CH:8]=[CH:9][CH:10]=[CH:11][C:5]=3[S:4][C:3]=12
Reactant: CCOC([O-])[O-]
Reactant: NNc1nc2ccccc2s1
Solvent: Cc1ccccc1C
Solvent: CCO
Product: c1ccc2c(c1)sc1nncn12
Temperature: 105 °C

Procedure:
2-Hydrazinobenzothiazole (125 grams; 0.76 mole), ethyl orthoformate (112.4 grams, 0.76 mole), and 2 liters of xylene were heated together with stirring in a three-necked 5-liter flask. An 8-inch column with a condenser was placed in one neck. The reaction was heated to 105° C. and soon all the solid had gone into solution and the solution turned red. Ethanol began to distill from the reaction and about 125 milliliters of it was collected before the reaction was stopped and allowed to cool to room temperature. The yellow precipitate was collected and triturated with diethyl ether. The s-triazolo(3,4-b)benzothiazole product thus obtained was recrystallized from chloroform, m.p. 174.5°-7° C.
Reaction SMILES: [CH:1]([NH:5][C:6]1[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][C:9]([CH3:15])=[C:8](Cl)[C:7]=1[N+:17]([O-:19])=[O:18])([CH2:3][CH3:4])[CH3:2].[NH3:20]>>[CH:1]([NH:5][C:6]1[C:7]([N+:17]([O-:19])=[O:18])=[C:8]([NH2:20])[C:9]([CH3:15])=[CH:10][C:11]=1[N+:12]([O-:14])=[O:13])([CH2:3][CH3:4])[CH3:2]
Reactant: N
Reactant: CCC(C)Nc1c([N+](=O)[O-])cc(C)c(Cl)c1[N+](=O)[O-]
Product: CCC(C)Nc1c([N+](=O)[O-])cc(C)c(N)c1[N+](=O)[O-]

Procedure:
This compound was prepared in a similar manner by reaction of N-sec-butyl-3-chloro-2,6-dinitro-4-methylaniline with ammonia. The crystalline product melts at 151.5°-152.5°C.
Reaction SMILES: [O:1]1[CH:5]=[CH:4][C:3]2[CH:6]=[CH:7][CH:8]=[CH:9][C:2]1=2.[Li][C:11](C)(C)[CH3:12].ICC>C1COCC1>[CH2:11]([C:5]1[O:1][C:2]2[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=2[CH:4]=1)[CH3:12]
Reactant: c1ccc2occc2c1
Reactant: [Li]C(C)(C)C
Solvent: C1CCOC1
Solvent: CCI
Product: CCc1cc2ccccc2o1

Procedure:
2-Ethylbenzo[b]furan was prepared by the method of example 40A with benzo[b]furan (7.3 mmols), 0.86 9) t-BuLi (1.7 m, 9.4 mmols) iodoethane (4 mmols, 0.9 mls) and THF (15 ml). 1.0 g (95%) of a yellow liquid was isolated.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][C:11]=1[O:12][CH2:13][CH2:14][N:15]([CH3:17])[CH3:16].O.O.[Sn](Cl)Cl.CO>CCO>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][C:11]=1[O:12][CH2:13][CH2:14][N:15]([CH3:17])[CH3:16]
Reactant: CN(C)CCOc1cc([N+](=O)[O-])ccc1-c1nc2ccccc2s1
Agent: Cl[Sn]Cl
Solvent: CO
Solvent: CCO
Solvent: O
Product: CN(C)CCOc1cc(N)ccc1-c1nc2ccccc2s1
Yield: 76 %

Procedure:
Prepared as described in the Nitro Reduction section using 2-[2-(1,3-benzothiazol-2-yl)-5-nitrophenoxy]-N,N-dimethylethanamine (0.073 g, 0.21 mmol) and tin (II) dichloride dihydrate (0.38 g, 1.7 mmol) in EtOH (7 ml) to give the title compound (0.05 g, 75%) as a cream-coloured solid after work-up and flash chromatography (MeOH).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:15]2[CH2:19][C@H:18]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:17][C:16]2=[O:25])[CH:5]=[CH:6][C:7]=1[N:8]1[CH:12]=[C:11]([CH2:13][OH:14])[N:10]=[CH:9]1.[O:26]1[CH:30]=[CH:29][CH:28]=[C:27]1[C:31](O)=[O:32].C(OC(OCC(C)(C)C)N(C)C)C(C)(C)C>ClCCl>[F:1][C:2]1[CH:3]=[C:4]([N:15]2[CH2:19][C@H:18]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:17][C:16]2=[O:25])[CH:5]=[CH:6][C:7]=1[N:8]1[CH:12]=[C:11]([CH2:13][O:14][C:31]([C:27]2[O:26][CH:30]=[CH:29][CH:28]=2)=[O:32])[N:10]=[CH:9]1
Reactant: O=C(O)c1ccco1
Reactant: CC(=O)NC[C@H]1CN(c2ccc(-n3cnc(CO)c3)c(F)c2)C(=O)O1
Agent: CN(C)C(OCC(C)(C)C)OCC(C)(C)C
Solvent: ClCCl
Product: CC(=O)NC[C@H]1CN(c2ccc(-n3cnc(COC(=O)c4ccco4)c3)c(F)c2)C(=O)O1
Temperature: 25 °C
Reaction time: 48 h
Yield: 83.3 %

Procedure:
N-[(5S)-3-(3-Fluoro-4-(4-hydroxymethylimidazol-1-yl)phenyl)-2-oxooxazolidin-5-yl-methyl]acetamide (174 mg, 0.5 mM) and furan-2-carboxylic acid (168 mg, 1.5 mM) were suspended in dry dichloromethane (20 ml) under argon, and N,N-dimethylformamide dineopentyl acetal (462 mg, 2 mM) added. The mixture was stirred at ambient temperature for 48 hours giving a solution. The mixture was diluted with an equal volume of dichworomethane, and washed with sufficent 5% aqueous sodium bicarbonate to remove all acids. The organic phase was dried over magnesium sulfate, evaporated, and the residue dissolved in dichloromethane and chromatographed on a 5 g silica Mega Bond Elut® column, eluting with a gradient increasing in polarity from 0 to 10% methanol in dichloromethane. Relevant fractions were combined and evaporated to give the title product (184 mg).
Reaction SMILES: [H-].[Na+].[F:3][C:4]1[CH:9]=[C:8]([NH2:10])[CH:7]=[CH:6][C:5]=1[OH:11].[Cl:12][C:13]1[CH:18]=[C:17]([N+]([O-])=O)[CH:16]=[CH:15][N:14]=1>CN(C=O)C>[Cl:12][C:13]1[CH:18]=[C:17]([O:11][C:5]2[CH:6]=[CH:7][C:8]([NH2:10])=[CH:9][C:4]=2[F:3])[CH:16]=[CH:15][N:14]=1
Reactant: O=[N+]([O-])c1ccnc(Cl)c1
Reactant: Nc1ccc(O)c(F)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Nc1ccc(Oc2ccnc(Cl)c2)c(F)c1
Temperature: 90 °C
Reaction time: 0.5 h
Yield: 76.3 %

Procedure:
Sodium hydride (60%, 0.104 g, 2.60 mmol, 1.1 eq) was added to a solution of 2-fluoro-4-aminophenol (0.30 g, 2.36 mmol, 1.0 eq) in DMF (6.5 mL) at room temperature and the reaction mixture was stirred for 30 minutes. 2-Chloro-4-nitropyridine (Aldrich, 0.374 g, 2.36 mmol, 1.0 eq) was added and the reaction mixture was heated to 90° C. for 12 h. The reaction mixture was cooled to room temperature, quenched with saturated aqueous NaCl solution and extracted with ethyl acetate (3×70 mL). The combined organic extracts were washed with 10% aq. LiCl solution (3×70 mL), dried over Na2SO4, filtered and the filtrate concentrated in vacuo to afford the title compound (0.430 g, 76%) which was used without further purification. 1H NMR (DMSO-d6) δ 8.27 (d, 1H, J=5.7 Hz), 6.90-7.04 (m, 3H), 6.42-6.54 (m, 2H), 5.54 (s, 2H); MS (ESI+) m/z 239 (M+H)+; HRMS (ESI+) calcd.: 239.0387. found: 239.0391.