Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:12]=[CH:11][C:5]([CH2:6][S:7](O)(=[O:9])=[O:8])=[CH:4][CH:3]=1.[Na].P(Cl)(Cl)(Cl)(Cl)[Cl:15]>C(OCC)C>[Br:1][C:2]1[CH:12]=[CH:11][C:5]([CH2:6][S:7]([Cl:15])(=[O:9])=[O:8])=[CH:4][CH:3]=1
Reactant: ClP(Cl)(Cl)(Cl)Cl
Reactant: O=S(=O)(O)Cc1ccc(Br)cc1
Agent: [Na]
Solvent: CCOCC
Product: O=S(=O)(Cl)Cc1ccc(Br)cc1
Temperature: 80 °C
Reaction time: 0.5 h

Procedure:
The 4-bromobenzylsulfonic acid, sodium salt (12.9 g, 43.6 mmol) was combined without further purification with phosphorus pentachloride (10.8 g, 52 mmol) to form an intimate mixture. The mixture was heated to 80° C. under a nitrogen atmosphere and became homogeneous after about 30 minutes. The reaction mixture was maintained at this temperature for about 5 hours. It was then cooled, diluted with diethyl ether and added to a large volume of ice. The ether layer was separated, washed with water and a saturated brine solution and dried over magnesium sulfate. The solvent was then removed with a rotary evaporator to obtain 4-bromobenzylsulfonyl chloride (13.3 g), a small quantity of which was recrystallized from hexane for analysis. The m.p. was about 114° C. to about 116° C. and the 1H NMR spectrum confirmed that the reaction product was 4-bromobenzylsulfonylchloride. The theoretical elemental analysis for bromobenzylsulfonylchloride is: C, 31.19%; H, 2.24%; S, 11.89% and the actual analysis was: C, 31.23%; H, 2.41%; S, 11.73%.
Reaction SMILES: Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([C:12](=[O:14])[CH3:13])=[C:4]([OH:15])[CH:3]=1.[OH:16][C:17]1[CH:22]=[CH:21][C:20](B(O)O)=[CH:19][CH:18]=1.C(=O)([O-])[O-].[K+].[K+]>O.O1CCOCC1.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>[OH:15][C:4]1[CH:3]=[C:2]([C:20]2[CH:21]=[CH:22][C:17]([OH:16])=[CH:18][CH:19]=2)[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]=1[C:12](=[O:14])[CH3:13]
Reactant: CC(=O)c1c(O)cc(Br)c2ccccc12
Reactant: OB(O)c1ccc(O)cc1
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: [K+]
Solvent: C1COCCO1
Solvent: O
Product: CC(=O)c1c(O)cc(-c2ccc(O)cc2)c2ccccc12
Temperature: 100 °C
Yield: 83.5 %

Procedure:
A mixture of 1-(4-bromo-2-hydroxynapthalen-1-yl)ethanone (0.255 g, 0.96 mmol), (4-hydroxyphenyl)boronic acid (0.140 g, 1.06 mmol), Pd(PPh3)4 (0.056 g, 0.048 mmol) and potassium carbonate (0.4 g, 2.88 mmol) in water (9.7 mL) in dioxane (32.0 mL) was flushed with nitrogen, sealed and heated for 2 h in a 100° C. oil bath. The solution was cooled to room temperature and partitioned between 200 mL of 10% methanol in ethyl acetate and 100 mL saturated aqueous sodium chloride. The layers were separated and the aqueous layer was extracted (2×50 mL 10% methanol in ethyl acetate). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Column chromatography (SiO2, 5:1 hexanes/ethyl acetate) gave 0.223 g (83%) of 1-[2-hydroxy-4-(4-hydroxyphenyl)napthalen-1-yl]ethanone. 1H NMR (400 MHz, d6-DMSO): 8.11 (d, 1H), 7.87 (d, 1H), 7.56 (dt, 1H), 7.33 (m, 3H), 7.07 (s, 1H), 6.99 (d, 2H), 2.89 (s, 3H); MS (EI) for C18H14O3: 279 (MH+).
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[C:6]1([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:11]=[CH:10][C:9]([CH2:12][CH2:13][CH:14]([O:26][CH2:27][C:28]2[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=2)[CH:15]([CH2:23][CH2:24][OH:25])[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:8][CH:7]=1.C(N(CC)CC)C>ClCCl>[C:6]1([C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH:7]=[CH:8][C:9]([CH2:12][CH2:13][CH:14]([O:26][CH2:27][C:28]2[CH:29]=[CH:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=2)[CH:15]([CH2:23][CH2:24][O:25][S:2]([CH3:1])(=[O:4])=[O:3])[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])=[CH:10][CH:11]=1
Reactant: COc1ccc(COC(CCc2ccc(-c3ccccc3)cc2)C(CCO)C(=O)OC(C)(C)C)cc1
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COc1ccc(COC(CCc2ccc(-c3ccccc3)cc2)C(CCOS(C)(=O)=O)C(=O)OC(C)(C)C)cc1
Yield: 95.8 %

Procedure:
Methanesulfonyl chloride (64 μL, 0.83 mmol) was added in one portion to a stirred solution of 1,1-dimethylethyl 5-(4-biphenylyl)-2-(2-hydroxyethyl)-3-({[4-(methyloxy)phenyl]methyl}oxy)pentanoate (368 mg, 0.751 mmol) and triethylamine (15.4 mg, 209 μL, 1.52 mmol) in dichloromethane (2 mL) at room temperature under nitrogen. After stirring at room temperature for 1 h the crude mixture was partitioned between saturated aqueous citric acid solution (20 mL) and dichloromethane (20 mL). The phases were separated and the organic layer was evaporated to give the title compound (409 mg, 79%) as a yellow oil which was a mixture of diastereomers. LC/MS: 4.08 min; z/e 586, calcd (M+1) 586. 1H NMR (400 MHz: CDCl3): 7.50 (6H), 7.25 (4H), 7.15 (1H), 6.90 (2H), 4.50 (2H), 4.25 (2H), 3.80 (3H), 3.75 (1H), 2.95 (3H), 2.90-2.50 (3H), 2.05 (2H), 1.95-1.65 (2H), 1.55-1.35 (9H).
Reaction SMILES: [C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([F:14])=[C:10]([O:15][C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][N:17]=2)[CH:9]=1)([CH3:4])([CH3:3])[CH3:2].O1CCCC1>CO.[C].[Pd]>[C:1]([O:5][C:6](=[O:25])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([F:14])=[C:10]([O:15][C:16]2[CH:21]=[CH:20][C:19]([NH2:22])=[CH:18][N:17]=2)[CH:9]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)Nc1ccc(F)c(Oc2ccc([N+](=O)[O-])cn2)c1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)(C)OC(=O)Nc1ccc(F)c(Oc2ccc(N)cn2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 73.2 %

Procedure:
A suspension of tert-butyl{4-fluoro-3-[(5-nitropyridin-2-yl)oxy]phenyl}carbamate (3.75 g, 10.7 mmol) and 10% palladium-carbon (0.5 g) in methanol (10 mL)-tetrahydrofuran (10 mL) was vigorously stirred at room temperature under a hydrogen atmosphere overnight. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was poured into water (100 mL), and the mixture was extracted with ethyl acetate (100 mL×2). The ethyl acetate layers were combined and dried over anhydrous sodium sulfate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the residue was triturated with diethyl ether to give the title compound (2.50 g, 73%) as a pale-yellow amorphous.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:17]=1[NH:16][CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH3:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Cl)=[CH:23][CH:22]=1.O>CN(C)C=O>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:17]=1[N:16]([CH2:20][C:21]1[CH:28]=[CH:27][C:24]([CH3:25])=[CH:23][CH:22]=1)[CH:15]=[CH:14]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Cc1ccc(CCl)cc1
Reactant: c1ccc(COc2cccc3cc[nH]c23)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Cc1ccc(Cn2ccc3cccc(OCc4ccccc4)c32)cc1
Reaction time: 0.17 h

Procedure:
To a solution of 7-benzyloxy-1H-indole (0.3 g) in N,N-dimethylformamide (5 mL) was added sodium hydride (55% 70 mg) under ice-cooling, and the mixture was stirred for 10 minutes. To the reaction mixture was added 4-methylbenzyl chloride (0.19 mL), and the mixture was stirred at room temperature for 2 hours. The reaction mixture was poured into water, and the resulting mixture was extracted with diethyl ether. The extract was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to give 7-benzyloxy-1-(4-methylbenzyl)-1H-indole (0.43 g). This material was dissolved in tetrahydrofuran (6 mL). To the solution was added 10% palladium-carbon powder (50 mg), and the mixture was stirred at room temperature under a hydrogen atmosphere for 5 hours. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=5/1) to give the title compound (86 mg).
Reaction SMILES: [NH2:1][C@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:12]3[CH:13]=[N:14][N:15]([CH2:17][CH2:18][O:19][CH3:20])[CH:16]=3)[CH:10]=2)[N:5]([C:21](=[O:23])[CH3:22])[C@@H:4]([CH3:24])[CH2:3]1.Cl[C:26]1[CH:31]=[N:30][C:29]([CH3:32])=[CH:28][N:27]=1.CN(C1C(C2C(P(C3CCCCC3)C3CCCCC3)=CC=CC=2)=CC=CC=1)C.CC(C)([O-])C.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:20][O:19][CH2:18][CH2:17][N:15]1[CH:16]=[C:12]([C:9]2[CH:10]=[C:11]3[C:6](=[CH:7][CH:8]=2)[N:5]([C:21](=[O:23])[CH3:22])[C@@H:4]([CH3:24])[CH2:3][C@H:2]3[NH:1][C:26]2[CH:31]=[N:30][C:29]([CH3:32])=[CH:28][N:27]=2)[CH:13]=[N:14]1
Reactant: Cc1cnc(Cl)cn1
Reactant: COCCn1cc(-c2ccc3c(c2)[C@H](N)C[C@H](C)N3C(C)=O)cn1
Agent: [Pd]
Agent: CC(C)(C)[O-]
Agent: CN(C)c1ccccc1-c1ccccc1P(C1CCCCC1)C1CCCCC1
Solvent: C1COCCO1
Product: COCCn1cc(-c2ccc3c(c2)[C@H](Nc2cnc(C)cn2)C[C@H](C)N3C(C)=O)cn1
Temperature: 120 °C
Yield: 47 %

Procedure:
1-((2S,4R)-4-Amino-6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone (for a preparation see Intermediate 7) (150 mg, 0.457 mmol), 2-chloro-5-methylpyrazine (147 mg, 1.142 mmol), Davephos (71.9 mg, 0.183 mmol), Pd2(dba)3 (84 mg, 0.091 mmol) and sodium tert-butoxide (132 mg, 1.370 mmol) were combined in 1,4-dioxane (4 ml) and the mixture heated at 120° C. for 25 min (microwave). The reaction mixture was partitioned between water (75 ml) and DCM (3×75 ml). The organics were combined, dried (hydrophobic frit) and evaporated under vacuum. The resulting brown oil was dissolved in DMSO (3×1 ml) and purified by MDAP (formate ×3). The solvent was evaporated under vacuum to give 1-((2S,4R)-6-(1-(2-methoxyethyl)-1H-pyrazol-4-yl)-2-methyl-4-((5-methylpyrazin-2-yl)amino)-3,4-dihydroquinolin-1(2H)-yl)ethanone (91 mg, 0.216 mmol, 47% yield) as a yellow glass. LCMS (formate), Rt 0.75 min, MH+ 421.
Reaction SMILES: [NH2:1][C:2]1[C:3]2[C:4](=[N:8][S:9][N:10]=2)[N:5]=[CH:6][N:7]=1.[Cl:11][C:12]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[C:13]=1[CH2:14]N.O.CCCCCC>C(Cl)(Cl)Cl.CO>[Cl:11][C:12]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[C:13]=1[CH2:14][NH:1][C:2]1[C:3]2[C:4](=[N:8][S:9][N:10]=2)[N:5]=[CH:6][N:7]=1
Reactant: NCc1c(F)cccc1Cl
Reactant: Nc1ncnc2nsnc12
Solvent: CCCCCC
Solvent: O
Solvent: CO
Product: Fc1cccc(Cl)c1CNc1ncnc2nsnc12
Temperature: 105 °C

Procedure:
A flask was charged with 1.54 g. (0.01 mole) of 7-amino[1,2,5]thiadiazolo[3,4-d]pyrimidine prepared by the process set forth in Example 1 and 4.0 g. (0.025 mole) of 2-chloro-6-fluorobenzylamine prepared by the process set forth in Example 2. The suspension was stirred and heated at 105° C. for 18 hours. Ten ml. water and 20 ml. hexane were added in one portion and the resulting solid collected by filtration. The cake was washed with hexane and dried at 50° C. in vacuo to afford 2.86 g. (97%) of product. M.p. 224°-226° C.; tlc on silica gel in chloroform-methanol (8:1) showed a single fluorescent blue spot at Rf = 0.8; NMR (DMSO-d6) δ 4.92 (2H, s); 7.21 (broad s, 3H); 8.44 (s, 1H); 9.45 (s, 1H).
Reaction SMILES: [CH3:1][N:2]([CH3:14])[C:3]1[CH:4]=[C:5]([CH:8]=[CH:9][C:10]=1[N+:11]([O-])=O)[C:6]#[N:7].[H][H]>[Pd].CO>[NH2:11][C:10]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][C:3]=1[N:2]([CH3:14])[CH3:1]
Reactant: CN(C)c1cc(C#N)ccc1[N+](=O)[O-]
Reactant: [H][H]
Agent: [Pd]
Solvent: CO
Product: CN(C)c1cc(C#N)ccc1N
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To 16 g (84 mmol) of 3-(dimethylamino)-4-nitrobenzonitrile was added 1 g of palladium on carbon (10%, w/w) and 100 mL of methanol. The mixture was saturated with hydrogen and stirred at room temperature overnight. The palladium on carbon was then filtered off. Concentration of the filtration gave 12.8 of a dark-red solid as the desired product. MS ESI (m/z) 162 (M+1)+.
Reaction SMILES: [NH2:1][C@H:2]([C:4]([OH:6])=[O:5])[CH3:3].[BH4-].[Na+].[CH:9](=O)[C:10]1[C:11](=[CH:13][CH:14]=[CH:15][CH:16]=1)[OH:12]>[OH-].[Na+]>[OH:12][C:11]1[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=1[CH2:9][NH:1][C@H:2]([C:4]([OH:6])=[O:5])[CH3:3]
Reactant: C[C@H](N)C(=O)O
Reactant: O=Cc1ccccc1O
Agent: [BH4-]
Agent: [Na+]
Agent: [OH-]
Product: C[C@H](NCc1ccccc1O)C(=O)O
Reaction time: 1 h

Procedure:
L-alanine (2.9 g) was dissolved in 20 ml of a 2-N sodium hydroxide aqueous solution, and 3.5 ml of salicylaldehyde and 0.4 g of sodium borohydride were then added thereto in this order. After the mixture was stirred for 1 hour, 3.5 ml of salicylaldehyde and 0.4 g of sodium borohydride were added thereto again. The mixture was stirred at room temperature for 1 hour, and the insoluble matter was then separated through filtration. The filtrate was extracted with diethyl ether. The pH was adjusted to 6 with hydrochloric acid to obtain 5.8 g of N-(2-hydroxybenzyl)-L-alanine. The resulting N-(2-hydroxybenzyl)-L-alanine (4.6 g) and 8.8 g of 1-dodecanol were added to 150 ml of toluene, and a hydrogen chloride gas was blown thereto up to the saturation. Ten grams of a molecular sieve were added thereto, and the mixture was stirred overnight. After the insoluble matter was separated through filtration, the filtrate was concentrated, and the resulting oil was dissolved in methylene chloride. The mixture was washed with a saturated aqueous solution of sodium chloride. The resulting mixture was dried over magnesium sulfate, and concentrated under reduced pressure to give 8 g of N-(2-hydroxybenzyl)-L-alanine lauryl ester.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:9]2[N:18]=[C:17]([O:19][CH:20]3[CH2:37][CH:36]4[CH:22]([C:23](=[O:43])[N:24]([CH3:42])[CH2:25][CH2:26][CH2:27][CH2:28][CH:29]=[CH:30][CH:31]5[C:33]([C:39](O)=[O:40])([NH:34][C:35]4=[O:38])[CH2:32]5)[CH2:21]3)[C:16]3[C:11](=[C:12]([CH3:46])[C:13]([O:44][CH3:45])=[CH:14][CH:15]=3)[N:10]=2)[CH:5]=[C:6]([F:8])[CH:7]=1.[CH:47]1([S:50]([NH2:53])(=[O:52])=[O:51])[CH2:49][CH2:48]1>>[F:8][C:6]1[CH:5]=[C:4]([C:9]2[N:18]=[C:17]([O:19][CH:20]3[CH2:37][CH:36]4[CH:22]([C:23](=[O:43])[N:24]([CH3:42])[CH2:25][CH2:26][CH2:27][CH2:28][CH:29]=[CH:30][CH:31]5[C:33]([C:39]([NH:53][S:50]([CH:47]6[CH2:49][CH2:48]6)(=[O:52])=[O:51])=[O:40])([NH:34][C:35]4=[O:38])[CH2:32]5)[CH2:21]3)[C:16]3[C:11](=[C:12]([CH3:46])[C:13]([O:44][CH3:45])=[CH:14][CH:15]=3)[N:10]=2)[CH:3]=[C:2]([F:1])[CH:7]=1
Reactant: COc1ccc2c(OC3CC4C(=O)NC5(C(=O)O)CC5C=CCCCCN(C)C(=O)C4C3)nc(-c3cc(F)cc(F)c3)nc2c1C
Reactant: NS(=O)(=O)C1CC1
Product: COc1ccc2c(OC3CC4C(=O)NC5(C(=O)NS(=O)(=O)C6CC6)CC5C=CCCCCN(C)C(=O)C4C3)nc(-c3cc(F)cc(F)c3)nc2c1C
Yield: 7 %

Procedure:
Reaction of the acid 169 with cyclopropane sulfonic acid amide according to the procedure described in example 159, followed by purification on HPLC using an Ace-5 C8 column (100×21.2 mm) and an ammonium acetate buffer 5 mM, pH 6.8, 5% acetonitrile, going from 35 to 60% acetonitrile, gave the title compound as a white solid (8 mg, 7%). LRMS (M+H) 738.
Reaction SMILES: [BH4-].[Li+].[CH3:3][O:4][C:5]1[CH:22]=[C:21]([O:23][CH3:24])[CH:20]=[CH:19][C:6]=1[CH2:7][N:8]1[C:12](=[O:13])[CH2:11][C:10]([CH3:18])([C:14](OC)=[O:15])[CH2:9]1>C1COCC1.O>[CH3:3][O:4][C:5]1[CH:22]=[C:21]([O:23][CH3:24])[CH:20]=[CH:19][C:6]=1[CH2:7][N:8]1[CH2:9][C:10]([CH2:14][OH:15])([CH3:18])[CH2:11][C:12]1=[O:13]
Reactant: COC(=O)C1(C)CC(=O)N(Cc2ccc(OC)cc2OC)C1
Agent: [BH4-]
Agent: [Li+]
Solvent: O
Solvent: C1CCOC1
Product: COc1ccc(CN2CC(C)(CO)CC2=O)c(OC)c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
Lithium borohydride (28 mg, 1.3 mmol) was added to a solution of methyl 1-(2,4-dimethoxybenzyl)-3-methyl-5-oxopyrrolidine-3-carboxylate (200 mg, 0.65 mmol) in THF (2 mL) at 0° C. The mixture was stirred at room temperature for 16 hours and then diluted with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (ethyl acetate/petroleum ether) to give 1-(2,4-dimethoxybenzyl)-4-(hydroxymethyl)-4-methylpyrrolidin-2-one. MS ESI calc'd. for C15H22NO4[M+H]+ 280. found 280. 1H NMR (400 MHz, CD3OD): δ 7.08 (d, J=8.4 Hz, 1H), 6.52 (s, 1H), 6.46 (d, J=8.4 Hz, 1H), 4.40-4.31 (m, 2H), 3.79 (s, 3H), 3.77 (s, 3H), 3.30-3.20 (m, 3H), 2.88-2.86 (m, 1H), 2.43 (d, J=16.8 Hz, 1H), 2.08 (d, J=16.8 Hz, 1H), 1.04 (s, 3H).
Reaction SMILES: [C:1]([Si:5]([CH3:19])([CH3:18])[O:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:17])[CH2:15]Cl)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:20][C:21]1[CH:34]=[CH:33][C:24]([CH2:25][C:26]2([OH:32])[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]2)=[CH:23][CH:22]=1>>[C:1]([Si:5]([CH3:19])([CH3:18])[O:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14](=[O:17])[CH2:15][N:29]2[CH2:30][CH2:31][C:26]([OH:32])([CH2:25][C:24]3[CH:33]=[CH:34][C:21]([CH3:20])=[CH:22][CH:23]=3)[CH2:27][CH2:28]2)=[CH:9][CH:8]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[Si](C)(C)Oc1ccc(NC(=O)CCl)cc1
Reactant: Cc1ccc(CC2(O)CCNCC2)cc1
Product: Cc1ccc(CC2(O)CCN(CC(=O)Nc3ccc(O[Si](C)(C)C(C)(C)C)cc3)CC2)cc1

Procedure:
The title compound, m.p. 136°-138° C. and MS: m/e=468 (M+), was prepared from N-[4-(tert-Butyl-dimethyl-silanyloxy)-phenyl]-2-chloro-acetamide and 4-(4-Methyl-benzyl)-piperidin-4-ol.
Reaction SMILES: Cl.Cl.[NH2:3][C:4]1[C:13]2[N:14]=[C:15]([CH2:25][O:26][CH2:27][CH3:28])[N:16]([CH2:17][C:18]3([OH:24])[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]3)[C:12]=2[C:11]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[N:5]=1.C(Cl)(Cl)Cl.C(N(CC)CC)C.[CH3:40][S:41](Cl)(=[O:43])=[O:42]>CN(C)C=O.N1C=CC=CC=1>[NH2:3][C:4]1[C:13]2[N:14]=[C:15]([CH2:25][O:26][CH2:27][CH3:28])[N:16]([CH2:17][C:18]3([OH:24])[CH2:19][CH2:20][N:21]([S:41]([CH3:40])(=[O:43])=[O:42])[CH2:22][CH2:23]3)[C:12]=2[C:11]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=2[N:5]=1
Reactant: CS(=O)(=O)Cl
Reactant: CCOCc1nc2c(N)nc3ccccc3c2n1CC1(O)CCNCC1
Agent: Cl
Solvent: CN(C)C=O
Solvent: c1ccncc1
Solvent: ClC(Cl)Cl
Product: CCOCc1nc2c(N)nc3ccccc3c2n1CC1(O)CCN(S(C)(=O)=O)CC1
Reaction time: 4 h
Yield: 36 %

Procedure:
To the 1.5 hydrate of 4-{[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}piperidin-4-ol dihydrochloride (1.00 g, 2.20 mmol, prepared in a similar manner as described in Example 5) was added chloroform (150 mL) and triethylamine (1.1 mL, 7.7 mmol). The starting material did not completely dissolve. To the mixture was added methanesulfonyl chloride (MeSO2Cl, 0.19 mL, 2.42 mmol) and more triethylamine (0.3 mL). After 4 h at rt, more MeSO2Cl (0.06 mL) and triethylamine (0.3 mL) were added and the mixture was stirred overnight. Pyridine (20 mL) and dimethylformamide (DMF, 20 mL) were added, followed by MeSO2Cl (0.06 mL). To the mixture was added methanesulfonyl anhydride (115 mg) and the mixture was allowed to stand for 2 d. The mixture was filtered, and the filtrate was concentrated to approximately 25 mL, which was diluted with chloroform (400 mL) and extracted with 1 M NaOH (2×150 mL), water (150 mL), and brine (200 mL). The organic phase was dried over Na2SO4, filtered, and concentrated to a yellow oil. The crude product was purified by flash chromatography (silica gel, eluted with 1% CMA/CHCl3 where CMA is a solution comprised of 80:18:2 chloroform/methanol/concentrated ammonium hydroxide) to afford 4-{[4-amino-2-(ethoxymethyl)-1H-imidazo[4,5-c]quinolin-1-yl]methyl}-1-(methylsulfonyl)piperidin-4-ol as a white solid (0.34 g, 36%) after drying at 60° C. under reduced pressure, mp 254-256° C. 1H NMR (300 MHz, DMSO-d6) δ 8.35 (dm, J=8.4 Hz, 1H), 7.59 (dd, J=8.4, 1.4 Hz, 1H), 7.41 (m, 1H), 7.23 (m, 1H), 6.57 (br s, 2H), 5.16-4.60 (br m, 4H), 5.05 (s, 1H), 3.53 (q, J=7.0 Hz, 2H), 3.37-3.27 (br s, 2H), 2.89-2.79 (m, 2H), 2.81 (s, 3H), 1.93-1.78 (m, 2H), 1.62-1.29 (br s, 2H), 1.14 (t, J=7.0 Hz, 3H); MS (APCI) m/z 434 (M+H)+; Anal. calcd for C20H27N5O4S: C, 55.41; H, 6.28; N, 16.15; S, 7.40. Found: C, 55.21; H, 6.11; N, 16.35; S, 7.37.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]2([C:13]3=[CH:14][C:15]4[O:19][CH2:18][O:17][C:16]=4[CH:20]=[C:12]3[O:11][CH2:10]2)[C:2]1=[O:21].CC1(C)COC2=CC3OCC4(C=3C=C12)C1C(=CC=CC=1)NC4=O.Br[CH2:46][C:47]1[CH:52]=[CH:51][C:50]([O:53][C:54]([F:57])([F:56])[F:55])=[CH:49][CH:48]=1.BrCC1OC(C(F)(F)F)=CC=1>>[F:55][C:54]([F:56])([F:57])[O:53][C:50]1[CH:51]=[CH:52][C:47]([CH2:46][N:1]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3]3([C:13]4=[CH:14][C:15]5[O:19][CH2:18][O:17][C:16]=5[CH:20]=[C:12]4[O:11][CH2:10]3)[C:2]2=[O:21])=[CH:48][CH:49]=1
Reactant: FC(F)(F)Oc1ccc(CBr)cc1
Reactant: O=C1Nc2ccccc2C12COc1cc3c(cc12)OCO3
Agent: CC1(C)COc2cc3c(cc21)C1(CO3)C(=O)Nc2ccccc21
Agent: FC(F)(F)c1ccc(CBr)o1
Product: O=C1N(Cc2ccc(OC(F)(F)F)cc2)c2ccccc2C12COc1cc3c(cc12)OCO3

Procedure:
Following the procedure described in EXAMPLE 10.21, and making non-critical variations using spiro[furo[2,3-f][1,3]benzodioxole-7,3′-indol]-2′(1′H)-one to replace 5,5-dimethyl-5,6-dihydrospiro[benzo[1,2-b:5,4-b′]difuran-3,3′-indol]-2′(1′H)-one, and 1-(bromomethyl)-4-(trifluoromethoxy)benzene to replace 2-(bromomethyl)-5-(trifluoromethyl)furan, the title compound was obtained (50%) as a white solid: mp 99-101° C.; MS (ES+) m/z 456.3 (M+1).
Reaction SMILES: CO[C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[C:13]1[O:14][CH2:15][C:16]([CH3:19])([CH3:18])[N:17]=1.[Br-].[CH2:21]1[CH2:25]OC[CH2:22]1>>[CH:21]([C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:4]=1[C:13]1[O:14][CH2:15][C:16]([CH3:19])([CH3:18])[N:17]=1)([CH3:25])[CH3:22]
Reactant: C1CCOC1
Reactant: COc1cc(C(F)(F)F)ccc1C1=NC(C)(C)CO1
Agent: [Br-]
Product: CC(C)c1cc(C(F)(F)F)ccc1C1=NC(C)(C)CO1
Temperature: 25 °C
Reaction time: 1 h
Yield: 91 %

Procedure:
To a cooled (0° C.) solution of 2-(2-methoxy-4-trifluoromethyl-phenyl)-4,4-dimethyl-4,5-dihydro-oxazole (intermediate AG) (1.0 g, 3.66 mmol) in 6.0 ml THF, was added dropwise a 1M ispropylmagnesium bromide solution in THF (11.0 ml, 10.98 mmol) maintaining the temperature below 5° C. The mixture was allowed to warm to room temperature and stirred for 1 hour. The mixture was cooled in an ice bath and quenched dropwise with 25 ml saturated NH4Cl solution. Ethyl acetate was added. The organic layer was separated and the aqueous layer was reextracted once with ethyl acetate. The combined extracts were dried over Na2SO4, filtered and concentrated in vacuo. The crude oil was purified on silica gel (eluent: heptane/ethyl acetate 0 to 20%) to provide 0.95 g (91%) of the title compound as a light yellow oil. MS (m/e): 286.1 (M+H).
Reaction SMILES: [C:1]([C:5]1[CH:12]=[CH:11][C:8]([CH2:9]Br)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH2:13]([N+:17](CCCC)(CCCC)CCCC)CCC.[C-]#N.[Na+]>O>[C:1]([C:5]1[CH:12]=[CH:11][C:8]([CH2:9][C:13]#[N:17])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)c1ccc(CBr)cc1
Reactant: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [C-]#N
Agent: [Na+]
Solvent: O
Product: CC(C)(C)c1ccc(CC#N)cc1

Procedure:
A mixture consisting of 107 g p-tert.butylbenzyl bromide, 2 g tetra butyl-ammonium jodide and 37 g NaCN in 50 ml water was heated during 1 hour at 100° C. After cooling the reaction mixture, the organic layer was separated and distilled in vacuo with a yield of 78 g of the desired cyanide. Then this product was fractionated in vacuo. Yield of p-tert.butylbenzyl cyanide: 65 g (80%): boiling point: 118° C./0,7 kPa: nD =1,5110. This cyanide has a very strong odor which reminds one of algae, seaweed and ozone with ambergris-like, fatty and animal notes.