Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][C:8]([I:11])=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.[F:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>CN(C)C=O>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([I:11])=[CH:7][C:3]=1[C:4]([C:22]1[CH:23]=[CH:24][C:19]([F:18])=[CH:20][CH:21]=1)=[O:6]
Reactant: Fc1ccccc1
Reactant: O=C(O)c1cc(I)ccc1Cl
Agent: O=C(Cl)C(=O)Cl
Solvent: CN(C)C=O
Product: O=C(c1ccc(F)cc1)c1cc(I)ccc1Cl
Temperature: 20 °C
Reaction time: 2 h

Procedure:
To a solution of 48.94 g 2-chloro-5-iodo-benzoic acid in 180 mL of fluorobenzene and 0.3 mL of N,N-dimethylformamide is added 16.2 mL of oxalyl chloride at 0 to 10° C. The solution is stirred at about 20° C. for 2 hours. The excess amount of oxalyl chloride is evaporated. The residue is diluted in 166 mL of fluorobenzene and 25.93 g of aluminum chloride is added at 0° C. in five portions. The solution is stirred at 75° C. for 1.5 hours and quenched with 300 mL of water at 0 to 25° C. The product is extracted in 300 mL of isopropylacetate and washed with two times of 200 mL brine (3 weight-%). The residue water and solvent is removed upon evaporation.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([CH:17]([C:21](O)=O)[C:18]([OH:20])=[O:19])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1CCOCC1.C(O)(=O)C.C=O>O1CCCC1>[CH2:1]([O:8][C:9]([N:11]1[CH2:12][CH2:13][CH:14]([C:17]([C:18]([OH:20])=[O:19])=[CH2:21])[CH2:15][CH2:16]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)C(C(=O)O)C1CCN(C(=O)OCc2ccccc2)CC1
Agent: C=O
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: C1COCCN1
Product: C=C(C(=O)O)C1CCN(C(=O)OCc2ccccc2)CC1
Yield: 102.4 %

Procedure:
2-(1-Benzyloxycarbonyl-piperidin-4-yl)-malonic acid (18.06 g) was dissolved in tetrahydrofuran (140 ml) and morpholine (4.95 ml) followed by acetic acid (6.43 ml) was added, forming a white precipitate. Formaldehyde (4.56 g) was added, causing the precipitate to disappear, and the mixture heated to reflux for 4 h. The solvent was evaporated, diethyl ether (50 ml) added and the mixture extracted with water (3×60 ml). The aqueous was acidified to pH=3 with citric acid and extracted with diethyl ether (3×30 ml). The combined organic extracts were washed with water (40 ml) and brine (40 ml), dried (Na2SO4), filtered and the solvent removed under reduced pressure to give the title compound (16.65 g) as a mixture containing approximately 10% of the acid starting material.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:14][C:13](=[O:15])[CH2:12][CH2:11][N:10]2[C:16]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[O:17])[CH:5]=[CH:6][C:7]=1[F:8].C(=O)([O-])[O-].[Cs+].[Cs+].C[Si](C)(C)[C:34]([F:37])([F:36])[F:35].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.CO.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:9]2[CH2:14][C:13]([OH:15])([C:34]([F:37])([F:36])[F:35])[CH2:12][CH2:11][N:10]2[C:16]([O:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:17])[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: O=C1CCN(C(=O)OCc2ccccc2)C(c2ccc(F)c(F)c2)C1
Reactant: C[Si](C)(C)C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [Cs+]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Solvent: CO
Product: O=C(OCc1ccccc1)N1CCC(O)(C(F)(F)F)CC1c1ccc(F)c(F)c1
Temperature: 25 °C
Reaction time: 12 h
Yield: 96.3 %

Procedure:
To a solution of benzyl 2-(3,4-difluorophenyl)-4-oxopiperidine-1-carboxylate (0.21 g, 0.60 mmol) (reagent preparation 20, step 2) in dimethylformamide (4.0 mL) at 0° C. was added cesium carbonate (0.30 g, 0.90 mmol), followed by the addition of trimethyl(trifluoromethyl)silane (0.35 mL, 2.40 mmol). The reaction mixture was stirred at room temperature for 12 hours then partitioned between ethyl acetate and water. The organic layer was separated, washed with brine, dried over anhydrous magnesium sulfate then filtered and concentrated. To a solution of the residue in methanol was added potassium carbonate (0.16 g, 1.19 mmol) and the reaction mixture was stirred at room temperature for 24 hours. The mixture was diluted with ethyl acetate and washed with 1M aqueous hydrochloric acid, brine, dried over anhydrous magnesium sulfate then filtered and concentrated to give benzyl 2-(3,4-difluorophenyl)-4-hydroxy-4-(trifluoromethyl)piperidine-1-carboxylate (0.24 g, quantitative).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([C:8]([CH3:10])=[O:9])[CH:5]=[CH:4][C:3]=1[Cl:11].[N:12](C(C)(C)C#N)=NC(C)(C)C#N.C(Cl)(Cl)(Cl)Cl.[C:29]([O:32][CH2:33]C)(=[O:31])C>>[Cl:11][C:3]1[CH:4]=[CH:5][C:6]([C:8](=[O:9])[CH3:10])=[CH:7][C:2]=1[CH2:1][NH:12][C:29](=[O:31])[O:32][CH3:33]
Reactant: CC(C)(C#N)N=NC(C)(C)C#N
Reactant: CCOC(C)=O
Reactant: CC(=O)c1ccc(Cl)c(C)c1
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)NCc1cc(C(C)=O)ccc1Cl
Temperature: 25 °C
Reaction time: 4 h

Procedure:
25.0 g of 4-chloro-3-methylacetophenone, 26.6 g of N-bromosuccinic imide and a catalytic amount of azobisisobutyronitrile were added to 150 ml of carbon tetrachloride, followed by reflux under heating for 2 hours. After completion of the reaction, the reaction mixture was cooled to room temperature, insoluble matters were collected by filtration, and the filtrate was concentrated under reduced pressure. The obtained residue, 18.0 g of potassium cyanate and 38 ml of methanol were added to 150 ml of N,N-dimethylformamide, followed by stirring at 90° C. for 4 hours. After completion of the reaction, water was added to the reaction mixture, extraction with ethyl acetate was carried out, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (Wakogel C-200, eluent: hexane/ethyl acetate) and washed with isopropyl ether to obtain 6.8 g of methyl N-(2-chloro-5-acetylbenzyl)carbamate as colorless crystals.
Reaction SMILES: [C:1]([O:10]C)(=O)[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[SH:4].[C:12]([C:15]1[C:16](C#N)=[N:17][CH:18]=[CH:19][CH:20]=1)(=[O:14])[CH3:13].[CH2:23]([N:25](CC)CC)C>C1(C)C=CC=CC=1>[C:12]([C:15]1[CH:20]=[CH:19][C:18]([C:23]2[S:4][C:3]3[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=3[C:1](=[O:10])[N:25]=2)=[N:17][CH:16]=1)(=[O:14])[CH3:13]
Reactant: CCN(CC)CC
Reactant: COC(=O)c1ccccc1S
Reactant: CC(=O)c1cccnc1C#N
Solvent: Cc1ccccc1
Product: CC(=O)c1ccc(-c2nc(=O)c3ccccc3s2)nc1
Yield: 39.4 %

Procedure:
A mixture of methyl thiosalicylate (0.51 g, 3.0 mmol), 3-acetyl-2-cyanopyridine (0.40 g, 2.7 mmol), triethylamine (0.61 ml, 4.4 mmol) and toluene (2.0 ml) was refluxed for 20 hrs. After cooling, the precipitated crystals were collected by filtration and recrystallized from acetone to give the titled compound (0.30 g, 38%).
Reaction SMILES: [C:1]([CH2:3][C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5])#[N:2].[CH:11](OCC)(OCC)OCC.C(OC(=O)C)(=O)C.Cl.[NH:29]([C:31]1[CH:40]=[CH:39][C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:33][CH:32]=1)[NH2:30].CCN(C(C)C)C(C)C>C(OCC)(=O)C>[NH2:2][C:1]1[N:29]([C:31]2[CH:32]=[CH:33][C:34]([C:35]([O:37][CH3:38])=[O:36])=[CH:39][CH:40]=2)[N:30]=[CH:11][C:3]=1[C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5]
Reactant: COC(=O)c1ccc(NN)cc1
Reactant: CCOC(OCC)OCC
Reactant: CC(C)(C)OC(=O)CC#N
Agent: Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: CC(=O)OC(C)=O
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc(-n2ncc(C(=O)OC(C)(C)C)c2N)cc1
Temperature: 125 °C

Procedure:
t-Butyl cyanoacetate (14.1 g, 100 mmol) was dissolved in triethyl orthoformate (24.8 mL, 150 mmol). Acetic anhydride (9.625 mL, 100 mL) was added and the mixture heated to 125° C. for 3 h and then volatiles were removed by evaporation under reduced pressure. The residue was dissolved in ethanol (100 mL) and methyl 4-hydrazinylbenzoate hydrochloride (Intermediate#123) (6.06 g, 30 mmol) and DIPEA (5.23 mL, 30 mmol) was added. The mixture was heated to reflux for 5 h and then evaporated under reduced pressure to leave a brown oil which was dissolved in ethyl acetate (300 mL) and washed with water (2×100 mL) and brine (100 mL), dried (MgSO4) and evaporated. The residue was purified by chromatography on silica gel (120 g silica, EtOAc/Hexane 0-50%) to give the title compound as a yellow solid. (7.1 g)
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[C:11]([F:14])([F:13])[F:12].C(OC(C)C)(=O)C.[Br:22]([O-])(=O)=O.[Na+].S([O-])(O)=O.[Na+]>O>[Br:22][CH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[C:11]([F:12])([F:13])[F:14]
Reactant: [O-][Br+2]([O-])[O-]
Reactant: Cc1ccc(C(=O)O)cc1C(F)(F)F
Agent: O=S([O-])O
Agent: [Na+]
Solvent: O
Solvent: CC(=O)OC(C)C
Product: O=C(O)c1ccc(CBr)c(C(F)(F)F)c1
Temperature: 25 °C
Yield: 60.1 %

Procedure:
To 60.0 g of 4-methyl-3-trifluoromethylbenzoic acid was added 600 ml of isopropyl acetate. Under stirring at room temperature, a solution of 133.0 g of sodium bromate in 420 ml of water and a solution of 91.7 g of sodium hydrogensulfite in 180 ml of water were added in turn. The mixture was gradually heated from 30° C. up to 50° C. at intervals of 10° C. and stirred until the color of the reaction solution disappeared. The aqueous layer was separated to remove, and to the organic layer were added a solution of 133.0 g of sodium bromate in 420 ml of water and a solution of 91.7 g of sodium hydrogensulfite in 180 ml of water, and then the mixture was gradually heated up to 60° C. as above. After separation, to the organic layer were further added a solution of 133.0 g of sodium bromate in 420 ml of water and a solution of 91.7 g of sodium hydrogensulfite in 180 ml of water, and the mixture was gradually heated as above and heated to the temperature the mixture was finally refluxed. After the completion of the reaction, the reaction solution was separated, the organic layer was washed twice with a 5% aqueous sodium thiosulfate solution and twice with 15% saline, dried over anhydrous magnesium sulfate, and, then the solvent was distilled off under reduced pressure. To the residue was added 120 ml of n-heptane, the mixture was stirred, and then the crystals were collected by filtration to obtain 50.0 g of the objective compound as colorless crystals.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([Cl:20])[C:5]2[O:9][C:8]([CH2:10][CH2:11][NH:12][CH2:13][CH:14]([O:17][CH3:18])[O:15][CH3:16])=[CH:7][C:6]=2[CH:19]=1.C(N(C(C)C)CC)(C)C.Cl[C:31]([O:33][CH2:34][CH3:35])=[O:32].O>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([Cl:20])[C:5]2[O:9][C:8]([CH2:10][CH2:11][N:12]([CH2:13][CH:14]([O:15][CH3:16])[O:17][CH3:18])[C:31](=[O:32])[O:33][CH2:34][CH3:35])=[CH:7][C:6]=2[CH:19]=1
Reactant: CCOC(=O)Cl
Reactant: COC(CNCCc1cc2cc(Br)cc(Cl)c2o1)OC
Solvent: O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)N(CCc1cc2cc(Br)cc(Cl)c2o1)CC(OC)OC
Yield: 89.5 %

Procedure:
To a solution of the product obtained from step A (640 mg, 1.76 mmol) in dichloromethane (5 mL) at 0° C. was added diisopropylethylamine (0.61 mL, 3.53 mmol) followed by ethyl chloroformate (0.34 mL, 3.53 mmol). The reaction mixture was allowed to warm to ambient temperature over 2 h before addition of water (10 mL). The mixture was extracted with dichloromethane (2×20 mL) and the combined organic extracts washed with brine, dried over Na2SO4, filtered and the filtrate concentrated in vacuo. Purification by flash column chromatography (SiO2, 9:1 to 1:1 hexanes/ethyl acetate) afforded ethyl 2-(5-bromo-7-chlorobenzofuran-2-yl)ethyl(2,2-dimethoxyethyl)carbamate (685 mg, 89%) as a colorless oil: 1H NMR (CDCl3, 300 MHz) δ 7.51 (s, 1H), 7.37 (s, 1H), 6.50-6.39 (m, 1H), 4.53-4.38 (m, 1H), 4.21-3.98 (m, 2H), 3.75-3.64 (m, 2H), 3.47-3.35 (m, 6H), 3.34-3.22 (m, 2H), 3.13-2.99 (m, 2H), 1.30-1.11 (m, 3H).
Reaction SMILES: [OH:1][CH2:2][C@@H:3]1[CH2:7][C:6](=C)[CH2:5][C@H:4]1[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C[OH:16]>>[OH:1][CH2:2][C@H:3]1[C@H:4]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[CH2:5][C:6](=[O:16])[CH2:7]1
Reactant: CO
Reactant: C=C1C[C@@H](CO)[C@H](c2ccccc2)C1
Product: O=C1C[C@@H](CO)[C@H](c2ccccc2)C1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
Into a solution of (+−)-trans-1-hydroxymethyl-4-methylene-2-phenylcyclopentane from Step B (22.7 g, 121 mmol) in methanol (200 mL) cooled in a dry ice/acetone bath was bubbled ozone until the blue color persisted. The excess ozone was removed with a stream of nitrogen and then dimethylsulfide (20 mL) was added. After 10 min, the bath was removed and the reaction was allowed to warm to rt over 16 h. The volatiles were removed in vacuo and the residue was purified by FC (15-30% ethyl acetate in hexanes) to give the title compound (22.1 g).
Reaction SMILES: [C:1]([C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH:6]=[O:7])([OH:3])=[O:2].[CH3:12]OS(OC)(=O)=O.C(N(CC)CC)C>[Au].C(Cl)Cl>[C:1]([C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH:6]=[O:7])([O:3][CH3:12])=[O:2]
Reactant: COS(=O)(=O)OC
Reactant: O=Cc1ccccc1C(=O)O
Agent: [Au]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)c1ccccc1C=O
Temperature: 25 °C
Yield: 103.1 %

Procedure:
Into a 3-neck 1 liter round bottom flask equipped with a magnetic stirrer, reflux condenser fitted with a drying tube, addition funnel with a septum and a nitrogen inlet, 100 g (0.659 mole) 2-carboxybenzaldehyde, about 140 ml methylene chloride and 162.8 g [122.2 ml (1.291 moles)] dimethylsulfate were placed. The mixture was heated to reflux 135.89 g [187.2 ml (1.343 moles)] triethylamine was added dropwise, maintaining a brisk reflux. After the addition was complete, the resulting gold-colored solution was allowed to cool to room temperature, and then washed with 400 ml water. After the layers were separated, the aqueous phase was extracted with 400 ml methylene chloride. The organic layers were combined and washed with 500 ml of a saturated aqueous sodium bicarbonate solution and with 500 ml water. The organic phase was dried over magnesium sulfate and then concentrated to give 111.5 g of the product as a gold liquid.
Reaction SMILES: [ClH:1].[C:2]1([CH:8]2[CH:12]3[CH2:13][NH:14][CH2:15][C:16](=[CH:17][C:18]4[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=4)[C:11]3=[N:10][N:9]2[CH2:24][C:25]([F:28])([F:27])[F:26])[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:29]#[C:30][NH2:31]>C(O)C>[ClH:1].[C:2]1([CH:8]2[CH:12]3[CH2:13][N:14]([C:30](=[NH:29])[NH2:31])[CH2:15][C:16](=[CH:17][C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=4)[C:11]3=[N:10][N:9]2[CH2:24][C:25]([F:27])([F:26])[F:28])[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: FC(F)(F)CN1N=C2C(=Cc3ccccc3)CNCC2C1c1ccccc1
Reactant: N#CN
Agent: Cl
Solvent: CCO
Product: N=C(N)N1CC(=Cc2ccccc2)C2=NN(CC(F)(F)F)C(c3ccccc3)C2C1
Yield: 48 %

Procedure:
Ten grams of 3,3a,4,5,6,7-hexahydro-3-phenyl-7-(phenylmethylene)-2-(2,2,2-trifluoroethyl)-2H-pyrazolo[4,3-c]-pyridine, monohydrochloride (see Example 2) is reacted with 8.2 g of cyanamide in 350 ml of ethanol at reflux temperature for 24 hours. The bulk of ethanol is removed on a rotary evaporator and the residue (which does not crystallize) is converted to 10.8 g of the free base (using sodium hydroxide and chloroform extractions); melting point 155°-157° C (foaming), sintering at 120° C. The base is dissolved in 400 ml of dichloromethane, treated with 5 ml of 6.1 N alcoholic hydrogen chloride, and the solvents removed on a rotary evaporator. The foamy residue (11.7 g) is stirred with 50 ml of water and 150 ml of ether. The material becomes gummy, then slowly crystallizes on cooling in ice-water, continued stirring, and rubbing. After standing in the cold for about 16 hours, the product is filtered, washed with ether, and air-dried, yielding 5.3 g of material; melting point 222°-225° C, sintering at 210° C. Crystallization from acetonitrile (dissolved in 200 ml of boiling solvent, then concentrated to approximately 100 ml; crystallization proceeeds very slowly while standing in the cold for several days) yields 3.0 g of product; melting point 230°-232° C, sintering at 223° C.
Reaction SMILES: C(N(CC)CC)C.Cl.[CH2:9]([C:11]1[N:12]([CH3:19])[CH:13]=[CH:14][C:15](=[O:18])[C:16]=1[OH:17])[CH3:10].[N:20]([CH2:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])=[C:21]=[O:22]>C(#N)C.C(Cl)Cl>[CH2:27]([O:26][C:24]([CH2:23][NH:20][C:21]([O:17][C:16]1[C:15](=[O:18])[CH:14]=[CH:13][N:12]([CH3:19])[C:11]=1[CH2:9][CH3:10])=[O:22])=[O:25])[CH3:28]
Reactant: CCc1c(O)c(=O)ccn1C
Reactant: CCOC(=O)CN=C=O
Agent: Cl
Solvent: ClCCl
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCOC(=O)CNC(=O)Oc1c(CC)n(C)ccc1=O
Reaction time: 0.17 h

Procedure:
2.8 ml of triethylamine are added at room temperature to a suspension of 1.89 g of 2-ethyl-3-hydroxy-1-methyl-4(1H)-pyridinone hydrochloride in 50 ml of acetonitrile and 50 ml of methylene chloride followed by the addition of 2.27 ml of ethyl isocyanatoacetate. The ensuing reaction is slightly exothermic and a solution forms within 10 minutes. The reaction is complete after 1.5 hours. The reaction mixture is evaporated to dryness under reduced pressure, the residue is dried under a high vacuum and crystallised from ethyl acetate. A solution of 4.0 g of the resultant hydrochloride of 3-(ethoxycarbonylmethylaminocarbonyloxy)-2-ethyl-1-methyl-4(1H)-pyridinone in 40 ml of water is adjusted to pH 2.5 with phosphoric acid, saturated with sodium chloride and extracted with methylene chloride. The residue of the organic extract is crystallised from a 95:5 mixture of ethyl acetate and methylene chloride, affording 3-(ethoxycarbonylmethylaminocarbonyloxy)-2-ethyl-1-methyl-4(1H)-pyridinone with a melting point of 99°-100° C.
Reaction SMILES: [N:1]([CH2:4][C:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:6])=[N+:2]=[N-].C1(P(C2C=CC=CC=2)CCC(ON2C(=O)CCC2=O)=O)C=CC=CC=1>C1(C)C=CC=CC=1.C(Cl)Cl>[N+:1](=[CH:4][C:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=[O:6])=[N-:2]
Reactant: [N-]=[N+]=NCC(=O)c1ccccc1
Agent: O=C(CCP(c1ccccc1)c1ccccc1)ON1C(=O)CCC1=O
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: [N-]=[N+]=CC(=O)c1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 49.2 %

Procedure:
A solution of azide 2i (74 mg, 0.459 mmol) in anhydrous toluene (1.5 mL) was cooled to 0° C. A solution of phosphine 1e (171 mg, 0.482 mmol) in toluene (1.0 mL) was added dropwise. The resulting solution was maintained at 0° C. for 2 h and was then allowed to warm to room temperature. The mixture was then diluted with anhydrous CH2Cl2 (5 mL) and was stirred for an additional 30 min. The solution was then placed directly on a column of silica gel and eluted with 15% EtOAc/hexanes to give diazo-compound 5i as a yellow oil (33 mg, 0.226 mmol, 49% yield).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([CH2:8][CH3:9])[N:5]=[C:4]([CH2:10][CH3:11])[C:3]=1[CH:12]=O.[C:14]([CH:17]=P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)(O)=[O:15]>C1(C)C=CC=CC=1>[CH2:10]([C:4]1[N:5]=[C:6]([CH2:8][CH3:9])[CH:7]=[C:2]2[C:3]=1[CH:12]=[CH:17][C:14](=[O:15])[NH:1]2)[CH3:11]
Reactant: O=C(O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CCc1cc(N)c(C=O)c(CC)n1
Solvent: Cc1ccccc1
Product: CCc1cc2[nH]c(=O)ccc2c(CC)n1
Yield: 76.2 %

Procedure:
A mixture of 4-amino-2,6-diethylpyridine-3-carbaldehyde (40 g) and (carboxymethylene)triphenylphosphorane (82.5 g) in toluene (1 l) was stirred and heated at reflux for 3 hours. The solution was cooled and the solvent was removed by evaporation. A solution of sodium (20 g) in methanol (800 ml) was added to the residue and the resulting solution was heated at reflux for 4 hours. Methanol was removed by evaporation and water (500 ml) was added. The mixture was acidified to pH 1-2 by addition of concentrated hydrochloric acid. The mixture was then extracted with ethyl acetate (2×500 ml) and ether (1×500) and the extracts were discarded. The aqueous phase was then basified by addition of solid potassium carbonate and the solid which crystallised was collected by filtration and washed with water. The solid was recrystallised from acetone to give 5,7-diethyl-1,6-naphthyridin-2(1H)-one (34.6 g), m.p. 168°-169° C.; NMR (d6 -DMSO): 1.24(dt, 6H), 2.72(q, 2H), 3.0(q, 2H), 6.46(d, 1H), 6.9(s, 1H), 8.07(d, 1H); mass spectrum (CI): 203 (M+H)+ ; microanalysis, found: C, 70.9; H, 6.9; N, 13.8%; C12H14N2O requires: C, 71.3; H, 6.98; N, 13.9%.
Reaction SMILES: [CH3:1][O:2][C:3]([C@H:5]1[NH:8][C:7](=[O:9])[C@H:6]1[NH2:10])=[O:4].C(=O)([O-])O.[Na+].[Cl:16][CH2:17][C:18]([NH:20][C:21]1[S:22][CH:23]=[C:24]([C:26](=[N:30][O:31][CH3:32])[C:27](Cl)=[O:28])[N:25]=1)=[O:19].O>O1CCCC1>[CH3:1][O:2][C:3]([C@H:5]1[NH:8][C:7](=[O:9])[C@H:6]1[NH:10][C:27](=[O:28])[C:26]([C:24]1[N:25]=[C:21]([NH:20][C:18](=[O:19])[CH2:17][Cl:16])[S:22][CH:23]=1)=[N:30][O:31][CH3:32])=[O:4]
Reactant: COC(=O)[C@H]1NC(=O)[C@H]1N
Reactant: CON=C(C(=O)Cl)c1csc(NC(=O)CCl)n1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: CON=C(C(=O)N[C@@H]1C(=O)N[C@@H]1C(=O)OC)c1csc(NC(=O)CCl)n1

Procedure:
Under ice-cooling and stirring, 6 ml of an aqueous solution containing 288 mg of cis-3-amino-2-oxoazetidine-4-carboxylic acid methyl ester and 561 mg of sodium hydrogen carbonate is added to a suspension of 1.18 g of 2-(2-chloroacetamido-4-thiazolyl)-2-methoxyiminoacetyl chloride (syn isomer) in 10 ml of tetrahydrofuran. After the mixture is stirred for 2 hours at room temperature, the solvent is distilled off in vacuo to leave a residue, which solidifies. Water is added to the solid, followed by filtration, and the collected crystals are washed successively with water and ethanol to give cis-3-[2-(2-chloroacetamido-4-thiazolyl)-2-methoxyiminoacetamido]-2-oxoazetidine-4-carboylic acid methyl ester (syn isomer), m.p. 270°-275° C. (dec.).
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:8][C:9](N(C)C)=[O:10]>>[CH3:8][C:9]([C:4]1[CH:5]=[CH:6][C:1]([O:7][C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:2][CH:3]=1)=[O:10]
Reactant: Oc1ccccc1
Reactant: CC(=O)N(C)C
Product: CC(=O)c1ccc(Oc2ccccc2)cc1

Procedure:
4-Phenoxyacetophenone was prepared by refluxing 4-fluoroaceotone and phenol in DMAc for 16 hours. The solvent was removed under reduced pressure and the reside subjected to standard ethyl acetate/water work-up and the resulting material purified by silica gel chromatography.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:9](=O)[CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[C:12]=2[Cl:18])[C:5]([Cl:8])=[N:6][CH:7]=1.OI(C1C=CC=CC=1)OS(C1C=CC([N+]([O-])=O)=CC=1[N+]([O-])=O)(=O)=O.[C:44]([NH2:47])(=[O:46])[CH3:45]>C1COCC1.ClCCCl.CO>[Br:1][C:2]1[CH:3]=[C:4]([C:9]2[N:47]=[C:44]([CH3:45])[O:46][C:10]=2[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[C:12]=2[Cl:18])[C:5]([Cl:8])=[N:6][CH:7]=1
Reactant: O=C(Cc1cccc(Cl)c1Cl)c1cc(Br)cnc1Cl
Reactant: CC(N)=O
Agent: O=[N+]([O-])c1ccc(S(=O)(=O)OI(O)c2ccccc2)c([N+](=O)[O-])c1
Solvent: ClCCCl
Solvent: C1CCOC1
Solvent: CO
Product: Cc1nc(-c2cc(Br)cnc2Cl)c(-c2cccc(Cl)c2Cl)o1
Temperature: 25 °C
Yield: 24 %

Procedure:
To a solution of 1-(5-bromo-2-chloropyridin-3-yl)-2-(2,3-dichlorophenyl)ethanone (0.315 g, 0.83 mmol) in THF (3 mL) was added HDNIB (0.585 g, 1.2 mmol, [hydroxy(2,4-dinitrobenzenesulfonyloxy)iodo]benzene, see Lee et al., Synlett, 10: 1563-1564, 2001) in 1,2-dichloroethane (3 mL). The reaction mixture was heated to reflux in a sealed tube for 2 hours, at which point a solution formed. The reaction was cooled to RT and acetamide (2 eq., 0.115 g, 1.9 mmol) was added. The reaction was then heated to reflux for 18 hours. After cooling, the mixture was dissolved in MeOH, adsorbed onto Celite™ and purified by silica gel chromatography (5 to 40% EtOAc/hexanes) to give 5-bromo-2-chloro-3-(5-(2,3-dichlorophenyl)-2-methyloxazol-4-yl)pyridine as a colorless oil [0.084 g, 24% yield; LC-MS m/e=418.8 (M+H)].