Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[CH:7]=[C:6]([CH3:8])[N:5]([CH2:9][CH3:10])[C:4]=1[C:11]1[CH:30]=[CH:29][C:14]([CH2:15][N:16]2[C:20]3=[N:21][CH:22]=[CH:23][C:24]([CH3:25])=[C:19]3[N:18]=[C:17]2[S:26][CH2:27][CH3:28])=[CH:13][CH:12]=1)#[N:2].C[Sn]([N:35]=[N+:36]=[N-:37])(C)C>C1(C)C(C)=CC=CC=1>[CH2:9]([N:5]1[C:6]([CH3:8])=[CH:7][C:3]([C:1]2[NH:37][N:36]=[N:35][N:2]=2)=[C:4]1[C:11]1[CH:30]=[CH:29][C:14]([CH2:15][N:16]2[C:20]3=[N:21][CH:22]=[CH:23][C:24]([CH3:25])=[C:19]3[N:18]=[C:17]2[S:26][CH2:27][CH3:28])=[CH:13][CH:12]=1)[CH3:10]
Reactant: C[Sn](C)(C)N=[N+]=[N-]
Reactant: CCSc1nc2c(C)ccnc2n1Cc1ccc(-c2c(C#N)cc(C)n2CC)cc1
Solvent: Cc1ccccc1C
Product: CCSc1nc2c(C)ccnc2n1Cc1ccc(-c2c(-c3nnn[nH]3)cc(C)n2CC)cc1
Temperature: 125 °C
Reaction time: 24 h
Yield: 87.6 %

Procedure:
To a mixture of 3-[4-(3-cyano-1-ethyl-5-methyl-2-pyrrolyl)benzyl]-2-ethylthio-7-methyl-3H-imidazo[4,5-b]pyridine (1.52 g) in xylene (15 ml) was added trimethyltin azid (2.26 g) under nitrogen atmosphere, and stirred at 125° C. for 24 hours. The mixture was concentrated in vacuo. To the residue was added methanol and conc. hydrochloric acid (1 ml). The mixture was stirred at ambient temperature for one hour and concentrated in vacuo. The residue was diluted with methanol. The mixture was adjusted to pH4 with 1N sodium hydroxide. The organic layer was separated, and evaporated in vacuo. The residue was purified by flash column chromatography on silica gel (elution by dichloromethane/methanol=15/1) and subsequent crystallization from methyl cyanide to give amorphous powder (1.47 g) of 3-[4-[1-ethyl-5-methyl-3-(1H-tetrazol-5-yl)-2-pyrrolyl]benzyl]-2-ethylthio-7-methyl-3H-imidazo[4,5-b]pyridine.
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[CH:4][CH:3]=1.Cl[C:11]1[C:12]2[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[S:23][C:13]=2[N:14]=[C:15]([C:17]2[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=2)[N:16]=1>>[N:19]1[CH:20]=[CH:21][CH:22]=[C:17]([C:15]2[N:16]=[C:11]([NH:7][CH2:6][C:5]3[CH:8]=[CH:9][C:2]([F:1])=[CH:3][CH:4]=3)[C:12]3[CH:25]=[C:24]([C:26]([F:29])([F:27])[F:28])[S:23][C:13]=3[N:14]=2)[CH:18]=1
Reactant: FC(F)(F)c1cc2c(Cl)nc(-c3cccnc3)nc2s1
Reactant: NCc1ccc(F)cc1
Product: Fc1ccc(CNc2nc(-c3cccnc3)nc3sc(C(F)(F)F)cc23)cc1

Procedure:
With the procedure of Example 1, the reaction of 4-fluorobenzylamine with 4-chloro-2-(pyridin-3-yl)-6-trifluoromethyl-thieno-[2,3-d]-pyrimidine yields 2-(pyridin-3-yl)-4-(4-fluorobenzylamino)-6-trifluoromethyl-thieno-[2,3-d]-pyrimidine.
Reaction SMILES: C(N(CC)CC)C.[C:8](Cl)(=[O:12])[CH2:9][CH2:10][CH3:11].[NH2:14][C:15]1[CH:16]=[C:17]2[C:22](=[CH:23][CH:24]=1)[N:21]=[CH:20][C:19]([C:25]#[N:26])=[C:18]2[NH:27][C:28]1[CH:33]=[CH:32][CH:31]=[C:30]([Br:34])[CH:29]=1>O1CCCC1>[Br:34][C:30]1[CH:29]=[C:28]([NH:27][C:18]2[C:17]3[C:22](=[CH:23][CH:24]=[C:15]([NH:14][C:8](=[O:12])[C:9]#[C:10][CH3:11])[CH:16]=3)[N:21]=[CH:20][C:19]=2[C:25]#[N:26])[CH:33]=[CH:32][CH:31]=1
Reactant: CCCC(=O)Cl
Reactant: N#Cc1cnc2ccc(N)cc2c1Nc1cccc(Br)c1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC#CC(=O)Nc1ccc2ncc(C#N)c(Nc3cccc(Br)c3)c2c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 64.4 %

Procedure:
Triethylamine (0.359 g, 3.55 mmol) and butyryl chloride (0.380 g, 3.55 mmol) were added to an ice cold solution of 1.00 g (2.96 mmol) of 6-amino-4-[(3-bromophenyl)amino]-3-quinolinecarbonitrile in 12 mL of tetrahydrofuran under N2. After stirring overnight at 25° C., volatile material was removed, and the residue was slurried with water and collected. The residue was washed with boiling methanol and dried in vacuo to give 0.773 g of brown powder; mp 276-277° C.(dec).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][O:10][CH3:11])[CH:5]=[CH:4][C:3]=1[N+:12]([O-])=O.[H][H]>[C].[Pd].C(O)C>[F:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][O:10][CH3:11])[CH:5]=[CH:4][C:3]=1[NH2:12]
Reactant: [H][H]
Reactant: COCOc1ccc([N+](=O)[O-])c(F)c1
Agent: [Pd]
Solvent: CCO
Product: COCOc1ccc(N)c(F)c1
Yield: 73.1 %

Procedure:
10% Palladium-carbon (390 mg) as a catalyst was added to an ethanol (100 mL) solution of 2-fluoro-4-(methoxymethoxy)-1-nitrobenzene (3.86 g), and stirred overnight in a hydrogen atmosphere at room temperature. The catalyst was removed through filtration, the solvent was evaporated off under reduced pressure, and the resulting residue was purified through silica gel column chromatography (methanol/chloroform=from 0% to 20%, gradient) to give the entitled compound (2.40 g, 73%) as a brown oily substance.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]([C:12](=O)[CH3:13])[C:9]([N:15]2[CH2:20][CH2:19][N:18]([C:21]([C:23]3[CH:28]=[N:27][CH:26]=[CH:25][N:24]=3)=[O:22])[CH2:17][CH2:16]2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2.C([O-])(=O)C.[NH4+].C([BH3-])#[N:35].[Na+].O1CCCC1>CO.C(#N)C>[Cl:1][C:2]1[CH:11]=[C:10]([CH:12]([NH2:35])[CH3:13])[C:9]([N:15]2[CH2:20][CH2:19][N:18]([C:21]([C:23]3[CH:28]=[N:27][CH:26]=[CH:25][N:24]=3)=[O:22])[CH2:17][CH2:16]2)=[C:8]2[C:3]=1[CH:4]=[CH:5][CH:6]=[N:7]2
Reactant: [BH3-]C#N
Reactant: CC(=O)c1cc(Cl)c2cccnc2c1N1CCN(C(=O)c2cnccn2)CC1
Agent: CC(=O)[O-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Solvent: CC#N
Product: CC(N)c1cc(Cl)c2cccnc2c1N1CCN(C(=O)c2cnccn2)CC1
Temperature: 65 °C

Procedure:
A mixture of 1-{5-chloro-8-[4-(pyrazin-2-ylcarbonyl)piperazin-1-yl]quinolin-7-yl}ethanone (0.028 g, 0.071 mmol) and ammonium acetate (0.0545 g, 0.707 mmol) in methanol (0.3 mL) and acetonitrile (0.3 mL) was heated at 65° C. in a sealed tube for 1 hour. After cooling to room temperature, to the resulting mixture was added 1.0 M sodium cyanoborohydride in tetrahydrofuran (0.17 mL, 0.17 mmol). The reaction was heated at 65° C. overnight. The mixture was cooled to room temperature, quenched with sat. NaHCO3 solution, extracted with dichloromethane, dried over MgSO4 and concentrated to give the desired product. LCMS calculated for C20H22ClN6O (M+H)+: m/z=397.2; Found: 397.1.
Reaction SMILES: CN(CN(C)C)C.C(Cl)(=O)C.[N:12]1[CH:17]=[CH:16][CH:15]=[N:14][C:13]=1[O:18][C:19]1[CH:20]=[C:21]2[C:25](=[CH:26][CH:27]=1)[NH:24][CH:23]=[CH:22]2.C[N:29]([CH2:31][C:32]1C2C(=CC=C(OC3N=CC=CN=3)C=2)NC=1)C.[C-]#N.[K+].CI>C(Cl)Cl.CN(C=O)C>[C:31]([CH2:32][C:22]1[C:21]2[C:25](=[CH:26][CH:27]=[C:19]([O:18][C:13]3[N:14]=[CH:15][CH:16]=[CH:17][N:12]=3)[CH:20]=2)[NH:24][CH:23]=1)#[N:29]
Reactant: c1cnc(Oc2ccc3[nH]ccc3c2)nc1
Reactant: CN(C)Cc1c[nH]c2ccc(Oc3ncccn3)cc12
Agent: CN(C)CN(C)C
Agent: [C-]#N
Agent: [K+]
Solvent: CC(=O)Cl
Solvent: ClCCl
Solvent: CI
Product: N#CCc1c[nH]c2ccc(Oc3ncccn3)cc12

Procedure:
Treatment of a cooled solution of N,N,N',N'-tetramethyldiaminomethane (0.854 g, 1.14 mL, 8.36 mmol) in CH2Cl2 (10 mL) with acetyl chloride (0.657 g, 0.59 mL, 8.36 mmol) followed by a solution of 5-(pyrimidin-2-yloxy)indole (1.268 g, 6.00 mmol) in CH2Cl2 (110 mL), gave after work-up: 3-(N,N-dimethylaminomethyl)-5-(pyrimidin-2-yloxy)indole as a yellow solid. This was treated with finely ground potassium cyanide (1.37 g, 21 mmol) and methyl iodide (2.94 g, 1.28 mL, 21 mmol) in DMF (70 mL) for 16 hr, and after appropriate work-up, 3-cyanomethyl-5-(pyrimidin-2-yloxy)indole was obtained as a light yellow solid, 0.98 g (65%).
Reaction SMILES: [C:1]([C:4]([C@@H:17]1[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][C:24]2[CH:25]=[CH:26][C:27]3[O:31][CH:30]=[CH:29][C:28]=3[CH:32]=2)[CH2:18]1)([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)(=[O:3])[NH2:2]>C(O)(=O)C.[Pd]>[C:1]([C:4]([C@@H:17]1[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][C:24]2[CH:25]=[CH:26][C:27]3[O:31][CH2:30][CH2:29][C:28]=3[CH:32]=2)[CH2:18]1)([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)(=[O:3])[NH2:2]
Reactant: NC(=O)C(c1ccccc1)(c1ccccc1)[C@@H]1CCN(CCc2ccc3occc3c2)C1
Agent: [Pd]
Solvent: CC(=O)O
Product: NC(=O)C(c1ccccc1)(c1ccccc1)[C@@H]1CCN(CCc2ccc3c(c2)CCO3)C1
Reaction time: 6 h

Procedure:
10% Palladium-on-carbon (10 mg) was added to a solution of 3-(S)-(-)-(1-carbamoyl-1,1-diphenylmethyl)-1-[2-(benzofuran-5-yl)-ethyl]pyrrolidine (0.1 g-see Example 7) in acetic acid (2 ml) and the mixture was hydrogenated at 40° C. and atmospheric pressure for 6 hours. The catalyst was filtered off and washed with water (20 ml). The combined filtrate and washings were transferred to a separating funnel, dichloromethane (20 ml) was added, and the mixture was basified by the addition of 10% aqueous sodium hydroxide. The layers were separated and the aqueous layer was further extracted with dichloromethane (3×30 ml). The combined dichloromethane extracts were dried (MgSO4) and concentrated in vacuo to give a colourless solid which was purified by column chromatography on silica eluting with dichloromethane containing methanol (4%). The product-containing fractions were combined and concentrated in vacuo to give the title compound as a colourless glass, yield 0.048 g, which was characterised spectroscopically to be identical to the product of Example 1 (B).
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH:8]=O)=[CH:6][CH:5]=1)([O-:3])=[O:2]>[Cl-].C([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)C1C=CC=CC=1>[N+:1]([C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[CH:8][C:7]2[CH:10]=[CH:11][CH:4]=[CH:5][CH:6]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: O=Cc1ccc([N+](=O)[O-])cc1
Agent: [Cl-]
Agent: c1ccc(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Product: O=[N+]([O-])c1ccc(C=Cc2ccccc2)cc1

Procedure:
Using the procedure of Example 5 benzyltriphenylphosphonium chloride (0.1 mole) and 4-nitrobenzaldehyde (0.1 mole) are reacted to give 4-nitrostilbene. The 4-nitrostilbene is reduced with palladium on charcoal as the catalyst to 4-(2'-phenethyl)aniline, m.p. 46°-50° C.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[H-].[Na+].[CH3:12][N:13]([CH3:17])[CH2:14][CH2:15]Cl>C1(C)C=CC=CC=1>[CH3:12][N:13]([CH3:17])[CH2:14][CH2:15][O:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1
Reactant: CN(C)CCCl
Reactant: O=Cc1ccc(O)cc1
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CN(C)CCOc1ccc(C=O)cc1
Yield: 46.6 %

Procedure:
The reaction between 61.0 g (0.50 mole) of 4-hydroxybenzaldehyde, 24.0 g of 50% NaH, and 341 ml of 2.2 N (0.75 mole) 2-dimethylaminoethyl chloride in toluene in a procedure described for Example 2, part A, gives 45.0 g (46%) of colorless product, bp 140°-142°/2 mm. Lit. bp 185°-187°/15 mm.
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:4]=[C:5]([NH:11][C@H:12]([CH2:18][NH:19][CH2:20][CH3:21])[CH2:13][C:14](OC)=[O:15])[CH:6]=[CH:7][C:8]=1[C:9]#[N:10].O.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C>[Cl:2][C:3]1[CH:4]=[C:5]([NH:11][C@H:12]2[CH2:13][C:14](=[O:15])[N:19]([CH2:20][CH3:21])[CH2:18]2)[CH:6]=[CH:7][C:8]=1[C:9]#[N:10]
Reactant: CCNC[C@H](CC(=O)OC)Nc1ccc(C#N)c(Cl)c1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: CCOC(C)=O
Product: CCN1C[C@@H](Nc2ccc(C#N)c(Cl)c2)CC1=O
Yield: 84.3 %

Procedure:
Methyl (3S)-3-[(3-chloro-4-cyanophenyl)amino]-4-(ethylamino)butanoate, hydrochloride (4.0 g., 13.5 mmole) was redissolved in ethyl acetate (50 mL). Water was added (50 mL) and 10% sodium bicarbonate was added with stirring to bring the pH to 8.5. The organic layer was concentrated and redissolved in benzene (120 mL). The solution was heated with stirring at 75° C. for 6 h. The solvent was evaporated. The crude product was triturated with Et2O, chilled and the solid filtered to give the titled compound (3.0 g, 84%). LC-MS (ES) m/e 263 (M+H)+.
Reaction SMILES: [C:1]([O:4][C@H:5]1[CH2:10][CH2:9][C@H:8]2[C@H:11]3[C@H:20]([CH2:21][CH2:22][C@:6]12[CH3:7])[C@@H:19]1[C:14](=[CH:15][C:16](=[O:23])[CH2:17][CH2:18]1)[CH:13]=[CH:12]3)(=[O:3])[CH3:2].[Br-].[Li+].[S-][C:27]1C=CC=C[CH:28]=1.[Li+].[Cl-].[NH4+]>O1CCCC1>[C:1]([O:4][C@H:5]1[CH2:10][CH2:9][C@H:8]2[C@H:11]3[C@H:20]([CH2:21][CH2:22][C@:6]12[CH3:7])[C@@H:19]1[C:14](=[CH:15][C:16](=[O:23])[CH2:17][CH2:18]1)[CH2:13][C@H:12]3[CH:27]=[CH2:28])(=[O:3])[CH3:2]
Reactant: CC(=O)O[C@H]1CC[C@H]2[C@@H]3C=CC4=CC(=O)CC[C@@H]4[C@H]3CC[C@]12C
Reactant: [S-]c1ccccc1
Agent: [Br-]
Agent: [Cl-]
Agent: [Li+]
Solvent: C1CCOC1
Product: C=C[C@@H]1CC2=CC(=O)CC[C@@H]2[C@H]2CC[C@]3(C)[C@@H](OC(C)=O)CC[C@H]3[C@@H]21
Temperature: -15 °C
Reaction time: 0.5 h

Procedure:
—Vinylmagnesium chloride in tetrahydrofuran (2 M, 9.55 ml) was added dropwise to a mixture of (17β)-17-(acetyloxy)estra-4,6-dien-3-one (Example 3, step i; 3.0 g), copper(I) bromide-dimethyl sulfide complex (0.191 g), lithium bromide (0.083 g), and lithium thiophenoxide (0.96 ml of a 1 M solution in tetrahydrofuran), in dry tetrahydrofuran (10 ml), cooled to −15° C. After 25 min. stirring a saturated aqueous solution of ammonium chloride was added and the product extracted into ethyl acetate. The combined organic phases were concentrated under reduced pressure whereafter the residue was dissolved in acetone (100 ml) and treated with hydrochloric acid (4 M, 10 ml). After 30 min. stirring at room temperature, a saturated aqueous solution of sodium hydrogencarbonate was added. The product was extracted into ethyl acetate; the combined organic phases were washed with brine, dried over sodium sulfate and concentrated under reduced pressure, to give (7α,17β)-17-(acetyloxy)-7-ethenylestr-4-en-3-one (3.76 g). The product was used in the following step without further purification.
Reaction SMILES: [Br:1][C:2]1[NH:3][C:4]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)=[C:5]([S:8][CH:9]([F:11])[F:10])[C:6]=1[Br:7].ClC1C=C(C=CC=1)C(OO)=[O:24].S(S([O-])=O)([O-])(=O)=O.[Na+].[Na+]>C(Cl)(Cl)Cl.C(Cl)Cl.O>[Br:1][C:2]1[NH:3][C:4]([C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)=[C:5]([S:8]([CH:9]([F:11])[F:10])=[O:24])[C:6]=1[Br:7]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: FC(F)Sc1c(-c2ccc(Cl)cc2)[nH]c(Br)c1Br
Agent: O=S([O-])S(=O)(=O)[O-]
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Solvent: ClC(Cl)Cl
Product: O=S(c1c(-c2ccc(Cl)cc2)[nH]c(Br)c1Br)C(F)F
Temperature: 0 °C
Reaction time: 1 h
Yield: 522.9 %

Procedure:
A solution of 2,3-dibromo-5-(p-chlorophenyl)-4-[(difluoromethyl)thio]pyrrole (125 mg, 0.030 mmol) in chloroform is treated with 3-chloroperoxybenzoic acid (86 mg, 60%, 0.30 mmol) at 0° C. The reaction mixture is stirred for one hour at 0° C., warmed to room temperature, stirred overnight, poured into saturated sodium metabisulfite solution and diluted with a methylene chloride/water mixture. The organic phase is separated, washed with saturated sodium hydrogen carbonate solution, dried over anhydrous sodium sulfate and concentrated in vacuo to obtain a residue. Flash chromatography of the residue using silica gel and a 1:10 ethyl acetate/hexanes solution gives the title product as a yellow solid (68 mg, mp 180° C. (dec)) which is identified by 1HNMR and 13CNMR spectral analyses.
Reaction SMILES: C([N:8]([CH2:16][C@@H:17]1[O:21][C:20](=[O:22])[N:19]([C:23]2[CH:28]=[CH:27][C:26]([N:29]3[CH2:34][CH2:33][O:32][CH2:31][CH2:30]3)=[C:25]([F:35])[CH:24]=2)[CH2:18]1)CC1C=CC=CC=1)C1C=CC=CC=1.C(O)C.N#N>[Pd].O.C(N(CC)CC)C.C(O)=O>[NH2:8][CH2:16][C@@H:17]1[O:21][C:20](=[O:22])[N:19]([C:23]2[CH:28]=[CH:27][C:26]([N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)=[C:25]([F:35])[CH:24]=2)[CH2:18]1
Reactant: O=C1O[C@@H](CN(Cc2ccccc2)Cc2ccccc2)CN1c1ccc(N2CCOCC2)c(F)c1
Agent: [Pd]
Agent: N#N
Solvent: O
Solvent: CCN(CC)CC
Solvent: O=CO
Product: NC[C@H]1CN(c2ccc(N3CCOCC3)c(F)c2)C(=O)O1
Temperature: 80 °C
Reaction time: 12 h
Yield: 83 %

Procedure:
Compound 4 (0.95 g, 2 mmol) and 10% Pd—C (1 mmol) were added to the mixture of 20 mL of ethanol and 2 mL of water and the air was replaced with N2. The triethylamine-Formic acid azeotrope (704 mg, 4 mmol) was added and the mixture was stirred at 80° C. for 12 hours. Water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated to provide 0.49 g of white solid in 84% yield. HPLC: 99.3%.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([NH:12][C:13]2[CH:14]=[C:15]3[C:24](=[CH:25][C:26]=2Br)[O:23][CH2:22][C:21]2[N:16]3[CH:17]([CH3:29])[C:18](=[O:28])[NH:19][N:20]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:30][C:31]1(C)[C:35](C)(C)OB(C(C)=C)O1.C([O-])([O-])=O.[K+].[K+]>O.O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH:10]([NH:12][C:13]2[CH:14]=[C:15]3[C:24](=[CH:25][C:26]=2[C:31]([CH3:35])=[CH2:30])[O:23][CH2:22][C:21]2[N:16]3[CH:17]([CH3:29])[C:18](=[O:28])[NH:19][N:20]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: C=C(C)B1OC(C)(C)C(C)(C)O1
Reactant: CC1C(=O)NN=C2COc3cc(Br)c(NC4CN(C(=O)OC(C)(C)C)C4)cc3N21
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: C1COCCO1
Solvent: O
Product: C=C(C)c1cc2c(cc1NC1CN(C(=O)OC(C)(C)C)C1)N1C(=NNC(=O)C1C)CO2
Temperature: 80 °C
Yield: 83.5 %

Procedure:
A mixture of 3-(7-bromo-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (Example 1, Step B, 1.5 g, 3.22 mmol), 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (1.62 g, 9.66 mmol), K2CO3 (1.33 g, 9.66 mmol) and [1,1′-Bis(diphenylphosphino)ferrocene]palladium(II) chloride (0.544 g, 0.64 mmol) in a mixture of 10% water in dioxane (35 mL) was heated at 80° C. for 2 h. The reaction mixture was cooled to ambient temperature and concentrated in vacuo. The residue was purified by column chromatography on silica gel (eluting with 20% EtOAc in petroleum ether) to give 3-(7-isopropenyl-4-methyl-3-oxo-2,3,4,10-tetrahydro-9-oxa-1,2,4a-triaza-phenanthren-6-ylamino)-azetidine-1-carboxylic acid tert-butyl ester (1.15 g, 84%) as a pale solid. LC/MS (Table 1, Method 2) Rt=1.202 min.; MS m/z: 428 [M+H]+.
Reaction SMILES: C1N2CN3CN(C2)CN1C3.[C:11]1([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.FC(F)(F)[C:28](O)=[O:29]>>[CH2:17]([C:11]1[CH:16]=[CH:15][C:14]([CH:28]=[O:29])=[CH:13][CH:12]=1)[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25]
Reactant: CCCCCCCCCc1ccccc1
Reactant: O=C(O)C(F)(F)F
Agent: C1N2CN3CN1CN(C2)C3
Product: CCCCCCCCCc1ccc(C=O)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 57 %

Procedure:
Oxidative Formylation--Allow a two-phase mixture of trifluoroacetic acid (150 mL) and hexamethylene tetramine (14.0 g, 0.100 mol), and 1-phenyl-n-nonane (20.4 g, 0.100 mol) to stand 18 hrs. at 25° C., and then reflux for 22 hrs. Concentrate the homogenous reaction mixture and pour the residue over ice and H2O (total of 600 mL). Add diethyl ether (200 mL) and stir the mixture vigorously for 30 min. Raise the pH of the mixture to pH 8 with solid Na2CO3, and add diethyl ether (200 mL). Shake the layers and separate. Extract the aqueous phase with diethyl ether. Wash the combined organic solutions with H2O and brine, dry and filter. Evaporate the solvent, and distill the residue to give 4-(n-nonyl)benzaldehyde (57% yield, 13.2 g) b.p. 136°-139° C. at 0.55 mm.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[NH:12][C:11](=[O:13])[O:10][C:8](=[O:9])[C:7]=12.[CH2:14](Br)[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]>>[CH2:14]([C:7]12[C:2]([CH3:1])=[CH:3][CH:4]=[CH:5][CH:6]1[NH:12][C:11](=[O:13])[O:10][C:8]2=[O:9])[CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]
Reactant: Cc1cccc2[nH]c(=O)oc(=O)c12
Reactant: CCCCCCBr
Product: CCCCCCC12C(=O)OC(=O)NC1C=CC=C2C

Procedure:
Following the procedure of Step (2) of Preparation A, 6-methyl-isatoic anhydride was reacted with hexyl bromide to yield 1-hexyl-6-methyl-isatoic anhydride.
Reaction SMILES: [CH3:1][C:2]([CH3:19])([C@H:4]([N:7]([C:9](=[O:18])[C:10]1[CH:15]=[C:14]([CH3:16])[CH:13]=[C:12]([CH3:17])[CH:11]=1)[NH2:8])[CH2:5][CH3:6])[CH3:3].C(=O)([O-])[O-].[K+].[K+].[F:26][C:27]1[CH:35]=[C:34]([B:36]2[O:40]C(C)(C)C(C)(C)[O:37]2)[CH:33]=[CH:32][C:28]=1[C:29](Cl)=[O:30]>C(Cl)Cl.O>[CH3:17][C:12]1[CH:11]=[C:10]([CH:15]=[C:14]([CH3:16])[CH:13]=1)[C:9]([N:7]([C@H:4]([CH2:5][CH3:6])[C:2]([CH3:1])([CH3:3])[CH3:19])[NH:8][C:29]([C:28]1[CH:32]=[CH:33][C:34]([B:36]([OH:40])[OH:37])=[CH:35][C:27]=1[F:26])=[O:30])=[O:18]
Reactant: CC1(C)OB(c2ccc(C(=O)Cl)c(F)c2)OC1(C)C
Reactant: CC[C@@H](N(N)C(=O)c1cc(C)cc(C)c1)C(C)(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: O
Product: CC[C@@H](N(NC(=O)c1ccc(B(O)O)cc1F)C(=O)c1cc(C)cc(C)c1)C(C)(C)C
Reaction time: 0.17 h
Yield: 70.6 %

Procedure:
In a 25 mL round bottom flask equipped with a magnetic stir bar were added (R)—N-(2,2-dimethylpentan-3-yl)-3,5-dimethylbenzohydrazide (1.317 g, 5.02 mmol) in 7 mL CH2Cl2 and a solution of potassium carbonate (1.388 g, 10.04 mmol) in distilled water (4 mL) were cooled in an ice bath at 0-4° C. and stirred for 10 min. The 2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl chloride (1.714 g, 6.02 mmol) was added as a solution in 3.5 mL dichloromethane. The reaction was stirred at 0-4° C. for 30 min., the ice bath was removed and the mixture was stirred for 16 h at room temperature. The reaction was analyzed by LCMS and shows the reaction was complete. The organic layer was separated using a Biotage phase separator column and was transferred to a 40 g Redisep SiO2 column on the ISCO HPLC system. The compound was eluted with 0-100% EtOAc—hexanes and then with 10% MeOH—CH2Cl2. The desired fractions were combined and concentrated on a rotary evaporator to give the desired compound as an off-white foam (1.518 g, 59% yield). MS (ESI) calcd for C29H40BFN2O4 ([M+H]+) 511. found 511.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9](=O)[C:10]([NH:12][CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]#[CH:24])=[C:17]([O:25][CH3:26])[CH:16]=2)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8].N1C=CC=CC=1.Cl.[CH3:35][O:36][NH2:37]>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9](=[N:37][O:36][CH3:35])[C:10]([NH:12][CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH2:22][C:23]#[CH:24])=[C:17]([O:25][CH3:26])[CH:16]=2)=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: C#CCOc1ccc(CCNC(=O)C(=O)c2ccc(Cl)c(Cl)c2)cc1OC
Reactant: CON
Agent: Cl
Solvent: c1ccncc1
Solvent: CCO
Product: C#CCOc1ccc(CCNC(=O)C(=NOC)c2ccc(Cl)c(Cl)c2)cc1OC

Procedure:
To a solution of 1.30 g (3.20 mmol) 2-(3,4-dichloro-phenyl)-N-[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-2-oxo-acetamide in 7.0 ml ethanol, 0.52 ml pyridine (0.64 mmol) and 0.33 g (3.98 mmol) O-methylhydroxylamine hydrochloride are added. The solution is heated at +80° C. for 4 hours. After evaporation of the solvent, the residue is submitted to flash-chromatography to yield the 2-(3,4-dichloro-phenyl)-2-methoxyimino-N-[2-(3-methoxy-4-prop-2-ynyloxy-phenyl)-ethyl]-acetamide as a white solid (m.p. 107-108° C.)
Reaction SMILES: [N:1]([C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][C:12]=1[CH3:13])[C:7]([OH:9])=[O:8])=[N+:2]=[N-:3].[CH3:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]#[CH:22])=[CH:17][N:16]=1.ClC1N=CC(C2N=NN(C3C=C(C=CC=3C)C(O)=O)C=2)=CC=1>>[CH3:13][C:12]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=[O:8])=[CH:5][C:4]=1[N:1]1[CH:22]=[C:21]([C:18]2[CH:17]=[N:16][C:15]([CH3:14])=[CH:20][CH:19]=2)[N:3]=[N:2]1
Reactant: Cc1ccc(C(=O)O)cc1N=[N+]=[N-]
Reactant: C#Cc1ccc(C)nc1
Agent: Cc1ccc(C(=O)O)cc1-n1cc(-c2ccc(Cl)nc2)nn1
Product: Cc1ccc(-c2cn(-c3cc(C(=O)O)ccc3C)nn2)cn1

Procedure:
4-Methyl-3-[4-(6-methyl-pyridin-3-yl)-[1,2,3]triazol-1-yl]-benzoic acid was prepared from 3-azido-4-methyl benzoic acid and 2-methyl-5-ethynyl pyridine in the same manner as 3-[4-(6-chloro-pyridin-3-yl)-1,2,3-triazol-1-yl]-4-methyl-benzoic acid (Example 1).