Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[C:10]2[N:9]3[CH2:11][CH2:12][CH2:13][NH:14][C:15](=[O:16])[C:8]3=[CH:7][C:6]=2[CH:5]=[C:4]([CH3:17])[CH:3]=1.[F:18][C:19]1[CH:20]=[C:21](B(O)O)[CH:22]=[CH:23][C:24]=1[F:25]>>[F:18][C:19]1[CH:20]=[C:21]([C:2]2[C:10]3[N:9]4[CH2:11][CH2:12][CH2:13][NH:14][C:15](=[O:16])[C:8]4=[CH:7][C:6]=3[CH:5]=[C:4]([CH3:17])[CH:3]=2)[CH:22]=[CH:23][C:24]=1[F:25]
Reactant: OB(O)c1ccc(F)c(F)c1
Reactant: Cc1cc(Br)c2c(c1)cc1n2CCCNC1=O
Product: Cc1cc(-c2ccc(F)c(F)c2)c2c(c1)cc1n2CCCNC1=O

Procedure:
The title compound, white solid (42 mg, 76%), MS (ISP) m/z=327.4 [(M+H)+], mp 231° C., was prepared in accordance with the general method of example 1 from 7-bromo-9-methyl-2,3,4,5-tetrahydro-[1,4]diazepino[1,2-a]indol-1-one (intermediate 11) (50 mg, 0.17 mmol) and commercially available 3,4-difluoro-phenylboronic acid (35 mg, 0.22 mmol).
Reaction SMILES: [CH3:1][C:2]1([CH3:9])[CH2:7][CH2:6][C:5](=[O:8])[CH:4]=[CH:3]1.[CH3:10][Li]>C(OCC)C>[CH3:10][C:5]1([OH:8])[CH2:6][CH2:7][C:2]([CH3:9])([CH3:1])[CH:3]=[CH:4]1
Reactant: CC1(C)C=CC(=O)CC1
Reactant: [Li]C
Solvent: CCOCC
Product: CC1(C)C=CC(C)(O)CC1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a stirred solution of 4,4-dimethylcyclohex-2-enone (40.0 g, 322 mmol) in anhydrous diethyl ether (400 mL) at −78° C. was added an ethereal solution of methyllithium (220 mL of a 1.6 M). The resulting solution was allowed to warm to room temperature, stirred for 18 hours. The reaction was quenched by the addition of water (200 mL). The phases were separated and the aqueous layer extracted with diethyl ether (2×200 mL). The combined organic phase was washed with water (2×200 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure to give the title compound as clear, light yellow oil (41 g, Yield: 90%). Rf 0.5 (5:1 petroleum ether/ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 5.46 (d, J=10.0 Hz, 1H), 5.43 (d, J=10.0 Hz, 1H), 1.73-1.70 (m, 2H), 1.59-1.56 (m, 1H), 1.50-1.45 (m, 1H), 1.27 (s, 3H), 1.01 (s, 3H), 0.95 (s, 3H) ppm; Mass spectrum (ESI +ve) m/z 123 (M−H2O+H+).
Reaction SMILES: I[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1.[CH2:12]([OH:17])[CH2:13][CH2:14][C:15]#[CH:16]>C(NCC)C.[Cu]I.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>[C:2]1([C:16]#[C:15][CH2:14][CH2:13][CH2:12][OH:17])[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH:5]=[CH:4][CH:3]=1
Reactant: Ic1cccc2ccccc12
Reactant: C#CCCCO
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: CCNCC
Product: OCCCC#Cc1cccc2ccccc12
Yield: 68.7 %

Procedure:
Under a nitrogen atmosphere, a mixture of 4.0 mL (0.027 mole) of 1-iodonaphthalene, 0.1 gram (0.0003 mole) of copper(I)iodide, and 0.19 gram (0.0003 mole) of bis(triphenylphosphine)palladium(II) chloride in 75 mL of diethylamine was stirred, and 2.6 mL. (0.027 mole) of 4-pentyn-1-ol was added in one portion. Upon completion of addition, the reaction mixture was stirred at ambient temperature for about 18 hours. Gas chromatographic (GC) analysis of the reaction mixture indicated that the reaction had not gone to completion. An additional 0.5 mL of the 4-pentyn-1-ol was added, and the reaction mixture was stirred for an additional six hours. GC analysis of the reaction mixture indicated that the reaction was complete. The reaction mixture was passed through a column of silica gel. Elution was accomplished using methylene chloride. The eluate was concentrated under reduced pressure, yielding 3.9 grams of 5-(naphth-1-yl)-4-pentyn-1-ol. The NMR spectrum was consistent with the proposed structure.
Reaction SMILES: [Cl:1][C:2]1[CH:33]=[CH:32][C:5]2[N:6]([C@@H:13]3[CH2:18][CH2:17][C@H:16]([NH:19][CH2:20][C@@H:21]4[CH2:29][C:28]5[C:23](=[CH:24][CH:25]=[C:26]([C:30]#[N:31])[CH:27]=5)[CH2:22]4)[CH2:15][CH2:14]3)[C:7]([C:9]([OH:12])([CH3:11])[CH3:10])=[N:8][C:4]=2[CH:3]=1.C(N(CC)CC)C.[C:41](Cl)(=[O:43])[CH3:42]>C(Cl)Cl.CN(C)C1C=CN=CC=1>[Cl:1][C:2]1[CH:33]=[CH:32][C:5]2[N:6]([C@@H:13]3[CH2:14][CH2:15][C@H:16]([N:19]([CH2:20][C@@H:21]4[CH2:29][C:28]5[C:23](=[CH:24][CH:25]=[C:26]([C:30]#[N:31])[CH:27]=5)[CH2:22]4)[C:41](=[O:43])[CH3:42])[CH2:17][CH2:18]3)[C:7]([C:9]([OH:12])([CH3:11])[CH3:10])=[N:8][C:4]=2[CH:3]=1
Reactant: CC(C)(O)c1nc2cc(Cl)ccc2n1[C@H]1CC[C@@H](NC[C@H]2Cc3ccc(C#N)cc3C2)CC1
Reactant: CC(=O)Cl
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)N(C[C@H]1Cc2ccc(C#N)cc2C1)[C@H]1CC[C@@H](n2c(C(C)(C)O)nc3cc(Cl)ccc32)CC1
Temperature: 25 °C
Reaction time: 65 h
Yield: 55 %

Procedure:
To a solution of cis-(S)-2-({4-[5-chloro-2-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-cyclohexylamino}-methyl)-indan-5-carbonitrile (25 mg, 0.054 mmol) in methylene chloride (5 mL) was added triethylamine (11 mg, 0.108 mmol), acetyl chloride (5 mg, 0.063 mmol) and trace amount of 4-dimethylaminopyridine. The mixture was stirred at room temperature for 65 hours. The reaction mixture was diluted with dichloromethane and the solution was washed with saturated aqueous sodium bicarbonate solution followed by brine. The organic extract was dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was subjected to column chromatography, eluting with dichloromethane and ethyl acetate in the presence of 4% methanol to give cis-(S)—N-{4-[5-chloro-2-(1-hydroxy-1-methyl-ethyl)-benzoimidazol-1-yl]-cyclohexyl}-N-(5-cyano-indan-2-ylmethyl)-acetamide (15 mg). LC-MS showed a single peak, C29H33ClN4O2 (m/e) calcd 504.2292, obsd 505.3. 1H-NMR (CD3OD) □ 7.67 (br, 1H) 7.59 (s, 2H), 7.50 (d, 1H), 7.40 (d, 1H), 7.23 (d, 1H), 5.57 (m, 1H), 3.48 (br d, 2H), 3.15 (m, 2H), 2.97 (m, 1H), 2.84 (m, 2H), 2.59 (br, 2H), 2.32 (br, 1H), 2.11 (br s, 2H), 1.93 (m, 4H), 1.72 (s, 6H), 1.28 (s, 3H).
Reaction SMILES: [Br:1][C:2]1[N:7]=[CH:6][C:5]2[N:8]=[C:9]([C:17](=[N:20][OH:21])[C:18]#[N:19])[N:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:4]=2[CH:3]=1.C([N:24](CC)CC)C.NO.O>C1COCC1>[Br:1][C:2]1[N:7]=[CH:6][C:5]2[N:8]=[C:9]([C:17]3[C:18]([NH2:24])=[N:19][O:21][N:20]=3)[N:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[C:4]=2[CH:3]=1
Reactant: CCN(CC)CC
Reactant: N#CC(=NO)c1nc2cnc(Br)cc2n1-c1ccccc1
Agent: NO
Solvent: C1CCOC1
Solvent: O
Product: Nc1nonc1-c1nc2cnc(Br)cc2n1-c1ccccc1
Temperature: 120 °C
Yield: 60 %

Procedure:
The product from Step 6 (2.7 g, 7.93 mmol) in THF (5 mL) and triethylamine (1.1 mL, 7.93 mmol) was treated with a 50% solution of hydroxylamine in water (0.24 mL, 7.93 mmol). The mixture was heated at 120° C. in a sealed tube for 10 h and the reaction allowed to cool to room temperature. The resulting precipitate was filtered and dried in vacuo to afford the title compound (1.7 g, 60%). MS (ES+) m/e 357/359 [M+H]+.
Reaction SMILES: [CH2:1]1[CH2:7][S:4](=[O:6])(=[O:5])[O:3][CH2:2]1.[CH3:8][C:9]([NH2:14])([CH2:12][CH3:13])[CH2:10][CH3:11]>CC(=O)CC.C1(C)C=CC=CC=1>[CH2:10]([C:9]([NH:14][CH2:2][CH2:1][CH2:7][S:4]([OH:3])(=[O:6])=[O:5])([CH3:8])[CH2:12][CH3:13])[CH3:11]
Reactant: CCC(C)(N)CC
Reactant: O=S1(=O)CCCO1
Solvent: CCC(C)=O
Solvent: Cc1ccccc1
Product: CCC(C)(CC)NCCCS(=O)(=O)O
Temperature: 25 °C

Procedure:
A solution of 1,3-propanesultone (2.5 g, 20 mmol) in 2-butanone (10 mL) was added to a solution of 3-methyl-3-ethyl-3-propylamine in toluene (total volume: 30 mL). The mixture was heated to reflux for 5 hours then was cooled to room temperature. The solid was collected by suction-filtration and rinsed with acetone (2×5 mL). The solid was dried overnight at 45° C. in the vacuum oven. The title compound was obtained as a fine white solid (3.63 g, 16.3 mmol, 33% overall yield). 1H NMR (500 MHz, DMSO-d6) δ 0.79 (t, J=7.3 Hz, 6H), 1.15 (s, 3H), 1.53-1.59 (m, 4H), 1.97-2.00 (m, 2H), 2.89 (t, J=7.1 Hz, 2H), 3.03 (t, J=7.6 Hz, 2H); 13C NMR (125 MHz, DMSO-d6) δ 6.8, 20.2, 21.9, 27.7, 39.7, 48.2, 63.3 ES-MS 224; (M+H)
Reaction SMILES: [CH3:1][CH:2]([C:6]1[CH:7]=[C:8]([OH:13])[CH:9]=[C:10]([CH:12]=1)[OH:11])[CH:3]([CH3:5])[CH3:4].[CH3:14][N:15]1[CH2:20][CH2:19][C:18](=O)[CH2:17][CH2:16]1.[ClH:22]>C(O)(=O)C>[ClH:22].[CH3:14][N:15]1[CH2:16][CH:17]=[C:18]([C:9]2[C:10]([OH:11])=[CH:12][C:6]([CH:2]([CH3:1])[CH:3]([CH3:4])[CH3:5])=[CH:7][C:8]=2[OH:13])[CH2:19][CH2:20]1
Reactant: CN1CCC(=O)CC1
Reactant: CC(C)C(C)c1cc(O)cc(O)c1
Agent: Cl
Solvent: CC(=O)O
Product: CC(C)C(C)c1cc(O)c(C2=CCN(C)CC2)c(O)c1

Procedure:
5-(1,2-Dimethylpropyl) resorcinol (15.7 g) and N-methyl-4-piperidone (9.8 g) were dissolved in 35 ml acetic acid and treated with HCl gas as described in Example VI giving 18.8 g of product, m.p. 241°-243°.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][CH2:7][C:8]#[N:9].O.[OH-].[Na+]>CCOCC>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][CH2:7][CH2:8][NH2:9]
Reactant: N#CCCc1cccs1
Agent: [Na+]
Agent: [OH-]
Solvent: CCOCC
Solvent: O
Product: NCCCc1cccs1
Temperature: 25 °C
Reaction time: 18 h
Yield: 555.6 %

Procedure:
The product of Example 41 (8.3 g, 10.5 mmol) dissolved in 25 ml of Et2O was added dropwise (15 min.) to a stirred slurry of lithium aluminum hydride(LAH) in 125 ml of dry Et2O under an Ar atmosphere at room temperature. After the addition was complete the reaction was stirred at room temperature an additional 18 h. With great care, 8.0 ml of water were added dropwise to the vigorously stirred reaction mixture. Following this, 8.0 ml of 4N NaOH were then carefully added. Finally 22 ml of H2O were added and the aluminum salts were filtered from the Et2O solution. The filtrate was concentrated to give 8.24 g of the title products which was used without further purification.
Reaction SMILES: Br[C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][N:8]([C:12]3[CH:17]=[C:16]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[N:15]=[C:14]([NH2:25])[N:13]=3)[CH2:9]2)=[CH:4][CH:3]=1.[CH3:26][N:27]1[CH2:32][CH2:31][N:30]([C:33]2[CH:38]=[C:37](B3OC(C)(C)C(C)(C)O3)[CH:36]=[CH:35][N:34]=2)[CH2:29][CH2:28]1>>[CH3:24][N:21]1[CH2:22][CH2:23][N:18]([C:16]2[CH:17]=[C:12]([N:8]3[CH2:7][CH2:6][C:5]4[C:10](=[CH:11][C:2]([C:37]5[CH:36]=[CH:35][N:34]=[C:33]([N:30]6[CH2:29][CH2:28][N:27]([CH3:26])[CH2:32][CH2:31]6)[CH:38]=5)=[CH:3][CH:4]=4)[CH2:9]3)[N:13]=[C:14]([NH2:25])[N:15]=2)[CH2:19][CH2:20]1
Reactant: CN1CCN(c2cc(B3OC(C)(C)C(C)(C)O3)ccn2)CC1
Reactant: CN1CCN(c2cc(N3CCc4ccc(Br)cc4C3)nc(N)n2)CC1
Product: CN1CCN(c2cc(-c3ccc4c(c3)CN(c3cc(N5CCN(C)CC5)nc(N)n3)CC4)ccn2)CC1

Procedure:
This compound was prepared by using procedures analogous to those described for the synthesis of Example 2 starting from 4-(7-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine and 1-methyl-4-[4(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl]piperazine (Oadwood, Cat. No. 021854). LCMS (M+H)+: m/z=500.5.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([NH:8][NH2:9])=[O:7])=[CH:4][CH:3]=1.[CH3:12][C:13]1[S:17][C:16]([CH:18]=O)=[CH:15][CH:14]=1>C(O)(=O)C.CCO>[CH3:18][C:16]1[S:17][C:13]([CH:12]=[N:9][NH:8][C:6](=[O:7])[C:5]2[CH:10]=[CH:11][C:2]([OH:1])=[CH:3][CH:4]=2)=[CH:14][CH:15]=1
Reactant: Cc1ccc(C=O)s1
Reactant: NNC(=O)c1ccc(O)cc1
Solvent: CCO
Solvent: CC(=O)O
Product: Cc1ccc(C=NNC(=O)c2ccc(O)cc2)s1
Temperature: 25 °C
Yield: 57.6 %

Procedure:
To a solution of 4-hydroxy-benzoic acid hydrazide (0.25 g, 0.0016 mol) and 5-methyl-2-thiophenecarboxaldehyde (0.20 g, 0.0016 mol) in abs. EtOH (10 mL), was added 1 drop of acetic acid. The reaction mixture was refluxed for 4 hours. The reaction mixture was cooling to room temperature and concentrated to remove solvent. The resulting residue was solidified by EtOAc to give white solid 0.24 g, in 57% yield, mp: 215.7° C. 1H NMR (CD3OD) δ 8.38 (s, 1H), 7.79 (d, 2H), 7.17 (s, 1H), 6.86 (d, 2H), 6.77 (s, 1H), 2.49 (s, 3H), 1.31. 13C NMR (CDCl3) δ166.5, 162.8, 145.6, 144.8, 138.1, 132.4, 130.7, 127.1, 124.8, 116.3, 15.6. Anal. Calcd for C13H12N2O2S: C, 59.98; H, 4.65; N, 10.76. Found: C, 59.98; H, 4.45; N, 10.40.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9](I)[S:10][C:3]=12.C([Mg]Cl)(C)C.[CH2:17]([Sn:21](Cl)([CH2:26][CH2:27][CH2:28][CH3:29])[CH2:22][CH2:23][CH2:24][CH3:25])[CH2:18][CH2:19][CH3:20]>C1COCC1>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([Sn:21]([CH2:22][CH2:23][CH2:24][CH3:25])([CH2:26][CH2:27][CH2:28][CH3:29])[CH2:17][CH2:18][CH2:19][CH3:20])[S:10][C:3]=12
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Reactant: Clc1ccnc2cc(I)sc12
Agent: CC(C)[Mg]Cl
Solvent: C1CCOC1
Product: CCCC[Sn](CCCC)(CCCC)c1cc2nccc(Cl)c2s1
Temperature: 25 °C
Reaction time: 1 h
Yield: 51.9 %

Procedure:
In a round bottom flask, 7-chloro-2-iodothieno[3,2-b]pyridine (200 mg, 0.68 mmol) was suspended in THF (6 mL). The reaction mixture was cooled with a NaCl-ice bath (−12 to −8° C. internal temp) and isopropylmagnesium chloride (2.0 M in THF, 0.406 mL, 0.812 mmol) was added dropwise. The reaction mixture was stirred for 1 h at the same temperature, and then tributyltin chloride (0.29 mL, 1.08 mmol) was slowly added. The reaction mixture was allowed to warm to room temperature over ˜1 h then quenched with an aqueous solution of NH4Cl (20 mL) and extracted with EtOAc (30 mL). The organic layer was dried over Na2SO4 and evaporated to dryness. The crude residue was purified by column chromatography (SiO2-11 g-Et3N 2%, hexanes 100% 5 min, to hexanes:EtOAc, 9:1 in 15 min) to isolate 162 mg (52%) of 7-chloro-2-tributylstannanyl-thieno[3,2-b]pyridine as a colorless oil.
Reaction SMILES: C(OC([N:8]1[CH2:27][CH2:26][N:11]2[C:12](=[O:25])[C:13]3[C:18]([C@@H:10]2[CH2:9]1)=[CH:17][C:16]([CH2:19][OH:20])=[CH:15][C:14]=3[C:21]([F:24])([F:23])[F:22])=O)(C)(C)C.[ClH:28]>CCOCC.O>[ClH:28].[OH:20][CH2:19][C:16]1[CH:17]=[C:18]2[C:13]([C:12](=[O:25])[N:11]3[CH2:26][CH2:27][NH:8][CH2:9][C@H:10]32)=[C:14]([C:21]([F:23])([F:24])[F:22])[CH:15]=1
Reactant: CC(C)(C)OC(=O)N1CCN2C(=O)c3c(cc(CO)cc3C(F)(F)F)[C@@H]2C1
Agent: Cl
Solvent: O
Solvent: CCOCC
Product: O=C1c2c(cc(CO)cc2C(F)(F)F)[C@@H]2CNCCN12
Reaction time: 1 h

Procedure:
To a stirring solution of N-(t-butoxycarbonyl)-(R)-1,3,4,10b-tetrahydro-9-hydroxymethyl-7-trifluoromethyl-pyrazino[2,1-a]isoindol-6(2H)-one (14 mg, 0.04 mmol) in dry ether (2 mL) was added hydrochloric acid (1 mL). The reaction was stirred for 1 h and then conc. in vacuo to a white solid. The solid was dissolved in water and lyophilized to 10 mg of a white solid. MS (ESI) 287 (M−Cl).
Reaction SMILES: [H-].[Na+].CN(C=O)C.[OH:8][C:9]1[CH:10]=[C:11]([CH:17]=[C:18]([OH:21])[C:19]=1[I:20])[C:12]([O:14][CH2:15][CH3:16])=[O:13].I[CH2:23][CH3:24]>O>[CH2:23]([O:8][C:9]1[CH:10]=[C:11]([CH:17]=[C:18]([OH:21])[C:19]=1[I:20])[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH3:24]
Reactant: CCOC(=O)c1cc(O)c(I)c(O)c1
Reactant: CCI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)c1cc(O)c(I)c(OCC)c1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
Sodium hydride (60% oil, 3.99 g) was added to a DMF (100 mL) solution of ethyl 3,5-dihydroxy-4-iodobenzoate (15.0 g), and the mixture was stirred at 0° C. for 30 minutes in a nitrogen atmosphere. Iodoethane (4.09 mL) was added to the reaction mixture, and the mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture, followed by extraction with ethyl acetate. The obtained organic layer was washed with saturated saline and dried over anhydrous magnesium sulfate, and then, the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (7.59 g).
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:10]=[N:11][C:12]([N:15]3[CH2:19][CH2:18][CH2:17][C@H:16]3[C:20]([F:23])([F:22])[F:21])=[N:13][CH:14]=2)O1.Br[C:26]1[N:31]=[C:30]([NH2:32])[CH:29]=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Na+].[Na+]>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.O1CCOCC1>[F:23][C:20]([F:21])([F:22])[C@@H:16]1[CH2:17][CH2:18][CH2:19][N:15]1[C:12]1[N:13]=[CH:14][C:9]([C:26]2[N:31]=[C:30]([NH2:32])[CH:29]=[CH:28][CH:27]=2)=[CH:10][N:11]=1
Reactant: Nc1cccc(Br)n1
Reactant: CC1(C)OB(c2cnc(N3CCC[C@H]3C(F)(F)F)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: C1COCCO1
Product: Nc1cccc(-c2cnc(N3CCC[C@H]3C(F)(F)F)nc2)n1
Temperature: 90 °C
Yield: 83.3 %

Procedure:
A flask was charged with (S)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(2-(trifluoromethyl)pyrrolidin-1-yl)pyrimidine (Intermediate 2, 5 g, 14.57 mmol), 6-bromopyridin-2-amine (3.03 g, 17.48 mmol), Pd(PPh3)4 (1.684 g, 1.457 mmol) and 1,4-dioxane (36 mL). The reaction mixture was purged with nitrogen for several minutes before aqueous 2M sodium carbonate (14.57 mL, 29.1 mmol) solution was added. The reaction mixture was then purged with nitrogen for another 10 minutes at 25° C. before it was heated to 90° C. under nitrogen overnight. 1,4-Dioxane was removed in vacuo and the crude mixture was diluted with EtOAc. The product was washed with water (3×) and brine. The combined organic layers were dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified on silica gel chromatography eluting with MeOH:CH2Cl2 (2:98) to yield 3.75 g (12.13 mmol, 83%) of the title product as an off white solid; 1H NMR (300 MHz, DMSO-d6) δ 8.99 (s, 2H), 7.44 (dd, J=8.1, 7.5 Hz, 1H), 7.13-6.93 (m, 1H), 6.47-6.34 (m, 1H), 6.04 (s, 2H), 5.22-4.90 (m, 1H), 3.67 (t, J=6.1 Hz, 2H), 2.32-1.95 (m, 4H); m/z found [M+H]+=310.45.
Reaction SMILES: [C:1]([NH:5][C:6]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[CH:9]=[C:8]([C:18]2[CH:19]=[N:20][CH:21]=[C:22]([C:24]3[CH:29]=[CH:28][C:27]([C:30]([N:32]4[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]4)=[O:31])=[CH:26][CH:25]=3)[CH:23]=2)[CH:7]=1)([CH3:4])([CH3:3])[CH3:2].N1(C(C2C=CC(B3OC(C)(C)C(C)(C)O3)=CC=2)=O)CCNC[CH2:39]1.B(O)O>>[C:1]([NH:5][C:6]1[N:11]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=2)[CH:9]=[C:8]([C:18]2[CH:19]=[N:20][CH:21]=[C:22]([C:24]3[CH:25]=[CH:26][C:27]([C:30]([N:32]4[CH2:37][CH2:36][N:35]([CH3:39])[CH2:34][CH2:33]4)=[O:31])=[CH:28][CH:29]=3)[CH:23]=2)[CH:7]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC1(C)OB(c2ccc(C(=O)N3CCNCC3)cc2)OC1(C)C
Reactant: CC(C)(C)Nc1cc(-c2cncc(-c3ccc(C(=O)N4CCNCC4)cc3)c2)cc(-c2ccccn2)n1
Agent: OBO
Product: CN1CCN(C(=O)c2ccc(-c3cncc(-c4cc(NC(C)(C)C)nc(-c5ccccn5)c4)c3)cc2)CC1

Procedure:
The title compound is prepared analogously to [4-(6′-tert-Butylamino-[2,2′;4′,3″]terpyridin-5″-yl)-phenyl]-piperazin-1-yl-methanone (Example 2.48) by replacing piperazin-1-yl-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-methanone with the appropriate boronic acid.
Reaction SMILES: FC(F)(F)[C:3]([NH:5][C:6]1[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][N:8]([CH3:14])[N:7]=1)=O.CI.[OH-].[K+]>CC(C)=O>[CH3:14][N:8]1[CH:9]=[C:10]([N+:11]([O-:13])=[O:12])[C:6]([NH:5][CH3:3])=[N:7]1
Reactant: Cn1cc([N+](=O)[O-])c(NC(=O)C(F)(F)F)n1
Agent: [K+]
Agent: [OH-]
Solvent: CC(C)=O
Solvent: CI
Product: CNc1nn(C)cc1[N+](=O)[O-]
Reaction time: 0.08 h

Procedure:
100 g (4.20 mmoles) of 3-trifluoroacetylamino-1-methyl-4-nitropyrazol are heated with 2.12 g (16.8 mmoles) methyl iodide in 10 ml absolute acetone to 50° C. 940 mg (16.8 mmoles) powdered potassium hydroxide are then added and the reaction mixture is heated to boiling for 5 minutes. The solvent is distilled off in the rotary evaporator in vacuum and the residue is separated by means of column chromatography using silica gel with ether/toluene (5:1).
Reaction SMILES: [C:1](Cl)(=[O:3])[CH3:2].[CH3:5][O:6][C:7](=[O:26])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH:21]([NH:23][OH:24])[CH3:22])[C:16]=1[Cl:25].C([O-])(=O)C.[Na+].O1CCOCC1>O>[CH3:5][O:6][C:7](=[O:26])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH:21]([N:23]([C:1](=[O:3])[CH3:2])[OH:24])[CH3:22])[C:16]=1[Cl:25]
Reactant: COC(=O)c1ccccc1Nc1cccc(C(C)NO)c1Cl
Reactant: CC(=O)Cl
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: COC(=O)c1ccccc1Nc1cccc(C(C)N(O)C(C)=O)c1Cl
Temperature: 25 °C
Reaction time: 8 h
Yield: 15.1 %

Procedure:
Acetyl chloride (0.49 g, 6.2 mmol) is added dropwise to a mixture of 2[[2-chloro-3-[1-(N-hydroxyamino)ethyl]phenyl]amino]benzoic acid methyl ester (2.0 g, 6.2 mmol) and sodium acetate (0.77 g, 9.4 mmol) in 2:1 dioxane:water with ice bath cooling. The reaction mixture is stirred at room temperature overnight. It is then diluted with water (100 mL) and extracted with ethyl acetate (200 mL). The organic layer is washed with water (200 mL) and brine (100 mL), and is dried over magnesium sulfate. Evaporation of the ethyl acetate gives the crude product which is purified by flash chromatography (silica, 50% ethyl acetate/hexane). Recrystallization gives 2-[[3-[1-(acetylhydroxyamino)ethyl]-2-chlorophenyl]amino]benzoic acid methyl ester (0.34 g, 15%). mp=171-172° C.
Reaction SMILES: C(OC(=O)COC1C=CC(Cl)=CC=1[C:16]#[C:17][Si:18]([CH3:21])([CH3:20])[CH3:19])(C)(C)C.Br[C:24]1[CH:29]=[C:28]([S:30]([CH2:33][CH2:34][CH3:35])(=[O:32])=[O:31])[CH:27]=[CH:26][C:25]=1[CH3:36]>>[CH3:19][Si:18]([CH3:21])([CH3:20])[C:17]#[C:16][C:24]1[CH:29]=[C:28]([S:30]([CH2:33][CH2:34][CH3:35])(=[O:32])=[O:31])[CH:27]=[CH:26][C:25]=1[CH3:36]
Reactant: CC(C)(C)OC(=O)COc1ccc(Cl)cc1C#C[Si](C)(C)C
Reactant: CCCS(=O)(=O)c1ccc(C)c(Br)c1
Product: CCCS(=O)(=O)c1ccc(C)c(C#C[Si](C)(C)C)c1
Yield: 75 %

Procedure:
Following the general method as outlined in Intermediate 2, starting from 2-bromo-1-methyl-4-(propylsulfonyl)benzene (Intermediate 37) and trimethylsilylacetilene, the title compound was obtained as a brown liquid in 75% yield.
Reaction SMILES: [C:1]([NH:9][C:10]1[C:15](F)=[CH:14][N:13]([C@:17]2([SeH:48])[S:21][C@@H:20]([CH2:22][O:23][Si:24]([C:37]([CH3:40])([CH3:39])[CH3:38])([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:19][C@:18]2([F:47])[C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:12](=[O:49])[N:11]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(=O)C>C(Cl)Cl>[C:1]([NH:9][C:10]1[CH:15]=[CH:14][N:13]([C@:17]2([SeH:48])[S:21][C@@H:20]([CH2:22][O:23][Si:24]([C:37]([CH3:40])([CH3:39])[CH3:38])([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:19][C@:18]2([F:47])[C:41]2[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=2)[C:12](=[O:49])[N:11]=1)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(C)[Si](OC[C@H]1C[C@](F)(c2ccccc2)[C@]([SeH])(n2cc(F)c(NC(=O)c3ccccc3)nc2=O)S1)(c1ccccc1)c1ccccc1
Agent: CC(=O)[O-]
Solvent: ClCCl
Product: CC(C)(C)[Si](OC[C@H]1C[C@](F)(c2ccccc2)[C@]([SeH])(n2ccc(NC(=O)c3ccccc3)nc2=O)S1)(c1ccccc1)c1ccccc1

Procedure:
(−)-N4-Benzoyl-1-[(1S,2S,4R)-5-O-(tert-butyldiphenylsilyl)-2,3-dideoxy-2-fluoro-2-phenylselenyl-4-thio-β-L-ribofuranosyl]-5-fluorocytosine (L-10, FIG. 4a) was made using the general procedure for condensation reaction of the acetate L-8 with pyrimidines. The compound L-10 was obtained on 0.849-mmol scale in 59% yield: [α]24D −209.1° (c 0.693, CH2Cl2); UV(CH2Cl2) λmax 332.5 nm; 1H NMR (CDCl3) δ 12.70 (br s, 1H), 8.33 (d, J=7.5 Hz, 2H), 7.87 (dd, J=5.9, 1.7 Hz, 1H), 7.72˜7.28 (m, 18H), 6.73 (d, J=16.3 Hz, 1H), 3.92˜3.76 (m, 2H), 3.67˜3.58 (dt J=11.5, 6.8 Hz, 1H), 2.63˜2.46 (m, 2H), 1.07 (s, 9H); 13C NMR (CDCl3) δ 151.88 (d J=19.2 Hz), 147.15, 139.01 (d, J=237.9 Hz), 136.78, 135.90, 135.49, 135.47, 133.00, 132.71, 130.01, 129.96, 129.91, 129.51, 129.18, 128.24, 127.76, 126.85 (d, J=34.4 Hz), 124.74, 105.60 (d, J=247.5 Hz), 67.01 (d, J=18.6), 66.43, 47.19, 41.64 (d, J=21.0 Hz), 26.68, 19.09; FABMS m/z 762 (M+H)+; Anal. Calcd for C38H37F2N3O3SSeSi: C, 59.99; H, 4.90; N 5.52; S, 4.21. Found: C, 59.97; H, 5.05; N, 5.44; S, 4.23.