Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [SH:1][C:2]1[NH:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.C[O-].[Na+].[CH2:14]([O:24][C:25]1[CH:30]=[CH:29][N:28]=[C:27]([CH2:31]Cl)[C:26]=1[CH3:33])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23]>CO.C(OCC)(=O)C>[CH2:14]([O:24][C:25]1[CH:30]=[CH:29][N:28]=[C:27]([CH2:31][S:1][C:2]2[NH:6][C:5]3[CH:7]=[CH:8][CH:9]=[CH:10][C:4]=3[N:3]=2)[C:26]=1[CH3:33])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23]
Reactant: CCCCCCCCCCOc1ccnc(CCl)c1C
Reactant: Sc1nc2ccccc2[nH]1
Agent: C[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CO
Product: CCCCCCCCCCOc1ccnc(CSc2nc3ccccc3[nH]2)c1C
Yield: 99.9 %

Procedure:
To a liquid prepared by dissolving with stirring 6.8 g (0.045 mol, 0.9 eq.) of 2-mercaptobenzimidazole and 11.6 g (0.06 mol, 1.2 eq.) of a 28% sodium methoxide solution in 150 mL of methanol, a liquid containing 15.0 g of 4-decyloxy-2-chloromethyl-3-methylpyridine dissolved in 75 mL of methanol was added at 30° C. Subsequently, the mixture was heated to reflux for 0.5 hours and cooled, and then methanol was solid dried under reduced pressure. An orange-colored oily residue resulting therefrom was dissolved in 300 mL of ethyl acetate, and then the organic layer was washed with 150 mL of water. 45 g of silica gel was added with stirring to the organic layer, subsequently the silica gel was removed by filtration, and then the filtrate was concentrated to dryness under reduced pressure, to obtain 18.5 g of pale orange crystals. The pale orange crystals were recrystallized from ethyl acetate (10 vol.), to obtain 9.7 g of pale orange crystals (HPLC: 99.6 Area %, yield 47.1%).
Reaction SMILES: [F:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH2:4]Cl.[CH2:11]([N:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([CH2:27][C:28]([OH:30])=[O:29])[CH:25]=2)[CH:20]=[CH:19]1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1>>[F:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH2:4][N:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([CH2:27][C:28]([OH:30])=[O:29])[CH:25]=2)[CH:20]=[CH:19]1.[CH2:11]([N:18]1[C:26]2[C:21](=[CH:22][CH:23]=[C:24]([CH2:27][C:28]([OH:30])=[O:29])[CH:25]=2)[CH:20]=[CH:19]1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: Fc1ccc(CCl)c(F)c1
Agent: O=C(O)Cc1ccc2ccn(Cc3ccccc3)c2c1
Product: O=C(O)Cc1ccc2ccn(Cc3ccc(F)cc3F)c2c1

Procedure:
The titled compound (35 mg) as a white solid was prepared from the compound [4-6] obtained in the process (6) of Example 4 (100 mg) and 2,4-difluorobenzyl chloride according to the method of the process (7) of Example 4.
Reaction SMILES: ClC1C=C(C=CC=1)C(OO)=[O:6].[N:12]1[CH:17]=[CH:16][C:15]([CH2:18][NH:19][C:20]2[CH:38]=[CH:37][CH:36]=[CH:35][C:21]=2[C:22]([NH:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:26]=2)=[O:23])=[CH:14][CH:13]=1>ClCCl>[O-:6][N+:12]1[CH:17]=[CH:16][C:15]([CH2:18][NH:19][C:20]2[CH:38]=[CH:37][CH:36]=[CH:35][C:21]=2[C:22]([NH:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:32])([F:33])[F:34])[CH:26]=2)=[O:23])=[CH:14][CH:13]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: O=C(Nc1cccc(C(F)(F)F)c1)c1ccccc1NCc1ccncc1
Solvent: ClCCl
Product: O=C(Nc1cccc(C(F)(F)F)c1)c1ccccc1NCc1cc[n+]([O-])cc1
Temperature: 25 °C
Reaction time: 15 h

Procedure:
3-Chloroperoxybenzoic acid (2.06 g of 70%, 8.4 mmol) is added to a stirred mixture of 2-[(4-pyridyl)methyl]amino-N-[3-(trifluoromethyl)phenyl]benzamide (Example 14; 1.86 g, 5 mmol) in dichloromethane (50 mL) at 0° C. The resulting mixture is then stirred at room temperature for 15 hours. The mixture is diluted with dichloromethane (100 mL) and washed sequentially with aqueous sodium hydroxide (2×100 mL) and aqueous sodium thiosulphate (2×50 mL of 10%). The organic phase is dried (Na2SO4), filtered and the solvent is evaporated off under reduced pressure to yield the crude product which is purified by column chromatography on silica gel, eluent 20% ethanol in ethyl acetate, and recrystallised from ethyl acetate-hexane to give the title compound as a colourless crystalline solid, m.p. 181-184° C.
Reaction SMILES: [C:1]([C:3]1[C:7]([C:8]2[CH:13]=[CH:12][C:11](OC)=[CH:10][CH:9]=2)=[CH:6][NH:5][C:4]=1[NH:16][CH:17]=[NH:18])#[N:2].NC1NC=C(C2C=CC=CC=2)C=1C#N>C(OCC)(OCC)OCC>[C:8]1([C:7]2[C:3]3[C:1]([NH2:2])=[N:18][CH:17]=[N:16][C:4]=3[NH:5][CH:6]=2)[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: COc1ccc(-c2c[nH]c(NC=N)c2C#N)cc1
Agent: N#Cc1c(-c2ccccc2)c[nH]c1N
Solvent: CCOC(OCC)OCC
Product: Nc1ncnc2[nH]cc(-c3ccccc3)c12
Temperature: 140 °C
Reaction time: 1 h

Procedure:
N-[3-Cyano-4-(4-methoxy-phenyl)-1H-pyrrol-2-yl]-formamidine: 6.0 g of 2-amino-4-phenyl-1H-pyrrole-3-carbonitrile are dissolved in 80 ml of triethyl orthoformate, and the solution is stirred for 1 hour at 140° C. The triethyl orthoformate is removed under a high vacuum and the residue is dissolved in methanol saturated with ammonia. Stirring is carried out for 24 hours at room temperature, followed by filtration. The product is recrystallised from ethanol. M.p.: 238-239° C.
Reaction SMILES: Br[C:2]1[CH:11]=[CH:10][C:9]2[N:8]=[CH:7][C:6]3[N:12]([CH3:23])[C:13](=[O:22])[N:14]([C:15]4[C:16]([CH3:21])=[N:17][N:18]([CH3:20])[CH:19]=4)[C:5]=3[C:4]=2[CH:3]=1.[CH3:24][N:25]1[CH2:30][CH2:29][O:28][C:27]2[CH:31]=[C:32](B3OC(C)(C)C(C)(C)O3)[CH:33]=[N:34][C:26]1=2>>[CH3:20][N:18]1[CH:19]=[C:15]([N:14]2[C:5]3[C:4]4[CH:3]=[C:2]([C:32]5[CH:33]=[N:34][C:26]6[N:25]([CH3:24])[CH2:30][CH2:29][O:28][C:27]=6[CH:31]=5)[CH:11]=[CH:10][C:9]=4[N:8]=[CH:7][C:6]=3[N:12]([CH3:23])[C:13]2=[O:22])[C:16]([CH3:21])=[N:17]1
Reactant: CN1CCOc2cc(B3OC(C)(C)C(C)(C)O3)cnc21
Reactant: Cc1nn(C)cc1-n1c(=O)n(C)c2cnc3ccc(Br)cc3c21
Product: Cc1nn(C)cc1-n1c(=O)n(C)c2cnc3ccc(-c4cnc5c(c4)OCCN5C)cc3c21

Procedure:
The title compound was synthesized in a similar manner as described for Example 1.1 using 8-bromo-1-(1,3-dimethyl-1H-pyrazol-4-yl)-3-methyl-1,3-dihydro-imidazo[4,5-c]quinolin-2-one (Intermediate A) and 4-methyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine (ABCR, Karlsruhe, Germany) to give the title compound as a yellow foam. (HPLC: tR 2.15 min (Method A); M+H=442 MS-ES; 1H-NMR (d6-DMSO, 400 MHz) 8.90 (s, 1H), 8.13 (s, 1H), 8.03-7.99 (m, 1H), 7.89-7.82 (m, 2H), 7.40-7.37 (m, 1H), 6.97-6.94 (m, 1H), 4.25 (t, 2H), 3.92 (s, 3H), 3.56 (s, 3H), 3.47 (t, 2H), 3.06 (s, 3H), 1.95 (s, 3H))
Reaction SMILES: C([O:3][C:4]([C:6]1[N:7]([CH2:16][C:17]2[CH:21]=[C:20]([C:22]3[S:23][C:24]([Cl:27])=[CH:25][CH:26]=3)[O:19][N:18]=2)[N:8]=[C:9]([C:11]2[S:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=1)=[O:5])C.O.[OH-].[Li+].Cl>C1COCC1.O>[Cl:27][C:24]1[S:23][C:22]([C:20]2[O:19][N:18]=[C:17]([CH2:16][N:7]3[C:6]([C:4]([OH:5])=[O:3])=[CH:10][C:9]([C:11]4[S:12][CH:13]=[CH:14][CH:15]=4)=[N:8]3)[CH:21]=2)=[CH:26][CH:25]=1
Reactant: CCOC(=O)c1cc(-c2cccs2)nn1Cc1cc(-c2ccc(Cl)s2)on1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)c1cc(-c2cccs2)nn1Cc1cc(-c2ccc(Cl)s2)on1
Temperature: 60 °C
Reaction time: 2 h

Procedure:
To a solution of 4 g 2-[5-(5-Chloro-thiophen-2-yl)-isoxazol-3-ylmethyl]-5-thiophen-2-yl-2H-pyrazole-3-carboxylic acid ethyl ester in 20 ml THF, 10 ml water and 500 mg lithium hydroxide monohydrate were added. After stirring for 2 h at 60° C. the reaction was cooled to RT. The mixture was acidified with half concentrated hydrochloric acid to pH 3 and the precipitate collected by filtration and washed with 10 ml water. The product was obtained as a white solid which was dried under reduced pressure. Yield: 3.8 g.
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:7]=[C:8](/[CH:13]=[C:14](\[O:18][CH2:19][CH3:20])/[C:15]([OH:17])=[O:16])[CH:9]=[CH:10][C:11]=1[I:12])[CH2:2][CH2:3][CH3:4].S(=O)(=O)(O)O.O.[CH3:27]O>>[CH2:1]([O:5][C:6]1[CH:7]=[C:8](/[CH:13]=[C:14](\[O:18][CH2:19][CH3:20])/[C:15]([O:17][CH3:27])=[O:16])[CH:9]=[CH:10][C:11]=1[I:12])[CH2:2][CH2:3][CH3:4]
Reactant: CCCCOc1cc(/C=C(\OCC)C(=O)O)ccc1I
Reactant: CO
Agent: O=S(=O)(O)O
Solvent: O
Product: CCCCOc1cc(/C=C(\OCC)C(=O)OC)ccc1I
Yield: 61 %

Procedure:
In an Emrys Optimizer microwave reactor, 0.8 g (2 mmol) of (Z)-3-(3-butoxy-4-iodophenyl)-2-ethoxyacrylic acid is dissolved in 10 mL of methanol and 1 mL of concentrated sulfuric acid and heated at 70° C. by microwave for 2 hours. After addition of water, the reaction medium is extracted with ethyl acetate. The organic phase is washed with water, dried over magnesium sulfate, filtered and evaporated. 0.5 g (61%) of methyl (Z)-3-(3-butoxy-4-iodophenyl)-2-ethoxyacrylate is obtained.
Reaction SMILES: [CH2:1]([C:4]1([CH3:22])[O:9][C:8](=[O:10])[NH:7][C:6]2[CH:11]=[CH:12][C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=3)=[CH:14][C:5]1=2)[CH:2]=[CH2:3].ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl>C1COCC1>[CH2:1]([C:4]1([CH3:22])[O:9][C:8](=[O:10])[NH:7][C:6]2[CH:11]=[CH:12][C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([Cl:21])[CH:16]=3)=[CH:14][C:5]1=2)[C:2]1[CH:3]=[CH:2][CH:1]=[CH:4][CH:3]=1
Reactant: C=CCC1(C)OC(=O)Nc2ccc(-c3cccc(Cl)c3)cc21
Agent: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Solvent: C1CCOC1
Product: CC1(Cc2ccccc2)OC(=O)Nc2ccc(-c3cccc(Cl)c3)cc21
Reaction time: 0.17 h
Yield: 58.9 %

Procedure:
A mixture of 1-(4-amino-3′-chloro-biphenyl-3-yl)-1-benzyl-ethanol (prepared from 1-(4-amino-3′-chloro-biphenyl-3-yl)-ethanone and benzylmagnesium bromide according to Procedure C, 0.14 g, 0.42 mmol) and triphosgene (0.04 g, 0.14 mmol) in dry THF (10 mL) was stirred under a blanket of nitrogen for 10 minutes. Upon completion of the reaction, the THF was removed and the residue purified via flash chromatography (silica gel, 35% ethyl acetate/hexane) to give 4-benzyl-6-(3-chloro-phenyl)-4-methyl-1,4-dihydro-benzo[d][1,3]oxazin-2-one (0.045 g, 30%) as an off-white solid: mp 187-188° C.; 1H-NMR (DMSO-d6) δ10.1 (s, 1H), 7.70 (t, 1H, J=2.3 Hz), 7.6 (d, 1H, J=8.0 Hz), 7.58-7.53 (m, 2H), 7.46 (t, 1H, J=8.0 Hz), 7.38 (d, 1H, J=8.0 Hz), 7.22-7.17 (m, 3H), 7.06-7.0 (m, 2H), 6.84 (d, 1H, J=9.14 Hz), 3.24 (d, 1H, J=14.3 Hz), 3.06 (d, 1H, J=14.3 Hz), 1.68 (s, 3H); MS (ESI) m/z 364 ([M+H]+, 100%); Anal. Calc. For C22H18ClNO2: C, 72.63; H, 4.99; N, 3.85. Found: C, 71.82; H, 5.09; N, 3.58.
Reaction SMILES: [O-2].[In+3:2].[O-2].[O-2].[In+3].[In].[N+:7]([O-:10])([OH:9])=[O:8]>>[N+:7]([O-:10])([O-:9])=[O:8].[In+3:2].[N+:7]([O-:10])([O-:9])=[O:8].[N+:7]([O-:10])([O-:9])=[O:8]
Reactant: O=[N+]([O-])O
Agent: [In+3]
Agent: [In]
Agent: [O-2]
Product: O=[N+]([O-])[O-]

Procedure:
For example, Japanese Patent Application Laid-open No. HEI 08-091838 (hereinafter, referred to as Patent Document 1) discloses a method of manufacturing an indium oxide including: a first step of leaching out an indium inclusion with a nitric acid to obtain an indium nitrate solution; a second step of extracting, with an organic solvent, an indium ion from the indium nitrate solution obtained in the first step, and performing back extraction on an extract obtained, to obtain an indium aqueous solution; and a third step of hydrolyzing the indium aqueous solution obtained in the second step, and roasting an indium hydroxide obtained, to obtain an indium oxide.
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:9][C:10]3[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=3[N:12]=2)=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:25]2[CH:26]=[CH:27][C:28]([C:31]3[S:32][C:33]4[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=4[N:35]=3)=[N:29][CH:30]=2)O1.C([O-])([O-])=O.[Na+].[Na+].O>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.C1COCC1>[S:32]1[C:33]2[CH:39]=[CH:38][CH:37]=[CH:36][C:34]=2[N:35]=[C:31]1[C:28]1[N:29]=[CH:30][C:25]([C:2]2[CH:7]=[N:6][C:5]([C:8]3[O:9][C:10]4[CH:16]=[CH:15][CH:14]=[CH:13][C:11]=4[N:12]=3)=[CH:4][CH:3]=2)=[CH:26][CH:27]=1
Reactant: Brc1ccc(-c2nc3ccccc3o2)nc1
Reactant: CC1(C)OB(c2ccc(-c3nc4ccccc4s3)nc2)OC1(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: c1ccc2oc(-c3ccc(-c4ccc(-c5nc6ccccc6s5)nc4)cn3)nc2c1
Yield: 84.8 %

Procedure:
Following the procedure for 17, 11 (0.558 g, 2.03 mmol), 16 (0.700 g, 2.07 mmol), tetrakis(triphenylphosphine)palladium(0) (117 mg, 102 μmol), Na2CO3 (1.59 g, 15.0 mmol), H2O (15 mL) and THF (25 mL) yielded an insoluble white solid (0.70 g, 84%) after filtration.
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-])=[O:9])[C:3]=1[CH2:11][C:12]([OH:14])=O>C(O)C.[Pd]>[OH:9][N:8]1[C:4]2[C:3](=[C:2]([I:1])[CH:7]=[CH:6][CH:5]=2)[CH2:11][C:12]1=[O:14]
Reactant: O=C(O)Cc1c(I)cccc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCO
Product: O=C1Cc2c(I)cccc2N1O
Reaction time: 2 h
Yield: 62.5 %

Procedure:
(2-Iodo-6-nitro-phenyl)-acetic acid 74d (0.91 g, 3 mmol) was dissolved in ethanol (30 ml, 95%), and added with palladium on activated carbon (30 mg, 3%) to the solution. Upon completion of the addition, the reaction mixture was stirred for 2 hours under a hydrogen atmosphere. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound 1-hydroxy-4-iodo-1,3-dihydro-indol-2-one 74e (516 mg, yield 63.4%) as a white solid.
Reaction SMILES: [F:1][C:2]([C:17]([F:20])([F:19])[F:18])([O:6][C:7]([F:16])([F:15])[C:8]([F:14])([F:13])[C:9]([F:12])([F:11])[F:10])[C:3](F)=[O:4].C[Si](C)(C)[O-:23].[Na+:26]>C1(C)C=CC=CC=1>[F:1][C:2]([C:17]([F:18])([F:19])[F:20])([O:6][C:7]([F:15])([F:16])[C:8]([F:13])([F:14])[C:9]([F:12])([F:10])[F:11])[C:3]([O-:4])=[O:23].[Na+:26]
Reactant: O=C(F)C(F)(OC(F)(F)C(F)(F)C(F)(F)F)C(F)(F)F
Reactant: C[Si](C)(C)[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: O=C([O-])C(F)(OC(F)(F)C(F)(F)C(F)(F)F)C(F)(F)F
Yield: 65.6 %

Procedure:
The procedure of Example 1 was followed using perfluoro-2-methyl-3-oxahexanoyl fluoride (33.2 g, 0.1 mol), sodium trimethylsilanolate (11.2 g, 0.1 mol), dry toluene (200 mL), and 1.5 h of heating at reflux. Sodium perfluoro-2-methyl-3-oxahexanoate (23.1 g, 66% yield) was isolated as a white solid: The 19F NMR data were the same as reported in Example 15. Anal. Calcd. for C6F11NaO3 : C, 19.77; H, 57.33; Na, 7.63. Found: C, 19.56; H, 56.93; Na, 7.80.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[CH2:10][CH2:11][CH3:12].[CH2:13](Br)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.O>[CH2:13]([O:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[CH2:10][CH2:11][CH3:12])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: BrCc1ccccc1
Reactant: CCCc1cc(C#N)ccc1O
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCc1cc(C#N)ccc1OCc1ccccc1
Temperature: 25 °C
Reaction time: 12 h
Yield: 81.6 %

Procedure:
To a solution of 4-hydroxy-3-propylbenzonitrile (0.97 g, 6 mmol) (Example 29) in DMF (20 mL) were added 10 drops of water, benzyl bromide (2.05 g, 12 mmol), and Cs2CO3 (2.93 g, 9 mmol), and the mixture was stirred for 12 h at rt. The reaction mixture was concentrated under reduced pressure, and the residue was suspended in EtOAc and filtered. The precipitate was washed with more EtOAc. The combined filtrates were concentrated and purified by silica gel chromatography (EtOAc/hexanes (v/v)=1:19) to give 1.23 g (82%) of the title compound. 1H NMR (400 MHz, CDCl3): δ 7.48-7.32 (m, 7H), 6.92 (d, 1H), 5.13 (s, 2H), 2.67 (t, 2H), 1.72-1.60 (m, 2H), 0.98 (t, 3H).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][Si:9]([CH:16]([CH3:18])[CH3:17])([CH:13]([CH3:15])[CH3:14])[CH:10]([CH3:12])[CH3:11])=[CH:4][N:3]=1.C([Li])CCC.[Br:24][C:25]1[CH:30]=[C:29]([O:31][CH2:32][O:33][CH3:34])[CH:28]=[CH:27][C:26]=1[CH2:35][C:36](=[O:38])[CH3:37].[Cl-].[NH4+]>CCOCC>[Br:24][C:25]1[CH:30]=[C:29]([O:31][CH2:32][O:33][CH3:34])[CH:28]=[CH:27][C:26]=1[CH2:35][C:36]([C:2]1[CH:7]=[CH:6][C:5]([O:8][Si:9]([CH:16]([CH3:18])[CH3:17])([CH:13]([CH3:15])[CH3:14])[CH:10]([CH3:12])[CH3:11])=[CH:4][N:3]=1)([OH:38])[CH3:37]
Reactant: COCOc1ccc(CC(C)=O)c(Br)c1
Reactant: CC(C)[Si](Oc1ccc(Br)nc1)(C(C)C)C(C)C
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: CCOCC
Product: COCOc1ccc(CC(C)(O)c2ccc(O[Si](C(C)C)(C(C)C)C(C)C)cn2)c(Br)c1
Reaction time: 0.17 h
Yield: 45.4 %

Procedure:
To a solution of 2-bromo-5-(triisopropylsilyloxy)pyridine (26.6 g) in ether (80 mL) at −78° C. was added n-butyllithium (2.5 M in hexane, 32.2 mL) dropwise. After being stirred at the same temperature for 10 min, a solution of 1-(2-bromo-4-(methoxymethoxy)phenyl)propan-2-one (11 g) in diethylether (40 mL) was added dropwise. The mixture was stirred at −78° C. for 5 hr, and poured into iced saturated ammonium chloride and extracted with ethyl acetate. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether/ethyl acetate) to afford the title compound (9.6 g).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8]([NH2:10])[CH:7]=[CH:6][C:5]=1[O:11][CH3:12].C(N(CC)CC)C.[C:21](Cl)(=[O:28])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:13])[C:4]1[CH:9]=[C:8]([NH:10][C:21](=[O:28])[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:7]=[CH:6][C:5]=1[O:11][CH3:12]
Reactant: O=C(Cl)c1ccccc1
Reactant: COC(=O)c1cc(N)ccc1OC
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COC(=O)c1cc(NC(=O)c2ccccc2)ccc1OC
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
A solution of 9.92 grams (55 mmol) of methyl-2-methoxy-5-aminobenzoate was taken up in 250 ml methylene chloride, treated with 8.4 mL (61 mmol) triethylamine and cooled to 0° C. The reaction mixture was then treated with 8.1 grams (57 mmol) benzoyl chloride in a dropwise fashion. The reaction mixture was stirred for 30 minutes while warming to room temperature. The reaction mixture was diluted with 500 mL of methylene chloride, washed with 200 mL saturated bicarbonate solution and then rewashed with water and brine. The organic phase was dried and evaporated to a flaky white solid (15.7 grams). This material was used without further purification.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:24])[C@H:4]([CH:21]([CH3:23])[CH3:22])[NH:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]#[N:20])=[CH:9][CH:8]=1.[CH3:25][CH2:26][CH2:27][CH2:28][C:29](Cl)=[O:30]>C(N(CC)CC)C>[CH3:1][O:2][C:3](=[O:24])[C@H:4]([CH:21]([CH3:22])[CH3:23])[N:5]([C:29](=[O:30])[CH2:28][CH2:27][CH2:26][CH3:25])[CH2:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:19]#[N:20])=[CH:9][CH:8]=1
Reactant: CCCCC(=O)Cl
Reactant: COC(=O)[C@@H](NCc1ccc(-c2ccccc2C#N)cc1)C(C)C
Solvent: CCN(CC)CC
Product: CCCCC(=O)N(Cc1ccc(-c2ccccc2C#N)cc1)[C@H](C(=O)OC)C(C)C

Procedure:
Reaction of 1.15 g of N-[(2'-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester, 0.625 ml of triethylamine and 0.56 ml of n-valeryl chloride analogously to Example 1c) yields N-valeryl-N-[(2'-cyanobiphenyl-4-yl)methyl]-(L)-valine methyl ester after flash chromatography (N3). (TLC: N2) Rf : 0.63.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:17])[C@H:5]([CH2:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[NH:10][CH:9]=1)[NH2:6])[CH3:2].[CH3:18][N:19]([CH3:28])[C:20]1[CH:27]=[CH:26][C:23]([CH:24]=O)=[CH:22][CH:21]=1>>[CH3:18][N:19]([CH3:28])[C:20]1[CH:27]=[CH:26][C:23]([CH:24]2[C:9]3[NH:10][C:11]4[C:16]([C:8]=3[CH2:7][CH:5]([C:4]([O:3][CH2:1][CH3:2])=[O:17])[NH:6]2)=[CH:15][CH:14]=[CH:13][CH:12]=4)=[CH:22][CH:21]=1
Reactant: CCOC(=O)[C@@H](N)Cc1c[nH]c2ccccc12
Reactant: CN(C)c1ccc(C=O)cc1
Product: CCOC(=O)C1Cc2c([nH]c3ccccc23)C(c2ccc(N(C)C)cc2)N1

Procedure:
The same method as employed in the preparation of Intermediates 1 and 2 but starting from racemic tryptophan ethyl ester and 4-dimethylaminobenzaldehyde gave the title compound as white crystals m.p.:170° C.
Reaction SMILES: O=C(Cl)OC(Cl)(Cl)Cl.[Cl:9][CH2:10][C:11]([NH:13][C:14]1[S:15][CH:16]=[C:17]([C:19](=[N:23][O:24][CH3:25])[C:20]([OH:22])=O)[N:18]=1)=[O:12].[NH2:26][C@H:27]1[C@H:30]([N:31]=[N+:32]=[N-:33])[NH:29][C:28]1=[O:34].C1OC1C>C(Cl)Cl.C(N(CC)CC)C.CN(C=O)C>[N:31]([C@@H:30]1[NH:29][C:28](=[O:34])[C@H:27]1[NH:26][C:20](=[O:22])[C:19]([C:17]1[N:18]=[C:14]([NH:13][C:11](=[O:12])[CH2:10][Cl:9])[S:15][CH:16]=1)=[N:23][O:24][CH3:25])=[N+:32]=[N-:33]
Reactant: CON=C(C(=O)O)c1csc(NC(=O)CCl)n1
Reactant: [N-]=[N+]=N[C@@H]1NC(=O)[C@H]1N
Agent: CC1CO1
Agent: O=C(Cl)OC(Cl)(Cl)Cl
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CON=C(C(=O)N[C@@H]1C(=O)N[C@H]1N=[N+]=[N-])c1csc(NC(=O)CCl)n1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
To a solution of 0.127 g of DMF in 5 ml of methylene chloride is added 0.104 ml of diphosgene at -10° C. The mixture is stirred for 30 minutes at room temperature, followed by addition of a solution of 15 ml of methylene chloride containing 0.483 g of 2-(2-chloroacetamidothiazol-4-yl)-2-methoxyiminoacetic acid and 0.176 g of triethylamine at -70° C. The mixture is stirred for two hours at -25° C., then cooled to -70° C., followed by addition of 0.352 g of triethylamine, 0.40 g of tosyl salt of (3S,4S)-3-amino-4-azido-2-oxoazetidine and 2 ml of propylene oxide. The temperature of the mixture is raised up to room temperature in the course of one hour while stirring, followed by ice-cooling for one hour. The crystals separated out are collected by filtration to yield 0.383 g of (3S,4S)-4-azido-3-[2-(2-chloroacetamidothiazol-4-yl)-2-methoxyiminoacetamido]-2-oxoazetidine.
Reaction SMILES: O[C:2]([C:10]1[CH:15]=[CH:14][C:13]([CH:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)=[CH:12][CH:11]=1)([CH3:9])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].C1(C)C=CC(S(O)(=O)=O)=CC=1>C1C=CC=CC=1.C([O-])(O)=O.[Na+]>[CH:16]1([C:13]2[CH:12]=[CH:11][C:10]([C:2]([CH3:9])=[CH:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])=[CH:15][CH:14]=2)[CH2:17][CH2:18][CH2:19][CH2:20]1
Reactant: CCOC(=O)CC(C)(O)c1ccc(C2CCCC2)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: c1ccccc1
Product: CCOC(=O)C=C(C)c1ccc(C2CCCC2)cc1
Yield: 79.3 %

Procedure:
To a solution of ethyl 3-hydroxy-(4′-cyclopentylphenyl)-butanoate (2a, 12 g) in benzene (150 ml) was added p-toluenesulfonic acid and refluxed for 1 h. The mixture was diluted with sat. NaHCO3 (100 ml) and organic layer was separated. The organic phase was washed with water, dried (Na2SO4) and concentrated. The crude product was purified by column chromatography on silica gel to give 8.9 g (79.4% yield) of ethyl 3-(4-cyclopentylphenyl)-but-2-enoate (3a, formula 3, R=cyclopentyl) as oil.
Reaction SMILES: [Br:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[O:13][C:14]4[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:15]=4[C:16]=3[C:17](=[O:22])[CH2:18][CH2:19][CH2:20][CH3:21])=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[O:28][CH2:29][C:30]#[N:31].[N-:32]=[N+:33]=[N-:34].[Na+].[Cl-].[NH4+]>CN(C=O)C>[Br:1][C:2]1[C:3]([O:28][CH2:29][C:30]2[NH:34][N:33]=[N:32][N:31]=2)=[CH:4][CH:5]=[C:6]2[C:11]=1[CH:10]=[CH:9][C:8]([C:12]1[O:13][C:14]3[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][C:15]=3[C:16]=1[C:17](=[O:22])[CH2:18][CH2:19][CH2:20][CH3:21])=[CH:7]2
Reactant: CCCCC(=O)c1c(-c2ccc3c(Br)c(OCC#N)ccc3c2)oc2ccc(Cl)cc12
Reactant: [N-]=[N+]=[N-]
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCC(=O)c1c(-c2ccc3c(Br)c(OCc4nnn[nH]4)ccc3c2)oc2ccc(Cl)cc12

Procedure:
Following the procedure described in Step 6, of Example 1, the title compound was prepared from [1-bromo-6-(5-chloro-3-pentanoyl-benzofuran-2-yl)-naphthalen-2-yloxy]-acetonitrile (0.4 g, 0.8 mmol), sodium azide (0.325 g, 5 mmol) and ammonium chloride (0.268 g, 5 mmol) in DMF (20 mL). The compound was purified by flash chromatography on acid treated silica gel using 50% ethyl acetate in hexane as the mobile phase. The title compound was obtained as an off-white solid (0.32 g), mp 133-135° C. Mass spectrum (−ESI, [M−H]−) m/z 537. 1HNMR (400 MHz, DMSO-d6): δ8.51 (d, 1H, J=1.5 Hz), 8.26-8.20 (m, 2H), 8.03-7.99 (m, 2H), 7.80-7.76 (m, 2H), 7.48 (dd, 1H, J=8.8, 2.2 Hz), 5.78 (s, 2H), 2.73 (t, 2H, J=7.3 Hz), 1.56-1.49 (m, 2H), 1.17-1.08 (m, 2H), and 0.70 ppm (t, 3H, J=7.3 Hz). Elemental Analysis for C25H20BrClN4O3: Calculated: C, 55.63; H, 3.73; N, 10.38. Found: C, 55.54; H, 3.59; N, 10.24.