Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl-].[CH3:2][SiH:3]([CH3:5])[CH3:4].[Cl:6][S:7]([OH:10])(=[O:9])=[O:8].Cl>ClC(Cl)C>[Cl:6][S:7]([O:10][Si:3]([CH3:5])([CH3:4])[CH3:2])(=[O:9])=[O:8]
Reactant: C[SiH](C)C
Reactant: O=S(=O)(O)Cl
Agent: Cl
Agent: [Cl-]
Solvent: CC(Cl)Cl
Product: C[Si](C)(C)OS(=O)(=O)Cl

Procedure:
In a first step, a film of 100 cm2 with a thickness of 100 μm, dried beforehand at 110° C. under vacuum (10 mbar), was immersed in 200 ml of dichloroethane (DCE) and the whole mixture is brought to 60° C. In parallel, an anhydrous solution of trimethylsilyl chlorosulfonate was prepared by dissolving 47.2 g (0.434 moles) of trimethylsilane chloride and 42.2 g (0.36 moles) of ClSO3H, both the constituents being anhydrous, in 50 ml of dry DCE with magnetic stirring and under argon, for a duration of 30 minutes, with HCl formed being trapped.
Reaction SMILES: [N+:1]([C:4]1[CH:17]=[CH:16][C:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[CH:14][C:5]=1[CH2:6][N:7]1[CH:11]=[CH:10][CH:9]=[C:8]1[CH:12]=O)([O-])=O.[H][H]>C(O)C.[Pd]>[CH:9]1[CH:10]=[CH:11][N:7]2[CH2:6][C:5]3[CH:14]=[C:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:16]=[CH:17][C:4]=3[NH:1][CH2:12][C:8]=12
Reactant: CCOC(=O)c1ccc([N+](=O)[O-])c(Cn2cccc2C=O)c1
Reactant: [H][H]
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)c1ccc2c(c1)Cn1cccc1CN2

Procedure:
A solution of 10.0 g of 1-[2-nitro-5-(ethoxycarbonyl)benzyl]-pyrrole-2-carboxaldehyde in 150 ml of absolute ethanol containing 1.0 g of 10% Pd/C is hydrogenated in a Parr apparatus for 16 hours under 40 psi of hydrogen. The reaction mixture is filtered through a pad of diatomaceous earth and the filtrate concentrated in vacuo to a residue of 5.5 g of the desired product as a solid; mass spectrum (M+H)255.
Reaction SMILES: Cl.[CH2:2]([O:4][C:5]([C@H:7]1[CH2:11][C@@H:10]([OH:12])[CH2:9][NH:8]1)=[O:6])[CH3:3].C(=O)([O-])[O-].[Na+].[Na+].[CH3:19][O:20][C:21]1[CH:29]=[CH:28][C:24]([CH2:25][CH2:26]Br)=[CH:23][CH:22]=1>C(#N)C.[I-].[Na+]>[CH2:2]([O:4][C:5]([C@H:7]1[CH2:11][C@@H:10]([OH:12])[CH2:9][N:8]1[CH2:26][CH2:25][C:24]1[CH:28]=[CH:29][C:21]([O:20][CH3:19])=[CH:22][CH:23]=1)=[O:6])[CH3:3]
Reactant: COc1ccc(CCBr)cc1
Reactant: CCOC(=O)[C@H]1C[C@@H](O)CN1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [I-]
Solvent: CC#N
Product: CCOC(=O)[C@H]1C[C@@H](O)CN1CCc1ccc(OC)cc1
Temperature: 42.5 °C
Reaction time: 65 h
Yield: 59.2 %

Procedure:
To a suspension of 6.60 g (33.7 mmol) of (2R, 4R)-(+)-2-(ethoxycarbonyl)-4-hydroxypyrrolidine hydrochloride in acetonitrile (60 ml) were added 8.22 g (77.6 mmol) of sodium carbonate, 4-methoxyphenethyl bromide (8.71 g, 40.5 mmol), and sodium iodide (150mg, 1.0 mmol) and the mixture was stirred at 40-45° C. for 65 h. The mixture was concentrated in vacuo and water was added to the residue, and the products were extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride and the products were extracted with 10% aqueous hydrochloride. The extract was washed with ethyl acetate, basified with potassium carbonate and extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain oily (2R, 4R)-(+)-2-(ethoxycarbonyl)-4-hydroxy-1-(4-methoxy phenethyl) pyrrolidine (5.85 g, 59.1%).
Reaction SMILES: Br[CH2:2][C:3]1[C:11]2[O:10][CH2:9][CH2:8][C:7]=2[CH:6]=[CH:5][CH:4]=1.[N-:12]=[N+:13]=[N-:14].[Na+].O>CN(C)C=O>[N:12]([CH2:2][C:3]1[C:11]2[O:10][CH2:9][CH2:8][C:7]=2[CH:6]=[CH:5][CH:4]=1)=[N+:13]=[N-:14]
Reactant: [N-]=[N+]=[N-]
Reactant: BrCc1cccc2c1OCC2
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: [N-]=[N+]=NCc1cccc2c1OCC2
Reaction time: 3 h

Procedure:
The product of Example 48B (4.40 g) in N,N-dimethylformamide (60 mL) at room temperature was treated in one portion with sodium azide (5.37 g), stirred for 3 hours, poured into water and extracted with diethylether (2×100 mL). The organics were dried (sodium sulfate), filtered, and the filtrate concentrated under reduced pressure. The residue was purified by flash chromatography (5% ethyl acetate/hexane) to provide the title compound. 1H NMR (CDCl3) δ 3.23 (t, 2H), 4.31 (s, 2H), 4.60 (t, 2H), 6.85 (t, 1H), 7.06 (d, 1H), 7.19 (dd, 1H).
Reaction SMILES: [C:1]1([S:7]([O-:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Na+].[C:11](#[N:14])[CH:12]=[CH2:13].S(=O)(=O)(O)O>O>[C:1]1([S:7]([CH2:13][CH2:12][C:11]#[N:14])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C=CC#N
Reactant: O=S([O-])c1ccccc1
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Product: N#CCCS(=O)(=O)c1ccccc1
Temperature: 100 °C
Reaction time: 0.5 h

Procedure:
650 ml of water are introduced into the flask and are heated to 80° to 90° C., and 935 g (4 mols) of 70% strength sodium benzenesulphinate are added to the water. 215 g (4.04 mols) of acrylonitrile and 382 g (1.95 mols) of 50% strength sulphuric acid are then added simultaneously, in the course of about 1 hour at 100° C., at such a rate that the pH value remains at 6 to 7. The mixture is stirred for 30 minutes at 100° C. and the pH value is again readjusted. Excess acrylonitrile is distilled off over a Vigreux column in an azeotropic mixture with water at normal pressure, and 255 g of xylene are then added and the phases are separated at about 95° C. This is carried out by sucking off the lower aqueous phase with a suction tube. The salt precipitate remains for the most part in the flask. 800 ml of washing water is now stirred in at >95° C. and the phases are separated as described above. In this process most of the salt is dissolved, and the remainder does not interfere in the following reaction. A further 17 g of 3-phenylsulphonyl-propionitrile are isolated from the combined aqueous phases. 255 g (300 ml) of xylene are now added to the organic phase in the flask, at 95° to 100° C., and the remaining water is distilled off azeotropically with xylene (boiling point 92° C.) The remaining xylene is completely removed in vacuo at a trough temperature of 100° to 120° C. The trough now contains 730 g (94%) of 3-phenylsulphonyl-propionitrile in 97% purity, and 50 g of salt.
Reaction SMILES: [OH-].[Na+].C[Si](C)(C)[C:5]#[C:6][C:7]([O:14][CH2:15][CH3:16])([O:11][CH2:12][CH3:13])[O:8][CH2:9][CH3:10]>O.C(O)C>[CH2:15]([O:14][C:7]([O:8][CH2:9][CH3:10])([O:11][CH2:12][CH3:13])[C:6]#[CH:5])[CH3:16]
Reactant: CCOC(C#C[Si](C)(C)C)(OCC)OCC
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: C#CC(OCC)(OCC)OCC
Temperature: 25 °C
Reaction time: 1 h
Yield: 55.8 %

Procedure:
A solution of sodium hydroxide (0.14 g, 3.60 mmol) in water (50 mL) was added to a solution of trimethyl-triethoxyprop-1-ynyl-silane (50.0 g, 208 mmol) in ethanol (250 mL). After stirring for 1 hour at room temperature, water was added and the mixture was extracted with ethyl acetate. The organic extracts were dried with magnesium sulfate and the solvent was removed under reduced pressure to give the title compound (20.0 g, 52% yield) as yellow oil. 1H NMR (CDCl3) δ 3.70 (q, 6H, J=8.0 Hz), 2.56 (s, 1H) 1.24 (t, 9H, J=8.0 Hz).
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH:6]([C:8]1[C:16]2[O:15][CH2:14][CH:13]([C:17]3[CH:22]=[CH:21][C:20]([CH:23]([CH3:25])[CH3:24])=[CH:19][CH:18]=3)[C:12]=2[C:11]([CH3:26])=[C:10]([NH:27][C:28](=[O:34])[CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:9]=1[CH3:35])=O.[BH4-].[Na+].O>CO.CC(C)[O-].CC(C)[O-].CC(C)[O-].CC(C)[O-].[Ti+4]>[CH:23]([C:20]1[CH:21]=[CH:22][C:17]([CH:13]2[C:12]3[C:11]([CH3:26])=[C:10]([NH:27][C:28](=[O:34])[CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[C:9]([CH3:35])=[C:8]([CH2:6][N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)[C:16]=3[O:15][CH2:14]2)=[CH:18][CH:19]=1)([CH3:24])[CH3:25]
Reactant: C1CCNC1
Reactant: Cc1c(C=O)c2c(c(C)c1NC(=O)CC(C)(C)C)C(c1ccc(C(C)C)cc1)CO2
Agent: [Ti+4]
Agent: CC(C)[O-]
Agent: [BH4-]
Solvent: CO
Solvent: O
Product: Cc1c(CN2CCCC2)c2c(c(C)c1NC(=O)CC(C)(C)C)C(c1ccc(C(C)C)cc1)CO2
Temperature: 25 °C
Reaction time: 14 h
Yield: 49.6 %

Procedure:
To a solution of pyrrolidine (0.20 mL, 2.4 mmol) in methanol (5 mL) was added titanium tetraisopropoxide (0.36 mL, 1.20 mmol) and N-(7-formyl-3-(4-isopropylphenyl)-4,6-dimethyl-2,3-dihydro-1-benzofuran-5-yl)-3,3-dimethylbutanamide (250 mg; 0.61 mmol) obtained in Example 20 at 0° C. and the resulting mixture was stirred at room temperature for 14 hours. To the reaction solution was added sodium borohydride (23.2 mg, 0.61 mol) at room temperature and the resulting mixture was stirred for 1.5 hours. Water was added to the reaction solution and the product was concentrated under reduced pressure, and the residue was extracted with ethyl acetate. The obtained residue was purified by basic silica gel column chromatography (hexane:ethyl acetate=2:1) to obtain 140 mg (yield: 49%) of the title compound. Amorphous substance.
Reaction SMILES: [F:1][C:2]([F:11])([F:10])[C:3]1[C:4]([NH2:9])=[N:5][CH:6]=[CH:7][CH:8]=1.[Br:12]Br.O>C(O)(=O)C>[Br:12][C:7]1[CH:8]=[C:3]([C:2]([F:1])([F:10])[F:11])[C:4]([NH2:9])=[N:5][CH:6]=1
Reactant: Nc1ncccc1C(F)(F)F
Reactant: BrBr
Solvent: CC(=O)O
Solvent: O
Product: Nc1ncc(Br)cc1C(F)(F)F
Yield: 74 %

Procedure:
3-(trifluoromethyl)pyridin-2-amine (20 g, 123 mmol) was stirred in acetic acid (200 ml) at RT. Bromine (19.72 g, 123 mmol) was added drop wise with stirring. The reaction mixture was stirred for 2 h; followed by dilution with water. The product was extracted with ethyl acetate. Organic layer was washed with water, dried over sodium sulfate and concentrated to obtain the title product in 74% yield.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:12]3[CH2:17][CH:16]([CH3:18])[NH:15][CH:14]([CH3:19])[CH2:13]3)=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([N:27]=[C:28]=[O:29])=[CH:23][CH:22]=1>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([N:12]3[CH2:13][CH:14]([CH3:19])[N:15]([C:28]([NH:27][C:24]4[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=4)=[O:29])[CH:16]([CH3:18])[CH2:17]3)=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1
Reactant: O=C=Nc1ccc(F)cc1
Reactant: CC1CN(c2ccnc3cc(Cl)ccc23)CC(C)N1
Solvent: CO
Solvent: ClCCl
Product: CC1CN(c2ccnc3cc(Cl)ccc23)CC(C)N1C(=O)Nc1ccc(F)cc1

Procedure:
7-Chloro-4-(3,5-dimethylpiperazin-1-yl)quinoline (100 mg, 0.36 mmol) and 4-fluorophenyl isocyanate (70 mg, 0.51 mmol) are reacted according to method C yielding the title product as colorless solid after column chromatography with CH2Cl2-MeOH.
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]2[CH:20]=[CH:19][C:11]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[C:10]([F:21])[CH:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.C1C(=O)N([Br:29])C(=O)C1.C([O-])(O)=O.[Na+].[O-]S([O-])(=S)=O.[Na+].[Na+]>C(#N)C.C(OCC)(=O)C>[NH2:1][C:2]1[C:7]([C:8]2[CH:20]=[CH:19][C:11]([C:12]([O:14][C:15]([CH3:17])([CH3:18])[CH3:16])=[O:13])=[C:10]([F:21])[CH:9]=2)=[CH:6][C:5]([Br:29])=[CH:4][N:3]=1
Reactant: CC(C)(C)OC(=O)c1ccc(-c2cccnc2N)cc1F
Reactant: O=C1CCC(=O)N1Br
Agent: O=C([O-])O
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: CC#N
Solvent: CCOC(C)=O
Product: CC(C)(C)OC(=O)c1ccc(-c2cc(Br)cnc2N)cc1F
Reaction time: 0.17 h
Yield: 90 %

Procedure:
A solution of tert-butyl 4-(2-aminopyridin-3-yl)-2-fluorobenzoate (700 mg, 2.43 mmol) in acetonitrile (10 mL) was treated with NBS (453 mg, 2.55 mmol). After 10 min, the reaction was completed. The reaction was treated with 1:1 sat. aq. NaHCO3: sat.aq. Na2S2O3 (10 mL). The mixture was stirred vigorously for 10 min. The mixture was diluted with ethyl acetate (30 mL) and the layers were separated. The organics were washed with brine, dried over magnesium sulfate, filtered and concentrated to provide tert-butyl 4-(2-amino-5-bromopyridin-3-yl)-2-fluorobenzoate (803 mg, 90% yield). LCMS (m/z): 367.2, 369.2 (MH+), 0.75 min.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([OH:23])[CH:5]=[CH:6][C:7]=1[CH:8]([CH3:22])[C:9]([OH:21])([C:14]1[CH:19]=[CH:18][N:17]=[C:16]([CH3:20])[CH:15]=1)[C:10]([F:13])([F:12])[F:11].[CH2:24]([O:26][C:27]([C:29]1[CH:34]=[CH:33][C:32]([CH2:35]Cl)=[CH:31][N:30]=1)=[O:28])[CH3:25]>>[CH2:24]([O:26][C:27]([C:29]1[CH:34]=[CH:33][C:32]([CH2:35][O:23][C:4]2[CH:5]=[CH:6][C:7]([CH:8]([CH3:22])[C:9]([OH:21])([C:14]3[CH:19]=[CH:18][N:17]=[C:16]([CH3:20])[CH:15]=3)[C:10]([F:13])([F:11])[F:12])=[C:2]([Cl:1])[CH:3]=2)=[CH:31][N:30]=1)=[O:28])[CH3:25]
Reactant: Cc1cc(C(O)(C(C)c2ccc(O)cc2Cl)C(F)(F)F)ccn1
Reactant: CCOC(=O)c1ccc(CCl)cn1
Product: CCOC(=O)c1ccc(COc2ccc(C(C)C(O)(c3ccnc(C)c3)C(F)(F)F)c(Cl)c2)cn1

Procedure:
The title compound was prepared in analogy to Example 93, step 7 from 3-chloro-4-[3,3,3-trifluoro-2-hydroxy-1-methyl-2-(2-methyl-pyridin-4-yl)-propyl]-phenol (obtained in Example 93, step 6) by alkylation with ethyl-5-(chloromethyl)-pyridine-2-carboxylate [CAS Reg. No. 39977-48-5]. MS (m/e)=509.1 [MH+].
Reaction SMILES: [C:1]([CH2:3][CH2:4][N:5]([CH2:21][CH2:22][C:23]#[N:24])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][N:12]([CH2:17][CH2:18][C:19]#[N:20])[CH2:13][CH2:14][C:15]#[N:16])#[N:2].[H][H]>O1CCOCC1>[NH2:16][CH2:15][CH2:14][CH2:13][N:12]([CH2:17][CH2:18][CH2:19][NH2:20])[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][N:5]([CH2:4][CH2:3][CH2:1][NH2:2])[CH2:21][CH2:22][CH2:23][NH2:24]
Reactant: N#CCCN(CCC#N)CCCCCCN(CCC#N)CCC#N
Reactant: [H][H]
Solvent: C1COCCO1
Product: NCCCN(CCCN)CCCCCCN(CCCN)CCCN
Yield: 88.5 %

Procedure:
16.42 g of N,N,N′,N′-tetrakis(2-cyanoethyl)-1,6-hexanediamine, 1.64 g of Raney Co and 90 mL of 1,4-dioxane were charged in an autoclave and a hydrogenation reaction was carried out at an initial hydrogen pressure of 9.0 MPa at 180° C. for 2.5 hours. After the catalyst was removed by filtration, the obtained filtrate was concentrated to dryness to give 15.24 g of the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[NH:9][CH:10]=[CH:11][C:12]=2[S:13]([C:16]([F:19])([F:18])[F:17])(=[O:15])=[O:14])=[CH:4][CH:3]=1.[N+:20]([O-])([OH:22])=[O:21].O>C(OC(=O)C)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[NH:9][C:10]([N+:20]([O-:22])=[O:21])=[CH:11][C:12]=2[S:13]([C:16]([F:17])([F:19])[F:18])(=[O:14])=[O:15])=[CH:6][CH:7]=1
Reactant: O=[N+]([O-])O
Reactant: O=S(=O)(c1cc[nH]c1-c1ccc(Cl)cc1)C(F)(F)F
Solvent: O
Solvent: CC(=O)OC(C)=O
Product: O=[N+]([O-])c1cc(S(=O)(=O)C(F)(F)F)c(-c2ccc(Cl)cc2)[nH]1
Temperature: 25 °C
Reaction time: 20 h
Yield: 37.5 %

Procedure:
A solution of 2-(p-chlorophenyl)-3-[(trifluoromethyl)sulfonyl]pyrrole (1.0 g, 0.00323 mol) in acetic anhydride is cooled with an ice bath, treated with nitric acid (0.15 mL, 0.00329 mol), warmed to room temperature, stirred for 20 hours and poured into water. The mixture is decanted and the insolubles are dissolved in ethyl acetate. The ethyl acetate solution is washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to obtain an amber residue. Flash chromatography of the residue using silica gel and a 1:1 ethyl acetate/hexanes solution gives the title product as a tan solid (0.43 g, mp 174°-180° C.) which is identified by 1HNMR spectral analysis.
Reaction SMILES: [F:1][C:2]1[CH:28]=[CH:27][CH:26]=[C:25]([F:29])[C:3]=1[C:4]([NH:6][C:7]1[S:8][C:9]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)=[C:10]([CH:12]([OH:14])[CH3:13])[N:11]=1)=[O:5].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[C:12]([C:10]1[N:11]=[C:7]([NH:6][C:4](=[O:5])[C:3]2[C:25]([F:29])=[CH:26][CH:27]=[CH:28][C:2]=2[F:1])[S:8][C:9]=1[C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:22])([F:23])[F:24])[CH:16]=1)(=[O:14])[CH3:13]
Reactant: CC(O)c1nc(NC(=O)c2c(F)cccc2F)sc1-c1cccc(C(F)(F)F)c1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: CC(=O)c1nc(NC(=O)c2c(F)cccc2F)sc1-c1cccc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 82.1 %

Procedure:
To the solution of Compound 74 (22 mg, 0.05 mmol) in CH2Cl2 (2 mL) was added Dess-Martin periodinate (22 mg, 0.05 mmol). The reaction mixture was stirred at room temperature for 30 minutes. The solvent was removed and the residue was purified by column chromatography on silica gel (eluted with 10-70% ethyl acetate in hexanes) gave Compound 84 (17.5 mg, 82%) as a white solid.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:6]=[CH:5]2.[CH3:17][Si:18]([C:21]#[CH:22])([CH3:20])[CH3:19]>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.[Cu]I.C1COCC1.C(N(CC)CC)C>[O:12]1[CH2:13][CH2:14][CH2:15][CH2:16][CH:11]1[N:7]1[C:8]2[C:4](=[CH:3][C:2]([C:22]#[C:21][Si:18]([CH3:20])([CH3:19])[CH3:17])=[CH:10][CH:9]=2)[CH:5]=[N:6]1
Reactant: C#C[Si](C)(C)C
Reactant: Brc1ccc2c(cnn2C2CCCCO2)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: C[Si](C)(C)C#Cc1ccc2c(cnn2C2CCCCO2)c1
Temperature: 80 °C

Procedure:
To a 250-mL pressure tube, 5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (11.9 g, 42.3 mmol; Intermediate 1), Pd(Ph3P)2Cl2 (1.48 g, 0.05 mmol), CuI (0.8 g, 4.2 mmol) and THF/triethylamine (5:1, 85 mL) were added. This mixture was degassed with three vacuum/N2 cycles, and then trimethylsilylacetylene (9 mL, 63.5 mmol) was added. The pressure tube was sealed and heated at 80° C. for 2 days. Upon completion by LCMS, the reaction mixture was cooled down to room temperature and filtered through Celite with ethyl acetate (200 mL). The filtrate was concentrated to give the crude product that was used directly in the next step. LCMS: 299 (M+H)+.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[N:8]=[CH:7][C:6]([N+:13]([O-:15])=[O:14])=[C:5]2Cl.Cl.[CH3:18][C:19]1([NH2:25])[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1.CCN(C(C)C)C(C)C>CC(N(C)C)=O.O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[N:8]=[CH:7][C:6]([N+:13]([O-:15])=[O:14])=[C:5]2[NH:25][C:19]1([CH3:18])[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1
Reactant: O=[N+]([O-])c1cnc2cc(F)c(Br)cc2c1Cl
Reactant: CC1(N)CCOCC1
Agent: Cl
Solvent: O
Solvent: CC(=O)N(C)C
Solvent: CCN(C(C)C)C(C)C
Product: CC1(Nc2c([N+](=O)[O-])cnc3cc(F)c(Br)cc23)CCOCC1
Temperature: 100 °C
Reaction time: 4 h
Yield: 96.7 %

Procedure:
6-Bromo-4-chloro-7-fluoro-3-nitroquinoline (1 g, 3.27 mmol) was added to a solution of 4-methyltetrahydro-2H-pyran-4-amine hydrochloride (0.596 g, 3.93 mmol) and DIPEA (1.715 mL, 9.82 mmol) in DMA (10 mL) and the resulting mixture stirred at 100° C. for 4 h. The reaction mixture was diluted with water and the solid collected by filtration and dried to afford the desired material (1.215 g, 97%) as a brown solid which was used without further purification.
Reaction SMILES: [CH2:1]([SH:5])[CH2:2][CH2:3][SH:4].C(=O)([O-])[O-].[K+].[K+].F[C:13]1[CH:18]=[CH:17][C:16]([C:19](=[O:29])[C:20]([CH3:28])([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[CH3:21])=[CH:15][CH:14]=1>CC(N(C)C)=O>[SH:4][CH2:3][CH2:2][CH2:1][S:5][C:13]1[CH:14]=[CH:15][C:16]([C:19](=[O:29])[C:20]([CH3:21])([N:22]2[CH2:23][CH2:24][O:25][CH2:26][CH2:27]2)[CH3:28])=[CH:17][CH:18]=1
Reactant: CC(C)(C(=O)c1ccc(F)cc1)N1CCOCC1
Reactant: SCCCS
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Product: CC(C)(C(=O)c1ccc(SCCCS)cc1)N1CCOCC1
Temperature: 40 °C
Reaction time: 5 h

Procedure:
52.8 g (0.488 mol) of 1,3-propanedithiol are dissolved in 100 ml of dry dimethylacetamide, 22.0 g of potassium carbonate are added and the solution is heated to about 40° C. 20.0 g (0.08 mol) of 1-(4-fluorophenyl)-2-methyl-2-morpholine-4-yl-propan-1-one in 50 ml of dry dimethylacetamide are added dropwise over 14 h. The resulting suspension is stirred for additional 5 h, then the solid is filtered off and washed with toluene. From the filtrate the excess 1,3-propanedithiol and toluene are distilled off. The residue is dissolved in ethyl acetate and the resulting solution is washed with saturated ammonium chloride solution, is dried over MgSO4 and concentrated. The residue is recrystallized from ethanol. The obtained product has a melting point of 67-68° C. The structure is confirmed by the 1H-NMR-spectrum, measured in CDCl3. The signals (δ in ppm) are 1.31 (s, 6H), 1.39 (t, 1H), 2.00 (m,2H), 2.57 (t,4H), 2.70 (q,2H), 3.13 (t,2H), 3.69 (t,4H), 7.28 (d,2H), 8.50 (d, 2H).
Reaction SMILES: [C:1]([O:18][CH:19]([CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45])[CH2:20][C:21]([NH:23][CH2:24][CH2:25][CH2:26][CH2:27][C:28]([OH:30])=O)=[O:22])(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].[NH2:46][C@H:47]([C:60]([O:62][CH2:63][C:64]1[CH:69]=[CH:68][CH:67]=[CH:66][CH:65]=1)=[O:61])[CH2:48][CH2:49][C:50]([O:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=[O:51]>>[C:1]([O:18][CH:19]([CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH2:43][CH2:44][CH3:45])[CH2:20][C:21]([NH:23][CH2:24][CH2:25][CH2:26][CH2:27][C:28]([NH:46][C@H:47]([C:60]([O:62][CH2:63][C:64]1[CH:65]=[CH:66][CH:67]=[CH:68][CH:69]=1)=[O:61])[CH2:48][CH2:49][C:50]([O:52][CH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)=[O:51])=[O:30])=[O:22])(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: N[C@@H](CCC(=O)OCc1ccccc1)C(=O)OCc1ccccc1
Reactant: CCCCCCCCCCCCCCCC(=O)OC(CCCCCCCCCCCCCCC)CC(=O)NCCCCC(=O)O
Product: CCCCCCCCCCCCCCCC(=O)OC(CCCCCCCCCCCCCCC)CC(=O)NCCCCC(=O)N[C@@H](CCC(=O)OCc1ccccc1)C(=O)OCc1ccccc1
Yield: 79.7 %

Procedure:
Starting from N-(3-hexadecanoyloxyoctadecanoyl)-5-aminopentanoic acid (1.27 g) prepared by the method of Preparation B-6 and dibenzyl L-glutamate (0.65 g), dibenzyl N-[N-(3-hexadecanoyloxyoctadecanoyl)-5-aminopentanoyl]-L-glutamate (1.5 g) was obtained as crystal according to a similar manner to that of Example 2.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH3:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][CH:10]=1.[CH:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[CH:19]=[CH:18][C:17]=1[O:26][CH2:27][CH2:28]Cl>CS(C)=O.O>[CH3:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][CH2:28][CH2:27][O:26][C:17]2[CH:18]=[CH:19][C:20]3[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH:16]=2)=[CH:11][CH:10]=1
Reactant: COc1ccc(N)cc1
Reactant: ClCCOc1ccc2ccccc2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: O
Product: COc1ccc(NCCOc2ccc3ccccc3c2)cc1
Temperature: 145 °C

Procedure:
A mixture of anhydrous potassium carbonate (10 gm, in excess) and p-anisidine (0.45 gm, 0.003 mole) was taken in dry dimethylsulphoxide (DMSO, 40 ml). Now 2-(2-naphthyloxy)-1-chloroethane (0.5 gm, 0.002 mole) was added in it. Reaction mixture was refluxed at 145° C. for 7 hrs. The reaction was completed as checked by TLC. Reaction mixture was poured in distilled water (60 ml) and extracted with ethyl acetate thrice. The organic layer was separated and concentrated to get oily compound which was later crystallized by benzene hexane to get N-(4-methoxyphenyl)-[2-(naphthalen-2-yloxy) ethyl] amine yellow solid, m.p. 92° C., (yield 0.67 gm, 94%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([S:15][CH2:16][CH2:17][NH:18]C(=O)OC(C)(C)C)[N:12]2[CH:26]=[CH:27][N:28]=[C:11]2[CH:10]=1.[F:29][C:30]([F:35])([F:34])[C:31]([OH:33])=[O:32].ClC1C=C(Cl)C=CC=1C1N=C(NCCS)N2C=CN=C2C=1>ClCCl>[F:29][C:30]([F:35])([F:34])[C:31]([OH:33])=[O:32].[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:14]=[C:13]([S:15][CH2:16][CH2:17][NH2:18])[N:12]2[CH:26]=[CH:27][N:28]=[C:11]2[CH:10]=1
Reactant: CC(C)(C)OC(=O)NCCSc1nc(-c2ccc(Cl)cc2Cl)cc2nccn12
Agent: SCCNc1nc(-c2ccc(Cl)cc2Cl)cc2nccn12
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: NCCSc1nc(-c2ccc(Cl)cc2Cl)cc2nccn12

Procedure:
2-{[7-(2,4-Dichlorophenyl)imidazo[1,2-c]pyrimidin-5-yl]thio}ethanamine trifluoroacetate (Example 47A) is prepared in analogy to Example 40A from tert-butyl (2-{[7-(2,4-dichlorophenyl)imidazo[1,2-c]pyrimidin-5-yl]thio}ethyl)carbamate (Example 44A) (950 mg, 2.2 mmol) and trifluoroacetic acid (3.3 ml, 43 mmol) in dichloromethane (20 ml). The crude product consists of a 50:50 mixture of Example 47A and the regioisomeric product 2-{[7-(2,4-dichlorophenyl)imidazo[1,2-c]pyrimidin-5-yl]amino}ethanethiol. The mixture is processed further without purification.