Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6](C#N)=[O:7])=[CH:4][CH:3]=1.[CH3:12][N:13]1[CH:17]=[C:16]([CH3:18])[CH:15]=[C:14]1[CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21].C(O)(=O)C(O)=O>CCOCC.C(Cl)Cl>[Cl:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([C:17]2[N:13]([CH3:12])[C:14]([CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:15][C:16]=2[CH3:18])=[O:7])=[CH:4][CH:3]=1
Reactant: N#CC(=O)c1ccc(Cl)cc1
Reactant: CCOC(=O)Cc1cc(C)cn1C
Agent: O=C(O)C(=O)O
Solvent: CCOCC
Solvent: ClCCl
Product: CCOC(=O)Cc1cc(C)c(C(=O)c2ccc(Cl)cc2)n1C
Yield: 32.5 %

Procedure:
A solution of 1.65 g (0.01 mole) of p-chlorobenzoylcyanide, 1.81 g (0.01 mole) of ethyl 1,4-dimethylpyrrole-2-acetate and 0.08 g of anhydrous oxalic acid in 4 ml of ether was stored in the dark under nitrogen for four days. The solution was diluted with CH2Cl2. The organic solution was washed with 10 percent NaOH solution, dried (MgSO4), and the solvent evaporated in vacuo. The residue was recrystallized from 1,1,1-trichloroethane to give 1.04 g of ethyl 5-(4-chlorobenzoyl)-1,4-dimethylpyrrole-2-acetate, mp 105°-108° C., undepressed by admixture with authentic material.
Reaction SMILES: Cl[C:2]1[C:3]([NH:32]C2C=CC=CC=2S(C(C)C)(=O)=O)=[N:4][C:5](NC2C(OC(C)C)=CC(C3CCN(C(=O)CN(C)C)CC3)=C(C)C=2)=[N:6][CH:7]=1.[CH3:45][C:46]([O-:48])=O.[Na+].ClCC=[O:53].Cl>O>[N:4]1[C:5]2[NH:6][CH:7]=[CH:2][C:45]=2[C:46]([OH:48])=[N:32][C:3]=1[OH:53]
Reactant: Cc1cc(Nc2ncc(Cl)c(Nc3ccccc3S(=O)(=O)C(C)C)n2)c(OC(C)C)cc1C1CCN(C(=O)CN(C)C)CC1
Reactant: CC(=O)[O-]
Reactant: O=CCCl
Agent: Cl
Agent: [Na+]
Solvent: O
Product: Oc1nc(O)c2cc[nH]c2n1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To 40 g 6-aminopyrimidine-2,4-diol (1) (315 mmol) in 1.0 L of water was added 54.3 g NaOAc (662 mmol) and 48 mL of 2-chloroacetaldehyde (50 wt % in H2O, 378 mmol). The resulting mixture was heated to reflux and stirred for three hours. The reaction mixture was cooled to room temperature followed by slow addition of 300 mL of 2N HCl in H2O. The precipitate was filtered, washed with H2O and dried at 50° C. under vacuum to give the title compound.
Reaction SMILES: [CH3:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6](=[O:21])[N:7]3[C:14]4[CH:15]=[C:16]([CH3:20])[C:17]([CH3:19])=[CH:18][C:13]=4[NH:12][C:8]3=[N:9]2)=[CH:4][CH:3]=1.[CH:22]([O:25][C:26]1[CH:34]=[CH:33][C:29]([C:30](Cl)=[O:31])=[CH:28][CH:27]=1)([CH3:24])[CH3:23]>>[CH:22]([O:25][C:26]1[CH:34]=[CH:33][C:29]([C:30]([N:12]2[C:8]3=[N:9][C:10]4[C:5]([C:6](=[O:21])[N:7]3[C:14]3[CH:15]=[C:16]([CH3:20])[C:17]([CH3:19])=[CH:18][C:13]2=3)=[CH:4][CH:3]=[C:2]([CH3:1])[CH:11]=4)=[O:31])=[CH:28][CH:27]=1)([CH3:24])[CH3:23]
Reactant: CC(C)Oc1ccc(C(=O)Cl)cc1
Reactant: Cc1ccc2c(=O)n3c(nc2c1)[nH]c1cc(C)c(C)cc13
Product: Cc1ccc2c(=O)n3c4cc(C)c(C)cc4n(C(=O)c4ccc(OC(C)C)cc4)c3nc2c1

Procedure:
6-(4-Isopropoxybenzoyl)-3,8,9-trimethylbenzimidazo[2,1-b]-quinazolin-12(6H)one is prepared with 3,8,9-trimethylbenzimidazo[2,1-b]quinazolin-12(6H)one and 4-isopropoxybenzoyl chloride.
Reaction SMILES: Cl.[N:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH2:8]Cl.[Cl:10][C:11]1[CH:12]=[C:13]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][C:27]=3[O:29][CH2:30][C@@H:31]([N:33]([CH3:39])[C:34](=[O:38])[CH2:35][O:36][CH3:37])[CH3:32])[N:22]=[CH:21][N:20]=2)[CH:14]=[CH:15][C:16]=1[OH:17]>>[Cl:10][C:11]1[CH:12]=[C:13]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][C:27]=3[O:29][CH2:30][C@@H:31]([N:33]([CH3:39])[C:34](=[O:38])[CH2:35][O:36][CH3:37])[CH3:32])[N:22]=[CH:21][N:20]=2)[CH:14]=[CH:15][C:16]=1[O:17][CH2:8][C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][N:2]=1
Reactant: ClCc1ccccn1
Reactant: COCC(=O)N(C)[C@@H](C)COc1cccc2ncnc(Nc3ccc(O)c(Cl)c3)c12
Agent: Cl
Product: COCC(=O)N(C)[C@@H](C)COc1cccc2ncnc(Nc3ccc(OCc4ccccn4)c(Cl)c3)c12
Yield: 39 %

Procedure:
The procedure described in Example 3 was repeated using picolyl chloride hydrochloride and N-[(1S)-2-({4-[(3-chloro-4-hydroxyphenyl)amino]quinazolin-5-yl}oxy)-1-methylethyl]-2-methoxy-N-methylacetamide to give the title compound in 39% yield; NMR spectrum (DMSO-d6, 373K) 1.20 (m, 3H), 2.80 (s, 3H), 3.10 (s, 3H), 3.90 (m, 2H), 4.20 (m, 1H), 4.50 (m, 1H), 5.10 (m, 1H), 5.30 (s, 2H), 7.20 (m, 2H), 7.40 (m, 2H), 7.50 (d, 1H), 7.60 (d, 1H), 7.70 (t, 1H), 7.90 (t, 1H), 7.95 (s, 1H), 8.40 (s, 1H), 8.60 (d, 1H), 9.60 (s, 1H); Mass spectrum F 522.2.
Reaction SMILES: [C:1]([C:4]1[C:27]([CH3:28])=[CH:26][C:7]2[NH:8][C:9]([S:11][CH2:12][C:13]3[C:18]([O:19][CH3:20])=[C:17]([O:21][CH2:22][CH:23]4[CH2:25][CH2:24]4)[CH:16]=[CH:15][N:14]=3)=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2].C1C=C(Cl)C=C(C(OO)=[O:37])C=1.S([O-])([O-])(=O)=S.[Na+].[Na+]>C(Cl)Cl.C(=O)([O-])O.[Na+]>[C:1]([C:4]1[C:27]([CH3:28])=[CH:26][C:7]2[NH:8][C:9]([S:11]([CH2:12][C:13]3[C:18]([O:19][CH3:20])=[C:17]([O:21][CH2:22][CH:23]4[CH2:25][CH2:24]4)[CH:16]=[CH:15][N:14]=3)=[O:37])=[N:10][C:6]=2[CH:5]=1)(=[O:3])[CH3:2]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COc1c(OCC2CC2)ccnc1CSc1nc2cc(C(C)=O)c(C)cc2[nH]1
Agent: O=C([O-])O
Agent: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: ClCCl
Product: COc1c(OCC2CC2)ccnc1CS(=O)c1nc2cc(C(C)=O)c(C)cc2[nH]1
Temperature: 25 °C

Procedure:
5-Acetyl-6-methyl-2-[[(4-cyclopropylmethoxy-3-methoxy-2-pyridinyl)methyl]thio]-1H-benzimidazole (40 mg, 0.10 mmol) was dissolved in methylene chloride (10 ml) and sodium hydrogen carbonate (3 ml,1M). The mixture was stirred at ambient temperature and MCPBA (25 mg, 0.10 mmol, 70%) dissolved in methylene chloride (5 ml) was added portionwise. After 10 min sodium thiosulphate (30 mg) was added whereupon the phases were separated. The organic phase was dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was chromatographed on silica (CH2Cl2 /MeOH/NH3, 97.5:2.5:sat.) Yield 30 mg (73%) of the title compound.
Reaction SMILES: [CH:1]1(Br)[CH2:5][CH2:4][CH2:3][CH2:2]1.S(C)C.[Si:10]([O:17][CH2:18][CH:19]1[CH2:21][N@@:20]1[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11]>C1COCC1.CCOCC>[CH:1]1([CH2:21][C@H:19]([NH:20][C:22](=[O:23])[O:24][C:25]([CH3:28])([CH3:27])[CH3:26])[CH2:18][O:17][Si:10]([C:13]([CH3:15])([CH3:16])[CH3:14])([CH3:12])[CH3:11])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: BrC1CCCC1
Reactant: CC(C)(C)OC(=O)N1CC1CO[Si](C)(C)C(C)(C)C
Solvent: CCOCC
Solvent: C1CCOC1
Solvent: CSC
Product: CC(C)(C)OC(=O)N[C@H](CO[Si](C)(C)C(C)(C)C)CC1CCCC1
Reaction time: 2 h
Yield: 81.1 %

Procedure:
A 100 mL, three-neck flask was charged with Mg powder (720 mg, 30 mmol), and a solution of cyclopentylbromide (3.73 g, 25 mmol) in THF (25 mL) was added dropwise while the flask was heated with a heat gun. After stirring for about 2 h, most of the Mg had been consumed. The Grignard reagent was added to a suspension of CuBr.SMe2 (307.5 mg, 1.5 mmol) in THF (80 mL) at −78° C., the cuprate was stirred for 30 min and a solution of (S)-tert-butyl 2-(t-butyldimethylsilyloxymethyl)aziridine-1-carboxylate (2.87 g, 10 mmol) in ether (30 mL) was added. The mixture was stirred for 2 h, washed with sat'd aq NaHCO3 (2×20 mL) and brine (30 mL), dried over MgSO4, and evaporated. The residue was purified by silica chromatography to obtain tert-butyl (S)-3-cyclopentyl-1-(t-butyldimethylsilyloxy)propan-2-ylcarbamate (2.9 g, 81%) as an oil. 1H NMR (CDCl3, 400 MHz) δ 0.04 (s, 6H), 0.89 (s, 9H), 1.10 (m, 2H), 1.44 (s, 9H), 1.50 (m, 3H), 1.60 (m, 3H), 1.81 (m, 3H), 3.58 (m, 3H), 4.60 (brs, 1H).
Reaction SMILES: [NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:10]2[CH:15]=[CH:14][C:13]([NH2:16])=[CH:12][CH:11]=2)[C:6]=1[C:7]([NH2:9])=[O:8].[C:17]1([N:23]=[C:24]=[O:25])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>C1COCC1.CO.C(N(CC)CC)C>[NH2:1][C:2]1[S:3][CH:4]=[C:5]([C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:24]([NH:23][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)=[O:25])=[CH:12][CH:11]=2)[C:6]=1[C:7]([NH2:9])=[O:8]
Reactant: O=C=Nc1ccccc1
Reactant: NC(=O)c1c(-c2ccc(N)cc2)csc1N
Solvent: C1CCOC1
Solvent: CO
Solvent: CCN(CC)CC
Product: NC(=O)c1c(-c2ccc(NC(=O)Nc3ccccc3)cc2)csc1N
Reaction time: 0.5 h

Procedure:
Crude 2-amino-4-(4-amino-phenyl)-thiophene-3-carboxylic acid amide (0.15 mmoles, 1 eq) is dissolved in 5 mL THF and treated with 400 μL of 0.35 M THF solution of phenyl isocyanate (0.15 mmoles, 1 eq). When the reaction is complete, as judged by TLC analysis, the reaction mixture is diluted with 1 mL methanol and 1 mL triethylamine, stirred for 30 minutes, and concentrated to dryness. The residue is purified by prep HPLC yielding pure 2-amino-4-{4-[3-phenyl-ureido]-phenyl}-thiophene-3-carboxylic acid amide.
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[C:3]1[CH:16]=[CH:15][C:6]([O:7][C:8]2[CH:14]=[CH:13][C:11]([NH2:12])=[CH:10][CH:9]=2)=[CH:5][CH:4]=1.C([O:26][C:27]1[C:28]([C:36](Cl)=[O:37])=[N:29][C:30](Br)=[CH:31][C:32]=1[O:33][CH3:34])C1C=CC=CC=1.Cl.C(N(CC)CC)C.[H][H]>CN(C1C=CN=CC=1)C.C(Cl)Cl.CCOC(C)=O.[Pd]>[OH:26][C:27]1[C:28]([C:36]([NH:12][C:11]2[CH:10]=[CH:9][C:8]([O:7][C:6]3[CH:15]=[CH:16][C:3]([C:2]([F:17])([F:18])[F:1])=[CH:4][CH:5]=3)=[CH:14][CH:13]=2)=[O:37])=[N:29][CH:30]=[CH:31][C:32]=1[O:33][CH3:34]
Reactant: COc1cc(Br)nc(C(=O)Cl)c1OCc1ccccc1
Reactant: [H][H]
Reactant: Nc1ccc(Oc2ccc(C(F)(F)F)cc2)cc1
Agent: [Pd]
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Solvent: CCOC(C)=O
Solvent: CCN(CC)CC
Product: COc1ccnc(C(=O)Nc2ccc(Oc3ccc(C(F)(F)F)cc3)cc2)c1O
Temperature: 25 °C
Reaction time: 8 h
Yield: 43.3 %

Procedure:
To a stirred solution of 4-(4-trifluoromethylphenoxy)aniline (0.20 g, 0.8 mmol) and DMAP (0.10 g, 0.085 mmol) in CH2Cl2 (10 mL) was added all at once a solution of 3-benzyloxy-6-bromo-4-methoxypyridin-2-carbonylchloride (3) (0.29 g, 0.8 mmol) in CH2Cl2 (5 mL). The resulting mixture was stirred overnight at room temperature then poured into 2N HCl (10 mL). The organic layer was separated and the aqueous layer extracted with CH2Cl2 (2×10 mL). The organic layers were combined, dried (MgSO4) and concentrated to give a gummy solid. This solid was taken up in EtOAc (20 mL), and triethylamine (0.80 g, 0.8 mmol) and 5% Pd on carbon (0.10 g) were added. The resulting mixture was subjected to a hydrogen atmosphere (initial pressure=50 psi) on a Parr shaker for 30 minutes. The mixture was filtered, washed with 0.1N HCl (20 mL), dried (MgSO4) and concentrated to give the title compound as an off-white solid (0.14 g), m.p.=122-129° C.
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[F:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.Cl[C:13](=[O:22])[CH2:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH3:21])=[O:19]>ClCCl.O>[F:5][C:6]1[CH:11]=[CH:10][C:9]([C:13](=[O:22])[CH2:14][CH2:15][CH2:16][CH2:17][C:18]([O:20][CH3:21])=[O:19])=[CH:8][CH:7]=1
Reactant: Fc1ccccc1
Reactant: COC(=O)CCCCC(=O)Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Solvent: ClCCl
Product: COC(=O)CCCCC(=O)c1ccc(F)cc1
Temperature: -5 °C
Reaction time: 15 h

Procedure:
A suspension of 2.59 g (19.4.10−3 mol) of aluminum chloride in 4 ml of dichloromethane is prepared. It is cooled to −5° C. and a mixture of 0.97 ml (10.3.10−3 mol) of fluorobenzene and 1.31 ml (8.4.10−3 mol) of methyl 6-chloro-6-oxohexanoate in 3 ml of dichloromethane is added gradually, the temperature being maintained between −4 and −7° C. The temperature is then allowed to rise to 20° C. and, after 15 hours, the mixture is hydrolyzed in acidified iced water. It is extracted with dichloromethane and the organic phase obtained is washed with water, dried over magnesium sulfate and concentrated under reduced pressure. The 2 g of crude product recovered in this way are purified by chromatography on silica gel using a petroleum ether/ethyl acetate mixture (96/4) as the eluent to give 1.26 g of the expected product in the form of a white powder (yield=63%).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][C:11](=[O:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[CH3:15][N:16]([CH3:20])[CH2:17][CH2:18]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[CH3:15][N:16]([CH3:20])[CH2:17][CH2:18][O:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:9][CH2:10][C:11](=[O:14])[CH2:12][CH2:13]2)=[CH:6][CH:7]=1
Reactant: CN(C)CCO
Reactant: O=C1CCC(c2ccc(O)cc2)CC1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CN(C)CCOc1ccc(C2CCC(=O)CC2)cc1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
Into a solution of 4-(4-hydroxy-phenyl)cyclohexanone (as prepared in Example 40, Step E, 2.4 g, 12.6 mmol), N,N-dimethylethanolamine (Aldrich, 3.37 g, 37.8 mmol) and triphenylphosphine (Aldrich, 9.91 g, 37.8 mmol) in THF (100 mL) at 0° C. was added dropwise a solution of diisopropyl azodicarboxylate (7.44 mL, 37.8 mmol) in THF (15 mL) under Ar. The resulting solution was stirred at 0° C. for 1 h and at room temperature overnight. The solvent was removed and the residue was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over anhydrous Na2SO4, filtered, and the filtrate concentrated in vacuo to give a colorless oil, which was purified on a silica gel column by a CombiFlash® system using hexanes and ethyl acetate as eluent (from pure hexanes to pure ethyl acetate) to afford the title compound as a white solid.
Reaction SMILES: [Pt:1].[C:2]([O:19]C(=O)CCCCCCCCCCCCCCC)(=O)[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][CH2:16][CH3:17]>C(=O)(O)[O-].C([NH+](CC)CC)C.C(O)(C)C.O>[C:2]([Pt:1])(=[O:19])[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][CH2:16][CH3:17]
Reactant: [Pt]
Reactant: CCCCCCCCCCCCCCCC(=O)OC(=O)CCCCCCCCCCCCCCC
Agent: CC[NH+](CC)CC
Agent: O=C([O-])O
Solvent: CC(C)O
Solvent: O
Product: CCCCCCCCCCCCCCCC(=O)[Pt]
Temperature: 25 °C
Reaction time: 1 h

Procedure:
An estimated 30 nmol of the amino-derivatized 2-3 nm platinum cluster dissolved in 0.6 M triethylammonium bicarbonate in 20% isopropanol/water was evaporated to dryness five times from methanol, then dissolved in 3 mL of diclhoromethane, and treated with 200 nmol of palmitic anhydride. The mixture was stirred for one hour at room temperature, then washed three times with 0.1 M sodium phosphate buffer at pH 6.5. The remaining reaction mixture was evaporated to dryness, redissolved in 2:1 methanol/chloroform, then separated by gel filtration (GH25, Amicon eluted with 2:1 methanol:chloroform); the first species to elute is the dark brown palmitamido-platinum cluster. After evaporation to dryness, lipid conjugation was demonstrated by the extraction of the cluster into the chloroform layer when the palmitoyl cluster was shaken in a chloroform/water mixture with a small amount of methanol as a phase transfer agent.
Reaction SMILES: C[N:2]1[CH:7]=[N:6][C:5]([NH:8][C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([Cl:15])[CH:10]=2)=[N:4][CH:3]1Cl.[CH3:17]CN(C(C)C)C(C)C.[NH2:26][C:27]1[CH:28]=[C:29]([NH:33][C:34](=[O:37])[CH:35]=[CH2:36])[CH:30]=[CH:31][CH:32]=1>>[Cl:15][C:11]1[CH:10]=[C:9]([N:8]([CH3:17])[C:5]2[N:6]=[CH:7][N:2]=[C:3]([NH:26][C:27]3[CH:28]=[C:29]([NH:33][C:34](=[O:37])[CH:35]=[CH2:36])[CH:30]=[CH:31][CH:32]=3)[N:4]=2)[CH:14]=[CH:13][CH:12]=1
Reactant: CCN(C(C)C)C(C)C
Reactant: CN1C=NC(Nc2cccc(Cl)c2)=NC1Cl
Reactant: C=CC(=O)Nc1cccc(N)c1
Product: C=CC(=O)Nc1cccc(Nc2ncnc(N(C)c3cccc(Cl)c3)n2)c1
Temperature: 100 °C

Procedure:
To a slurry of N-methyl-2-chloro-4-(3-chloroanilino)-1,3,5-triazine (Step 1) (44.6 mg, 0.175 mmol) in IpOH (2.0 ml) was added DIEA (0.046 mL, 0.26 mmol) and N-(3-aminophenyl)acrylamide (31 mg, 0.192 mmol). The mix was heated at 100° C. for 18 h. The solution was then cooled to RT. The organics were concentrated under reduced pressure and the crude product was purified via column chromatography (elution with EtOAc) to give N-(3-{4-[(3-chlorophenyl)-methyl-amino]-[1,3,5]triazin-2-ylamino}-phenyl)-acrylamide: MS m/z=381 [M+H]+. Calc'd for C19H17ClN6O: 380.12.
Reaction SMILES: Cl[C:2]1C=C(C=C[CH:11]=1)C(OO)=O.C(S[C:15]1[C:20]([C:21]2[N:33]([CH3:34])[C:24]3=[N:25][CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=[C:23]3[N:22]=2)=[CH:19][N:18]=[CH:17][N:16]=1)C.[S:35]([O-:39])([O-])(=[O:37])=S.[Na+].[Na+]>C(Cl)(Cl)Cl>[CH2:2]([S:35]([C:19]1[C:20]([C:21]2[N:33]([CH3:34])[C:24]3=[N:25][CH:26]=[C:27]([C:29]([F:32])([F:30])[F:31])[CH:28]=[C:23]3[N:22]=2)=[CH:15][N:16]=[CH:17][N:18]=1)(=[O:39])=[O:37])[CH3:11]
Reactant: CCSc1ncncc1-c1nc2cc(C(F)(F)F)cnc2n1C
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: O=S([O-])([O-])=S
Agent: [Na+]
Solvent: ClC(Cl)Cl
Product: CCS(=O)(=O)c1ncncc1-c1nc2cc(C(F)(F)F)cnc2n1C
Temperature: 25 °C
Reaction time: 8 h

Procedure:
189 mg of 3-chloroperoxybenzoic acid (purity of 65% or more) was added to a mixture of 130 mg of 2-(4-ethylsulfanylpyrimidin-5-yl)-3-methyl-6-trifluoromethyl-3H-imidazo[4,5-b]pyridine and 4 ml of chloroform, then the mixture was stirred at room temperature for 8 hours. A 10% aqueous sodium thiosulfate solution was poured to the reaction mixture, and the mixture was extracted with chloroform. The organic layer was washed with a saturated aqueous sodium bicarbonate solution and dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure to obtain 130 mg of 2-(4-ethylsulfonylpyrimidin-5-yl)-3-methyl-6-trifluoromethyl-3H-imidazo[4,5-b]pyridine (hereinafter, referred to as Compound of Present Invention 15).
Reaction SMILES: [C:1](OC)(OC)(OC)[CH2:2][CH2:3][CH2:4][CH3:5].[CH3:12][S:13]([CH2:16][CH2:17][O:18][CH2:19][CH2:20][NH:21][C:22]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[N:25]=[CH:24][C:23]=1[NH2:32])(=[O:15])=[O:14].Cl.N1C=CC=CC=1>C(#N)C>[CH2:2]([C:1]1[N:21]([CH2:20][CH2:19][O:18][CH2:17][CH2:16][S:13]([CH3:12])(=[O:15])=[O:14])[C:22]2[C:31]3[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=3[N:25]=[CH:24][C:23]=2[N:32]=1)[CH2:3][CH2:4][CH3:5]
Reactant: CS(=O)(=O)CCOCCNc1c(N)cnc2ccccc12
Reactant: CCCCC(OC)(OC)OC
Agent: Cl
Solvent: CC#N
Solvent: c1ccncc1
Product: CCCCc1nc2cnc3ccccc3c2n1CCOCCS(C)(=O)=O
Reaction time: 0.25 h
Yield: 100.8 %

Procedure:
Trimethyl orthovalerate (1.3 g, 8.1 mmol) was added to a solution of N4-{2-[2-(methylsulfonyl)ethoxy]ethyl}quinoline-3,4-diamine (˜2.3 g, ˜7.4 mmol) in acetonitrile (37 mL). Pyridine hydrochloride (˜100 mg) was added and the reaction mixture was heated to reflux with the volatiles being collected in a Dean Stark trap. After 15 minutes analysis by TLC indicated that the starting material was consumed. The reaction mixture was cooled and then concentrated under reduced pressure to provide ˜2.8 g of 2-butyl-1-{2-[2-(methylsulfonyl)ethoxy]ethyl}-1H-imidazo[4,5-c]quinoline as a greenish-yellow powder.
Reaction SMILES: [CH3:1][C:2]([CH3:46])=[CH:3][CH2:4][CH2:5]/[C:6](/[CH3:45])=[CH:7]/[CH2:8][CH2:9]/[C:10](/[CH3:44])=[CH:11]/[CH2:12][CH2:13]/[C:14](/[CH3:43])=[CH:15]/[CH2:16][CH2:17]/[C:18](/[CH3:42])=[CH:19]/[CH2:20][CH2:21]/[C:22](/[CH3:41])=[CH:23]/[CH2:24][CH2:25]/[C:26](/[CH3:40])=[CH:27]/[CH2:28][CH2:29]/[C:30](/[CH3:39])=[CH:31]/[CH2:32][CH2:33]/[C:34](/[CH3:38])=[CH:35]/[CH2:36][OH:37].[C:47](O)(=[O:65])[CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH3:64].C(=O)([O-])O.[Na+]>C(Cl)(Cl)Cl.O>[C:47]([O:37][CH2:36][CH:35]=[C:34]([CH3:38])[CH2:33][CH2:32][CH:31]=[C:30]([CH3:39])[CH2:29][CH2:28][CH:27]=[C:26]([CH3:40])[CH2:25][CH2:24][CH:23]=[C:22]([CH3:41])[CH2:21][CH2:20][CH:19]=[C:18]([CH3:42])[CH2:17][CH2:16][CH:15]=[C:14]([CH3:43])[CH2:13][CH2:12][CH:11]=[C:10]([CH3:44])[CH2:9][CH2:8][CH:7]=[C:6]([CH3:45])[CH2:5][CH2:4][CH:3]=[C:2]([CH3:46])[CH3:1])(=[O:65])[CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH3:64]
Reactant: CCCCCCCCCCCCCCCCCC(=O)O
Reactant: CC(C)=CCC/C(C)=C/CC/C(C)=C/CC/C(C)=C/CC/C(C)=C/CC/C(C)=C/CC/C(C)=C/CC/C(C)=C/CC/C(C)=C/CO
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClC(Cl)Cl
Product: CCCCCCCCCCCCCCCCCC(=O)OCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C
Reaction time: 4 h

Procedure:
16 Grams of solanesol, 7.5 g. of stearic acid and 10 g. of polyphosphoric acid ethyl ester were dissolved in 40 ml of chloroform and the solution was refluxed under stirring for 4 hours. After completion of the reaction, the reaction product was poured in water and added with about 10 g. of sodium hydrogencarbonate to decompose the polyphosphoric acid ester. After extraction with ether, the ether layer was washed with water and subjected to distillation under reduced pressure. The residual oily substance was purified by column chromatography with 100 g. of silica gel to obtain 12.5 g. (54.8%) of white solid (m.p. 36°-37° C.).______________________________________Elementary analysis as C63H108O2 : C H______________________________________Theoretical (%): 84.31 12.13Found (%): 84.27 12.11______________________________________
Reaction SMILES: C1(N=C=NC2CCCCC2)CCCCC1.[F:16][C:17]([F:29])([F:28])[C:18]1[CH:19]=[C:20]([CH2:24][C:25]([OH:27])=O)[CH:21]=[CH:22][CH:23]=1.[Cl:30][C:31]1[CH:32]=[CH:33][C:34]([O:38][CH3:39])=[C:35]([CH:37]=1)[NH2:36]>ClCCl>[CH3:39][O:38][C:34]1[CH:33]=[CH:32][C:31]([Cl:30])=[CH:37][C:35]=1[NH:36][C:25](=[O:27])[CH2:24][C:20]1[CH:21]=[CH:22][CH:23]=[C:18]([C:17]([F:16])([F:29])[F:28])[CH:19]=1
Reactant: O=C(O)Cc1cccc(C(F)(F)F)c1
Reactant: COc1ccc(Cl)cc1N
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: ClCCl
Product: COc1ccc(Cl)cc1NC(=O)Cc1cccc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 60.9 %

Procedure:
Dicyclohexylcarbodiimide (2.20 g, 10.7 mmol) was added to a solution of 3-(trifluoromethyl)phenylacetic acid (2.00 g, 9.8 mmol) and 5-chloro-2-methoxyaniline (1.55 g, 9.8 mmol) in dichloromethane (50 ml). The reaction was stirred at RT overnight. The reaction mixture was filtered and the filtrate evaporated to dryness. The residue was recrystallized from methanol/water 2:1 (30 ml). 2.05 g (61%) of the title compound was isolated.
Reaction SMILES: [C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1B(O)O)(=O)[CH3:2].[S:13]1[C:25]2C3C=CC=CC=3C=[N:17][C:16]=2[CH:15]=[CH:14]1>>[CH3:2][C:1]1[C:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[C:25]2[S:13][CH:14]=[CH:15][C:16]=2[N:17]=1
Reactant: CC(=O)c1ccccc1B(O)O
Reactant: c1ccc2c(c1)cnc1ccsc12
Product: Cc1nc2ccsc2c2ccccc12
Yield: 86 %

Procedure:
Starting from 2-Acetylphenylboronic acid (15 g, 91 mmol) in place of 2-formylphenylboronic acid in Step 3, the title compound (12 g, 86%, m.p. 74-76° C.) was synthesized in essentially the same manner as described in Steps 1-3 for Thieno[3,2-c]isoquinoline.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[C:9]1([OH:15])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.C(N(C(C)C)CC)(C)C.[CH2:25]([O:32][CH2:33][C:34](Cl)=[O:35])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>ClCCl>[CH2:25]([O:32][CH2:33][C:34]([N:12]1[CH2:11][CH2:10][C:9]([C:3]2[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=2[Cl:1])([OH:15])[CH2:14][CH2:13]1)=[O:35])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: OC1(c2ccc(Cl)cc2Cl)CCNCC1
Reactant: O=C(Cl)COCc1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: O=C(COCc1ccccc1)N1CCC(O)(c2ccc(Cl)cc2Cl)CC1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 4-(2,4-dichloro-phenyl)-piperidin-4-ol (0.10 g, 0.40 mmol) in dichloromethane (2 mL) was added diisopropyl ethylamine (0.073 mL, 0.42 mmol) followed by benzyloxy acetyl chloride (0.078 g, 0.42 mmol). The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with dichloromethane (10 mL) and washed with saturated aqueous sodium bicarbonate (10 mL). The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo. The residual oil was chromatographed on silica gel using dichloromethane/methanol from 100% to 97% dichloromethane in a gradient fashion, to give the title compound as a glassy solid. The material was used as is without further purification. 1H NMR (300 MHz, CDCl3): δ 7.35 (m, 8H), 4.58 (m, 3H), 4.22 (m, 2H), 3.86 (bm, 1H), 3.57 (bm, 1H), 3.13 (bm, 1H), 2.64 (s, 1H), 2.26 (m, 2H), 1.97 (m, 2H).