Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O)C.C1COCC1.[CH2:9]([CH:14]1[CH2:19][CH2:18][CH:17]([CH2:20][CH2:21][C:22]2[CH2:27][CH2:26][CH:25]([CH:28]3[CH2:33][CH2:32][C:31](=[O:34])[CH2:30][CH2:29]3)[CH2:24][CH:23]=2)[CH2:16][CH2:15]1)[CH2:10][CH2:11][CH2:12][CH3:13].[BH4-].[Na+]>O>[CH2:9]([CH:14]1[CH2:15][CH2:16][CH:17]([CH2:20][CH2:21][C:22]2[CH2:27][CH2:26][CH:25]([CH:28]3[CH2:33][CH2:32][CH:31]([OH:34])[CH2:30][CH2:29]3)[CH2:24][CH:23]=2)[CH2:18][CH2:19]1)[CH2:10][CH2:11][CH2:12][CH3:13]
Reactant: CCCCCC1CCC(CCC2=CCC(C3CCC(=O)CC3)CC2)CC1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: O
Solvent: C1CCOC1
Product: CCCCCC1CCC(CCC2=CCC(C3CCC(O)CC3)CC2)CC1
Temperature: 0 °C
Reaction time: 1 h
Yield: 40.7 %

Procedure:
To 1 l of mixed solvent of ethanol/THF (4/1) was dissolved 15.0 g (41.8 mmol) of the 4-(4-(2-(4-n-pentylcyclohexyl)ethyl)-3-cyclohexenyl)cyclohexanone described above, and the solution was cooled down to 0° C. To this mixture was gradually added 0.80 g (21.1 mmol) of sodium borohydride such that the liquid temperature did not exceed 15° C., and the mixture was stirred for 1 hour. Water in an amount of 350 ml was added to the reaction solution, the product thus formed was extracted with ether, the extract was washed with 1N-hydrochloric acid and water in this turn, and then the solvent was distilled off. After the residue was purified by column chromatography on silica gel (eluent: heptane/ethyl acetate=3/1), the solvent was distilled off. The residue was recrystallized from ethanol to give 6.0 g (17 mmol) of 4-(4-(2-(4-n-pentyl-cyclohexyl)ethyl)-3-cyclohexenyl)cyclohexanol. Yield of this compound based on 4-(4-(2-(4-n-pentylcyclohexyl)ethyl)-3-cyclohexenyl)cyclohexanone was 41%.
Reaction SMILES: [F:1][C:2]([F:17])([F:16])[C:3]([NH:5][CH2:6][CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12](I)=[CH:11][CH:10]=1)=[O:4].[CH3:18][O:19][C:20]([C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1)=[O:21].C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C(OCC)(=O)C.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>[F:1][C:2]([F:17])([F:16])[C:3]([NH:5][CH2:6][CH2:7][CH2:8][C:9]1[CH:14]=[CH:13][C:12]([C:25]2[CH:26]=[CH:27][C:22]([C:20]([O:19][CH3:18])=[O:21])=[CH:23][CH:24]=2)=[CH:11][CH:10]=1)=[O:4]
Reactant: COC(=O)c1ccc(B(O)O)cc1
Reactant: O=C(NCCCc1ccc(I)cc1)C(F)(F)F
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: COCCOC
Solvent: CCOC(C)=O
Solvent: O
Product: COC(=O)c1ccc(-c2ccc(CCCNC(=O)C(F)(F)F)cc2)cc1
Temperature: 75 °C
Reaction time: 10 h
Yield: 36 %

Procedure:
To a solution of 2,2,2-trifluoro-N-[3-(4-iodophenyl)-propyl]acetamide (2.5 g) in 1,2-dimethoxyethane (15 ml) was added [4-(methoxycarbonyl)phenyl]boronic acid (1.51 g), tetrakis(triphenylphosphine)palladium (809 mg) and aqueous solution of sodium carbonate (2M, 7 ml), and the mixture was stirred at 75° C. for 10 hours under nitrogen. The mixture was diluted with ethyl acetate and water. The organic layer was separated, washed with brine, dried over magnesium sulfate and evaporated. The residue was purified by column chromatography on silica gel (hexane/ethyl acetate=2/1) to give methyl 4′-[3-[(trifluoroacetyl)amino]propyl]-1,1′-biphenyl-4-carboxylate (920 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[O:13][C:12]([C:14]([OH:16])=O)=[CH:11][CH:10]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[NH2:17][C:18]1[CH:19]=[C:20]([CH2:24][C:25]#[N:26])[CH:21]=[CH:22][CH:23]=1>>[C:25]([CH2:24][C:20]1[CH:19]=[C:18]([NH:17][C:14]([C:12]2[O:13][C:9]([C:4]3[CH:5]=[C:6]([Cl:8])[CH:7]=[C:2]([Cl:1])[CH:3]=3)=[CH:10][CH:11]=2)=[O:16])[CH:23]=[CH:22][CH:21]=1)#[N:26]
Reactant: N#CCc1cccc(N)c1
Reactant: O=C(O)c1ccc(-c2cc(Cl)cc(Cl)c2)o1
Product: N#CCc1cccc(NC(=O)c2ccc(-c3cc(Cl)cc(Cl)c3)o2)c1

Procedure:
Carboxylic acid (67) (62 mg, 0.24 mmol) was coupled to aniline (80) (32 mg, 0.24 mmol) using Method C. After work-up, the solid was recrystallised from MeCN (3 ml) to give the title compound.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:28]=[CH:29][C:30]=1[F:31])[CH2:5][NH:6][C:7]([C:9]1[C:17]2[C:12](=[CH:13][C:14]([OH:18])=[CH:15][CH:16]=2)[N:11]([CH2:19][C:20]2[O:21][CH:22]=[CH:23][N:24]=2)[C:10]=1[CH:25]([CH3:27])[CH3:26])=[O:8].[CH:32](I)([CH3:34])[CH3:33]>>[F:1][C:2]1[CH:3]=[C:4]([CH:28]=[CH:29][C:30]=1[F:31])[CH2:5][NH:6][C:7]([C:9]1[C:17]2[C:12](=[CH:13][C:14]([O:18][CH:32]([CH3:34])[CH3:33])=[CH:15][CH:16]=2)[N:11]([CH2:19][C:20]2[O:21][CH:22]=[CH:23][N:24]=2)[C:10]=1[CH:25]([CH3:27])[CH3:26])=[O:8]
Reactant: CC(C)I
Reactant: CC(C)c1c(C(=O)NCc2ccc(F)c(F)c2)c2ccc(O)cc2n1Cc1ncco1
Product: CC(C)Oc1ccc2c(C(=O)NCc3ccc(F)c(F)c3)c(C(C)C)n(Cc3ncco3)c2c1

Procedure:
The title compound was prepared from N-(3,4-difluorobenzyl)-6-hydroxy-2-isopropyl-1-(oxazol-2-ylmethyl)-1H-indole-3-carboxamide (Compound 210) and isopropyl iodide by General Procedure N.
Reaction SMILES: [CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9]([O:13][C:14]([N:16]1[CH2:23][C@H:22]2[C@H:18]([CH2:19][CH:20]([CH3:24])[CH2:21]2)[C@H:17]1[CH:25]=O)=[O:15])([CH3:12])([CH3:11])[CH3:10].[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>C(Cl)(Cl)Cl.CC(=O)OCC.CCCCCCC>[C:9]([O:13][C:14]([N:16]1[CH2:23][C@H:22]2[C@H:18]([CH2:19][CH:20]([CH3:24])[CH2:21]2)[C@H:17]1[CH2:25][NH:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[O:15])([CH3:12])([CH3:10])[CH3:11]
Reactant: NCc1ccccc1
Reactant: CC1C[C@H]2CN(C(=O)OC(C)(C)C)[C@H](C=O)[C@H]2C1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCCCCCC
Solvent: ClC(Cl)Cl
Solvent: CCOC(C)=O
Product: CC1C[C@H]2CN(C(=O)OC(C)(C)C)[C@H](CNCc3ccccc3)[C@H]2C1
Reaction time: 16 h

Procedure:
Benzylamine (0.155 mL, 1.75 eq) was added to a solution of (1S,2S,5R)-2-formyl-7-methyl-3-aza-bicyclo[3.3.0]-octane-3-carboxylic acid tert.-butyl ester (206 mg, 1 eq) in chloroform (6 mL). After 15 min the mixture was treated with NaBH(OAc)3 (173 mg, 1 eq), and stirred for 16 h. The reaction mixture was poured into a sat. aq. NaHCO3 solution. The layers were separated and the aq. layer was extracted twice with chloroform. The combined org. extracts were washed with sat. NaHCO3 solution, dried over anh. MgSO4, filtered and concentrated in vacuo to give a crude yellow oil. FC (EA/n-heptane: 3/7 to 7/3) gave the title compound as a colourless oil
Reaction SMILES: CC1(C)COB([C:8]2[CH:9]=[C:10]([C:14]3[CH:19]=[CH:18][N:17]=[C:16]([NH2:20])[N:15]=3)[CH:11]=[CH:12][CH:13]=2)OC1.Br[CH2:23][C:24]1[CH:42]=[CH:41][C:27]([CH2:28][O:29][C:30]2[CH:35]=[CH:34][C:33]([C:36](=[O:38])[CH3:37])=[C:32]([OH:39])[C:31]=2[Cl:40])=[CH:26][CH:25]=1>>[NH2:20][C:16]1[N:15]=[C:14]([C:10]2[CH:9]=[C:8]([CH:13]=[CH:12][CH:11]=2)[CH2:23][C:24]2[CH:25]=[CH:26][C:27]([CH2:28][O:29][C:30]3[CH:35]=[CH:34][C:33]([C:36](=[O:38])[CH3:37])=[C:32]([OH:39])[C:31]=3[Cl:40])=[CH:41][CH:42]=2)[CH:19]=[CH:18][N:17]=1
Reactant: CC1(C)COB(c2cccc(-c3ccnc(N)n3)c2)OC1
Reactant: CC(=O)c1ccc(OCc2ccc(CBr)cc2)c(Cl)c1O
Product: CC(=O)c1ccc(OCc2ccc(Cc3cccc(-c4ccnc(N)n4)c3)cc2)c(Cl)c1O

Procedure:
The title compound is prepared essentially as described in Example 92 using 4-[3-(5,5-dimethyl-[1,3,2]dioxaborinan-2-yl)-phenyl]-pyrimidin-2-ylamine (327 mg, 1.15 mmol) and 1-[4-(4-bromomethyl-benzyloxy)-3-chloro-2-hydroxy-phenyl]-ethanone (400 mg, 1.08 mmol). The title compound is isolated (109 mg, 0.237 mmol) as a yellow solid: 1H NMR (DMSO-d6) δ 2.10 (s, 3H), 4.04 (s, 2H), 5.30 (s, 2H), 6.62 (m, 2H), 6.88 (d, 1H), 7.08 (m, 1H), 7.29 (m, 2H), 7.40 (m, 4H), 7.92 (m, 3H), 8.28 (d, 1H), 13.12 (s, 1H); MS (m/z): 458.2 (M−1).
Reaction SMILES: [NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9](=[O:15])OC(C)(C)C)[CH2:4][CH2:3]1.[C:16](OC(=O)C)(=O)C.[ClH:23].O1CCOCC1>C(Cl)Cl>[ClH:23].[NH2:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([NH:8][C:9](=[O:15])[CH3:16])[CH2:4][CH2:3]1
Reactant: CC(=O)OC(C)=O
Reactant: CC(C)(C)OC(=O)N[C@H]1CC[C@H](N)CC1
Agent: Cl
Solvent: ClCCl
Solvent: C1COCCO1
Product: CC(=O)N[C@H]1CC[C@H](N)CC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of tert-butyl trans-4-aminocyclohexylcarbamate (500 mg, 2.333 mmol) in DCM (20 mL) was added acetic anhydride (0.231 mL, 2.450 mmol). The solution was stirred overnight at RT. After 16 hours, 4 M HCl in dioxane (2.333 mL, 9.33 mmol) was added, and the reaction was stirred at RT for 3 days. The resulting white solid was collected by vacuum filtration and dried in vacuo to generate N-(trans-4-aminocyclohexyl)acetamide hydrochloride as a white powder (0.49 g, 109% yield).
Reaction SMILES: Br[C:2]1[CH:10]=[CH:9][C:8]2[C:4](=[CH:5][N:6]([CH3:11])[N:7]=2)[C:3]=1[CH:12]1[CH2:14][CH:13]1[CH2:15][NH:16][C:17](=[O:19])[CH3:18].[C-:20]#[N:21].[Na+]>CN1CCCC1=O.C(OCC)(=O)C.[Ni](Br)Br>[C:20]([C:2]1[CH:10]=[CH:9][C:8]2[C:4](=[CH:5][N:6]([CH3:11])[N:7]=2)[C:3]=1[CH:12]1[CH2:14][CH:13]1[CH2:15][NH:16][C:17](=[O:19])[CH3:18])#[N:21]
Reactant: CC(=O)NCC1CC1c1c(Br)ccc2nn(C)cc12
Reactant: [C-]#N
Agent: Br[Ni]Br
Agent: [Na+]
Solvent: CN1CCCC1=O
Solvent: CCOC(C)=O
Product: CC(=O)NCC1CC1c1c(C#N)ccc2nn(C)cc12
Temperature: 180 °C
Reaction time: 0.67 h
Yield: 31.2 %

Procedure:
To a solution of N-{[2-(5-bromo-2-methyl-2H-indazol-4-yl)cyclopropyl]methyl}acetamide (200 mg, 0.621 mmol) obtained in Example 29 in N-methylpyrrolidinone (3 mL) were added nickel(II) bromide (136 mg, 0.621 mmol) and sodium cyanide (61 mg, 1.241 mmol), and the mixture was stirred at 180° C. for 40 min using microwave. The reaction solution was diluted with ethyl acetate, washed with water and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (methanol/ethyl acetate=0/100→5/95) and recrystallization (ethyl acetate/hexane) to give the title compound (52 mg, yield 31%).
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[C:6]([CH3:16])([CH3:15])[CH2:7][CH:8]([OH:14])[C:9]([CH3:13])([CH3:12])[C:10]=2[CH:11]=1.[Br:17]Br.[C:19]([OH:22])(=O)[CH3:20]>[Cl-].[Na+].O>[Br:17][C:3]1[C:2]([CH3:1])=[CH:11][C:10]2[C:9]([CH3:12])([CH3:13])[CH:8]([O:14][C:19](=[O:22])[CH3:20])[CH2:7][C:6]([CH3:16])([CH3:15])[C:5]=2[CH:4]=1
Reactant: CC(=O)O
Reactant: BrBr
Reactant: Cc1ccc2c(c1)C(C)(C)C(O)CC2(C)C
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Product: CC(=O)OC1CC(C)(C)c2cc(Br)c(C)cc2C1(C)C
Temperature: 25 °C
Reaction time: 16 h
Yield: 97 %

Procedure:
To a solution of 4 g (18.3 mmol) of 3-methyl-6-hydroxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene in 20 mL of acetic acid was added 3.25 g (20.15 mmol) of bromine dropwise and the reaction was stirred at room temperature. After 16 hours, the reaction mixture was poured into brine and extracted with ethyl acetate. The organic extracts were washed with brine, dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by flash chromatography (gradient elution with hexane-15% ethyl acetate/hexane) to give 6 g (97%) of 2-bromo-3-methyl-6-acetoxy -5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene.(M+=338).
Reaction SMILES: F[C:2]1[C:3]([F:13])=[CH:4][C:5]2[O:10][CH2:9][C:8](=[O:11])[NH:7][C:6]=2[CH:12]=1.[Cl:14][CH2:15][CH2:16][CH2:17]I.C([O-])([O-])=O.[Cs+].[Cs+]>CC#N>[Cl:14][CH2:15][CH2:16][CH2:17][N:7]1[C:6]2[CH:12]=[CH:2][C:3]([F:13])=[CH:4][C:5]=2[O:10][CH2:9][C:8]1=[O:11]
Reactant: O=C1COc2cc(F)c(F)cc2N1
Reactant: ClCCCI
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC#N
Product: O=C1COc2cc(F)ccc2N1CCCCl
Temperature: 25 °C
Reaction time: 40 h
Yield: 95.3 %

Procedure:
A reaction flask was charged with 6,7-difluoro-4H-benzo[1,4]oxazin-3-one (1.5 g, 8.1 mmol), 1-chloro-3-iodopropane (1.44 g, 8.1 mmol), and Cs2CO3 (4.0 g, 12.2 mmol) in MeCN (10 mL) and stirred at rt for 40 h. The reaction mixture was concentrated, water added, and the product extracted into EtOAc. The combined organic phases were dried over Na2SO4, filtered, and concentrated. The product was purified by flash column chromatography (SiO2; n-heptane/EtOAc 2:1) to give the title compound (1.88 g, 89%). 1H NMR (CDCl3) δ 6.99 (dd, J=8.0 Hz, J=5.6 Hz, 1H), 6.79-6.72 (m, 2H), 4.59 (s, 2H), 4.08 (t, J=7.2 Hz, 2H), 3.62 (t, J=6.0 Hz, 2H) 2.18-2.10 (m, 2H); 13C NMR (CDCl3) δ 163.9, 159.1 (d, J=244.1 Hz), 146.4 (d, J=11.9 Hz), 124.9 (d, J=3.0 Hz), 115.4 (d, J=9.6 Hz), 109.5 (d, J=22.7 Hz), 105.4 (d, J=26.2 Hz), 67.7, 42.4, 39.2, 30.1.
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.[CH3:9][O:10][CH2:11][CH2:12][CH2:13][O:14][C:15]1[C:20]2[CH2:21][CH2:22][O:23][C:19]=2[CH:18]=[C:17]([CH2:24][OH:25])[CH:16]=1>ClCCl>[Br:1][C:16]1[C:17]([CH2:24][OH:25])=[CH:18][C:19]2[O:23][CH2:22][CH2:21][C:20]=2[C:15]=1[O:14][CH2:13][CH2:12][CH2:11][O:10][CH3:9].[Br:1][C:18]1[C:19]2[O:23][CH2:22][CH2:21][C:20]=2[C:15]([O:14][CH2:13][CH2:12][CH2:11][O:10][CH3:9])=[CH:16][C:17]=1[CH2:24][OH:25]
Reactant: O=C1CCC(=O)N1Br
Reactant: COCCCOc1cc(CO)cc2c1CCO2
Solvent: ClCCl
Product: COCCCOc1c(Br)c(CO)cc2c1CCO2
Product: COCCCOc1cc(CO)c(Br)c2c1CCO2
Reaction time: 0.5 h

Procedure:
N-Bromosuccinimide (1.04 g) was added to a solution of [4-(3-methoxypropoxy)-2,3-dihydro-1-benzofuran-6-yl]methanol (1.27 g) in dichloromethane (25 ml) under ice-cooling and the mixture was stirred at the same temperature for 30 minutes. The reaction mixture was concentrated in vacuo and the resulted residue was purified with a silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=3/2) to give [5-bromo-4-(3-methoxypropoxy)-2,3-dihydro-1-benzofuran-6-yl]methanol (860 mg) and [7-bromo-4-(3-methoxypropoxy)-2,3-dihydro-1-benzofuran-6-yl]methanol (540 mg) as a colorless oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:28]=[CH:29][C:30]=1[F:31])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([OH:26])[C:10](=[O:25])[N:11]([CH2:19][CH2:20][CH2:21][CH2:22][NH:23][CH3:24])[C:12]=2[C:16](O)=[O:17])[C:7]1=[O:27].Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.CN1CCOCC1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:28]=[CH:29][C:30]=1[F:31])[CH2:5][N:6]1[CH2:15][CH2:14][C:13]2[C:8](=[C:9]([OH:26])[C:10](=[O:25])[N:11]3[CH2:19][CH2:20][CH2:21][CH2:22][N:23]([CH3:24])[C:16](=[O:17])[C:12]3=2)[C:7]1=[O:27]
Reactant: CNCCCCn1c(C(=O)O)c2c(c(O)c1=O)C(=O)N(Cc1ccc(F)c(Cl)c1)CC2
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2cccnc21
Solvent: CN1CCOCC1
Solvent: CN(C)C=O
Product: CN1CCCCn2c(c3c(c(O)c2=O)C(=O)N(Cc2ccc(F)c(Cl)c2)CC3)C1=O

Procedure:
A solution of 6-(3-chloro-4-fluorobenzyl)-4-hydroxy-2-[4-(methylamino)butyl]-3,5-dioxo-2,3,5,6,7,8-hexahydro-2,6-naphthyridine-1-carboxylic acid (0.18 g, 0.40 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrocloride (0.08 g, 0.41 mmol), and 1-hydroxy-7-azabenzotriazole (0.07 g, 0.51 mmol), and N-methylmorpholine (0.35 mL, 3.16 mmol) in anhydrous DMF (3 mL) was stirred at room temperature overnight. The reaction mixture was concentrated under vacuum. The residue was purified by reverse phase high pressure liquid chromatography. Collection and concentration of appropriate fractions provided the title compound.
Reaction SMILES: [CH2:1]([Si:9]([CH2:16][CH:17]=[CH2:18])([CH2:13][CH:14]=[CH2:15])[CH2:10][CH:11]=[CH2:12])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8].[Cl:19][SiH:20]([Cl:22])[Cl:21]>C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.[Pt+2]>[CH2:1]([Si:9]([CH2:16][CH2:17][CH2:18][Si:20]([Cl:22])([Cl:21])[Cl:19])([CH2:10][CH2:11][CH2:12][Si:20]([Cl:22])([Cl:21])[Cl:19])[CH2:13][CH2:14][CH2:15][Si:20]([Cl:22])([Cl:21])[Cl:19])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH3:8]
Reactant: Cl[SiH](Cl)Cl
Reactant: C=CC[Si](CC=C)(CC=C)CCCCCCCC
Agent: [Pt+2]
Agent: CC(=O)/C=C(/C)[O-]
Product: CCCCCCCC[Si](CCC[Si](Cl)(Cl)Cl)(CCC[Si](Cl)(Cl)Cl)CCC[Si](Cl)(Cl)Cl
Temperature: 40 °C
Reaction time: 288 h
Yield: 74.1 %

Procedure:
In an inert atmosphere enclosure, into a 200 Ml glass ampoule equipped with a Teflon/glass valve and magnetic stirring bar were added platinum acetylacetonate (0.04 g, 0.1 mmol) and n-octyltriallylsilane (20.0 g, 75.6 mmol). Subsequently, trichlorosilane (87.17 g, 643.5 mmol) was distilled into the ampoule using a vacuum line transfer system. The ampoule was placed in an oil bath and heated slowly to 40° C., at which temperature it was kept for 12 days. The excess trichlorosilane was removed in vacuo, and distillation of the product yielded 37.6 g (74.1% yield), b.p. 202°-20° C. at 0.001 mm Hg of n-octyl-tris-[3-(trichlorosilyl)propyl]silane.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:7]C[CH:9]([Cl:11])[CH3:10].Br[CH2:13]CCBr>O1CCCC1>[Br-:7].[Cl:11][CH2:9][CH2:10][CH2:13][N+:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(Cl)CBr
Reactant: c1ccncc1
Reactant: BrCCCBr
Solvent: C1CCOC1
Product: ClCCC[n+]1ccccc1
Product: [Br-]

Procedure:
1-(3-chloropropyl)pyridinium bromide was prepared by the reaction of pyridine and 1-bromo-2-chloropropane. Pyridine (66 mL, 64.35 grams, 0.81 moles), 1,3-dibromopropane (166.23 grams, 0.82 moles) and tetrahydrofuran (150 mL) were added to a 1 L, round bottom flask equipped with air condensers and a magnetic stirring plate. The reagents were allowed to react at room temperature for 4 days. The reaction became cloudy as precipitate accumulated. Solids were collected by vacuum filtration, resuspended in tetrahydrofuran (250 mL) and collected by vacuum filtration. Solids were dried under vacuum at 35° C. for 24 hours. Yield 63.64 grams (0.27 moles, 30%).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[C:10]([OH:12])=O)[CH:3]=[CH:2]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.C(N(CC)C(C)C)(C)C.[C:44]([C:48]1[CH:64]=[CH:63][C:51]([CH2:52][NH:53][CH2:54][CH2:55][C:56]2[CH:61]=[CH:60][C:59]([CH3:62])=[CH:58][CH:57]=2)=[CH:50][CH:49]=1)([CH3:47])([CH3:46])[CH3:45]>CN(C=O)C.O>[C:44]([C:48]1[CH:64]=[CH:63][C:51]([CH2:52][N:53]([CH2:54][CH2:55][C:56]2[CH:57]=[CH:58][C:59]([CH3:62])=[CH:60][CH:61]=2)[C:10]([C:8]2[CH:7]=[CH:6][CH:5]=[C:4]3[C:9]=2[NH:1][CH:2]=[CH:3]3)=[O:12])=[CH:50][CH:49]=1)([CH3:47])([CH3:45])[CH3:46]
Reactant: Cc1ccc(CCNCc2ccc(C(C)(C)C)cc2)cc1
Reactant: O=C(O)c1cccc2cc[nH]c12
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: CN(C)C=O
Product: Cc1ccc(CCN(Cc2ccc(C(C)(C)C)cc2)C(=O)c2cccc3cc[nH]c23)cc1
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 87.1 %

Procedure:
To a solution of 48 mg (0.3 mmol) of 1H-indole-7-carboxylic acid and 96 mg of TBTU (0.3 mmol) in 4 ml DMF, were added 0.26 ml (1.5 mmol) of N,N-diisopropylethyl amine. After stirring for 5 min at rt, 89 mg (0.3 mmol) (4-tert-butyl-benzyl)-(2-p-tolyl-ethyl)-amine in 1 ml DMF was added. After stirring for 3 h at rt, the reaction mixture was diluted with 50 ml water and extracted with 2×50 ml EtOAc. The combined organic phases were washed with water and brine, dried with magnesium sulfate, filtered and concentrated in vacuo. The yellow residue was purified by column chromatography (8 g silica gel; heptane/EtOAc 9:1) to give 111 mg (86%) of a white solid. MS (ISP) 425.3 (M+H)+.
Reaction SMILES: Cl[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([CH3:12])=[N:7]2.[NH2:13][C:14]1[CH:33]=[C:32]([Cl:34])[CH:31]=[CH:30][C:15]=1[O:16][C:17]1[CH:29]=[CH:28][C:20]([C:21]([N:23]([CH2:26][CH3:27])[CH2:24][CH3:25])=[O:22])=[CH:19][CH:18]=1>>[Cl:34][C:32]1[CH:31]=[CH:30][C:15]([O:16][C:17]2[CH:29]=[CH:28][C:20]([C:21]([N:23]([CH2:24][CH3:25])[CH2:26][CH3:27])=[O:22])=[CH:19][CH:18]=2)=[C:14]([NH:13][C:2]2[C:3]3[C:8](=[N:7][C:6]([CH3:12])=[CH:5][CH:4]=3)[N:9]=[CH:10][CH:11]=2)[CH:33]=1
Reactant: Cc1ccc2c(Cl)ccnc2n1
Reactant: CCN(CC)C(=O)c1ccc(Oc2ccc(Cl)cc2N)cc1
Product: CCN(CC)C(=O)c1ccc(Oc2ccc(Cl)cc2Nc2ccnc3nc(C)ccc23)cc1

Procedure:
The product from Example 1d (111 mg, 0.62 mmol) was reacted with the product from Example 129b (199 mg, 0.62 mmol) for 18 h following the procedure from Example 1g giving the crude title compound which was purified by HPLC with TFA providing the product as a trifluoroacetic acid (49.2 mg, 14%). 1H NMR (300 MHz, DMSO-d6) δ ppm: 1.01 (s, 6H) 2.73 (s, 3H) 3.35 (s, 1H) 3.53-3.81 (m, 4H) 6.70 (d, J=7.35 Hz, 1H) 6.93 (d, J=8.46 Hz, 2H) 7.22 (d, J=8.82 Hz, 2H) 7.34 (d, J=8.82 Hz, 1H) 7.62 (dd, J=8.82, 2.57 Hz, 1H) 7.73 (d, J=6.25 Hz, 1H) 7.75 (s, 1H) 8.53 (d, J=6.99 Hz, 1H) 8.82 (d, J=8.82 Hz, 1H) 10.92 (s, 1H) 14.55 (s, 1H); MS (ESI+) m/z 461 (M+H−TFA)+.
Reaction SMILES: [CH:1]1([N:4]2[C:13]3[C:8](=[C:9]([NH2:16])[CH:10]=[C:11](F)[C:12]=3[F:14])[C:7](=[O:17])[C:6]([C:18]([OH:20])=[O:19])=[CH:5]2)[CH2:3][CH2:2]1.[NH:21]1[CH2:26][CH2:25][CH:24]([OH:27])[CH2:23][CH2:22]1.[H-].[Na+]>>[NH:21]1[CH2:26][CH2:25][CH:24]([O:27][C:11]2[C:12]([F:14])=[C:13]3[C:8]([C:7](=[O:17])[C:6]([C:18]([OH:20])=[O:19])=[CH:5][N:4]3[CH:1]3[CH2:3][CH2:2]3)=[C:9]([NH2:16])[CH:10]=2)[CH2:23][CH2:22]1
Reactant: Nc1cc(F)c(F)c2c1c(=O)c(C(=O)O)cn2C1CC1
Reactant: OC1CCNCC1
Agent: [H-]
Agent: [Na+]
Product: Nc1cc(OC2CCNCC2)c(F)c2c1c(=O)c(C(=O)O)cn2C1CC1

Procedure:
1-Cyclopropyl-5-amino-7,8-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid, 4-piperidinol and sodium hydride were reacted and treated in a similar manner to Example 9, whereby the title compound was obtained as colorless powder.
Reaction SMILES: C(NC1CCNCC1)(C)C.[CH:11]([N:14]([CH:17]([CH3:19])[CH3:18])[CH2:15][CH3:16])([CH3:13])[CH3:12].[CH2:20]([Br:22])[CH3:21].[CH3:23][CH2:24][N:25]([CH:29](C)C)[CH:26](C)C.Br>C(#N)C>[Br-:22].[CH2:15]([N:14]([CH:17]([CH3:19])[CH3:18])[CH:11]1[CH2:13][CH2:29][N+:25]([CH2:20][CH3:21])([CH2:24][CH3:23])[CH2:26][CH2:12]1)[CH3:16]
Reactant: CCN(C(C)C)C(C)C
Reactant: CCBr
Agent: Br
Agent: CC(C)NC1CCNCC1
Solvent: CC#N
Product: CCN(C(C)C)C1CC[N+](CC)(CC)CC1
Product: [Br-]
Temperature: 40 °C
Reaction time: 24 h
Yield: 99 %

Procedure:
14.23 g Freshly distilled 4-(isopropylamino)piperidine (100 mmole, fw=142.25), 28.43 g diisopropylethylamine (DIPEA, 220 mmole, fw=129.25) and 75 mL acetonitrile are placed in a 200 mL heavy-walled, glass pressure vessel that is equipped with a magnetic stirring-bar, thermocouple and pressure head with relief valve. 35.96 g ethyl bromide (330 mmole, fw=108.97) is added to the stirring mixture and pressure vessel is sealed. Initially there is a mild exotherm. The reaction mixture is heated and stirred at 40° C. for 24 hours, and then it is cooled to room temperature. During cooling, white crystals of DIPEA hydrobromide begin to form. The reaction vessel is vented in a hood, and then the reaction mixture is filtered through sintered-glass to remove the unwanted solid. The solvent is removed on a rotary evaporator, and then just enough 50% aqueous NaOH is added (˜28 g) until the mixture is strongly basic. The liquid (acetonitrile, water, DIEPA) is removed using a rotary evaporator and then a vacuum pump (0.5 torr). The residue is twice extracted with 100 mL hot acetonitrile, and the liquids are combined. Anhydrous magnesium sulfate (˜15 g) is added, the liquid is filtered and then placed on a rotary evaporator to remove most of the solvent. Small amounts of acetonitrile are added back to ensure a homogeneous solution, and then peroxide-free diethylether is added to induce crystallization. The mixture is allowed to stand at room temperature for about 4 hours and then at 4° C. overnight. The cold acetonitrile/ether mixture is filtered through sintered glass, washed with ether and then dried by passing dry N2 through the filter. The off-white solid is dried in a vacuum oven overnight yielding 22.1 g (72%) of a sticky, white crystalline solid with purity (HPLC) of about 97%. Recrystallization from acetonitrile/isopropanol/ether mixtures yields a purified product (˜99%). This reaction illustrates a method to carry out multiple alkylations of primary and secondary amines in the presence of a strong, soluble, nonreactive base. Despite the excess alkylating agent, there was no evidence (HPLC) of the tetraalkylated impurity in the reaction mixture or in the final trialkylated product.