Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][CH2:12][CH2:13][OH:14])[N:6]=[CH:5]2.[Si:15](Cl)([C:28]([CH3:31])([CH3:30])[CH3:29])([C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.N1C=CN=C1>C(Cl)Cl.CCOCC>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][CH2:12][CH2:13][O:14][Si:15]([C:28]([CH3:31])([CH3:30])[CH3:29])([C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[N:6]=[CH:5]2
Reactant: OCCCn1ncc2cc(Br)ccc21
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: c1c[nH]cn1
Solvent: ClCCl
Solvent: CCOCC
Product: CC(C)(C)[Si](OCCCn1ncc2cc(Br)ccc21)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 96.5 %

Procedure:
Crude 3-(5-Bromoindazol-1-yl)-propan-1-ol (2s) (2.1 mmol) and imidzaole (0.22 g, 3.2 mmol) were dissolved in 10 mL CH2Cl2. tert-Butyldiphenylsilyl chloride (0.58 g, 2.1 mmol) was added to the solution and the reaction was stirred at room temperature for 4 hours. Additional amounts of imidazole (0.07 g, 1.0 mmol) and tert-butyldiphenylsilyl chloride (0.16 g, 0.63 mmol) were added and the reaction was stirred at room temperature overnight. The mixture was diluted with Et2O and washed sequentially with an aqueous 3% HCl solution and brine. The aqueous phases were extracted once with Et2O. The organic phases were combined, dried (MgSO4), filtered, and concentrated in vacuo. The crude product was purified on silica gel with 1:6 Et2O/hexane to afford (3s) (1.0 g, 96% over two steps) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.92 (s, 1H), 7.86 (s, 1H), 7.61 (d, J=7.8 Hz, 4H), 7.44-7.42 (m, 3H), 7.36-7.33 (m, 5H), 4.53 (t, J=10.2 Hz, 2H), 3.63 (t, J=9.0 Hz, 2H), 2.16-10 (m, 2H), 1.08 (s, 9H); HPLC (5 to 95%) 4.72 min.
Reaction SMILES: C(O[C:4]1[C:5]([NH:11][C@@H:12]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([O:22][C:23]([F:26])([F:25])[F:24])[CH:20]=3)[O:15][C:14]([CH3:28])([CH3:27])[C@H:13]2[OH:29])=[N:6][S:7](=[O:10])(=[O:9])[N:8]=1)C.[F:30][C:31]([F:41])([F:40])[C:32]1[CH:39]=[CH:38][C:35]([CH2:36][NH2:37])=[CH:34][CH:33]=1>>[O:10]=[S:7]1(=[O:9])[N:8]=[C:4]([NH:37][CH2:36][C:35]2[CH:34]=[CH:33][C:32]([C:31]([F:30])([F:40])[F:41])=[CH:39][CH:38]=2)[C:5]([NH:11][C@@H:12]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([O:22][C:23]([F:25])([F:26])[F:24])[CH:20]=3)[O:15][C:14]([CH3:27])([CH3:28])[C@H:13]2[OH:29])=[N:6]1
Reactant: CCOC1=NS(=O)(=O)N=C1N[C@@H]1c2cc(OC(F)(F)F)ccc2OC(C)(C)[C@H]1O
Reactant: NCc1ccc(C(F)(F)F)cc1
Product: CC1(C)Oc2ccc(OC(F)(F)F)cc2[C@@H](NC2=NS(=O)(=O)N=C2NCc2ccc(C(F)(F)F)cc2)[C@@H]1O

Procedure:
In a method similar to Example 5, the product of Example 1, Step 2 (0.250 g, 0.572 mmol) was converted to the title compound with 4-(trifluoromethyl)benzylamine (0.09 mL, 0.629 mmol) to afford 0.25 g (77%) of product as a white solid: mp 283°-284° C.; 1H NMR (DMSO-D6): δ 8.94 (d, 1H), 8.92 (t, 1H), 7.78 (d, 2H), 7.64 (d, 2H), 7.32 (d, 1H), 7.21 (dd, 1H), 6.90 (d, 1H), 6.00 (d, 1H), 4.80 (t, 1H), 4.62 (d, 2H), 3.62 (m, 1H), 1.40 (s, 3H), 1.20 (s, 3H); IR (KBr) 3300, 1610 cm-1 ; MS (m/z) 567 (MH+, 100%); [α]D25 =-44.8 (THF).
Reaction SMILES: [CH2:1]=[O:2].[CH3:3][O:4][C:5]1[CH:10]=[CH:9][N:8]=[C:7]([CH2:11][S:12][C:13]2[NH:17][C:16]3=[CH:18][S:19][CH:20]=[C:15]3[N:14]=2)[CH:6]=1>C(#N)C>[OH:2][CH2:1][N:14]1[C:15]2=[CH:20][S:19][CH:18]=[C:16]2[N:17]=[C:13]1[S:12][CH2:11][C:7]1[CH:6]=[C:5]([O:4][CH3:3])[CH:10]=[CH:9][N:8]=1
Reactant: COc1ccnc(CSc2nc3cscc3[nH]2)c1
Reactant: C=O
Solvent: CC#N
Product: COc1ccnc(CSc2nc3cscc3n2CO)c1
Temperature: 70 °C
Reaction time: 0.25 h

Procedure:
Under a nitrogen atmosphere, 0.7 ml of 37% strength aqueous formaldehyde solution in 3 ml of acetonitrile was added dropwise to 1.6 g (5.8 mmol) of 2-(4methoxy-2-picolylmercapto)-1H-thieno[3,4-d]imidazole dissolved in 50 of acetonitrile. The mixture was then stirred at 70° C. for 15 minutes. The solution was concentrated in vacuo, washed with water and saturated aqueous NaCl solution and dried over MgSO4. The residue obtained after evaporation resulted, after treatment with diisopropyl ether, in a semicrystalline crude product which crystallized from ethyl acetate. Melting point 125°-127° C.
Reaction SMILES: [H-].[Na+].[Br:3][C:4]1[C:5]2[NH:12][CH:11]=[CH:10][C:6]=2[CH:7]=[N:8][CH:9]=1.[CH3:13]I>CN(C=O)C.C(Cl)Cl>[Br:3][C:4]1[C:5]2[N:12]([CH3:13])[CH:11]=[CH:10][C:6]=2[CH:7]=[N:8][CH:9]=1
Reactant: CI
Reactant: Brc1cncc2cc[nH]c12
Agent: [H-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: Cn1ccc2cncc(Br)c21
Temperature: 25 °C
Reaction time: 17 h

Procedure:
Sodium hydride (0.25 g, 6.2 mmol) is added under ice bath cooling to a mixture of 7-bromo-1H-pyrrolo[3,2-c]pyridine (0.8 g, 4.1 mmol) in DMF (10 ml). The mixture is stirred for 30 minutes before methyl iodide (0.25 ml, 4.1 mmol) is added. The mixture is warmed to RT and stirred for 17 h. The mixture is diluted with DCM and extracted with a saturated aqueous sodium hydrogencarbonate solution. The combined organic layers are dried over MgSO4 and concentrated in vacuo. The product is purified by RP HPLC. Yield: 0.61 g (71%). HPLC-MS: tR=0.88 min (METHOD—1).
Reaction SMILES: [Cl:1][C:2]1([Cl:11])[CH2:7][CH2:6][CH2:5][C:4]([Cl:9])([F:8])[CH:3]1[OH:10].C1C=C[NH+]=CC=1.[O-:18][Cr](Cl)(=O)=O.CCOCC>ClC(Cl)C>[Cl:1][C:2]1([Cl:11])[CH2:7][CH2:6][CH2:5][C:4]([Cl:9])([F:8])[C:3]1([OH:18])[OH:10]
Reactant: OC1C(F)(Cl)CCCC1(Cl)Cl
Reactant: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: CC(Cl)Cl
Solvent: CCOCC
Product: OC1(O)C(F)(Cl)CCCC1(Cl)Cl
Yield: 73.9 %

Procedure:
0.96 g (4.33 mmol) of trichlorofluoro alcohol 1b in solution in 10 cm3 of dichloroethane were introduced into a 25-cm3 round bottom flask fitted with a condenser and with magnetic stirring. 2.33 g (2.5 eq.) of PCC were added with a spatula and the mixture was heated to reflux under argon atmosphere for 7 h. The reaction mixture was allowed to cool and was then taken up with 100 cm3 of ether, the whole being filtered on florisil. The solvents were evaporated off, the residue was incorporated on silica and purified by flash chromatography (eluent: ether/petroleum ether=15/85 then 20/80). 0.03 g of starting alcohol 1b, that was approximately 3%, and 0.05 g of a mixture of alcohol 1b, diol 3a and 0.76 g of pure diol 3a were isolated. The yield of compound was therefore higher than 74%.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[C:9]([N:14]=[N+:15]=[N-:16])[CH:8]=1)[C:3]([OH:5])=[O:4].[CH:17]1([N:23]2[C:27]3[CH:28]=[CH:29][C:30]([C:32](O)=[O:33])=[CH:31][C:26]=3[N:25]=[C:24]2[C:35]2[CH:39]=[CH:38][O:37][CH:36]=2)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1>>[N:14]([C:9]1[CH:8]=[C:7]([CH2:6][C@H:2]([NH:1][C:32]([C:30]2[CH:29]=[CH:28][C:27]3[N:23]([CH:17]4[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]4)[C:24]([C:35]4[CH:39]=[CH:38][O:37][CH:36]=4)=[N:25][C:26]=3[CH:31]=2)=[O:33])[C:3]([OH:5])=[O:4])[CH:12]=[CH:11][C:10]=1[OH:13])=[N+:15]=[N-:16]
Reactant: [N-]=[N+]=Nc1cc(C[C@H](N)C(=O)O)ccc1O
Reactant: O=C(O)c1ccc2c(c1)nc(-c1ccoc1)n2C1CCCCC1
Product: [N-]=[N+]=Nc1cc(C[C@H](NC(=O)c2ccc3c(c2)nc(-c2ccoc2)n3C2CCCCC2)C(=O)O)ccc1O

Procedure:
To a solution of 3-amino-L-tyrosine.2HCl.H2O (2.50 g, 8.8 mmol) in 0.5 N HCl (28 mL) at 0° C., an aqueous solution of NaNO2 (0.724 g, 10.5 mmol, in 10 mL H2O) was added slowly. The reaction mixture was stirred for 10 min at 0° C., in the dark, and then a solution of NaN3 (1.43 g, 21.9 mmol, in 10 mL H2O) was added and stirring was continued for 1 h at 0° C. The white solid formed was filtered and dried to give (S)-2-amino-3-(3-azido-4-hydroxy-phenyl)-propionic acid (1.16 g) as of a beige solid. This amino acid was coupled to the carboxylic acid of example 2 in the usual manner to give the title compound of example 146 after purification by preparative C18 reversed-phase HPLC.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][N:12]=[CH:11][C:10]=2[N+:15]([O-])=O)[CH:5]=[CH:6][CH:7]=1.O>C(O)C.[Fe]>[Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]2[CH:14]=[CH:13][N:12]=[CH:11][C:10]=2[NH2:15])[CH:5]=[CH:6][CH:7]=1
Reactant: O=[N+]([O-])c1cnccc1Nc1cccc(Cl)c1
Agent: [Fe]
Solvent: CCO
Solvent: O
Product: Nc1cnccc1Nc1cccc(Cl)c1
Yield: 88.5 %

Procedure:
The product of Step 1 (325 mg, 1.302 mmol), was dissolved in ethanol (20 ml), and treated with iron powder (727 mg, 13.017 mmol), 20 drops of 37%. hydrochloric add and water (2 ml), and refluxed for 1 hour. The reaction was then filtered hot, and the filtrate evaporated in vacuo. The residue was dissolved in ethyl acetate then washed with saturated sodium bicarbonate solution, water, and brine, separated, dried over anhydrous sodium sulfate and evaporated in vacuo to afford the title compound (253 mg, 88%). MS (ES+), m/e 220/222 [M+H]+.
Reaction SMILES: [C:1](OC(=O)C)(=[O:3])[CH3:2].[NH2:8][C@@H:9]([CH3:29])[CH2:10][O:11][C:12]1[CH:13]=[CH:14][C:15]([C:18]2([CH3:28])[CH2:22][C:21]3[CH:23]=[CH:24][C:25]([OH:27])=[CH:26][C:20]=3[O:19]2)=[N:16][CH:17]=1>N1C=CC=CC=1.CO.[OH-].[Na+]>[OH:27][C:25]1[CH:24]=[CH:23][C:21]2[CH2:22][C:18]([C:15]3[N:16]=[CH:17][C:12]([O:11][CH2:10][C@@H:9]([NH:8][C:1](=[O:3])[CH3:2])[CH3:29])=[CH:13][CH:14]=3)([CH3:28])[O:19][C:20]=2[CH:26]=1
Reactant: C[C@H](N)COc1ccc(C2(C)Cc3ccc(O)cc3O2)nc1
Reactant: CC(=O)OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: c1ccncc1
Solvent: CO
Product: CC(=O)N[C@@H](C)COc1ccc(C2(C)Cc3ccc(O)cc3O2)nc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of acetic anhydride (0.126 mL) was added dropwise to a solution of diastereomer of 2-(5-{[(2S)-2-aminopropyl]oxy}pyridin-2-yl)-2-methyl-2,3-dihydro-1-benzofuran-6-ol (500 mg) in pyridine (15 mL) at ambient temperature. After being stirred at ambient temperature for 2 hr, the mixture was diluted with methanol (15 mL) and 4 M sodium hydroxide (10 mL). The mixture was stirred at ambient temperature for 15 hr. The organic solvent was removed under reduced pressure, and the aqueous solution was acidified with 4 M hydrochloric acid and extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (350 mg).
Reaction SMILES: [C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[Na].[CH3:13][O:14][CH2:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][CH2:23]Br)=[CH:18][CH:17]=1.Cl>CO>[CH2:10]([O:9][C:1]([CH:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[CH2:23][CH2:22][C:19]1[CH:20]=[CH:21][C:16]([CH2:15][O:14][CH3:13])=[CH:17][CH:18]=1)=[O:8])[CH3:11]
Reactant: COCc1ccc(CCBr)cc1
Reactant: CCOC(=O)CC(=O)OCC
Agent: Cl
Agent: [Na]
Solvent: CO
Product: CCOC(=O)C(CCc1ccc(COC)cc1)C(=O)OCC

Procedure:
Diethyl malonate (0.32 g) is added to a solution of 0.05 g sodium in 10 ml of methanol. The 1-(methoxymethyl)-4-(2-bromoethyl)benzene (13) (0.5 g) is then added and allowed to react for 8 h. The solution is neutralized with methanolic HCl and is extracted with ether. The ether extract is dried over Na2SO4, and evaporated to yield 1-[3,3-di(ethoxycarbonyl)propyl]-4-methoxymethylbenzene (14). The methyl group is removed by treatment with aqueous HBr in acetic acid, followed by neutralization with aqueous NaOH and extraction with ether. The ether extract is dried over Na2SO4, and evaporated to yield 1-[3,3-di(ethoxycarbonyl)propyl]-4-hydroxymethylbenzene (4).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([CH3:15])=[CH:10][C:11](=O)[NH:12][N:13]=2)=[CH:4][CH:3]=1.P(Cl)(Cl)([Cl:18])=O>O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:13]=[N:12][C:11]([Cl:18])=[CH:10][C:9]=2[CH3:15])=[CH:4][CH:3]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: Cc1cc(=O)[nH]nc1-c1ccc(Br)cc1
Solvent: O
Product: Cc1cc(Cl)nnc1-c1ccc(Br)cc1

Procedure:
A 10.0 g. portion of 6-(p-bromophenyl)-5-methyl-3(2H)-pyridazinone [Journal of Medicinal Chemistry 17, 281 (1974)] and 100 ml. of phosphorus oxychloride is heated at steam bath temperature for 3 hours. The mixture is added dropwise to cold water while stirring. The resulting solid is filtered and washed with water to afford 3-(p-bromophenyl)-6-chloro-4-methylpyridazine as a grey solid.
Reaction SMILES: [C@@H:1]1(O)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C@H:2]1[OH:10].C(#[N:14])C.S(=O)(=O)(O)O.O1[C@@H]2CC3C([C@H]12)=CC=CC=3>O>[NH2:14][C@@H:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C@@H:2]1[OH:10]
Reactant: O[C@@H]1Cc2ccccc2[C@H]1O
Reactant: CC#N
Agent: O=S(=O)(O)O
Agent: c1ccc2c(c1)C[C@H]1O[C@@H]21
Solvent: O
Product: N[C@@H]1c2ccccc2C[C@@H]1O
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 59.7 %

Procedure:
Into a 100 ml four-neck flask, 4.48 g (30.3 mmol) of trans-(±)-1,2-indandiol (I') and 40 ml of acetonitrile were introduced. This mixture was suspended. While this suspension was stirred at room temperature, 6.14 g (60.6 mmol) of 97% sulfuric acid was added thereto at room temperature in a period of 20 minutes. The temperature within the mixture increased from 19° C. to 35° C. The slurry was completely dissolved to form a slightly yellow transparent solution. The solution was stirred at 24° C. for 1 hour and then at 60° C. for 1 hour. An HPLC analysis of the contents revealed that 70.8% of cis-oxazoline derivative (IV: R=CH3) had been generated, while no trans-amide derivative (III': R=CH3, Y=OH) was detected. Then, 30 ml of water was added thereto and the resulting mixture was stirred at 60° C. for 3 hours. Acetonitrile was removed by azeotropic distillation. The remaining mixture was washed with dichloromethane and then subjected to liquid separation. When an aqueous solution of 25% sodium hydroxide was added to the water phase, a crystal deposited. This crystal was filtered off under reduced pressure, washed with water, and then dried to yield 2.70 g (yield: 59.7%) of cis-(±)-1-aminoindan-2-ol (V) as a white crystal. Its purity determined by an HPLC was 97.7%.
Reaction SMILES: [Mg].Br[C:3]1[CH:4]=[C:5]([O:18][C:19]([F:22])([F:21])[F:20])[C:6]([O:16][CH3:17])=[C:7]([CH:9]([O:13]CC)OCC)[CH:8]=1.C[Mg]Br.[O:26]1[CH2:30]CCC1.Cl.[O:32]1CCCC1>>[CH:9]([C:7]1[CH:8]=[C:3]([CH:4]=[C:5]([O:18][C:19]([F:20])([F:21])[F:22])[C:6]=1[O:16][CH3:17])[C:30]([OH:26])=[O:32])=[O:13]
Reactant: C1CCOC1
Reactant: CCOC(OCC)c1cc(Br)cc(OC(F)(F)F)c1OC
Agent: C[Mg]Br
Agent: Cl
Agent: [Mg]
Product: COc1c(C=O)cc(C(=O)O)cc1OC(F)(F)F
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To magnesium (403 mg), tetrahydrofuran (16 mL), 5-bromo-1-diethoxymethyl-2-methoxy-3-trifluoromethoxybenzene (6.19 g) and a 0.97M methylmagnesium bromide-tetrahydrofuran solution (0.42 mL) were added to the solution, and then the mixture was stirred at room temperature for 1 hour. The reaction solution was cooled to 0° C. and stirred for 45 minutes under a carbon dioxide atmosphere. 4N hydrochloric acid (25 mL) was added and then the mixture was stirred at room temperature for 30 minutes. The organic solvent was distilled off under reduced pressure and the mixture was extracted with diisopropylether. The organic layer was extracted with 1N sodium hydroxide (100 mL) added thereto and the aqueous layer was washed twice with diisopropylether. The aqueous layer was acidified with 4N hydrochloric acid and then extracted with ethyl acetate. The organic layer was washed with saturated brine, and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain the title compound (4.22 g) as a brown solid.
Reaction SMILES: [C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][C:14]([OH:16])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:17]([O:19][C:20](=[O:47])[CH:21]=[CH:22][CH:23]([NH:39]C(OC(C)(C)C)=O)[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[CH:27][CH:26]=1)[CH3:18]>>[CH2:17]([O:19][C:20](=[O:47])[CH2:21][CH2:22][CH:23]([NH:39][C:14](=[O:16])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[CH:27][CH:26]=1)[CH3:18]
Reactant: CCOC(=O)C=CC(Cc1ccc(OCc2ccccc2)cc1)NC(=O)OC(C)(C)C
Reactant: O=C(O)CCCCCCCc1ccccc1
Product: CCOC(=O)CCC(Cc1ccc(OCc2ccccc2)cc1)NC(=O)CCCCCCCc1ccccc1

Procedure:
From 8-phenyloctanoic acid 71c and (RS)-5-(4-Benzyloxy-phenyl)-4-tertbutoxycarbonylamino-pent-2-enoic acid ethyl ester 77 (96% yield): 1H nmr (CDCl3) δ 1.20 (t, J=7.1 Hz, 3H), 1.27-1.55 (m, 10H), 2.06 (t, J=7.4 Hz, 2H), 2.52 (t, J=7.4 Hz, 2H), 2.74-2.79 (m, 2H), 4.10 (q, J=7.0 Hz, 2H), 4.84-4.88 (m, 1H), (4.94, s, 2H), 5.80 (br d, J=15.8 Hz, 1H), 6.00 (d J=8.2 Hz, 1H), 6.82-7.36 (m, 15H). 13C nmr (CDCl3) δ 172.5, 165.9, 157.5, 147.2, 142.5, 136.7, 130.1, 128.6, 128.3, 128.1, 128.0, 127.7, 127.2, 121.0, 114.7, 69.7, 60.2, 50.6, 39.3, 36.3, 35.7, 31.2, 29.0, 28.9, 28.1, 25.4, 14.0.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11].[CH3:13][C:14]1([CH3:29])[CH2:19][CH2:18][C:17](B2OC(C)(C)C(C)(C)O2)=[CH:16][CH2:15]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC>[CH3:13][C:14]1([CH3:29])[CH2:19][CH2:18][C:17]([C:2]2[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=2[N+:10]([O-:12])=[O:11])=[CH:16][CH2:15]1
Reactant: CC1(C)CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Reactant: COc1ccc(Br)c([N+](=O)[O-])c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: COCCOC
Product: COc1ccc(C2=CCC(C)(C)CC2)c([N+](=O)[O-])c1
Temperature: 25 °C

Procedure:
To a mixture of 4-bromo-3-nitroanisole (3.3 g, 14.1 mmol), 2-(4,4-dimethylcyclohex-1-enyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (4.0 g, 16.9 mmol) prepared in Example (1b), tripotassium phosphate (4.5 g, 21.3 mmol) and 1,2-dimethoxyethane (30 mL) was added tetrakis(triphenylphosphine)palladium(0) (0.82 g, 0.71 mmol) with stirring at room temperature under a nitrogen atmosphere. The mixture was then stirred at an external temperature of 80° C. for 24 hours.
Reaction SMILES: [N+:1]([C:4]1[CH:20]=[CH:19][C:7]([CH2:8][O:9][C:10]([NH:12][CH2:13][CH2:14][CH2:15][C:16]([OH:18])=[S:17])=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH2:21]([CH:23]1[CH:26](OC(=O)C)[NH:25][C:24]1=[O:31])[CH3:22]>[OH-].[Na+].O1CCOCC1>[CH2:21]([CH:23]1[CH:26]([S:17][C:16](=[O:18])[CH2:15][CH2:14][CH2:13][NH:12][C:10]([O:9][CH2:8][C:7]2[CH:19]=[CH:20][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)=[O:11])[NH:25][C:24]1=[O:31])[CH3:22]
Reactant: O=C(NCCCC(O)=S)OCc1ccc([N+](=O)[O-])cc1
Reactant: CCC1C(=O)NC1OC(C)=O
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: CCC1C(=O)NC1SC(=O)CCCNC(=O)OCc1ccc([N+](=O)[O-])cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution, prepared in the cold, of 7.95 g (26.7 mmole) of 4-p-nitrobenzyloxycarbonylaminothiobutyric acid in 26.7 ml of 1N sodium hydroxide solution is added dropwise to a pre-cooled solution of 3.24 g (20 mmole) of 3-ethyl-4-acetoxyazetidin-2-one (racemic cis-trans compound in a ratio of 6:4) in 50 ml of dioxan and the mixture is stirred for 2 hours at room temperature. The reaction mixture is exhaustively extracted with methylene chloride. The combined organic phases are dried over sodium sulphate and concentrated by evaporation in vacuo. The residue is chromatographed over silica gel with toluene/ethyl acetate (9:1, 4:1 and 1:1) and yields the title compound with the following physico-chemical properties.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][C:5]([C:7]1[CH:12]=[CH:11][C:10]([C:13]([CH3:18])([CH3:17])[C:14](O)=[O:15])=[CH:9][CH:8]=1)=[O:6].[N:19]1(C(N)=O)[CH2:23]CC[CH2:20]1>>[CH3:20][N:19]([CH3:23])[C:14](=[O:15])[C:13]([C:10]1[CH:11]=[CH:12][C:7]([C:5](=[O:6])[CH2:4][CH2:3][CH2:2][Cl:1])=[CH:8][CH:9]=1)([CH3:18])[CH3:17]
Reactant: CC(C)(C(=O)O)c1ccc(C(=O)CCCCl)cc1
Reactant: NC(=O)N1CCCC1
Product: CN(C)C(=O)C(C)(C)c1ccc(C(=O)CCCCl)cc1

Procedure:
2-[4-(4-Chloro-butyryl)-phenyl]-2-methyl-propionic acid, pyrroldineamide;
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[N+:10]([O-])=O.C([O-])([O-])=O.[Cs+].[Cs+].[CH2:19]([O:21]C(=O)C)[CH3:20].O>CN(C=O)C>[O:21]=[C:19]1[NH:10][C:3]2[CH:4]=[C:5]([C:6]#[N:7])[CH:8]=[CH:9][C:2]=2[O:1][CH2:20]1
Reactant: N#Cc1ccc(O)c([N+](=O)[O-])c1
Reactant: CCOC(C)=O
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: N#Cc1ccc2c(c1)NC(=O)CO2
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
24 mmol of 4-Hydroxy-3-nitrobenzonitrile were dissolved in DMF. 1.1 eq of Cs2CO3 were added and the reaction stirred at rt for 15 min. 1.5 eq of ethylbromo acetate were added and the reaction mixture heated to 50° C. for 2 h. The intermediate was isolated via extraction from ethylacetate/water. The organic layer was separated and dried over Na2SO4. After evaporation the resulting solid was redissolved in MeOH and sat. NH4Cl (1:1). 8 g of Zn powder were added and the suspension stirred at rt for 2 h. The solid was filtered off and the organic layer evaporated. Ethylacetate was added and the organic layer washed with sat. NaHCO3. The organic layer was separated again, dried over Na2SO4 and reduced resulting in a light brown solid. MS(ISO): 175.2 (MH+)
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[S:20](Cl)(=[O:22])=[O:21]>CN(C1C=CN=CC=1)C>[CH3:12][O:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[S:20]([NH:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2)(=[O:22])=[O:21]
Reactant: COc1ccccc1S(=O)(=O)Cl
Reactant: Nc1cccc2cccnc12
Agent: CN(C)c1ccncc1
Product: COc1ccccc1S(=O)(=O)Nc1cccc2cccnc12
Yield: 57.6 %

Procedure:
In the similar fashion using route 14 general procedure 27, 8-aminoquinoline (200 mg, 1.38 mmol), 2-methoxybenzenesulfonyl chloride (280 mg, 1.38 mmol) and DMAP (cat.) gave the title compound (250 mg, 58%) after purification by column chromatography with DCM as the eluent.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[Cl:17])[CH2:5][N:6]1[CH2:11][CH2:10][O:9][CH:8]([CH2:12][NH2:13])[CH2:7]1.[O:18]([CH2:25][C:26](O)=[O:27])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:14]=[CH:15][C:16]=1[Cl:17])[CH2:5][N:6]1[CH2:11][CH2:10][O:9][CH:8]([CH2:12][NH:13][C:26](=[O:27])[CH2:25][O:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:7]1
Reactant: NCC1CN(Cc2ccc(Cl)c(Cl)c2)CCO1
Reactant: O=C(O)COc1ccccc1
Product: O=C(COc1ccccc1)NCC1CN(Cc2ccc(Cl)c(Cl)c2)CCO1
Yield: 62.4 %

Procedure:
Example 21 was prepared in an analogous manner to Example 1 using a mixture of Intermediate 1 (0.028 g) and phenoxyacetic acid (0.017 g) to give the title compound (0.026 g).