Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([CH3:12])[O:6][C@H:5]([C:7](OC)=[O:8])[C@@H:4]([CH3:11])[O:3]1.[H-].[H-].[H-].[H-].[Li+].[Al+3].C1COCC1.CCOC(C)=O.O>C(Cl)Cl>[CH3:1][C:2]1([CH3:12])[O:6][C@H:5]([CH2:7][OH:8])[C@@H:4]([CH3:11])[O:3]1
Reactant: COC(=O)[C@H]1OC(C)(C)O[C@@H]1C
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: C[C@H]1OC(C)(C)O[C@@H]1CO
Temperature: 25 °C
Reaction time: 8 h
Yield: 56.1 %

Procedure:
To a solution of commercial (4S,5R)-methyl 2,2,5-trimethyl-1,3-dioxolane-4-carboxylate (2.5 g, 14.4 mmol) in CH2Cl2 (50 ml) at 0° C. was added 1M LiAlH4/THF (35.9 ml, 35.9 mmol). After stirring overnight at RT and cooling to 0° C., EtOAc (5.0 mL) was added. Stirring was continued at RT for 30 min prior to addition of water (50 mL); whereupon, the aqueous mixture was extracted with EtOAc (2×100 mL). The combined organic extracts were washed with sat'd NaCl, dried (Na2SO4), and concentrated. Chromatography (SiO2 230-400 mesh, Hex to 85/15 Hex/EtOAc) of the crude product afforded the expected alcohol (1.18 g, 56% yield) as a clear liquid: 1H NMR ∂ (CDCl3) 4.02 (m, 1H), 3.81 (dd, J=12.1, 2.8 Hz, 1H), 3.65 (m, 1H), 3.60 (dd, J=12.1, 4.4 Hz, 1H), 1.43 (s, 1H), 1.40 (s, 3H), 1.29 (d, J=6.1 Hz, 3H).
Reaction SMILES: [K].[Cl:2][C:3]1[C:4]([C:15]#[N:16])=[C:5]([C:9]([Cl:14])=[C:10]([Cl:13])[C:11]=1[Cl:12])[C:6]([OH:8])=[O:7].S(OC)(O[CH3:21])(=O)=O.[OH-].[K+]>C(C(C)=O)C.O>[Cl:2][C:3]1[C:4]([C:15]#[N:16])=[C:5]([C:9]([Cl:14])=[C:10]([Cl:13])[C:11]=1[Cl:12])[C:6]([O:8][CH3:21])=[O:7]
Reactant: COS(=O)(=O)OC
Reactant: N#Cc1c(Cl)c(Cl)c(Cl)c(Cl)c1C(=O)O
Agent: [K+]
Agent: [K]
Agent: [OH-]
Solvent: CCC(C)=O
Solvent: O
Product: COC(=O)c1c(Cl)c(Cl)c(Cl)c(Cl)c1C#N

Procedure:
A reaction vessel containing 30 ml of water and 60 ml of methyl ethyl ketone is charged with 16.15 g of the dry potassium salt of 3,4,5,6-tetrachloro-2-cyanobenzoic acid. With stirring, the mixture is heated to 72°-74° C. and 9.45 g of dimethyl sulfate are added dropwise at the same temperature to the resultant suspension, while keeping the pH at 6-8 by the gradual addition of 30% potassium hydroxide solution. The reaction mixture is kept under reflux for 2 hours and the aqueous layer is then separated. The organic layer is completely evaporated, affording 12.4 g of methyl 3,4,5,6-tetrachloro-2-cyanobenzoate with a melting point of 82°-83° C.
Reaction SMILES: [C:1]1([C:7]2[CH:8]=[CH:9][C:10]([NH2:13])=[N:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:14][C:15]1[CH:20]=[CH:19][C:18]([S:21](Cl)(=[O:23])=[O:22])=[CH:17][CH:16]=1>N1C=CC=CC=1>[CH3:14][C:15]1[CH:20]=[CH:19][C:18]([S:21]([NH:13][C:10]2[CH:9]=[CH:8][C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[CH:12][N:11]=2)(=[O:23])=[O:22])=[CH:17][CH:16]=1
Reactant: Nc1ccc(-c2ccccc2)cn1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)Nc2ccc(-c3ccccc3)cn2)cc1
Temperature: 25 °C
Yield: 32.2 %

Procedure:
To a solution of 5-phenylpyridin-2-amine (340 mg, 2 mmol) in dry pyridine (10 mL) was added 4-methylbenzenesulfonyl chloride (427 mg, 2.24 mmol). The solution was stirred at room temperature under Argon. The pyridine was then removed in vacuo and flashed off with toluene. The residue was partitioned between EtOAc and 1M NaOH. The organic phase was washed with 1M NaOH until no turbidity was observed on rectification of a small sample. The alkaline phase was made acidic (˜pH 3) with 1M HCl and extracted with EtOAc. After drying over Na2SO4, solvent was removed in vacuo. The crude product weighed 0.24 g. The crude product was taken up in 10 mL of hot EtOAc, diluted with 10 mL of hexane and seeded to give 209 mg of white needles with mp 187-189° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:9]=2[CH2:10][C:11](=[O:17])[NH:12]3)[CH:5]=[CH:6][CH:7]=1.[N:18]1([CH2:23][CH2:24][NH:25][C:26]([C:28]2[C:32]([CH3:33])=[C:31]([CH:34]=O)[NH:30][C:29]=2[CH3:36])=[O:27])[CH2:22][CH2:21][CH2:20][CH2:19]1>C(O)C.N1CCCCC1>[N:18]1([CH2:23][CH2:24][NH:25][C:26]([C:28]2[C:32]([CH3:33])=[C:31]([CH:34]=[C:10]3[C:9]4[C:13](=[CH:14][CH:15]=[CH:16][C:8]=4[C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=4)[NH:12][C:11]3=[O:17])[NH:30][C:29]=2[CH3:36])=[O:27])[CH2:22][CH2:21][CH2:20][CH2:19]1
Reactant: Cc1[nH]c(C=O)c(C)c1C(=O)NCCN1CCCC1
Reactant: O=C1Cc2c(cccc2-c2cccc(Cl)c2)N1
Solvent: C1CCNCC1
Solvent: CCO
Product: Cc1[nH]c(C=C2C(=O)Nc3cccc(-c4cccc(Cl)c4)c32)c(C)c1C(=O)NCCN1CCCC1
Temperature: 25 °C
Reaction time: 72 h
Yield: 61.3 %

Procedure:
To a solution of 4-(3-chloro-phenyl)-1,3-dihydro-indol-2-one (60.9 mg, 0.25 mmol) and 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide (68.5 mg, 0.26 mmol) in ethanol (2 mL) was added piperidine (3 drops). The reaction mixture was stirred at room temperature for three days. The reaction solution was evaporated, and purified on a silica gel column eluting with MeOH —CH2Cl2 5:95 to provide pure product 5-[4-(3-chloro-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidenemethyl)-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (2-pyrrolidin-1-yl-ethyl)-amide as a yellow solid (75 mg, 61%).
Reaction SMILES: [C:1]([O:4][C@@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([CH2:14][O:15][C:16](=[O:18])[CH3:17])[O:7][C@H:6]1[N:19]1[CH:27]=[N:26][C:25]2[CH:24]([CH2:28][OH:29])[NH:23][CH:22]=[N:21][C:20]1=2)(=[O:3])[CH3:2].[H-].[Na+].[S:32](Cl)([CH3:35])(=[O:34])=[O:33].O.C(Cl)(Cl)Cl>C(COC)OC>[C:1]([O:4][C@@H:5]1[C@H:9]([O:10][C:11](=[O:13])[CH3:12])[C@@H:8]([CH2:14][O:15][C:16](=[O:18])[CH3:17])[O:7][C@H:6]1[N:19]1[CH:27]=[N:26][C:25]2[CH:24]([CH2:28][O:29][S:32]([CH3:35])(=[O:34])=[O:33])[NH:23][CH:22]=[N:21][C:20]1=2)(=[O:3])[CH3:2]
Reactant: CS(=O)(=O)Cl
Reactant: CC(=O)OC[C@H]1O[C@@H](n2cnc3c2N=CNC3CO)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Agent: [H-]
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: O
Solvent: COCCOC
Product: CC(=O)OC[C@H]1O[C@@H](n2cnc3c2N=CNC3COS(C)(=O)=O)[C@H](OC(C)=O)[C@@H]1OC(C)=O
Reaction time: 17 h
Yield: 91 %

Procedure:
9-(2,3,5-Tri-O-acetyl-β-D-ribofuranosyl)-6-hydroxymethyl-1,6-dihydropurine (VI) (217 mg.) obtained in (2) was dissolved in purified anhydrous dimethoxyethane (10 ml.) and cooled to -10° to -15° C. To the cooled solution were added sodium hydride (76 mg., 3 moles) and mesyl chloride (180 mg., 3 moles), successively. The reaction was conducted at 0° - 5° C. for 17 hours. The reaction mixture was then treated with water-chloroform and the chloroform layer thus separated was washed with 0.5% aqueous sodium hydrogen carbonate, then with water, dried over anhydrous sodium sulfate and concentrated to yield II as a pale-yellow oil (235 mg., yield: 91%). This substance is unstable and decomposes in chloroform within 2-3 hours.
Reaction SMILES: [CH2:1]([C:3]1[CH:24]=[C:23]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[C:22]([OH:32])=[CH:21][C:4]=1[O:5][CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH2:16][CH2:17][C:18](O)=[O:19])[CH3:2].S(Cl)(Cl)=O.[CH3:37][NH:38][CH3:39]>ClCCl.O>[CH3:37][N:38]([CH3:39])[C:18](=[O:19])[CH2:17][CH2:16][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=1[O:9][CH2:8][CH2:7][CH2:6][O:5][C:4]1[CH:21]=[C:22]([OH:32])[C:23]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)=[CH:24][C:3]=1[CH2:1][CH3:2]
Reactant: CNC
Reactant: CCc1cc(-c2ccc(F)cc2)c(O)cc1OCCCOc1ccccc1CCC(=O)O
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Solvent: O
Product: CCc1cc(-c2ccc(F)cc2)c(O)cc1OCCCOc1ccccc1CCC(=O)N(C)C

Procedure:
A solution of 3-(2-(3-(2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy)propoxy)phenyl)propionic acid and several equivalents of thionyl chloride in dichloromethane was kept at room temperature for 3 hours, and then poured into a stirred solution of 40% dimethylamine in water. The organic layer was washed with aqueous hydrochloric acid, washed with saturated sodium chloride, dried over sodium sulfate, and evaporated in vacuo. The residue was chromatographed on silica gel eluting with ethyl acetate to provide the desired title product. NMR, MS.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:39]=[C:40]([O:44][CH3:45])[C:41]=1[O:42][CH3:43])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][CH:26]([NH:29][C:30]3[NH:34][C:33]4[CH:35]=[CH:36][CH:37]=[CH:38][C:32]=4[N:31]=3)[CH2:25][CH2:24]2)([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[C:15]([F:20])[CH:14]=2)[CH2:9]1)=[O:7].Br[CH2:47][C:48]1[S:49][CH:50]=[CH:51][CH:52]=1>>[CH3:45][O:44][C:40]1[CH:39]=[C:5]([CH:4]=[C:3]([O:2][CH3:1])[C:41]=1[O:42][CH3:43])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:21][CH2:22][N:23]2[CH2:28][CH2:27][CH:26]([NH:29][C:30]3[N:31]([CH2:47][C:48]4[S:49][CH:50]=[CH:51][CH:52]=4)[C:32]4[CH:38]=[CH:37][CH:36]=[CH:35][C:33]=4[N:34]=3)[CH2:25][CH2:24]2)([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[C:15]([F:20])[CH:14]=2)[CH2:9]1)=[O:7]
Reactant: BrCc1cccs1
Reactant: COc1cc(C(=O)N2CCC(CCN3CCC(Nc4nc5ccccc5[nH]4)CC3)(c3ccc(F)c(F)c3)C2)cc(OC)c1OC
Product: COc1cc(C(=O)N2CCC(CCN3CCC(Nc4nc5ccccc5n4Cc4cccs4)CC3)(c3ccc(F)c(F)c3)C2)cc(OC)c1OC

Procedure:
Prepare by the method of Example 37.2 using 1-(3,4,5-trimethoxybenzoyl)-3-(2-(4-(1H-benzimidazol-2-yl-amino)piperidin-1-yl)ethyl)-3-(3,4-difluorophenyl) pyrrolidine and 2-(bromomethyl)thiophene (J. Am. Chem. Soc., 71 1201-1204 (1949)) to give the title compound.
Reaction SMILES: [CH2:1]1[O:9][C:8]2[CH:7]=[CH:6][C:5]([CH3:10])=[CH:4][C:3]=2[O:2]1.[N+:11]([O-])([OH:13])=[O:12]>C(O)(=O)C>[N+:11]([C:6]1[CH:7]=[C:8]2[O:9][CH2:1][O:2][C:3]2=[CH:4][C:5]=1[CH3:10])([O-:13])=[O:12]
Reactant: O=[N+]([O-])O
Reactant: Cc1ccc2c(c1)OCO2
Solvent: CC(=O)O
Product: Cc1cc2c(cc1[N+](=O)[O-])OCO2
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 64.4 %

Procedure:
To a solution of 10 (19.0 g, 139.6 mmol) in acetic acid (180 mL) was added a solution of fuming HNO3 (10 mL) in acetic acid (70 mL) dropwise over 30 minutes. The mixture was stirred at ambient temperature for 10 minutes, then poured into a beaker containing ice to give a crystalline precipitate, which was collected by vacuum filtration and washed with water to afford the crude product. Further purification via recrystallization from CH2Cl2/hexane gave the pure product (16.3 g, 64.4%).
Reaction SMILES: [CH2:1]([O:8][C@H:9]1[C@:15]2([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([CH2:24][C:25]4[CH:30]=[CH:29][C:28]([O:31][CH2:32][CH3:33])=[CH:27][CH:26]=4)[CH:18]=3)[O:16][C@@:12]3([CH2:34][O:35]C(C4C=CC=CC=4)[O:37][C@H:11]3[C@@H:10]1[O:44][CH2:45][C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1)[CH2:13][O:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[Na]>C(#N)C>[CH2:45]([O:44][C@@H:10]1[C@@H:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C@:15]2([C:17]3[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([CH2:24][C:25]4[CH:26]=[CH:27][C:28]([O:31][CH2:32][CH3:33])=[CH:29][CH:30]=4)[CH:18]=3)[O:16][C@@:12]([CH2:34][OH:35])([CH2:13][O:14]2)[C@H:11]1[OH:37])[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1
Reactant: CCOc1ccc(Cc2cc([C@@]34OC[C@]5(COC(c6ccccc6)O[C@H]5[C@H](OCc5ccccc5)[C@H]3OCc3ccccc3)O4)ccc2Cl)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Na]
Solvent: O
Solvent: CC#N
Product: CCOc1ccc(Cc2cc([C@]34OC[C@](CO)(O3)[C@@H](O)[C@H](OCc3ccccc3)[C@H]4OCc3ccccc3)ccc2Cl)cc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 69.3 %

Procedure:
To a solution of (4aS,7S,8R,9S,9aS)-8,9-bis(benzyloxy)-7-(4-chloro-3-(4-ethoxybenzyephenye-2-phenylhexahydro-4a,7-epoxy[1,3]dioxino[5,4-c]oxepine 28c (17.56 g, 27.3 mmol) in acetonitrile (40 mL) was added p-toluenesulfonic acid monohydrate (9.4 g, 54.6 mmol) at room temperature. The mixture was stirred at room temperature for 12 hours and adjusted with saturated aqueous sodium bicarnonate till pH becomes 7. The resulting mixture was extracted with ethyl actate (100 mL×3). The combined organic phases were washed with saturated aqueous sodium chloride (30 mL×2), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=3/1 to give the title compound 28d as a yellow solid (11.68 g, 76.0%). The compound was characterized by the following spectroscopic data: 1H NMR (600 MHz, CDCl3) δ (ppm): 7.35 (d, 1H), 7.29-7.26 (m, 4H), 7.24 (d, 3H), 7.11 (m, 3H), 6.99 (d, 2H), 6.82 (d, 2H), 6.67 (d, 2H), 4.79 (d, 1H), 4.62 (d, 1H), 4.15 (m, 2H), 3.99 (d, 1H), 3.90 (m, 4H), 3.76 (m, 4H), 3.57 (d, 2H), 1.31 (t, 3H).
Reaction SMILES: [C:1](Cl)(=[O:5])[O:2][CH2:3][CH3:4].[C:7]1([CH:13]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[S:14][CH:15]2[CH2:20][CH2:19][N:18](C)[CH2:17][CH2:16]2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>C1(C)C=CC=CC=1>[C:22]1([CH:13]([C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=2)[S:14][CH:15]2[CH2:20][CH2:19][N:18]([C:1]([O:2][CH2:3][CH3:4])=[O:5])[CH2:17][CH2:16]2)[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: CCOC(=O)Cl
Reactant: CN1CCC(SC(c2ccccc2)c2ccccc2)CC1
Solvent: Cc1ccccc1
Product: CCOC(=O)N1CCC(SC(c2ccccc2)c2ccccc2)CC1
Yield: 101.1 %

Procedure:
A quantity of 11.6 g of ethyl chlorocarbonate was added dropwise to a solution of 6.40 g of 4-(diphenylmethylthio)-1-methylpiperidine in 30 ml of toluene, and then the resulting mixture was refluxed for 2.5 hours. After cooling, the reaction mixture was washed with hydrochloric acid and water, dried and concentrated to give 7.73 g of pale yellowish brown solid, which were recrystallized from n-hexane to give colorless needles, mp 70°~71° C.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:29])[C:4]1[CH:9]=[CH:8][C:7]([C:10]([C:12]2[C:21]([CH2:22][CH2:23][CH3:24])=[CH:20][C:19]3[C:18]([CH3:26])([CH3:25])[CH2:17][CH2:16][C:15]([CH3:28])([CH3:27])[C:14]=3[CH:13]=2)=O)=[CH:6][CH:5]=1.[Br-].[CH3:31][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[N-]=[N+]=[N-].[Na+]>C1COCC1>[CH3:1][O:2][C:3](=[O:29])[C:4]1[CH:5]=[CH:6][C:7]([CH:10]=[CH:12][C:21]2[C:22]([CH2:23][CH2:24][CH3:31])=[CH:13][C:14]3[C:15]([CH3:28])([CH3:27])[CH2:16][CH2:17][C:18]([CH3:26])([CH3:25])[C:19]=3[CH:20]=2)=[CH:8][CH:9]=1
Reactant: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CCCc1cc2c(cc1C(=O)c1ccc(C(=O)OC)cc1)C(C)(C)CCC2(C)C
Agent: [Br-]
Agent: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCCc1cc2c(cc1C=Cc1ccc(C(=O)OC)cc1)C(C)(C)CCC2(C)C
Temperature: 25 °C
Reaction time: 3 h
Yield: 78 %

Procedure:
4-[(3-n-Propyl-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)carbonyl]benzoic acid methyl ester (2.7 mmol) in THF (25 mL) was treated with methyltriphenylphosphonium bromide/sodium azide (1.2 g, 3.1 mmol) and the solution was allowed to stir at ambient temperature for 3 h. The reaction was quenched with saturated aqueous NH4Cl and diluted with EtOAc. The organic solution was separated and washed with water and brine, dried (MgSO4), filtered, and concentrated to give a yellow oil. The crude product was crystallized (CH2Cl2/hexanes) to give 4-[(3-n-propyl-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthyl)ethenyl] benzoic acid methyl ester as white crystal (78%): TLC (20% ethyl acetate: 80% hexanes) Rf 0.8; mp 120-121° C.; 1H-NMR (400 MHz, CDCl3) δ7.94 (½ABq, J=8.0 Hz, 2H, ArH), 7.33 (½ABq, J=8.0 Hz, 2H, ArH), 7.09 (s, 1H, ArH), 7.08 (s, 1H, ArH), 5.80 (s, 1H, olefinic), 5.30 (s, 1H, olefinic), 3.90 (s, 3H, OCH3), 2.24 (t, J=8.0 Hz, 2H, CH2), 1.70 (s, 4H, 2CH2), 1.39 (m, 2H, CH2), 1.30 (s, 6H, 2CH3), 1.26 (s, 6H, 2CH3), 0.73 (t, J=7.5 Hz, 3H, CH3), Anal. (C27H34O2) C, H. The ester was hydrolized using the standard conditions of Example 1 to yield 4-[(3-n-propyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)ethyl]benzoic acid (102). Crystallization gave white crystals (83%): TLC (10% MeOH-90% CHCl3) Rf 0.5; mp 263-265° C. 1H-NMR (400 MHz, CDCl3) δ8.00 (½ABq, J=8.0 Hz, 2H, ArH), 7.09 (s, 1H, ArH), 7.08 (s, 1H, ArH), 5.81 (s, 1H, olefinic), 5.31 (s, 1H, olefinic), 2.23 (t, J=8.0 Hz, 2H, CH2), 1.70 (s, 4H, 2CH2), 1.39 (m, 2H, CH2), 1.30 (s, 6H, 2CH3), 1.26 (s, 6H, 2CH3), 0.73 (t, J=7.5 Hz, 3H, CH3), FAB-MS m/z 377 (MH+); Anal. (C26H32O2) C, H.
Reaction SMILES: C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.[NH2:13][CH:14]1[C:35](=[O:36])[N:16]2[C:17]([C:32]([OH:34])=[O:33])=[C:18]([CH2:21][S:22][C:23]3[N:24]([CH3:31])[N:25]=[C:26]([OH:30])[C:27](=[O:29])[N:28]=3)[CH2:19][S:20][C@H:15]12.S1C2C=CC=CC=2N=C1S[C:47](=[O:56])[C:48]([C:50]1[N:51]=[C:52]([NH2:55])[S:53][CH:54]=1)=[O:49].C(O)C>ClCCl>[NH2:55][C:52]1[S:53][CH:54]=[C:50]([C:48](=[O:49])[C:47]([NH:13][CH:14]2[C:35](=[O:36])[N:16]3[C:17]([C:32]([OH:34])=[O:33])=[C:18]([CH2:21][S:22][C:23]4[N:24]([CH3:31])[N:25]=[C:26]([OH:30])[C:27](=[O:29])[N:28]=4)[CH2:19][S:20][C@H:15]23)=[O:56])[N:51]=1
Reactant: Cn1nc(O)c(=O)nc1SCC1=C(C(=O)O)N2C(=O)C(N)[C@H]2SC1
Reactant: Nc1nc(C(=O)C(=O)Sc2nc3ccccc3s2)cs1
Agent: C/C(=N\[Si](C)(C)C)O[Si](C)(C)C
Solvent: CCO
Solvent: ClCCl
Product: Cn1nc(O)c(=O)nc1SCC1=C(C(=O)O)N2C(=O)C(NC(=O)C(=O)c3csc(N)n3)[C@H]2SC1
Reaction time: 2 h

Procedure:
14.85 ml of N,O-bis(trimethylsilyl)acetamide are added at 30° to 7.4 g of 7-amino-3-[(2,5-dihydro-6-hydroxy-2-methyl-5-oxo-1,2,4-triazin-3-yl)thiomethyl]ceph-3-em-4-carboxylic acid (water content: 3.7%) in 50 ml of dichloromethane. After two hours at 30°, the mixture is cooled to -15°. 8.1 g of 2-(2-amino-4-thiazolyl)-2-oxothioacetic-acid-S-benzothiazol-2-ylester are added, and stirred for six hours at -15°. The preparation is added to 500 ml of ethanol which has been warmed to 50°, then cooled whilst stirring and stirred for one hour at 0°. The deposit is filtered off, washed and dried. 9.1 g of the title compound are obtained as a yellow powder. IR: 3320 NH, 1805 c=o, 1735 c=o, 1690 c=o, 1645 (amide I), 1555 (amide II).
Reaction SMILES: [N+](=[CH:3][Si](C)(C)C)=[N-].[Br:8][C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=3)[C:21]([OH:23])=[O:22])[CH:16]=2)[O:11][C:10]=1[C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=1.C(Cl)Cl.C1COCC1>CO.CCOCC>[Br:8][C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15]([C:18]3[CH:19]=[C:20]([CH:24]=[CH:25][CH:26]=3)[C:21]([O:23][CH3:3])=[O:22])[CH:16]=2)[O:11][C:10]=1[C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=1
Reactant: C[Si](C)(C)C=[N+]=[N-]
Reactant: O=C(O)c1cccc(-c2cnc3oc(-c4ccc(F)cc4)c(Br)c3c2)c1
Solvent: ClCCl
Solvent: CCOCC
Solvent: CO
Product: COC(=O)c1cccc(-c2cnc3oc(-c4ccc(F)cc4)c(Br)c3c2)c1
Reaction time: 8 h
Yield: 96.7 %

Procedure:
(Diazomethyl)trimethylsilane (467 μL, 0.934 mmol) was added to a stirring solution of 3-(3-bromo-2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)benzoic acid (350 mg, 0.849 mmol) in MeOH (5.7 mL) and Ether (2.8 mL) at room temperature. It was allowed to stir overnight. The mixture was concentrated and resubjected to the reaction conditions using DCM as the solvent. This was repeated again using THF as the solvent. The reaction was concentrated to give the expected product methyl 3-(3-bromo-2-(4-fluorophenyl)furo[2,3-b]pyridin-5-yl)benzoate (350 mg, 0.821 mmol, 97% yield) consistent by LCMS. LC-MS retention time: 2.01 min; m/z (MH+): 426, 428. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters XBridge 5u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 5 ml/min, a gradient of 100% solvent A/0% solvent B to 0% solvent A/100% solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 min where solvent A was 5% acetonitrile/95% H2O/10 mM ammonium acetate and solvent B was 5% H2O/95% acetonitrile/10 mM ammonium acetate. MS data was determined using a Micromass Platform for LC in electrospray mode.
Reaction SMILES: [CH2:1]([C@@H:3]1[CH2:24][O:23][C:6]2=[C:7]3[C:12](=[CH:13][CH:14]=[C:5]2[NH:4]1)[N:11]=[C:10]([O:15][CH:16]([CH3:18])[CH3:17])[CH:9]=[C:8]3[C:19]([F:22])([F:21])[F:20])[CH3:2].C=O.[BH3-][C:28]#N.[Na+]>C(O)(=O)C>[CH2:1]([C@@H:3]1[CH2:24][O:23][C:6]2=[C:7]3[C:12](=[CH:13][CH:14]=[C:5]2[N:4]1[CH3:28])[N:11]=[C:10]([O:15][CH:16]([CH3:18])[CH3:17])[CH:9]=[C:8]3[C:19]([F:21])([F:22])[F:20])[CH3:2]
Reactant: CC[C@@H]1COc2c(ccc3nc(OC(C)C)cc(C(F)(F)F)c23)N1
Reactant: [BH3-]C#N
Agent: C=O
Agent: [Na+]
Solvent: CC(=O)O
Product: CC[C@@H]1COc2c(ccc3nc(OC(C)C)cc(C(F)(F)F)c23)N1C
Yield: 89.8 %

Procedure:
This compound was prepared by General Method 5 (EXAMPLE 1) from (3R)-3-ethyl-3,4-dihydro-8-isopropoxy-10-(trifluoromethyl)-2H-[1,4]oxazino[2,3-f]quinoline (0.015 g, 0.044 mmol), paraformaldehyde (0.013 g, 0.44 mmol) and NaCNBH3 (0.014 g, 0.22 mmol) in 1 mL glacial acetic acid to afford 0.014 g (93%) of (3R)-3-ethyl-3,4-dihydro-8-isopropoxy-4-methyl-10-(trifluoromethyl)-2H-[1,4]oxazino[2,3-f]quinoline, of sufficient purity as to be used directly in the next reaction. Rf0.5 (9:1 hexane:EtOAc); 1H NMR (400 MHz, CDCl3) δ 7.44 (d, 1H, J=9.0), 7.20 (d, 1H, J=9.0), 7.18 (s, 1H), 5.48 (septet, 1H, J=6.2), 4.29 (dd, ABX, 1H, J=10.7, 2.5), 4.02 (dd, ABX, 1H, J=10.7, 2.7), 3.21–3.16 (m, 1H), 3.03 (s, 3H), 1.74–1.56 (m, 2H), 1.39 (d, 3H, J=6.2), 1.37 (d, 3H, J=6.2), 0.99 (t, 3H, J=7.5).
Reaction SMILES: C([NH:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=[O:10])=[C:7]([CH3:14])[CH:6]=1)(=O)C.S(=O)(=O)(O)O.[OH-].[Na+].[CH3:22]O>>[NH2:4][C:5]1[CH:13]=[CH:12][C:8]([C:9]([O:11][CH3:22])=[O:10])=[C:7]([CH3:14])[CH:6]=1
Reactant: CO
Reactant: CC(=O)Nc1ccc(C(=O)O)c(C)c1
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Product: COC(=O)c1ccc(N)cc1C

Procedure:
15 g (78 mmol) 4-acetamido-2-methyl-benzoic acid are suspended in 150 ml of methanol and combined with 11.2 ml (210 mmol) conc. sulphuric acid. The mixture is refluxed for three hours. Then excess methanol is eliminated in vacuo. The residue is poured onto ice water, made alkaline with 5 N sodium hydroxide solution and extracted twice with ethyl acetate. The combined organic phases are dried over sodium sulphate and evaporated to dryness.
Reaction SMILES: Br[CH2:2][C:3]1[CH:4]=[C:5]([N:9]([CH2:15][C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[S:10]([CH2:13][CH3:14])(=[O:12])=[O:11])[CH:6]=[CH:7][CH:8]=1.[CH3:22][O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1B(O)O.C([O-])([O-])=O.[Na+].[Na+]>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.COCCOC>[CH3:22][O:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[CH2:2][C:3]1[CH:4]=[C:5]([N:9]([CH2:15][C:16]2[CH:17]=[N:18][CH:19]=[CH:20][CH:21]=2)[S:10]([CH2:13][CH3:14])(=[O:12])=[O:11])[CH:6]=[CH:7][CH:8]=1
Reactant: COc1ccccc1B(O)O
Reactant: CCS(=O)(=O)N(Cc1cccnc1)c1cccc(CBr)c1
Agent: [Pd]
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: COCCOC
Product: CCS(=O)(=O)N(Cc1cccnc1)c1cccc(Cc2ccccc2OC)c1
Temperature: 50 °C

Procedure:
The flask was charged with N-(3-bromomethylphenyl)-N-(ethylsulfonyl)pyrid-3-ylmethylamine (0.180 g, 0.500 mmol), 2-methoxyphenylboronic acid (0.113 g, 0.75 mmol), 4.5 ml of DME, 1.5 ml of 2 M Na2CO3, and terakis(triphenylphosphine) palladium(0) (0.018 g, 0.016 mmol). After N2-flushing, the mixture was heated at 50° C. overnight. The reaction mixture was concentrated, diluted with water, and extracted with EtOAc. The organic layer was washed with brine and concentrated. The residue was chromatographed on a silica-gel column with 1:1 to 1:3 toluene/EtOAc to afford the title compound. 1H NMR:, 8.37 (d,1H,J=3.9 Hz), 8.24 (s,1H), 7.55 (d,1H,J=7.8 Hz), 6.74-7.17 (m,9H), 4.76 (s,2H), 3.80 (s,2H), 3.69 (s,2H), 2.94 (q,2H,J=7.3 Hz), 1.32 (t,3H,J=7.3 Hz). MS calcd. 396.2; MS (M+1) 397.2.