Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[CH:15][C:5]([O:6][CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[C:4]([CH:17](O)[CH3:18])[CH:3]=1.CCN(C(C)C)C(C)C.CS([Cl:33])(=O)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([O:6][CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[C:4]([CH:17]([Cl:33])[CH3:18])[CH:3]=1
Reactant: CS(=O)(=O)Cl
Reactant: CC(O)c1cc(Cl)ccc1OCC(=O)OC(C)(C)C
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(Cl)c1cc(Cl)ccc1OCC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To the product of step b) (0.34 g) in DCM (5 ml) was added Hunigs base (1 ml) followed by methanesulfonyl chloride (0.46 ml) and the reaction stirred at room temperature for 2 h followed by heating at 45° C. for 2 h. After cooling to 0° C. the bulk of the volatiles were removed in vacuo. Diethyl ether and water were added and the organic layer separated.
Reaction SMILES: C([NH:8][C:9]1[CH:14]=[C:13]([O:15][CH3:16])[C:12]([CH3:17])=[C:11]([F:18])[CH:10]=1)C1C=CC=CC=1.[H][H]>CO.[OH-].[Pd+2].[OH-]>[F:18][C:11]1[CH:10]=[C:9]([CH:14]=[C:13]([O:15][CH3:16])[C:12]=1[CH3:17])[NH2:8]
Reactant: COc1cc(NCc2ccccc2)cc(F)c1C
Reactant: [H][H]
Agent: [Pd+2]
Agent: [OH-]
Solvent: CO
Product: COc1cc(N)cc(F)c1C
Yield: 82.9 %

Procedure:
To a solution of N-benzyl-3-fluoro-5-methoxy-4-methylaniline (223 mg, 0.91 mmol) in methanol (25 mL) prepared in a Parr shaker flask was added palladium hydroxide (20% on carbon). This was subjected to 45 psi of hydrogen gas overnight until the LCMS showed complete conversion. The catalyst was filtered and the solution concentrated in vacuo to yield 117 mg (83%) of 3-fluoro-5-methoxy-4-methylaniline as an oil. 1H NMR (300 MHz, CDCl3) δ 6.03 (d, J=12.0 Hz, 1H), 6.01 (s, 1H), 3.77 (s, 3H), 2.09 (s, 3H); LCMS (m/z): 156 (MH+). Compound I-120 was made using this aniline.
Reaction SMILES: [CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][N:11]=[CH:12][C:7]=2[NH:6][CH2:5][C:4]2=[CH:13][CH:14]=[CH:15][N:3]12.[CH3:16][N:17]=[C:18]=[O:19]>C1C=CC=CC=1>[CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][N:11]=[CH:12][C:7]=2[N:6]([C:18](=[O:19])[NH:17][CH3:16])[CH2:5][C:4]2=[CH:13][CH:14]=[CH:15][N:3]12
Reactant: CN1c2ccncc2NCc2cccn21
Reactant: CN=C=O
Solvent: c1ccccc1
Product: CNC(=O)N1Cc2cccn2N(C)c2ccncc21
Temperature: 70 °C
Reaction time: 5 h

Procedure:
A solution of 3.7 g of 10,11-dihydro-5-methyl-5H-pyrido[3,4-f]pyrrolo[1,2-b][1,2,5]triazepine in 100 ml of benzene was treated with 1.6 ml of methyl isocyanate and then stirred at 70° C. for five hours. After cooling, the mixture was evaporated under reduced pressure and the residue was dissolved in water. The aqueous layer extracted with ethyl acetate. The combined organic layer was washed with water followed by a saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and concentrated. Purification of the residue was achieved by means of high pressure liquid chromatography (silica gel; elution with 2.5% methanol/dichloromethane) to afford 2.3 g of 10,11-dihydro-5-methyl-11-methylcarbamyl-5H-pyrido[3,4-f]pyrrolo[1,2-b][1,2,5]triazepine m.p. 197°-200° C. (dec.). The solid was dissolved in ethanol and acidified with an ethanol solution of maleic acid to precipitate the corresponding maleate salt. Recrystallization of the salt from ethanol yielded 1.8 g of 10,11-dihydro-5-methyl-11 -methylcarbamyl-5H-pyrido[3,4-f]pyrrolo[1,2-b][1,2,5]triazepine maleate, m.p. 160°-161° C.
Reaction SMILES: [CH2:1]1[CH2:7][O:6][CH2:5][CH2:4][NH:3][CH2:2]1.Cl.Cl[C:10]1[N:14]([CH3:15])[N:13]=[C:12]([CH3:16])[C:11]=1[CH:17]=[O:18].CN(P(N(C)C)(N(C)C)=O)C.C(=O)([O-])[O-].[K+].[K+]>O>[CH3:15][N:14]1[C:10]([N:3]2[CH2:2][CH2:1][CH2:7][O:6][CH2:5][CH2:4]2)=[C:11]([CH:17]=[O:18])[C:12]([CH3:16])=[N:13]1
Reactant: Cc1nn(C)c(Cl)c1C=O
Reactant: C1CNCCOC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: Cc1nn(C)c(N2CCCOCC2)c1C=O
Temperature: 25 °C
Yield: 61.2 %

Procedure:
Homomorpholine hydrochloride (28.2 g, 200 mol) was added to a mixture of 5-chloro-1,3-dimethyl-1H-pyrazole-4-carbaldehyde (21.68 g, 0.1368 mol, Example B(45), Step 2), HMPA (30 mL), water (50 mL), and potassium carbonate (59 g, 0.6 mol) at constant stirring and room temperature. The reaction mixture was heated at 80° C. for 50 h, diluted with water, and extracted with ethyl acetate (3×100 mL). The organic extracts were washed with water to weakly alkaline pH and dried with sodium sulfate. The product was purified chromatographically using hexane/ethyl acetate mixture as eluent to afford the title product (18.7 g, 61%). Satisfactory C,H,N-analysis was obtained.
Reaction SMILES: [Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:4]=1[F:10].[C:11]1([P:17](Cl)([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:18])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.[Cl-].[NH4+]>O1CCCC1>[F:10][C:4]1[CH:5]=[C:6]([F:9])[CH:7]=[CH:8][C:3]=1[P:17](=[O:18])([C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: Fc1ccc(Br)c(F)c1
Reactant: O=P(Cl)(c1ccccc1)c1ccccc1
Agent: [Cl-]
Agent: [Mg]
Agent: [NH4+]
Solvent: C1CCOC1
Product: O=P(c1ccccc1)(c1ccccc1)c1ccc(F)cc1F
Temperature: 5 °C
Reaction time: 3 h
Yield: 81 %

Procedure:
Into a 1 L three neck round bottomed flask equipped with a mechanical stirrer, thermometer, nitrogen gas inlet, pressure equalizing addition funnel, and reflux condenser with drying tube was placed predried magnesium turnings (13.5 g, 0.55 mol) and dry tetrahydrofuran (THF, 50 mL). The mixture was cooled to ˜5° C. using an ice/water bath. A solution of 1-bromo-2,4-difluorobenzene (107.2 g, 0.55 mol, 20% molar excess) in THF (200 mL) was placed in the pressure equalizing addition funnel and added dropwise over a 1.5 hour period. The mixture was allowed to warm to room temperature. The mixture was stirred at room temperature for 3 hours and the flask was subsequently placed in the ice/water bath to cool the solution to ˜5° C. A. solution of diphenylphosphinic chloride (107.9, 0.46 mol) in THF (100 mL) was added dropwise over a 1 hour period. The reaction mixture was allowed to warm to room temperature and was stirred under nitrogen for 15 hours. The resultant brown solution was poured into a mixture of concentrated ammonium chloride solution (700 mL) to give two layers. The organic layer was extracted successively with water, 5% aqueous sodium bicarbonate, and water and subsequently dried over magnesium sulfate. The THF was removed via rotoevaporation to give a dark red viscous liquid, 142.8 g, 98% crude yield. The viscous liquid was vacuum distilled (product distilled between 178–181° C.) and a yellow semi-solid was collected (118.6 g, 81% yield). The material was dissolved in 120 mL of hot toluene, treated which charcoal, and filtered while hot through Celite. To the toluene solution was added 120 mL of hexanes. The solution was allowed to cool, with stirring, overnight. A white crystalline material was collected via filtration (100.9 g, 69% yield). The solid exhibited a melting point of 111.1–112.3° C. as determined by differential scanning calorimetry (DSC) at 10° C./min. Anal. Calcd. for C18H13F2OP: C, 68.79%; H, 4.17%; F, 12.09%; P, 9.86%. Found: C, 68.38%; H, 4.26%; F, 11.17%; P, 10.28%. Mass spectroscopic analysis: M+413.2 [C20H13F6OP+].
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:9]=[CH:8][O:7][C:6]=1Br)=[O:4].[C:11]([O:15][C:16]([N:18]1[CH2:23][CH:22]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C([O-])([O-])=O.[Na+].[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[C:11]([O:15][C:16]([N:18]1[CH2:19][CH:20]=[C:21]([C:6]2[O:7][CH:8]=[CH:9][C:5]=2[C:3]([O:2][CH3:1])=[O:4])[CH2:22][CH2:23]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]
Reactant: CC(C)(C)OC(=O)N1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Reactant: COC(=O)c1ccoc1Br
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1CCOC1
Product: COC(=O)c1ccoc1C1=CCN(C(=O)OC(C)(C)C)CC1
Temperature: 80 °C
Yield: 75.9 %

Procedure:
2-Bromofuran-3-carboxylic acid methyl ester (3.0 g, 15 mmol, 1.0 eq.), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid t-butyl ester (4.5 g, 15 mmol, 1.0 eq.), THF (150 mL) and Na2CO3 (30 mL, 60 mmol, 4.0 eq.) were combined. The mixture was degassed and purged with nitrogen (3×). PdCl2(PPh3)2 (0.3 g, 0.4 mmol, 0.03 eq.) was added, and the mixture was again degassed and purged with nitrogen (3×), then heated at 80° C. overnight. The mixture was then cooled and the layers were separated. The THF layer was diluted with EtOAc (150 mL), washed with saturated aqueous NaCl (80 mL) and dried over Na2SO4. The material was filtered and applied onto a silica gel column and purified by chromatography with PE/EtOAc (20:1 to 10:1) to yield 4-(3-methoxycarbonylfuran-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid t-butyl ester (3.5 g) as a white solid.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][C:4]2([O:11][C:10]3[C:12]4[C:17]([C:18](=[O:21])[C:19](=[O:20])[C:9]=3[S:8][CH2:7]2)=[CH:16][CH:15]=[CH:14][CH:13]=4)[CH2:3][CH2:2]1.[C:22]1(=[O:33])[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24][C:23]1=[O:32].C(N(CC)CC)C>ClCCl>[O:32]=[C:23]1[C:22](=[O:33])[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:25]([N:1]2[CH2:2][CH2:3][C:4]3([O:11][C:10]4[C:12]5[C:17]([C:18](=[O:21])[C:19](=[O:20])[C:9]=4[S:8][CH2:7]3)=[CH:16][CH:15]=[CH:14][CH:13]=5)[CH2:5][CH2:6]2)=[CH:24]1
Reactant: O=C1C(=O)c2ccccc2C2=C1SCC1(CCNCC1)O2
Reactant: O=C1C=Cc2ccccc2C1=O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C1C=C(N2CCC3(CC2)CSC2=C(O3)c3ccccc3C(=O)C2=O)c2ccccc2C1=O
Temperature: 25 °C
Reaction time: 2 h
Yield: 14.3 %

Procedure:
To a solution of spiro[naphtho[1,2-b][1,4]oxathiine-2,4′-piperidine]-5,6-dione (2.3 g, 7.64 mmol) in dichloromethane (200 mL) was added naphthalene-1,2-dione (1.2 g, 7.64 mmol) followed by triethylamine (1.05 mL, 8.4 mmol). The reaction mixture was stirred at room temperature for 2 hours. The mixture was then concentrated under reduced pressure. The residue was dissolved in minimal tetrahydrofuran and then precipitated with EtOAc. The precipitate was collected by vacuum filtration. The filtrate was then suspended in tetrahydrofuran:EtOAc (1:1, 100 mL). The suspension was stirred, sonicated, and the solid collected by vacuum filtration. The tituration was once more repeated and the resulting reddish brown powder was recrystallized from dichloromethane/methanol (1:1) to afford the product (0.5 g) as the pure reddish brown solid. M.p.=250-260° C.; 400 MHz 1H NMR (DMSO-d6) δ: 7.89-7.93 (m, 3H), 7.71-7.81 (m. 3H), 7.55-7.65 (m, 2H), 6.10 (s, 1H), 3.67-3.75 (m, 2H), 3.45-3.53 (m, 2H), 3.19 (s, 2H), 2.20 (m, 2H), 1.25 (m, 1H), 1.01 (m, 1H). LCMS: 458 [M+H].
Reaction SMILES: Cl.S(=O)(=O)(O)[OH:3].[CH2:7]([CH:9]([CH:15]([N+:17]([O-:19])=[O:18])[CH3:16])[CH2:10][CH:11]([OH:14])[C:12]#[N:13])[CH3:8]>CCOCC.O>[CH2:7]([CH:9]([CH:15]([N+:17]([O-:19])=[O:18])[CH3:16])[CH2:10][CH:11]([OH:14])[C:12]([NH2:13])=[O:3])[CH3:8]
Reactant: O=S(=O)(O)O
Reactant: CCC(CC(O)C#N)C(C)[N+](=O)[O-]
Agent: Cl
Solvent: CCOCC
Solvent: O
Product: CCC(CC(O)C(N)=O)C(C)[N+](=O)[O-]
Reaction time: 8 h

Procedure:
A mixture of conc. hydrochloric acid (2.4 ml) and conc. sulfuric acid (0.38 ml) was added to a solution of 4-ethyl-2-hydroxy-5-nitrohexanenitrile (1 g) in ether (2 ml) at 0° C. with stirring. The resulting mixture was allowed to stand at room temperature overnight, diluted with cold water, and then extracted with ethyl acetate. The extract was washed with successively with water and 5% aqueous sodium bicarbonate, dried over magnesium sulfate and then evaporated to dryness in vacuo to give 4-ethyl-2-hydroxy-5-nitrohexanamide (0.46 g).
Reaction SMILES: [C:1]([O:5][C:6](=[O:19])[NH:7][CH2:8][CH2:9][CH2:10][N:11]([C:13]1[S:17][N:16]=[C:15](Cl)[N:14]=1)[CH3:12])([CH3:4])([CH3:3])[CH3:2].[NH:20]1[CH:24]=[CH:23][N:22]=[CH:21]1.[H-].[Na+]>CS(C)=O.[Cl-].[Na+].O>[C:1]([O:5][C:6](=[O:19])[NH:7][CH2:8][CH2:9][CH2:10][N:11]([C:13]1[S:17][N:16]=[C:15]([N:20]2[CH:24]=[CH:23][N:22]=[CH:21]2)[N:14]=1)[CH3:12])([CH3:4])([CH3:3])[CH3:2]
Reactant: CN(CCCNC(=O)OC(C)(C)C)c1nc(Cl)ns1
Reactant: c1c[nH]cn1
Agent: [Cl-]
Agent: [H-]
Agent: [Na+]
Solvent: CS(C)=O
Solvent: O
Product: CN(CCCNC(=O)OC(C)(C)C)c1nc(-n2ccnc2)ns1
Temperature: 60 °C
Reaction time: 8 h
Yield: 94.5 %

Procedure:
{3-[(3-Chloro-[1,2,4]thiadiazol-5-yl)-methyl-amino]-propyl}-carbamic acid tert-butyl ester (6.50 g, 21.2 mmol) was combined with imidazole (7.20 g, 105 mmol) and dissolved in DMSO (100 mL). Next, the sodium hydride (833 mg of a 60% dispersion on mineral oil, 57.8 mmol) was added the reaction mixture was stirred at 60° C. overnight. After this period, brine was added to the reaction mixture and it was transferred to a separatory funnel. The product was extracted with copious DCM and the organic layer was dried over anhydrous Na2SO4. The crude material was purified by flash silica chromatography (Hex to 1:4 Hex/EtOAc) to yield 6.78 g (94%) of {3-[(3-imidazol-1-yl-[1,2,4]thiadiazol-5-yl)-methyl-amino]-propyl}-carbamic acid tert-butyl ester as a clear oil. [M+H]+ 339.10.
Reaction SMILES: [Br:1][C:2]1[C:6]([Br:7])=[CH:5][S:4][CH:3]=1.[S:8]1[CH:12]=[CH:11][CH:10]=[C:9]1[C:13](Cl)=[O:14].[Cl-].[Cl-].[Cl-].[Al+3]>C(=S)=S>[Br:1][C:2]1[C:6]([Br:7])=[CH:5][S:4][C:3]=1[C:13]([C:9]1[S:8][CH:12]=[CH:11][CH:10]=1)=[O:14]
Reactant: Brc1cscc1Br
Reactant: O=C(Cl)c1cccs1
Agent: [Al+3]
Agent: [Cl-]
Solvent: S=C=S
Product: O=C(c1cccs1)c1scc(Br)c1Br
Temperature: 0 °C
Reaction time: 3 h

Procedure:
To a solution of 30 g of 3,4-dibromothiophene and 13.5 mL of thiophene-2-carbonylchloride in 120 mL of carbon disulfide was added 16.5 g aluminum trichloride portionwise over 10 minutes. The mixture was stirred for 3 hours, poured into 900 g of ice-water and extracted with methylene chloride. The organic layer was washed with 1N NaOH (aq), water, and dried (MgSO4). Filtration and concentration of the filtrate, in vacuo, afforded an oil which crystallized upon trituration with n-chorobutane to yield 32 g of the subject compound as an off-white solid, m.p. 105°-109° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][N:13]=[CH:14][C:15]([OH:17])=[O:16])[CH2:9][N:8]=[C:7]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:6]=2[CH:24]=1.CO.[N+](=[CH2:29])=[N-]>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][N:13]=[CH:14][C:15]([O:17][CH3:29])=[O:16])[CH2:9][N:8]=[C:7]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)[C:6]=2[CH:24]=1
Reactant: C=[N+]=[N-]
Reactant: O=C(O)C=NNC1=Nc2ccc(Cl)cc2C(c2ccccc2)=NC1
Solvent: CO
Solvent: ClCCl
Product: COC(=O)C=NNC1=Nc2ccc(Cl)cc2C(c2ccccc2)=NC1

Procedure:
To a stirred suspension of 6.29 g. (0.017 mole) 7-chloro-2-[[1-carboxymethylene)hydrazino]-5-phenyl-3H-1,4-benzodiazepine, methanol solvate, in 300 ml. of methylene chloride is slowly added an ethereal solution of diazomethane (9.27 ml., 0.22 mole) under nitrogen, at ambient temperature. After an hour, the solvent is removed in vacuo and the residue is recrystallized from ethyl acetate to give 3.20 g. of 7-chloro-2-[[1-(methoxycarbonyl)methylene]hydrazino]-5-phenyl-3H-1,4benzodizepine. The analytical sample is recrystallized from ethyl acetate-hexane.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:14])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]([NH2:13])[CH:7]=1.C[O:16][C:17](=O)[CH:18]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=1[Cl:31])[C:19](=O)[CH2:20][CH3:21].O1CCOCC1>C(OCC)(=O)C>[CH3:1][O:2][C:3](=[O:14])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([F:12])=[C:8]2[C:7]=1[C:17](=[O:16])[C:18]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:25]=1[Cl:31])=[C:19]([CH2:20][CH3:21])[NH:13]2
Reactant: CCC(=O)C(Cc1ccc(Cl)cc1Cl)C(=O)OC
Reactant: COC(=O)COc1ccc(F)c(N)c1
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: CCc1[nH]c2c(F)ccc(OCC(=O)OC)c2c(=O)c1Cc1ccc(Cl)cc1Cl
Temperature: 120 °C

Procedure:
A mixture of (3-amino-4-fluorophenoxy)acetic acid methyl ester (0.75 g), 2-(2,4-dichlorobenzyl)-3-oxopentanoic acid methyl ester (1.3 g), polyphosphoric acid (5 mL) and dioxane (25 mL) was heated at 120° C. for 17 hours. The mixture was cooled to room temperature, diluted with ethyl acetate and this mixture washed with water, saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution and then dried over magnesium sulfate. The solvent was removed under reduced pressure to afford title compound as a brown oil, 1.7 μg.
Reaction SMILES: Cl[CH:2]([CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1)[C:3]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[N:4]=1.[NH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([NH:33][CH2:34][CH2:35][C:36]([O:38]CC)=[O:37])=[O:32])=[CH:27][CH:26]=1>>[CH:18]1([CH:2]([NH:24][C:25]2[CH:26]=[CH:27][C:28]([C:31]([NH:33][CH2:34][CH2:35][C:36]([OH:38])=[O:37])=[O:32])=[CH:29][CH:30]=2)[C:3]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[N:5]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[N:4]=2)[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1
Reactant: ClC(c1nn(-c2ccccc2)c2ccccc12)C1CCCCC1
Reactant: CCOC(=O)CCNC(=O)c1ccc(N)cc1
Product: O=C(O)CCNC(=O)c1ccc(NC(c2nn(-c3ccccc3)c3ccccc23)C2CCCCC2)cc1

Procedure:
Using 3-[chloro(cyclohexyl)methyl]-1-phenyl-1H-indazole (370 mg) synthesized above and ethyl 3-{[(4-aminophenyl)carbonyl]amino}propanoate (269 mg) synthesized in Example 1(2) and in the same manner as in Example A7(3), the title object compound (79.1 mg, 14%) was obtained as a pale-yellow solid.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:12])[CH:5]([O:9][CH2:10][CH3:11])[C:6]([OH:8])=O)[CH3:2].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.Cl.[NH2:41][CH2:42][C:43]1[CH:50]=[CH:49][C:46]([C:47]#[N:48])=[CH:45][CH:44]=1.C(N(C(C)C)C(C)C)C>C1COCC1>[CH2:1]([O:3][C:4](=[O:12])[CH:5]([O:9][CH2:10][CH3:11])[C:6]([NH:48][CH2:47][C:46]1[CH:49]=[CH:50][C:43]([C:42]#[N:41])=[CH:44][CH:45]=1)=[O:8])[CH3:2]
Reactant: N#Cc1ccc(CN)cc1
Reactant: CCOC(=O)C(OCC)C(=O)O
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CCOC(=O)C(OCC)C(=O)NCc1ccc(C#N)cc1
Reaction time: 24 h
Yield: 78.5 %

Procedure:
A solution under N2 of (RS)-2-ethoxy-malonic acid monoethyl ester (666 mg, 1.0) in THF (37 ml) was prepared. BOP (2.17 g), 4-aminomethyl-benzonitrile hydrochloride (555 mg) and N-ethyldiisopropylamine (733 mg) were added at 0° C. The ice bath was removed and the reaction was let to stir 24 h. THF was evaporated and the mixture was diluted with EtOAc. This organic phase was washed with a sat. aq. NaHCO3 sol. and with brine. The aqueous phases were extracted with one more portion of EtOAc and dried over MgSO4. The solvent was evaporated. The crude product was purified by flash chromatography. (heptane/EtOAc 3:1 to 2:1). 750 mg (68%) of (RS)-N-(4-cyano-benzyl)-2-ethoxy-malonamic acid ethyl ester were isolated as a yellow oil. MS 308.4 (100, [M+NH4]+), 291.1 (88, [M+H]+).
Reaction SMILES: [C:1]([O:4][C@@H:5]1[O:22][CH2:21][C@@H:16]([O:17][C:18](=[O:20])[CH3:19])[C@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:6]1[O:7][C:8](=[O:10])[CH3:9])(=O)[CH3:2].[Sn](Cl)(Cl)(Cl)Cl.[CH3:28][CH:29]([CH2:35][CH2:36][CH2:37][CH:38]([CH3:50])[CH2:39][CH2:40][CH2:41][CH:42]([CH3:49])[CH2:43][CH2:44][CH2:45][CH:46]([CH3:48])[CH3:47])[CH2:30][CH2:31]CCO.O.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:8]([O:7][C@@H:6]1[C@@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:16]([O:17][C:18](=[O:20])[CH3:19])[CH2:21][O:22][C@H:5]1[O:4][CH2:1][CH2:2][CH2:31][CH2:30][CH:29]([CH3:28])[CH2:35][CH2:36][CH2:37][CH:38]([CH3:50])[CH2:39][CH2:40][CH2:41][CH:42]([CH3:49])[CH2:43][CH2:44][CH2:45][CH:46]([CH3:48])[CH3:47])(=[O:10])[CH3:9]
Reactant: CC(C)CCCC(C)CCCC(C)CCCC(C)CCCCO
Reactant: CC(=O)O[C@@H]1OC[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O
Agent: Cl[Sn](Cl)(Cl)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O
Product: CC(=O)O[C@@H]1[C@@H](OC(C)=O)[C@H](OCCCCC(C)CCCC(C)CCCC(C)CCCC(C)C)OC[C@H]1OC(C)=O
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 15.9 %

Procedure:
Under an argon atmosphere, 318 mg of β-xylose tetraacetate was dissolved in 6 ml of dry methylene chloride, and the solution was cooled to 0° C. A solution of 0.12 ml of tin tetrachloride dissolved in 1 ml of methylene chloride was added dropwise thereto, the mixture was agitated at room temperature for 20 minutes, and then cooled to −10° C. A solution of 326.6 mg of 5,9,13,17-tetramethyloctadecanol in 1 ml of methylene chloride was added dropwise thereto, and the mixture was agitated for 4 hours. A sodium bicarbonate water was added to the reaction solution and extraction was carried out 3 times with methylene chloride. The extract was washed with water and dried over anhydrous sodium sulfate. After the filtration, the resultant was concentrated, and the concentrate was purified by column chromatography to obtain 93 mg of 1-O-(5,9,13,17-tetramethyloctadecyl)-β-D-xylopyranoside triacetate.
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH2:6][OH:7])([O-:3])=[O:2].[Br:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23](O)=[O:24].C1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C.C(Cl)Cl>[Br:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][C:23]([O:7][CH2:6][C:5]1[CH:8]=[CH:9][CH:10]=[CH:11][C:4]=1[N+:1]([O-:3])=[O:2])=[O:24]
Reactant: O=C(O)CCCCCCCCCCBr
Reactant: O=[N+]([O-])c1ccccc1CO
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: O=C(CCCCCCCCCCBr)OCc1ccccc1[N+](=O)[O-]

Procedure:
One equivalent of 2-nitrobenzyl alcohol (1.91 g, 12.49 mmol) was combined with one equivalent of 11-bromoundecanoic acid (3.31 g, 12.49 mmol), 0.1 equivalents DMAP (0.153 g, 1.25 mmol) and dissolved in 100 mL CH2Cl2. To this mixture a solution of DCC (2.58 g, 12.49 mmol) in 50 mL CH2Cl2 was slowly added while stirring. Upon addition a yellow-brown precipitate formed after a few minutes. The mixture was stirred at room temperature overnight. The precipitate was removed by vacuum filtration and the solvent was removed by rotovap. The product was purified using silica gel column chromatography with CH2Cl2/MeOH (v/v 50:1) as eluent. The product was dried over Na2SO4, the solvent removed by rotovap, and dried under vacuum, producing a white solid. Yield: 4.37 g (87.4%). 1H-NMR (CDCl3) δ (ppm): 8.1 (d, 1H, Ar), 7.6 (t, 1H, Ar), 7.5 (d, 1H, Ar), 7.4 (t, 1H, Ar), 5.5 (s, 2H, O—CH2), 3.4 (t, 2H, CH2—Br), 2.4 (t, 2H, CH2—C═O), 1.8 (m, 2H, CH2), 1.6 (m, 2H, CH2), 1.4 (m, 2H, CH2), 1.3 (m, 10H, CH2). 13C-NMR (CDCl3) δ (ppm): 173.5, 147.9, 134.1, 132.7, 129.5, 129.2, 125.5, 63.2, 34.6, 34.5, 33.2, 29.7, 29.6, 29.5, 29.4, 29.1, 28.5, 25.3.
Reaction SMILES: [C:1](Cl)(=[O:4])[CH2:2][CH3:3].CCN(CC)CC.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:37][C:38]1[CH:39]=[C:40]2[C:44](=[CH:45][CH:46]=1)[N:43]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[CH:42]=[C:41]2[C:54]1[CH:59]=[N:58][CH:57]=[C:56]([N:60]2[CH2:65][CH2:64][CH:63]([NH:66][C:67]([O:69][C:70]([CH3:73])([CH3:72])[CH3:71])=[O:68])[CH2:62][CH2:61]2)[N:55]=1>C(Cl)Cl>[C:70]([O:69][C:67]([NH:66][CH:63]1[CH2:62][CH2:61][N:60]([C:56]2[N:55]=[C:54]([C:41]3[C:40]4[C:44](=[CH:45][CH:46]=[C:38]([NH:37][C:1](=[O:4])[CH2:2][CH3:3])[CH:39]=4)[N:43]([C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])[CH:42]=3)[CH:59]=[N:58][CH:57]=2)[CH2:65][CH2:64]1)=[O:68])([CH3:73])([CH3:72])[CH3:71]
Reactant: CC(C)(C)OC(=O)NC1CCN(c2cncc(-c3cn(C(=O)OC(C)(C)C)c4ccc(N)cc34)n2)CC1
Reactant: CCC(=O)Cl
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCC(=O)Nc1ccc2c(c1)c(-c1cncc(N3CCC(NC(=O)OC(C)(C)C)CC3)n1)cn2C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 3 h
Yield: 45 %

Procedure:
To solution of propionyl chloride (52.5 mg, 0.708 mmol) in DCM (7 mL) at 0° C. was added Et3N (0.2 mL, 1.47 mmol), HBTU (292 mg, 0.75 mmol), tert-butyl 5-amino-3-(6-(4-(tert-butoxycarbonylamino)piperidin-1-yl)pyrazin-2-yl)-1H-indole-1-carboxylate (300 mg, 0.59 mmol) The resulting reaction mixture was stirred at RT for 3 h. The reaction mixture was extracted with DCM (14 mL), washed with brine, dried over Na2SO4, and concentrated to dryness. The crude product was purified by column chromatography to obtain the title compound (150 mg, 45%) as an off white solid. MS (ESI, pos. ion) m/z: 565.2 (M+1).