Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH:9]([CH2:14][CH2:15][CH3:16])[C:10]([O:12][CH3:13])=[O:11])=[C:4]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)[N:3]=1.[F:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:26]=1B(O)O.C(N(CC)C(C)C)(C)C>COCCOC.O.[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>[F:24][C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[C:26]=1[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([CH:9]([CH2:14][CH2:15][CH3:16])[C:10]([O:12][CH3:13])=[O:11])=[C:4]([C:17]2[CH:22]=[CH:21][C:20]([CH3:23])=[CH:19][CH:18]=2)[N:3]=1
Reactant: CCCC(C(=O)OC)c1c(C)nc(Cl)nc1-c1ccc(C)cc1
Reactant: OB(O)c1c(F)cccc1F
Agent: [Pd]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: COCCOC
Product: CCCC(C(=O)OC)c1c(C)nc(-c2c(F)cccc2F)nc1-c1ccc(C)cc1
Yield: 26.8 %

Procedure:
Methyl 2-(2-chloro-4-methyl-6-p-tolylpyrimidin-5-yl)pentanoate (100 mg; 0.300 mmol), 2,6-difluorophenylboronic acid (142 mg; 0.901 mmol), tetrakis(triphenylphosphine) palladium(0) (34.7 mg; 0.030 mmol) were placed in a 5 mL reaction tube and dissolved in a mixture of degassed DME (1.50 mL) and water (0.5 mL). N,N-Diisopropylethylamine (0.185 mL; 1.202 mmol) was added, the tube was sealed and irradiated in a microwave oven at 130° C. for 1 h. The reaction mixture was partitioned between brine and dichloromethane, filtered over a phase separator filter (1PS) and concentrated under reduced pressure. The crude material was purified by flash chromatography on silica gel using a linear gradient of ethylacetate (10-80%) in heptane to give 33 mg (16%) of the title compound as a colorless oil.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([C:8]([NH:10][C:11]2[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][C:12]=2C)=[O:9])[CH:3]=1.C(N(C(C)C)C(C)C)C.[NH2:28][C:29]1[C:30]([CH3:35])=[CH:31][CH:32]=[CH:33][CH:34]=1>C(O)C>[OH:17][C:14]1[CH:13]=[CH:12][C:11]([NH:10][C:8]([C:4]2[CH:3]=[C:2]([NH:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[CH3:35])[N:7]=[CH:6][N:5]=2)=[O:9])=[CH:16][CH:15]=1
Reactant: Cc1ccccc1N
Reactant: Cc1cc(O)ccc1NC(=O)c1cc(Cl)ncn1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCO
Product: Cc1ccccc1Nc1cc(C(=O)Nc2ccc(O)cc2)ncn1
Temperature: 160 °C

Procedure:
A solution of 6-chloro-N-(4-hydroxy-2-methylphenyl)pyrimidine-4-carboxamide, Intermediate 7 (50.0 mg; 0.20 mmol) in ethanol (3 mL) was treated with N-ethyldiisopropylamine (69 μl; 0.4 mmol) and o-toluidine (Fluka, 21.5 μl; 0.20 mmol). The reaction mixture was heated at 160° C. for 3 hours under microwave irradiation. The solvents were removed in vacuo, EtOAc was added and the organic phase was washed with a citric acid solution, dried over magnesium sulfate then evaporated in vacuo. The crude product was purified by column chromatography (silica), eluting with cyclohexane containing an increasing amount of EtOAc. The title compound was obtained as a yellow solid.
Reaction SMILES: [C:1]([C:4](=[CH:10]OCC)[C:5]([O:7][CH2:8][CH3:9])=[O:6])(=O)[CH3:2].[NH2:14][C:15]([S:17][CH3:18])=[NH:16].C(N(CC)CC)C>CCO>[CH2:8]([O:7][C:5]([C:4]1[C:1]([CH3:2])=[N:14][C:15]([S:17][CH3:18])=[N:16][CH:10]=1)=[O:6])[CH3:9]
Reactant: CSC(=N)N
Reactant: CCOC=C(C(C)=O)C(=O)OCC
Solvent: CCN(CC)CC
Solvent: CCO
Product: CCOC(=O)c1cnc(SC)nc1C
Yield: 81 %

Procedure:
Equimolar quantities of ethyl 2-acetyl-3-ethoxy-2-propenoate 1 (20.0 g, 107 mmol), ((amino(imino)methyl)-sulfanyl)methane 2 (9.68 g, 107 mmol) and triethylamine (10.8 g, 107 mmol) in EtOH (100 mL) were stirred at reflux for 48 hours. Then reaction mixture was concentrated and diluted with water. The biphasic mixture was transferred into a separatory funnel and extracted with DCM. Organic extract was washed with water, dried, filtered, and concentrated. The product was purified by crystallization from ethanol/water to yield in a colorless solid (18.4 g, 86.7 mmol, 81%).
Reaction SMILES: [C:1](Cl)(=[O:5])[C:2]([CH3:4])=[CH2:3].[N+:7]([C:10]1[CH:15]=[CH:14][C:13]([N:16]([CH2:18][CH2:19][OH:20])[CH3:17])=[CH:12][CH:11]=1)([O-:9])=[O:8].N1C=CC=CC=1.O>C(Cl)(Cl)Cl>[C:1]([O:20][CH2:19][CH2:18][N:16]([C:13]1[CH:12]=[CH:11][C:10]([N+:7]([O-:9])=[O:8])=[CH:15][CH:14]=1)[CH3:17])(=[O:5])[C:2]([CH3:4])=[CH2:3]
Reactant: CN(CCO)c1ccc([N+](=O)[O-])cc1
Reactant: C=C(C)C(=O)Cl
Solvent: O
Solvent: ClC(Cl)Cl
Solvent: c1ccncc1
Product: C=C(C)C(=O)OCCN(C)c1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Yield: 38.6 %

Procedure:
2.67 g of methacryloyl chloride in 5 ml of chloroform were added dropwise to 5 g of 2-[N-(p-nitrophenyl)-N-methylamino]-ethanol and 2.02 g of pyridine in 40 ml of chloroform while cooling. Thereafter, the resulting reaction solution was first stirred at room temperature and then refluxed for 3.5 hours. It was cooled to room temperature and then 40 ml of water were added to it, after which the chloroform phase was separated off and the aqueous phase was extracted with three times 20 ml of chloroform. After the combined chloroform phases had been dried with Na2SO4 and the chloroform evaporated off, the resulting product was washed with hexane and dried under reduced pressure. 2.6 g of 2-[N-(p-nitrophenyl)-N-methylamino]-ethyl methacrylate were obtained, the IR spectrum of the product in the form of a KBr pellet having bands at 2,950, 2,900, 1,720, 1,600, 1,510, 1,490, 1,320, 1,310, 1,160, 1,110 and 825 cm-1.
Reaction SMILES: C(O[CH2:5][CH:6]1[C:18]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[C:12]2[C:7]1=[CH:8][CH:9]=[CH:10][CH:11]=2)(=O)C.CC(C)([O-])C.[K+].Cl>CCOCC>[CH2:5]=[C:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:13]2[C:18]1=[CH:17][CH:16]=[CH:15][CH:14]=2
Reactant: CC(=O)OCC1c2ccccc2-c2ccccc21
Agent: CC(C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CCOCC
Product: C=C1c2ccccc2-c2ccccc21
Temperature: 5 °C
Reaction time: 6 h
Yield: 94 %

Procedure:
A 1000 mL flask was charged with 9-acetoxymethylfluorene (30.0 g, 126 mmol) and anhydrous petroleum ether (bp 35-60° C., 400 mL, Aldrich) and it was cooled to 5° C. Solid potassium tert-butoxide (16.0 g, 142 mmol, Aldrich) was added in one portion. After stirring for 6 hours, the mixture was poured into dilute HCl (200 mL, 0.1 N). Et2O was added (100 mL); the layers were separated and the product extracted into Et2O (2×100 mL). Combined organic portions were dried over anhydrous MgSO4 and the solvent was removed via rotary evaporation. The crude product dibenzofulvene was isolated as a yellow solid (21.3 g, 94% yield, >99% pure by GC). Further purification was accomplished by recrystallization from petroleum ether, to yield dibenzofulvene in the form of white needles (Tm 51.5-53° C.).
Reaction SMILES: O=[C:2]1[CH2:7][CH2:6][CH:5]([NH:8][C:9](=[O:18])[O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:4][CH2:3]1.Cl.[F:20][C:21]1[CH:26]=[CH:25][C:24]([NH:27]N)=[CH:23][CH:22]=1>CC(O)=O.CC(=O)OCC>[F:20][C:21]1[CH:22]=[C:23]2[C:24](=[CH:25][CH:26]=1)[NH:27][C:2]1[CH2:7][CH2:6][CH:5]([NH:8][C:9](=[O:18])[O:10][CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH2:4][C:3]2=1
Reactant: O=C1CCC(NC(=O)OCc2ccccc2)CC1
Reactant: NNc1ccc(F)cc1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: O=C(NC1CCc2[nH]c3ccc(F)cc3c2C1)OCc1ccccc1
Temperature: 25 °C

Procedure:
A solution of benzyl (4-oxocyclohexyl)carbamate (21.7 g, 87.8 mmol) and 4-fluorophenylhydrazine hydrochloride (14.3 g, 87.8 mmol) in glacial AcOH (148 ml) was stirred at reflux for 1 h30. After cooling to rt, the reaction mixture was diluted with EA and washed with sat.aq. NaHCO3 solution. The aqueous phase was extracted twice with EA, the combined organic extracts were washed with sat. aq. NaHCO3 solution, water and brine, dried over MgSO4, filtered and concentrated in vacuo to give the title compound as a light brown foam which was used for the next step without further purification.
Reaction SMILES: [Si](C=[N+]=[N-])(C)(C)[CH3:2].[NH2:8][C:9]1[C:17]([N+:18]([O-:20])=[O:19])=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[C:11]([F:21])[C:10]=1[F:22].CO>C1COCC1>[CH3:2][O:14][C:13](=[O:15])[C:12]1[CH:16]=[C:17]([N+:18]([O-:20])=[O:19])[C:9]([NH2:8])=[C:10]([F:22])[C:11]=1[F:21]
Reactant: Nc1c([N+](=O)[O-])cc(C(=O)O)c(F)c1F
Reactant: C[Si](C)(C)C=[N+]=[N-]
Solvent: CO
Solvent: C1CCOC1
Product: COC(=O)c1cc([N+](=O)[O-])c(N)c(F)c1F
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 92 %

Procedure:
A 2 M solution of TMS diazomethane in hexanes (6.88 mL, 13.75 mmol) is added to a suspension of 4-amino-2,3-difluoro-5-nitro-benzoic acid 3 (2.00 g, 9.17 mmol) in 25 mL of 4:1 THF:MeOH at 0° C. under nitrogen atmosphere. Upon completion of addition, reaction mixture is warmed to room temperature. After 0.5 hours, excess TMS diazomethane is destroyed by the careful addition of acetic acid. The reaction is then concentrated under reduced pressure and dried in vacuo to give 1.95 g (92%) of pure desired product: MS APCI (−) m/z 231 (M−1) detected.
Reaction SMILES: [CH3:1][C:2]([S:5]([N:7]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=1)[CH:8]([C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=1)[CH2:9][CH:10]=[CH2:11])=[O:6])([CH3:4])[CH3:3].[C:33]([O:37][CH3:38])(=[O:36])C=C>>[C:2]([S:5]([N:7]([CH2:22][C:23]1[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:30])[F:31])=[CH:25][CH:24]=1)[CH:8]([C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=1)[CH2:9]/[CH:10]=[CH:11]/[C:33]([O:37][CH3:38])=[O:36])=[O:6])([CH3:1])([CH3:3])[CH3:4]
Reactant: C=CCC(c1ccc(C(F)(F)F)cc1)N(Cc1ccc(C(F)(F)F)cc1)S(=O)C(C)(C)C
Reactant: C=CC(=O)OC
Product: COC(=O)/C=C/CC(c1ccc(C(F)(F)F)cc1)N(Cc1ccc(C(F)(F)F)cc1)S(=O)C(C)(C)C
Reaction time: 0.5 h

Procedure:
The alkene from Step 2 (800 mg, 1.67 mmol) was dissolved in methyl acrylate (1.5 mL) and Zhan I catalyst (110 mg) was added. This mixture was stirred for 30 min and TLC indicated all starting material had reacted. The mixture was evaporated and purified by chromatography on silica using 10-25% ethyl acetate in iso-hexane to give the product (500 mg) as a mixture of isomers:
Reaction SMILES: C([O:8][C:9]1[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[CH:11][C:10]=1[C:19]1[C:23]([CH3:25])([CH3:24])[CH2:22][CH2:21][CH:20]=1)C1C=CC=CC=1>CO.[Pd]>[CH3:24][C:23]1([CH3:25])[CH2:22][CH2:21][CH2:20][CH:19]1[C:10]1[CH:11]=[C:12]([CH:17]=[CH:18][C:9]=1[OH:8])[C:13]([O:15][CH3:16])=[O:14]
Reactant: COC(=O)c1ccc(OCc2ccccc2)c(C2=CCCC2(C)C)c1
Agent: [Pd]
Solvent: CO
Product: COC(=O)c1ccc(O)c(C2CCCC2(C)C)c1
Temperature: 25 °C
Reaction time: 27.5 h

Procedure:
To a flask containing 66.11D (3.03 g, 9.0 mmol) in MeOH (25.0 mL) was added palladium, 10% wt. on activated carbon (0.48 g, 0.45 mmol). After purging, the mixture was stirred under an atmosphere of hydrogen at room temperature. The reaction was monitored with TLC and LC-MS. After 27.5 hours, the reaction was filtered through Celite. After concentration, the residue was purified on silica gel using 0-50% EtOAc in hexanes to yield 66.11E as a colorless oil that solidified (1.99 g, 89%). 1H NMR (400 MHz, CDCl3) δ ppm 7.91 (1H, d, J=2.3 Hz), 7.79 (1H, dd, J=8.4, 2.2 Hz), 6.82 (1H, d, J=8.2 Hz), 5.54 (1H, s), 3.90 (3H, s), 3.17 (1H, dd, J=10.4, 8.0 Hz), 2.17 (1H, m), 2.04 (1H, m), 1.92 (1H, m), 1.81 (1H, m), 1.68 (2H, m), 1.06 (3H, s), 0.72 (3H, s).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][NH:4][CH2:5][CH2:6][NH:7][CH2:8][CH2:9][NH2:10].[CH:11]([CH:13]=O)=O.O.ClCCCl.O.NN.[OH-].[K+]>CO.CN(C)C=O>[NH:4]1[CH2:5][CH2:6][NH:7][CH2:8][CH2:9][NH:10][CH2:13][CH2:11][NH:1][CH2:2][CH2:3]1
Reactant: NCCNCCNCCN
Reactant: O=CC=O
Agent: NN
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: C1CNCCNCCNCCN1
Reaction time: 20 h

Procedure:
50 g of triethylenetetramine (0.342 mol) is dissolved in 1 ml of methanol and mixed at room temperature with 39 ml of 40% glyoxal in water (0.342 mol). After 20 hours of stirring, the solvent is distilled off in a vacuum, and an orange-colored oil is obtained, which then is taken up in 400 ml of dimethylformamide and mixed with 81.2 ml (101.5 g=1.026 mol) of 1,2-dichloroethane. After 8 hours of stirring at 40° C., it is concentrated by evaporation in a vacuum, the residue is taken up in 400 ml of ethanol and acidified to pH=3-4 with 37% aqueous hydrochloric acid. 166 ml (171 g=3.42 mol) of hydrazine hydrate is added to this reaction solution at room temperature, and it is heated under reflux for 30 hours. The reaction solution is set at pH=13 with solid potassium hydroxide. The reaction solution is subsequently concentrated by evaporation in a vacuum, taken up once more in 100 ml of ethanol, and the solvent is removed again in a vacuum. The residue is mixed with 25 g of activated carbon and 150 ml of formaldehyde diethylacetal, and it is heated under reflux for some time before the hot solution is filtered through a membrane. After the solution is cooled, the product is isolated by filtration.
Reaction SMILES: [CH3:1][C:2]1([CH3:10])[O:7][C:6](=[O:8])[CH2:5][C:4](=[O:9])[O:3]1.[C:11]([O:15][C:16]([NH:18][CH2:19][CH2:20][C:21](O)=[O:22])=[O:17])([CH3:14])([CH3:13])[CH3:12].Cl.C(N=C=NCCCN(C)C)C>CN(C)C1C=CN=CC=1.ClCCl>[C:11]([O:15][C:16](=[O:17])[NH:18][CH2:19][CH2:20][C:21](=[C:5]1[C:6](=[O:8])[O:7][C:2]([CH3:10])([CH3:1])[O:3][C:4]1=[O:9])[OH:22])([CH3:14])([CH3:12])[CH3:13]
Reactant: CC1(C)OC(=O)CC(=O)O1
Reactant: CC(C)(C)OC(=O)NCCC(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NCCC(O)=C1C(=O)OC(C)(C)OC1=O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A stirred solution of 2,2-dimethyl-[1,3]dioxane-4,6-dione (7.5 g, 52 mmol), 3-tert-butoxycarbonylamino-propionic acid (9.45 g, 50 mmol), 4-dimethylamino pyridine (9.6 g) in dichloromethane (525 ml) was added dropwise slowly with the solution of N-ethyl-N′-(dimethylaminopropyl)-carbodiimide hydrochloride (11 g, 57.5 mmol) in 352 ml of dichloromethane in an ice-water bath. Upon completion of the addition, the mixture was stirred at room temperature overnight, then washed with 5% aqueous potassium bisulfate solution (300 ml×4), dried with anhydrous sodium sulfate, filtered and concentrated to give [3-(2,2-dimethyl-4,6-dioxo-[1,3]dioxin-5-ylidene)-3-hydroxy-propyl]-carbamic acid tert-butyl ester which was used as such.
Reaction SMILES: [CH3:1][CH2:2]N=C=NCCCN(C)C.C(O)C.[Br:15][C:16]1[CH:20]=[CH:19][O:18][C:17]=1[C:21]([OH:23])=[O:22]>CN(C)C1C=CN=CC=1.ClCCl>[Br:15][C:16]1[CH:20]=[CH:19][O:18][C:17]=1[C:21]([O:23][CH2:1][CH3:2])=[O:22]
Reactant: CCN=C=NCCCN(C)C
Reactant: O=C(O)c1occc1Br
Agent: CN(C)c1ccncc1
Solvent: CCO
Solvent: ClCCl
Product: CCOC(=O)c1occc1Br
Temperature: 25 °C
Reaction time: 5 h
Yield: 88.7 %

Procedure:
WSC (17.3 g), 4-dimethylaminopyridine (1.1 g) and ethanol (5.2 ml) were added to a dichloromethane solution (100 ml) of 17.2 g 3-bromo-2-furancarboxylic acid and stirred for 5 hours at 25° C. The reaction solution was washed with saturated brine and dried over MgSO4. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (eluent: ethyl acetate/hexane=1/30), thereby giving 17.5 g of the desired compound.
Reaction SMILES: [O:1]=[C:2]([N:26]1[CH2:31][CH2:30][N:29]([C:32](=[O:43])[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=2[C:39]([F:42])([F:41])[F:40])[CH2:28][CH2:27]1)[CH2:3][NH:4][C:5]([C:7]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18]CC3C=CC=CC=3)[CH:13]=2)[NH:9][N:8]=1)=[O:6]>CO.C(Cl)Cl.[Pd]>[O:1]=[C:2]([N:26]1[CH2:27][CH2:28][N:29]([C:32](=[O:43])[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][C:34]=2[C:39]([F:40])([F:42])[F:41])[CH2:30][CH2:31]1)[CH2:3][NH:4][C:5]([C:7]1[CH:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([OH:18])[CH:13]=2)[NH:9][N:8]=1)=[O:6]
Reactant: O=C(NCC(=O)N1CCN(C(=O)c2ccccc2C(F)(F)F)CC1)c1cc(-c2cccc(OCc3ccccc3)c2)[nH]n1
Agent: [Pd]
Solvent: CO
Solvent: ClCCl
Product: O=C(NCC(=O)N1CCN(C(=O)c2ccccc2C(F)(F)F)CC1)c1cc(-c2cccc(O)c2)[nH]n1
Yield: 23.8 %

Procedure:
10% Pd/c (30 mg) was added to a stirred solution of 5-(3-benzyloxy-phenyl)-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide (120.3 mg, 0.2 mmol) in a mixture of MeOH (15 mL) and DCM (10 mL) and stirred under hydrogen atmosphere. The reaction mixture was then stirred overnight at room temperature. The mixture was filtered over a bed of celite. The celite was washed with MeOH and the filtrate was concentrated under reduced pressure. The crude was recrystallized from a mixture of ethyl acetate and methanol to afford 23.9 mg (23.7% yield) of 5-(3-Hydroxy-phenyl)-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide. LCMS Purity: 98.15%. 1H NMR (DMSO-d6): δ 13.6 (s, 1H), 9.6 (s, 1H), 8.6 (d, 1H), 8.1 (s, 1H), 7.6 (m, 3H), 7.5 (m, 1H), 7.1 (m, 3H), 7.0 (s, 1H), 6.7 (d, 1H), 4.1 (d, 2H), 3.6 (m, 2H), 3.5 (m, 2H), 3.4 (m, 2H), 3.1 (m, 2H).
Reaction SMILES: O[CH:2]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:3]1[CH:19]=[CH:18][C:6]([O:7][CH2:8][C:9]2[O:13][C:12]([C:14]([O:16][CH3:17])=[O:15])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1.C1(P([N:40]=[N+:41]=[N-:42])(C2C=CC=CC=2)=O)C=CC=CC=1.C1CCN2C(=NCCC2)CC1>C1(C)C=CC=CC=1>[N:40]([CH:2]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:3]1[CH:19]=[CH:18][C:6]([O:7][CH2:8][C:9]2[O:13][C:12]([C:14]([O:16][CH3:17])=[O:15])=[CH:11][CH:10]=2)=[CH:5][CH:4]=1)=[N+:41]=[N-:42]
Reactant: COC(=O)c1ccc(COc2ccc(C(O)c3ccccc3)cc2)o1
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: Cc1ccccc1
Solvent: C1CCC2=NCCCN2CC1
Product: COC(=O)c1ccc(COc2ccc(C(N=[N+]=[N-])c3ccccc3)cc2)o1
Temperature: 100 °C
Yield: 84 %

Procedure:
To a stirred solution of methyl 5-((4-(hydroxy(phenyl)methyl)phenoxy)methyl)-furan-2-carboxylate (325 mg, 0.96 mmol) in toluene (4.5 mL) under nitrogen was added diphenylphosphoryl azide (0.25 mL, 1.15 mmol) followed by DBU (0.17 mL, 1.15 mmol). The reaction was heated at 100° C. for 3 h. The reaction was quenched by the addition of saturated ammonium chloride solution. The aqueous phase was extracted with ethyl acetate (×2). The combined organic phases were washed with brine, dried over MgSO4, filtered and the solvent removed in vacuo. The residue was purified via silica gel chromatography, eluting with 0-25% EtOAc in isohexane, to give the title compound as a colourless oil (293 mg, 84%).
Reaction SMILES: C[O-].[Na+].[N+:4]([C:7]1[C:8]([NH:16]C(=O)C)=[CH:9][C:10]2[O:14][CH2:13][O:12][C:11]=2[CH:15]=1)([O-:6])=[O:5].CC(O)=O>CO>[N+:4]([C:7]1[C:8]([NH2:16])=[CH:9][C:10]2[O:14][CH2:13][O:12][C:11]=2[CH:15]=1)([O-:6])=[O:5]
Reactant: CC(=O)Nc1cc2c(cc1[N+](=O)[O-])OCO2
Agent: C[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: Nc1cc2c(cc1[N+](=O)[O-])OCO2
Yield: 80 %

Procedure:
NaOMe (4.82 g, 89.2 mmol) was added to a stirred solution of nitroacetamide 219 (5.0 g, 22.3 mmol) in MeOH (100 mL) at reflux temperature and the mixture stirred at reflux temperature for 15 min. HOAc (25 mL, 446 mmol) was added to quench the reaction and the solvent evaporated. Toluene (2×50 mL) was added and the azeotrope evaporated. The residue was dissolved in DCM (100 mL) and filtered through a short column of silica to give nitroaniline 220 (3.25 g, 80%) as an orange solid: mp 199-201° C. [lit (Krasso, A. & Ramuz, H., U.S. Pat. No. 4,599,347, 1986) mp (iPrOH) 203-204° C.]; 1H NMR δ 7.53 (s, 1H, H-7), 6.30 (br s, 2H, NH2), 6.22 (s, 1H, H-4), 5.98 (s, 2H, H-2).
Reaction SMILES: [Si:1]([O:8][C@@H:9]1[C@@:28]2([CH3:29])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:27]2[CH2:26][CH2:25][C@@:24]2([CH3:30])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@H:21]([OH:23])[CH3:22])[CH2:12][C@@H:11]([O:31][Si:32]([C:35]([CH3:38])([CH3:37])[CH3:36])([CH3:34])[CH3:33])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].C1OCCOCCOCCOCCOC1.Br[CH2:57]/[CH:58]=[CH:59]/[C:60]([CH2:71][CH3:72])([O:63][Si:64]([CH2:69][CH3:70])([CH2:67][CH3:68])[CH2:65][CH3:66])[CH2:61][CH3:62]>O1CCCC1>[Si:1]([O:8][C@@H:9]1[C@@:28]2([CH3:29])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:27]2[CH2:26][CH2:25][C@@:24]2([CH3:30])[C@H:17]3[CH2:18][CH:19]=[C:20]2[C@H:21]([O:23][CH2:57]/[CH:58]=[CH:59]/[C:60]([CH2:71][CH3:72])([O:63][Si:64]([CH2:69][CH3:70])([CH2:65][CH3:66])[CH2:67][CH3:68])[CH2:61][CH3:62])[CH3:22])[CH2:12][C@@H:11]([O:31][Si:32]([C:35]([CH3:37])([CH3:36])[CH3:38])([CH3:33])[CH3:34])[CH2:10]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
Reactant: CCC(/C=C/CBr)(CC)O[Si](CC)(CC)CC
Reactant: C[C@@H](O)C1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Agent: C1COCCOCCOCCOCCO1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCC(/C=C/CO[C@H](C)C1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C)(CC)O[Si](CC)(CC)CC
Yield: 72.9 %

Procedure:
Under the same conditions as in Example 83, 1α,3β-bis(tert-butyldimethylsilyloxy)-20(R)-hydroxypregna-5,7,16-triene (60.0 mg, 0.107 mmol), sodium hydride (60%, 17.1 mg, 0.428 mmol), 15-crown-5 (10 μl) and (E)-1-bromo-4-ethyl-4-triethylsilyloxy-2-hexene (134 mg, 0.420 mmol) were reacted in tetrahydrofuran (1 ml) and worked up, and then the residue was purified by preparative thin layer chromatography (0.5 mm×2, hexane:ethyl acetate=40:1, developed once) to give the title compound as a colorless oil (62.4 mg, 73%).
Reaction SMILES: C(Cl)(=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:10](=[O:19])([O:15][CH2:16][CH:17]=[CH2:18])OCC=C>>[C:10]([O:15][CH2:16][CH:17]=[CH2:18])(=[O:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: C=CCOC(=O)OCC=C
Product: C=CCOC(=O)c1ccccc1
Temperature: 170 °C
Yield: 90 %

Procedure:
The following example illustrates the use of basic amine catalysts. A mixture of benzoyl chloride (7.03 g, 0.05 mole), diallyl carbonate (7.10 g, 0.05 mole) and N,N-dimethylaminopyridine (0.06 g) were combined in a glass reaction vessel and heated to 170° C. for 4 hours. Distillation of the reaction mixture gave allyl benzoate, b.p. 110° C.-111° C. (13 mm Hg). Yield was 90 percent.
Reaction SMILES: [C:1]([C:3]1[S:4][C:5]2[C:11]([C:12]#[N:13])=[C:10](/[N:14]=[CH:15]/[N:16](C)C)[CH:9]=[CH:8][C:6]=2[N:7]=1)#[N:2].N[C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=1)[C:23]#[N:24].[K+].[Br-]>C(Cl)Cl.CCOC(C)=O>[C:23]([C:22]1[CH:21]=[C:20]([NH:13][C:12]2[C:11]3[C:10](=[CH:9][CH:8]=[C:6]4[N:7]=[C:3]([C:1]#[N:2])[S:4][C:5]4=3)[N:14]=[CH:15][N:16]=2)[CH:27]=[CH:26][CH:25]=1)#[N:24]
Reactant: CN(C)/C=N/c1ccc2nc(C#N)sc2c1C#N
Reactant: N#Cc1cccc(N)c1
Agent: [Br-]
Agent: [K+]
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: N#Cc1cccc(Nc2ncnc3ccc4nc(C#N)sc4c23)c1
Yield: 40 %

Procedure:
Prepared from VII and 3-aminobenzonitrile. Flash chromatography eluent (DCM-EtOAc, 5:5). Yield: 40%; yellow solid; mp>260° C.; IR (KBr) νmax/cm−1 3240, 3171, 3088, 2228, 1623, 1591, 1555, 1509, 1465, 1393, 1273, 1229, 1149, 969, 919, 825; 1H NMR (300 MHz, DMSO-d6) δ 8.54 (d, 1H, J=9.0 Hz), 8.43 (s, 1H), 7.74 (m, 2H), 7.55-7.53 (m, 3H); HRMS calcd for C17H9N6S (M+H+): 329.0609, found 329.0600.
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:21][C:10]3([CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11]3)[CH2:9]2)=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[I:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:9][C:10]3([CH2:13][NH:12][CH2:11]3)[CH2:21]2)=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N1CC2(C1)CN(c1ccc(I)cc1)C2
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Ic1ccc(N2CC3(CNC3)C2)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 94 %

Procedure:
tert-Butyl 6-(4-iodophenyl)-2,6-diazaspiro[3.3]heptane-2-carboxylate (2.14 g, 5.35 mmol) was dissolved in DCM (10 mL) and cooled to 0° C. TFA (5 mL) was added and then reaction was stirred at 0° C. for 30 min, warmed up to rt and stirred for 1 h. The mixture was concentrated under reduced pressure and purified using a Waters PoraPak Rxn CX 20 cc 2 g cartridge to give the title compound as a white solid (1.51 g, 94%). 1H NMR (400 MHz, CDCl3) 8 ppm 7.45 (d, J=8.5 Hz, 2H), 6.22 (d, J=8.5 Hz, 2H), 3.94 (s, 4H), 3.80 (s, 4H), 1.66 (br. s., 1H); MS ESI 301.0 [M+H]+, calcd for [C11H13IN2+H]+ 301.0.