Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[F:2][C@@:3]12[C@:16]3([CH3:17])[C:11](=[CH:12][C:13](=[O:18])[CH:14]=[CH:15]3)[C@@H:10]([F:19])[CH2:9][C@H:8]1[C@@H:7]1[CH2:20][C@@H:21]3[C@:25]([C:26](=[O:29])[CH2:27][F:28])([C@@:6]1([CH3:30])[CH2:5][C@@H:4]2[OH:31])[CH2:24][NH:23][CH2:22]3.[CH3:32][C:33]([CH3:38])([CH3:37])[CH2:34][CH:35]=O.C(O)=O>C(#N)C.CCOC(C)=O>[CH3:32][C:33]([CH3:38])([CH3:37])[CH2:34][CH2:35][N:23]1[CH2:24][C@:25]2([C:26](=[O:29])[CH2:27][F:28])[C@@H:21]([CH2:20][C@H:7]3[C@H:8]4[C@@:3]([F:2])([C@:16]5([CH3:17])[C:11]([C@@H:10]([F:19])[CH2:9]4)=[CH:12][C:13](=[O:18])[CH:14]=[CH:15]5)[C@@H:4]([OH:31])[CH2:5][C@@:6]32[CH3:30])[CH2:22]1
Reactant: C[C@]12C=CC(=O)C=C1[C@@H](F)C[C@H]1[C@@H]3C[C@H]4CNC[C@@]4(C(=O)CF)[C@@]3(C)C[C@H](O)[C@@]12F
Reactant: CC(C)(C)CC=O
Agent: Cl
Solvent: O=CO
Solvent: CCOC(C)=O
Solvent: CC#N
Product: CC(C)(C)CCN1C[C@@H]2C[C@H]3[C@@H]4C[C@H](F)C5=CC(=O)C=C[C@]5(C)[C@@]4(F)[C@@H](O)C[C@]3(C)[C@]2(C(=O)CF)C1
Temperature: 140 °C
Yield: 27.6 %

Procedure:
In a closed vessel, compound 166 (180 mg, 0.391 mmol), 3,3-dimethylbutanal (0.196 ml, 1.565 mmol) and TEA (0.055 ml, 0.391 mmol) are dissolved in acetonitrile (4 ml). Formic acid (0.120 ml, 3.13 mmol) is added and the mixture is heated under microwave irradiation for 15 minutes at 140° C. LC-MS shows that the reaction is complete. The reaction mixture is diluted with AcOEt and the organic phase is washed with a saturated solution of NaHCO3 and with brine. The organic layer is dried over Na2SO4 and filtered. The solvent is evaporated to give an orange oil which is purified by preparative HPLC (acetonitrile/water, neutral phase) to yield the title compound (55 mg, 0.108 mmol, 27.7% yield).
Reaction SMILES: C(Cl)(=O)C(Cl)=O.[C:7]([C:10]1[CH:11]=[CH:12][C:13]([O:19][CH2:20][CH2:21][CH3:22])=[C:14]([CH:18]=1)[C:15]([OH:17])=O)(=[O:9])[CH3:8].C(N(CC)CC)C.[NH2:30][C:31]1[C:32]([CH2:39][CH3:40])=[N:33][NH:34][C:35]=1[C:36]([NH2:38])=[O:37]>CN(C)C=O.ClCCl>[C:7]([C:10]1[CH:11]=[CH:12][C:13]([O:19][CH2:20][CH2:21][CH3:22])=[C:14]([CH:18]=1)[C:15]([NH:30][C:31]1[C:35]([C:36]([NH2:38])=[O:37])=[N:34][NH:33][C:32]=1[CH2:39][CH3:40])=[O:17])(=[O:9])[CH3:8]
Reactant: CCc1n[nH]c(C(N)=O)c1N
Reactant: CCCOc1ccc(C(C)=O)cc1C(=O)O
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: CCCOc1ccc(C(C)=O)cc1C(=O)Nc1c(C(N)=O)n[nH]c1CC
Reaction time: 1 h

Procedure:
Oxalyl chloride (5.45 ml, 46.4 mmol) was added to a solution of 5-acetyl-2-n-propoxy-benzoic acid (WO 9312095) (11.1 g, 30.9 mmol) in N,N-dimethylformamide (0.1 ml) and dichloromethane (200 ml) under nitrogen at room temperature. Once addition was complete the solution was stirred for 1 hour. The solution was concentrated under reduced pressure and azeotroped with toluene, and the intermediate acid chloride was dissolved in dichloromethane (200 ml). Triethylamine (10.4 ml, 46.4 mmol) was added followed by 4-amino-3-ethyl-1H-pyrazole-5-Carboxamide (WO 9849166) (7.7 g, 30.9 mmol) and the reaction was stirred at room temperature for 16 hours. The mixture was washed with 1N hydrochloric acid (2×100 ml), 10% sodium bicarbonate solution (100 ml) and brine (100 ml), dried over Na2SO4 and the solvent was removed under reduced pressure. The residue was recrystallised from acetonitrile to afford the title compound as a crystalline solid, 14.8 g.
Reaction SMILES: C([O:4][C:5]1[C:6](=[O:12])[CH:7]=[CH:8][C:9](=[O:11])[CH:10]=1)C=C.[C:13]([C:17]1[CH:24]=[CH:23][C:20]([CH:21]=[CH2:22])=[CH:19][CH:18]=1)([CH3:16])([CH3:15])[CH3:14].[CH:25](O)([CH3:27])[CH3:26]>>[CH2:27]([C:10]1[C:9](=[O:11])[C:8]2[CH:22]=[CH:21][C:20]3[C:19]([C:7]=2[C:6](=[O:12])[C:5]=1[OH:4])=[CH:18][C:17]([C:13]([CH3:16])([CH3:14])[CH3:15])=[CH:24][CH:23]=3)[CH:25]=[CH2:26]
Reactant: C=Cc1ccc(C(C)(C)C)cc1
Reactant: CC(C)O
Reactant: C=CCOC1=CC(=O)C=CC1=O
Product: C=CCC1=C(O)C(=O)c2c(ccc3ccc(C(C)(C)C)cc23)C1=O

Procedure:
2-Allyloxy-1,4-benzoquinone (6.56 g, 40 mM) and p-tert-Butylstyrene (70 g, 0.40 M) were dissolved in 80 ml of isopropanol to give 1.90 g (5.9 mM) of 2-Allyl-3-hydroxy-6-tert-butyl-1,4-phenanthrenequinone in the same manner as in Example 7.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[CH2:12][O:11][C:10]3[CH:13]=[C:14]([Cl:17])[CH:15]=[CH:16][C:9]=3[C:8](=[C:18]3[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[C:5]2=[N:6][CH:7]=1.[N+:24]1([O-])[CH:29]=[CH:28][C:27]([CH2:30][C:31](O)=[O:32])=[CH:26][CH:25]=1.C1C=CC2N([OH:44])N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.CN1CCOCC1>CN(C=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[CH2:12][O:11][C:10]3[CH:13]=[C:14]([Cl:17])[CH:15]=[CH:16][C:9]=3[C:8](=[C:18]3[CH2:23][CH2:22][N+:21]([O-:44])([C:31](=[O:32])[CH2:30][C:27]4[CH:28]=[CH:29][N:24]=[CH:25][CH:26]=4)[CH2:20][CH2:19]3)[C:5]2=[N:6][CH:7]=1
Reactant: O=C(O)Cc1cc[n+]([O-])cc1
Reactant: Clc1ccc2c(c1)OCc1cc(Br)cnc1C2=C1CCNCC1
Reactant: On1nnc2ccccc21
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: CN1CCOCC1
Solvent: CN(C)C=O
Product: O=C(Cc1ccncc1)[N+]1([O-])CCC(=C2c3ccc(Cl)cc3OCc3cc(Br)cnc32)CC1
Temperature: 0 °C
Reaction time: 2 h
Yield: 72.6 %

Procedure:
4-(3-Bromo-8-chloro-5,11-dihydro[1]benzoxepino[4,3-b]pyridin-11-ylidene)-piperidine (270 mg, 0.68 mmol), 4-pyridine-acetic acid 1-oxide (260 mg, 1.69 mmol), HOBT (200 mg, 1.48 mmol), and EDCl (320 mg, 1.67 mmol) were mixed and stirred at 0° C. in DMF (10 ml, anhydrous). NMM (0.5 ml, 4.53 mmol) was added, and the reaction mixture was stirred 2 hours at 0° C. and then overnight at 20° C. The solvent was evaporated off, water (20 ml) was added, and the mixture was extracted with methylene chloride (3×50 ml) and the extract was dried (MgSO4), filtered and evaporated, yielding a crude product which was chromatographed on silica gel and eluted with 12%ethylacetate/hexanes containing 2% ammonium hydroxide. The product was recrystallized from ether to afford a white powder, 4-(3-bromo-8-chloro-5,11-dihydro[1]benz-oxepino[4,3-b]pyridin-11-ylidene)-1-(4-pyridine-acetyl)piperidine N1-oxide (260 mg, 72%); MS (FAB, M+H)=526.
Reaction SMILES: [N+:1]([C:4]1[C:5]([CH3:16])=[C:6]2[C:11](=[C:12]([CH3:14])[CH:13]=1)[N:10]=[CH:9][CH:8]=[C:7]2[CH3:15])([O-])=O.C(O)C.[OH-].[Na+]>O>[NH2:1][C:4]1[C:5]([CH3:16])=[C:6]2[C:11](=[C:12]([CH3:14])[CH:13]=1)[N:10]=[CH:9][CH:8]=[C:7]2[CH3:15]
Reactant: Cc1cc([N+](=O)[O-])c(C)c2c(C)ccnc12
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: Cc1cc(N)c(C)c2c(C)ccnc12
Temperature: 25 °C

Procedure:
A mixture of 6-nitro-4,5,8-trimethylquinoline (0.60 g), tin(ll)chloride dihydrate (3.13 g), and ethanol (40 mL) is heated for 3 hours at 60°-65° C. and then cooled to room temperature. 10% Aqueous sodium hydroxide (24 mL) and water (48 mL) are added, and the mixture is extracted three times with chloroform. The combined organic layers are washed with saturated sodium bicarbonate solution, dried over sodium sulfate, filtered and evaporated to afford a crude product. The crude product is purified by flash chromatography using 25% ethyl acetate in hexane as eluent, providing 6-amino-4,5,8-trimethylquinoline.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH:14]=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.C(=O)=O.CC(C)=O.[CH2:23]([Mg]Cl)[CH2:24][CH2:25][CH3:26]>C1COCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH:14]([OH:15])[CH2:23][CH2:24][CH2:25][CH3:26])=[CH:10][CH:9]=2)=[CH:6][CH:7]=1
Reactant: CCCC[Mg]Cl
Reactant: O=Cc1ccc(-c2ccc(Cl)cc2)cc1
Agent: O=C=O
Solvent: C1CCOC1
Solvent: CC(C)=O
Product: CCCCC(O)c1ccc(-c2ccc(Cl)cc2)cc1
Temperature: -78 °C
Reaction time: 1 h

Procedure:
To a solution of 4′-chloro-4-biphenylcarbaldehyde (200 mg, 0.92 mmol) in anhydrous THF (10 mL) under nitrogen at −78° C. (dry ice/acetone) was added nBuMgCl (550 μL of a 2M solution in THF, 1.10 mmol). The reaction mixture was stirred at −78° C. for 1 hour and then at rt for 18 hours. The reaction was quenched by cautious addition of water (15 mL) and extracted with EtOAc (3×20 mL). The combined organic extract was then dried (MgSO4) and reduced under vacuum. Purification by flash chromatography (silica), eluting with cyclohexane:EtOAc (9:1) afforded the title compound as a colourless gum (140 mg).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH:13]1[O:15][CH2:14]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:16]([O:23][C:24]1[CH:29]=[CH:28][C:27]([OH:30])=[CH:26][CH:25]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>>[CH2:16]([O:23][C:24]1[CH:25]=[CH:26][C:27]([O:30][CH2:14][CH:13]([C@@H:9]2[CH2:10][CH2:11][CH2:12][N:8]2[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[OH:15])=[CH:28][CH:29]=1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1C1CO1
Reactant: Oc1ccc(OCc2ccccc2)cc1
Product: CC(C)(C)OC(=O)N1CCC[C@H]1C(O)COc1ccc(OCc2ccccc2)cc1
Yield: 59.1 %

Procedure:
By the same procedure as in Example 26-B), while using (2S)-1-(tert-butoxycarbonyl)-2-(1,2-epoxyethyl)pyrrolidine (1.50 g) and 4-(benzyloxy)phenol (2.96 g), there was obtained 1.72 g of the title compound.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([NH:9][CH:10]1[C:39](=[O:40])[N:12]2[C:13]([C:23]([O:25]C(C3C=CC=CC=3)C3C=CC=CC=3)=[O:24])=[C:14]([CH2:18][O:19][C:20](=[O:22])[CH3:21])[C@H:15]([CH3:17])[S:16][C@H:11]12)=[O:8]>C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([NH:9][CH:10]1[C:39](=[O:40])[N:12]2[C:13]([C:23]([OH:25])=[O:24])=[C:14]([CH2:18][O:19][C:20](=[O:22])[CH3:21])[C@H:15]([CH3:17])[S:16][C@H:11]12)=[O:8]
Reactant: CC(=O)OCC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)C(NC(=O)Cc3cccs3)[C@H]2S[C@H]1C
Solvent: COc1ccccc1
Solvent: O=C(O)C(F)(F)F
Product: CC(=O)OCC1=C(C(=O)O)N2C(=O)C(NC(=O)Cc3cccs3)[C@H]2S[C@H]1C

Procedure:
A solution of 1.4 g of diphenylmethyl 7-(2-thienylacetamido)-2β-methyl-3-acetoxymethylceph-3-em-4-carboxylate in 3 ml of anisole and 20 ml of CF3COOH was stirred at room temperature for 15 minutes. After distilling off CF3COOH under reduced pressure, the residue was dissolved in AcOEt, and then transferred into 5% aqueous NaHCO3. The water layer was adjusted to pH 2.0 with 5% H3PO4 to extract again with AcOEt. The AcOEt layer was washed with saturated aqueous NaCl solution, and dried over Na2SO4, and the AcOEt was distilled off under reduced pressure, thus yielding crude crystals of 7-(2-thienylacetamido)-2β-methyl-3-acetoxymethylceph-3-em-4-carboxylic acid. The crude crystals were dissolved in 5% aqueous NaHCO3, adjusted to pH 7.0 with addition of 5% H3PO4 and then added on a column of Amberlite XAD-II (produced by Rohm & Hass). The fractions eluted with H2O were collected, concentrated under reduced pressure and freeze-dried, thus yielding 829 mg (79%) of sodium 7-(2-thienylacetamido)-2β-methyl-3-acetoxymethylceph-3-em-4-carboxylate.
Reaction SMILES: [C:1]1([CH:7]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:8]2[CH2:11][CH:10]([C:12]([O:14]C)=[O:13])[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH-].[Na+]>CO.O1CCCC1>[C:16]1([CH:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[N:8]2[CH2:11][CH:10]([C:12]([OH:14])=[O:13])[CH2:9]2)[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1
Reactant: COC(=O)C1CN(C(c2ccccc2)c2ccccc2)C1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(O)C1CN(C(c2ccccc2)c2ccccc2)C1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 92.8 %

Procedure:
To a solution of 1-(diphenylmethyl)-3-methoxycarbonylazetidine (28 g) in methanol (270 ml) and tetrahydrofuran (130 ml) was added 1N sodium hydroxide (115 ml) and the solution was stirred at room temperature for 1.5 hours. The solution was then concentrated to remove organic solvents under reduced pressure. The resultant aqueous solution was adjusted to pH 2.95 with 10% hydrochloric acid, and resulting precipitates were collected by filtration, washed with water and dried to give 1-(diphenylmethyl)-3-carboxyazetidine (24.7 g).
Reaction SMILES: O.OS(O)(=O)=O.[Cl:7][C:8]1[CH:9]=[C:10]([C:14]2[N:15]=[N:16][N:17]([CH:19]([CH3:23])[CH2:20][CH2:21][OH:22])[N:18]=2)[CH:11]=[CH:12][CH:13]=1.CC([OH:27])C>CC(C)=O>[Cl:7][C:8]1[CH:9]=[C:10]([C:14]2[N:15]=[N:16][N:17]([CH:19]([CH3:23])[CH2:20][C:21]([OH:27])=[O:22])[N:18]=2)[CH:11]=[CH:12][CH:13]=1
Reactant: CC(CCO)n1nnc(-c2cccc(Cl)c2)n1
Reactant: CC(C)O
Agent: O=S(=O)(O)O
Solvent: CC(C)=O
Solvent: O
Product: CC(CC(=O)O)n1nnc(-c2cccc(Cl)c2)n1
Temperature: 25 °C
Reaction time: 1.5 h
Yield: 100 %

Procedure:
A mixture of CrO3 (0.46 g, 4.63 mmol), H2O (2.5 mL) and concentrated H2SO4 (0.46 mL) was added to a solution of 3-[5-(3-chlorophenyl)-2H-tetrazol-2-yl]butan-1-ol (0.9 g, 3.6 mmol) in acetone (30 mL) at 0° C. The reaction was stirred at r.t. for 1.5 h. 2-Propanol was added and the mixture was concentrated. Sat. NaCl (25 mL) and EtOAc (50 mL) were added to the residue and the mixture was extracted. The water phase was re-extracted with EtOAc (50 mL) and the combined organic phases were dried (MgSO4) and concentrated to give 0.95 g (100%) of the title compound.
Reaction SMILES: [CH:1]1([CH2:4][C:5]#[C:6][CH:7]([OH:9])[CH3:8])[CH2:3][CH2:2]1.[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1.C(Cl)Cl>CCOCC>[CH:1]1([CH2:4][C:5]#[C:6][C:7](=[O:9])[CH3:8])[CH2:3][CH2:2]1
Reactant: CC(O)C#CCC1CC1
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: ClCCl
Solvent: CCOCC
Product: CC(=O)C#CCC1CC1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
2-tetrahydropyranyl-but-3-yne (1.14 parts) in 15 parts by volume of tetrahydrofuran are cooled to -20° C. and 4.63 parts by volume of 1.6N n-butyl lithium are added. The reaction mixture is allowed to warm to 0° C. and again cooled to -20° C. and then 1 part of bromomethylcyclopropane in 3 parts by volume of tetrahydrofuran are added. The reaction mixture is allowed to warm to room temperature and 15 parts by volume of hexamethylphosphoric triamide is added and the reaction is stirred over three hours. The reaction mixture is poured into ether/water and extracted several times with ethyl acetate. The extracts are washed with water and saturated sodium chloride solution and dried over anhydrous sodium sulfate. The solvent is removed by evaporation at reduced pressure and the residual oil is chromotographed with 10% ethyl acetate/hexane to provide 5-cyclopropyl-2-tetrahydropyranyl-pent-3-yne. This material is dissolved in a solution of 25 parts by volume of tetrahydrofuran, 25 parts by volume methanol, and 25 parts by volume of 1N HCl and stirred at room temperature for 1 hour. The reaction mixture is poured into a mixture of ether and water. The aqueous layer is extracted with ethyl acetate and the extracts are combined and washed with water and saturated sodium chloride. The organic layer is dried over anhydrous sodium sulfate and chromatographed with 15% ethyl acetate/hexane to provide 5-cyclopropyl-pent-3-yne-2-ol. 1.5 parts of this alcohol is reacted with 3.25 parts of pyridinium chlorochromate in 35 parts by volume of methylene chloride. The reaction mixture is stirred for three hours at room temperature, 100 parts by volume of ether is added and the mixture is stirred for 1 hour then filtered through Florisil. The solvent is removed by evaporation at reduced pressure. The residue is dissolved in hexane and again filtered. The solvent is evaporated under reduced pressure to provide 5-cyclopropyl pent-3-yne-2-one.
Reaction SMILES: [CH3:1][C:2]([C:6]1[CH:14]=[CH:13][CH:12]=[CH:11][C:7]=1[C:8]([OH:10])=O)([CH3:5])[CH2:3][CH3:4].[CH2:15]([O:17][C:18]([C:20]1([NH2:29])[CH2:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:21]1)=[O:19])[CH3:16].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.O>[CH2:15]([O:17][C:18]([C:20]1([NH:29][C:8](=[O:10])[C:7]2[CH:11]=[CH:12][CH:13]=[CH:14][C:6]=2[C:2]([CH3:1])([CH3:5])[CH2:3][CH3:4])[CH2:28][C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH2:21]1)=[O:19])[CH3:16]
Reactant: CCC(C)(C)c1ccccc1C(=O)O
Reactant: CCOC(=O)C1(N)Cc2ccccc2C1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: CCOC(=O)C1(NC(=O)c2ccccc2C(C)(C)CC)Cc2ccccc2C1
Temperature: 25 °C
Reaction time: 8 h
Yield: 79.4 %

Procedure:
To a solution of 2-(1,1-dimethyl-propyl)-benzoic acid (140 mg, 0.73 mmol), 2-amino-indan-2-carboxylic acid ethyl ester (150 mg, 0.73 mmol), HATU (333 mg, 0.87 mmol) in anhydrous DMF (1 mL) is added DIPEA (1904, 1.1 mmol). The resulting solution is stirred at RT overnight. Water (10 mL) is then poured into the reaction mixture, and then the reaction mixture is extracted with EtOAc (3×5 mL). The combined organic layers are concentrated in vacuo. The residue is purified by flash column chromatography (12 g silica gel, gradient elution: 0-30% EtOAc in heptane) to give product (247) as yellow oil (220 mg, 89%).
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].[O-:12][C:13]#[N:14].[K+].C(O)(=O)C.[OH-].[Na+]>O>[F:11][C:9]1[CH:10]=[C:2]2[C:3]([C:4](=[O:5])[NH:14][C:13](=[O:12])[NH:1]2)=[CH:7][CH:8]=1
Reactant: N#C[O-]
Reactant: Nc1cc(F)ccc1C(=O)O
Agent: [K+]
Agent: [Na+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: O
Product: O=c1[nH]c(=O)c2ccc(F)cc2[nH]1
Temperature: 25 °C
Reaction time: 5 h
Yield: 64.1 %

Procedure:
To a mixture of 2-amino-4-fluorobenzoic acid (4.0 g, 26 mmol) and potassium cyanate (3.5 g, 43 mmol) in water (200 mL) was added acetic acid (3 mL, 45 mmol) and the mixture was stirred at room temperature for about 5 h. To the mixture was added NaOH (15 g, 375 mmol) and it was stirred for another 1 h. The mixture was filtered and the solid was mixed in hot water, and it was adjusted to pH=5˜6 by addition of acetic acid. The mixture was filtered and washed with water, dried to give the title compound (3.0 g, 65% yield) as gray solid. MS: m/z 181.1 [M+H]+
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH2:9][C:10]([O:12][CH3:13])=[O:11])=[CH:5][CH:4]=1)#[N:2].[ClH:14].[H][H]>CO.[Pd]>[ClH:14].[CH3:13][O:12][C:10]([CH2:9][C:6]1[CH:7]=[CH:8][C:3]([CH2:1][NH2:2])=[CH:4][CH:5]=1)=[O:11]
Reactant: [H][H]
Reactant: COC(=O)Cc1ccc(C#N)cc1
Agent: [Pd]
Agent: Cl
Solvent: CO
Product: COC(=O)Cc1ccc(CN)cc1

Procedure:
A solution of 8.8 g (0.05 Mol) of methyl 4-cyanobenzene acetate in 200 ml of methanol was hydrogenated, after the addition of 50 ml of 1 N aqueous hydrochloric acid and 3 g of palladium on activated charcoal (10%), at ambient temperature under a hydrogen pressure of 3 bar until the uptake of hydrogen had ended. The solution freed from catalyst was evaporated down, the residue was combined with two batches of 50 ml of toluene and evaporated down again. 10.7 g (99% of theory) of a crude crystalline material was obtained which was used without further purification in the next step.
Reaction SMILES: Cl[CH:2]([C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH:11]([CH3:13])[CH3:12])=[CH:6][CH:5]=1)[CH3:3].[Na].O>CN(C)C=O>[CH2:10]([C:7]1[CH:6]=[CH:5][C:4]([CH:2]=[CH2:3])=[CH:9][CH:8]=1)[CH:11]([CH3:13])[CH3:12]
Reactant: CC(C)Cc1ccc(C(C)Cl)cc1
Agent: [Na]
Solvent: CN(C)C=O
Solvent: O
Product: C=Cc1ccc(CC(C)C)cc1
Yield: 93.8 %

Procedure:
A flat bottomed vial was charged with a mixture of 1-chloro-1-(4-isobutylphenyl)ethane (500 mg; 2.54 mmol), 250 mg (11 mmol) of sodium spheres in 5 mL of dry dimethylformamide. The vial was immersed in an ultrasound cleaner filled with water, and sonicated at room temperature for 2 hours. The reaction mixture was carefully treated with 30 mL of water and extracted with ether (3×30 mL). The ether extract was washed with water (3 ×15 mL) and dried over anhydrous MgSO4. It was filtered and stripped off the solvent to obtain 382 mg (94% yield) of pure 4-isobutylstyrene.
Reaction SMILES: [H-].[Na+].[OH:3][N:4]1[CH:8]=[C:7]([C:9]([O:11][CH3:12])=[O:10])[CH:6]=[N:5]1.[H][H].Cl[CH2:16][CH2:17][CH2:18][CH:19]1[O:23][CH2:22][CH2:21][O:20]1>CN(C)C=O>[O:20]1[CH2:21][CH2:22][O:23][CH:19]1[CH2:18][CH2:17][CH2:16][O:3][N:4]1[CH:8]=[C:7]([C:9]([O:11][CH3:12])=[O:10])[CH:6]=[N:5]1
Reactant: COC(=O)c1cnn(O)c1
Reactant: [H][H]
Reactant: ClCCCC1OCCO1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)c1cnn(OCCCC2OCCO2)c1
Reaction time: 0.5 h

Procedure:
21.8 g of sodium hydride (80 percent strength suspension in mineral oil) is introduced into 1.5 l of dry dimethylformamide, and 90 g of methyl 1-hydroxypyrazole-4-carboxylate are added a little at a time to the stirred mixture. When the evolution of hydrogen is complete, stirring is continued for 30 minutes, after which 95.5 g of 2-(3-chloropropyl)-1,3-dioxolane are added dropwise and the mixture is kept at 120° C. for 10 hours. Thereafter, the dimethylformamide is distilled off under reduced pressure, the residue is taken up in methyl tertbutyl ether, and the solution is washed with water, boiled and evaporated down to give 151 g of a slightly colored oil which crystallizes completely. M.p. 40°-42° C. NMR (CDCl3): 7.82 s [1]; 7.70 s [1]; 4.50 t [1]; 4.39 t [2]; 3.85-3.95 m [4]; 3.80 s [3]; 1.75-1.95 m [4].
Reaction SMILES: [NH:1]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C@H:2]([C:4]([NH:6][C@H:7]([C:9]([OH:11])=O)[CH3:8])=[O:5])[CH3:3].CN1CCOCC1.Br.[NH2:27][CH2:28][CH2:29][CH2:30][Br:31].CN(C=O)C>C1COCC1>[NH:1]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[C@H:2]([C:4]([NH:6][C@H:7]([C:9]([NH:27][CH2:28][CH2:29][CH2:30][Br:31])=[O:11])[CH3:8])=[O:5])[CH3:3]
Reactant: NCCCBr
Reactant: C[C@H](NC(=O)[C@H](C)NC(=O)OC(C)(C)C)C(=O)O
Agent: Br
Solvent: C1CCOC1
Solvent: CN1CCOCC1
Solvent: CN(C)C=O
Product: C[C@H](NC(=O)OC(C)(C)C)C(=O)N[C@@H](C)C(=O)NCCCBr
Temperature: 25 °C

Procedure:
To a cold (−15° C.) solution of Boc-Ala-Ala-OH (908 mg, 3.5 mmol) and NMM (570 μl, 5.23 mmols) in THF (15 ml) was added ECF (341 μl, 3.6 mmols) under N2 atmosphere and vigorously stirred. After 2 min of stirring, a solution of 1-amino-3-propylbromide hydrobromide (976 mg, 4.90 mmols) in a mixture of THF:DMF (4 mL: 3 mL) was added to the mixture followed by NMM (951 μl, 8.73 mmols) and stirred. After 10 min the mixture was warmed to 25° C. and stirred for further 8 h. THF was removed under reduced pressure and the resulting viscous solution was diluted with water (10 mL) and thoroughly extracted with ethyl acetate. The combined organic extracts were washed with 5 ml saturated citric acid, 5 ml saturated NaHCO3 and dried over by Na2SO4 and concentrated to give a residue, which was purified by silica gel flash column chromatograph (EtOAc:Hexane—3:7) to give the desired product as a solid (m.p. 146° C.) in good yields (1.022 g, 78%). (TLC:EtOAc—Rf—0.39).
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH2:18])[CH:5]=[CH:4][N:3]=[CH:2]1.[N:19]1[C:27]2[C:22]3[C:23](=[CH:28][CH:29]=[CH:30][C:21]=3[C:20]=1S)[CH:24]=[CH:25][CH:26]=2>C(O)C>[N:1]1([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:20]2[C:21]3[CH:30]=[CH:29][CH:28]=[C:23]4[C:22]=3[C:27](=[CH:26][CH:25]=[CH:24]4)[N:19]=2)[CH:5]=[CH:4][N:3]=[CH:2]1
Reactant: SC1=Nc2cccc3cccc1c23
Reactant: NCCCCCCCCCCCCn1ccnc1
Solvent: CCO
Product: c1cc2c3c(cccc3c1)C(NCCCCCCCCCCCCn1ccnc1)=N2

Procedure:
A mixture of 2.5 g of 12-(1H-imidazol-l-yl)dodecanamine, 1.9 g of benz(cd)indole-2-thiol, 3.4 g of mercuric acetate and 400 ml of ethanol was reacted as described in Example 1. The crude product was purified by dissolved it in chloroform and chromatographing it on a silica gel column, eluting with 10% methanol in chloroform giving 490 mg of the desired product, mp 95° C.-97° C.