Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[Si](Cl)(C)C.C[O:7][CH2:8][C@H:9]1[CH2:14][CH2:13][C@H:12]([C:15]2[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[CH:17][CH:16]=2)[CH2:11][CH2:10]1.[I-].[Na+]>C(#N)C>[C:21]([C:18]1[CH:19]=[CH:20][C:15]([C@H:12]2[CH2:13][CH2:14][C@H:9]([CH2:8][OH:7])[CH2:10][CH2:11]2)=[CH:16][CH:17]=1)#[N:22]
Reactant: COC[C@H]1CC[C@H](c2ccc(C#N)cc2)CC1
Agent: C[Si](C)(C)Cl
Agent: [I-]
Agent: [Na+]
Solvent: CC#N
Product: N#Cc1ccc([C@H]2CC[C@H](CO)CC2)cc1
Temperature: 35 °C
Reaction time: 0.5 h

Procedure:
Trimethylsilyl chloride (305.6 g, 2.81 mol) was dropwise added to trans-4-methoxymethyl-1-(4-cyanophenyl)-cyclohexane (III) (322.5 g, 1.41 mol), sodium iodide (421.6 g, 2.81 mol) and acetonitrile (2.5 l) in nitrogen atmosphere with stirring at 35° C. over 30 minutes, followed by agitating the mixture for 20 minutes, cooling the reaction mixture down to 10° C., filtering it by suction, pouring the filtrate in ice water (2 Kg), extracting with chloroform (1.5 l), twice washing the resulting chloroform solution with a 10% by weight aqueous solution of sodium thiosulfate (0.5 l), three times washing with water (1 l), distilling off chloroform from the chloroform solution and three times recrystallizing the residue from toluene (300 m) for purification to obtain trans-4-(4-cyanophenyl)cyclohexylcarbinol (IV) (182.5 g, 0.848 mol) having a m.p. of 108.5°-110.8° C. On the other hand, pyridinium chlorochromate (161.7 g, 0.750 mol) was added to dichloromethane (1 l), followed by instantaneously adding to the mixture, a solution of trans-4-(4-cyanophenyl)cyclohexylcarbinol (IV) (107.6 g, 0.500 mol) obtained above, in dichloromethane (0.7 l) with stirring at room temperature, further agitating the mixture at room temperature for 1.5 hours, adding diethyl ether (1 l) to the reaction mixture, and concentrating the supernatant by passing it through a Florisil chromatography column to obtain trans-4-(4-cyanophenyl)cyclohexylcarbaldehyde (V) (101.2 g, 0.474 mol).
Reaction SMILES: CO[C:3]([C:5]1[N:6]=[CH:7][C:8]2[C:9](=[O:23])[N:10]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH:11]=[CH:12][C:13]=2[C:14]=1[OH:15])=[O:4].[C:24]([O:28][C:29](=[O:35])[N:30]([CH2:32][CH2:33][NH2:34])[CH3:31])([CH3:27])([CH3:26])[CH3:25]>CCO>[C:24]([O:28][C:29](=[O:35])[N:30]([CH2:32][CH2:33][NH:34][C:3]([C:5]1[N:6]=[CH:7][C:8]2[C:9](=[O:23])[N:10]([CH2:16][C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH:11]=[CH:12][C:13]=2[C:14]=1[OH:15])=[O:4])[CH3:31])([CH3:27])([CH3:25])[CH3:26]
Reactant: CN(CCN)C(=O)OC(C)(C)C
Reactant: COC(=O)c1ncc2c(=O)n(Cc3ccccc3)ccc2c1O
Solvent: CCO
Product: CN(CCNC(=O)c1ncc2c(=O)n(Cc3ccccc3)ccc2c1O)C(=O)OC(C)(C)C
Temperature: 25 °C
Yield: 97.4 %

Procedure:
A mixture of 7-benzyl-4-hydroxy-8-oxo-7,8-dihydro-[2,7]naphthyridine-3-carboxylic acid methyl ester (100 mg, 0.32 mmol) and (2-amino-ethyl)-methyl-carbamic acid tert-butyl ester (67 mg, 0.39 mmol) in EtOH (9 mL) was refluxed for 16 h. After cooling to r.t., the mixture was concentrated in vacuo. The residue was dissolved in EtOAc and washed with 0.1 M HCl. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (0-2% MeOH/CH2Cl2) to give 141 mg of the title compound. MS: (−) m/z 451.37 (M−1).
Reaction SMILES: [P:1](Cl)([S:6][CH2:7][CH2:8][CH3:9])([O:3][CH2:4][CH3:5])=[O:2].C(N(CC)CC)C.[OH:18][C:19]1[CH:26]=[CH:25][CH:24]=[CH:23][C:20]=1[CH:21]=[O:22]>C(Cl)Cl>[P:1]([O:18][C:19]1[CH:26]=[CH:25][CH:24]=[CH:23][C:20]=1[CH:21]=[O:22])([S:6][CH2:7][CH2:8][CH3:9])([O:3][CH2:4][CH3:5])=[O:2]
Reactant: CCCSP(=O)(Cl)OCC
Reactant: O=Cc1ccccc1O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCSP(=O)(OCC)Oc1ccccc1C=O
Temperature: 0 °C
Reaction time: 1 h

Procedure:
The solution of O-ethyl S-propyl chlorothiophosphate prepared in Example 1 was cooled to 10° C. and triethylamine (1.629 grams; 0.016 mole) was added. A solution of 2-hydroxybenzaldehyde (1.95 grams; 0.016 mole) in methylene chloride (5 ml) was slowly added to the mixture while maintaining the temperature at about 0° C. After this addition was completed the temperature of the reaction mixture was allowed to rise to room temperature and stirring was continued for a period of one hour. After this time the reaction mixture was transferred into a separatory funnel and methylene chloride (100 ml) was added. The resulting solution was washed twice with water (100 ml), twice with aqueous sodium hydroxide (0.1 N; 50 ml) and again twice with water (100 ml). The washed solution was then dried over anhydrous magnesium sulfate, filtered and stripped of solvent under vacuum in a rotary evaporator leaving a light orange oil as the residue. This oil was placed under high vacuum for a period of one hour to yield the desired product as a yellow oil.
Reaction SMILES: Br[C:2]1[C:3]([CH3:10])=[N:4][C:5]([O:8][CH3:9])=[CH:6][CH:7]=1.C([Li])CCC.CN([CH:19]=[O:20])C.O.[Cl-].[NH4+]>C1(C)C=CC=CC=1>[CH3:9][O:8][C:5]1[N:4]=[C:3]([CH3:10])[C:2]([CH:19]=[O:20])=[CH:7][CH:6]=1
Reactant: COc1ccc(Br)c(C)n1
Reactant: CN(C)C=O
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: Cc1ccccc1
Solvent: O
Product: COc1ccc(C=O)c(C)n1
Temperature: 25 °C

Procedure:
The 3-bromo-6-methoxy-2-methyl-pyridine (2.0 g, 9.9 mmol) obtained in (18-1) above was dissolved in toluene (dehydrated) (50 mL), and thereafter, n-butyllithium (6.4 mL, 10 mmol, 1.57 mmol/L hexane solution) was added dropwise to the solution at −78° C. in an argon atmosphere. The obtained mixture was stirred at the same temperature as described above for 30 minutes, and DMF (3.0 mL) was then added to the reaction solution. The obtained mixture was further stirred for 30 minutes. Thereafter, a saturated ammonium chloride water (100 mL) was slowly added to the reaction solution, and the temperature of the mixture was then increased to room temperature. The mixture was extracted with diethyl ether (100 mL) three times, and organic layers were gathered. The resultant was washed with water (100 mL) and saturated saline (100 mL), and was dried over anhydrous sodium sulfate and was then filtrated, followed by vacuum concentration. The obtained residue was purified by silica gel column chromatography (SiO2 30 g, hexane:ethyl acetate=98:2 to 90:10), so as to obtain 487 mg of 6-methoxy-2-methyl-3-pyridinecarboxaldehyde.
Reaction SMILES: [OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.Cl[C:11]1[N:19]=[CH:18][CH:17]=[CH:16][C:12]=1[C:13]([OH:15])=[O:14]>O1CCOCC1>[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:11]2[N:19]=[CH:18][CH:17]=[CH:16][C:12]=2[C:13]([OH:15])=[O:14])[CH2:6][CH2:5]1
Reactant: OCCN1CCNCC1
Reactant: O=C(O)c1cccnc1Cl
Solvent: C1COCCO1
Product: O=C(O)c1cccnc1N1CCN(CCO)CC1

Procedure:
Operation was carried out in a manner similar to the one previously described in Example 5, using 10.4 g of 1-(2-hydroxyethyl)piperazine and 6.3 g of 2-chloronicotinic acid in 100 ml dioxane under reflux for 18 hours. Grams 3.9 of 2-[4-(2-hydroxyethyl)piperazin-1-yl]nicotinic acid, melting at 148°-171° C. (with decomposition), were obtained.
Reaction SMILES: [CH3:1][C:2]1([C:8]2[CH:9]=[C:10]([CH:14]=[CH:15][C:16]=2[O:17][Si:18]([C:21]([CH3:24])([CH3:23])[CH3:22])([CH3:20])[CH3:19])[C:11]([OH:13])=O)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.[CH3:25][Li]>CCOCC>[CH3:1][C:2]1([C:8]2[CH:9]=[C:10]([C:11](=[O:13])[CH3:25])[CH:14]=[CH:15][C:16]=2[O:17][Si:18]([C:21]([CH3:22])([CH3:24])[CH3:23])([CH3:19])[CH3:20])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1
Reactant: [Li]C
Reactant: CC1(c2cc(C(=O)O)ccc2O[Si](C)(C)C(C)(C)C)CCCCC1
Solvent: CCOCC
Product: CC(=O)c1ccc(O[Si](C)(C)C(C)(C)C)c(C2(C)CCCCC2)c1
Reaction time: 8 h

Procedure:
28.82 g (0.083 mol) of 3-(1-methylcyclohexyl)-4-tert-butyldimethylsilyloxybenzoic acid, in 300 ml ether, are treated at -20° C. under nitrogen, with 0.166 mol of methyllithium (1.6M in ether). The reaction mixture is stirred under nitrogen overnight and it is then treated as for Example 25(a). After filtration of the residue on silica, 22 g (76%) of the expected product are isolated in the form of a yellow oil.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].[N+:6]([C:9]1[CH:10]=[C:11]([CH:15]([OH:29])[CH2:16][CH2:17][CH:18]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([N+:26]([O-:28])=[O:27])[CH:21]=2)[OH:19])[CH:12]=[CH:13][CH:14]=1)([O-:8])=[O:7].C(N(CC)CC)C>C1COCC1>[CH3:1][S:2]([O:19][CH:18]([C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([N+:26]([O-:28])=[O:27])[CH:21]=1)[CH2:17][CH2:16][CH:15]([O:29][S:2]([CH3:1])(=[O:4])=[O:3])[C:11]1[CH:12]=[CH:13][CH:14]=[C:9]([N+:6]([O-:8])=[O:7])[CH:10]=1)(=[O:4])=[O:3]
Reactant: CS(=O)(=O)Cl
Reactant: O=[N+]([O-])c1cccc(C(O)CCC(O)c2cccc([N+](=O)[O-])c2)c1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CS(=O)(=O)OC(CCC(OS(C)(=O)=O)c1cccc([N+](=O)[O-])c1)c1cccc([N+](=O)[O-])c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
Methanesulfonyl chloride (0.3 mL, 3.87 mmol) was added dropwise to a cold (0° C.) solution of Example 55B (0.5089 g, 1.531 mmol) and triethylamine (0.65 mL, 4.66 mmol) in THF (10 mL). The reaction was removed from the ice bath and stirred at ambient temperature for 30 minutes. Solvent was removed under vacuum to provide the title compound as a solid that was used without purification.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:35]2[C:36]([C:41]#[N:42])=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][C:9]1[C:10](=[O:34])[N:11]([C@H:21]2[CH2:26][CH2:25][C@H:24]([O:27][C@H:28]3[C:32](=[O:33])[CH2:31][O:30][CH2:29]3)[CH2:23][CH2:22]2)[C:12]2[N:13]([N:18]=[CH:19][N:20]=2)[C:14]=1[CH2:15][CH2:16][CH3:17].[CH3:43][Mg]Br.[Cl-].[NH4+]>O1CCCC1>[F:1][C:2]1[CH:3]=[C:4]([C:35]2[C:36]([C:41]#[N:42])=[CH:37][CH:38]=[CH:39][CH:40]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][C:9]1[C:10](=[O:34])[N:11]([C@H:21]2[CH2:22][CH2:23][C@H:24]([O:27][CH:28]3[C:32]([OH:33])([CH3:43])[CH2:31][O:30][CH2:29]3)[CH2:25][CH2:26]2)[C:12]2[N:13]([N:18]=[CH:19][N:20]=2)[C:14]=1[CH2:15][CH2:16][CH3:17]
Reactant: C[Mg]Br
Reactant: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2F)c(=O)n([C@H]2CC[C@H](O[C@@H]3COCC3=O)CC2)c2ncnn12
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CCCc1c(Cc2ccc(-c3ccccc3C#N)cc2F)c(=O)n([C@H]2CC[C@H](OC3COCC3(C)O)CC2)c2ncnn12
Reaction time: 3 h

Procedure:
3′-Fluoro-4′-{[5-oxo-4-(trans-4-{[(3R)-4-oxotetrahydrofuran-3-yl]oxy}cyclohexyl)-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (0.18 g) was dissolved in tetrahydrofuran (10 mL), and methylmagnesium bromide (1.0 M tetrahydrofuran solution, 0.95 mL) was added at room temperature. The reaction mixture was stirred for 3 hr, saturated aqueous ammonium chloride solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.077 g, 42%).
Reaction SMILES: [ClH:1].Cl.[NH:3]=[C:4]1[NH:10][CH:9]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([NH2:18])=[CH:14][CH:13]=2)[CH2:8][CH2:7][CH2:6][CH2:5]1.[H][H]>CCO.[Rh]>[ClH:1].[ClH:1].[NH:3]=[C:4]1[NH:10][CH:9]([CH2:11][CH:12]2[CH2:17][CH2:16][CH:15]([NH2:18])[CH2:14][CH2:13]2)[CH2:8][CH2:7][CH2:6][CH2:5]1
Reactant: [H][H]
Reactant: N=C1CCCCC(Cc2ccc(N)cc2)N1
Agent: [Rh]
Agent: Cl
Solvent: CCO
Product: N=C1CCCCC(CC2CCC(N)CC2)N1
Yield: 168.8 %

Procedure:
The product of Example 274 (0.31 g, 1.2 mmol) in 30 mL of EtOH was reduced with Rhodium on carbon under 60 psi of hydrogen at 60° C. Solvent removal in vacuo followed by lyophilization in water gave 0.3 g of the title material.
Reaction SMILES: [S:1]1[CH2:5][CH2:4][CH:3]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]([OH:13])=O)[S:2]1.[S:14]([NH2:18])([NH2:17])(=[O:16])=[O:15].[H-].[Na+]>C1(C)C=CC=CC=1.CN(C)C=O>[S:1]1[CH2:5][CH2:4][CH:3]([CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][C:11]([NH:17][S:14]([NH2:18])(=[O:16])=[O:15])=[O:13])[S:2]1
Reactant: O=C(O)CCCCCC1CCSS1
Reactant: NS(N)(=O)=O
Agent: [H-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Product: NS(=O)(=O)NC(=O)CCCCCC1CCSS1
Yield: 19.3 %

Procedure:
The reaction was carried out as described in Example 107, but using 5 ml of a solution of 1.6 mmol of 6(1,2-dithiolan-3-yl)hexanoic acid (prepared as described in Example 104) in toluene, 7 ml of anhydrous dimethylformamide, 308 mg of N,N'-carbonyldiimidazole, 365 mg of sulfamide and 83 mg of sodium hydride (as a 55% w/w dispersion in mineral oil). The solvent was removed from the reaction mixture by evaporation under reduced pressure, and water was added to the residue, after which it was extracted with ethyl acetate. The extraction solution was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. The ethyl acetate was removed from the extraction solution by evaporation under reduced pressure, and the residue was subjected to silica gel column chromatography, using 3:2 and 2:1 by volume mixtures of ethyl acetate and hexane as the eluent. The solvent was removed from the eluate by evaporation under reduced pressure, and the residue was recrystallized from a 1:2 by volume mixture of ethyl acetate and hexane, to obtain 92 mg of the title compound as pale yellow crystals, melting at 130 to 132° C.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([NH2:37])=[N:10][CH:11]=[N:12][C:13]=2[N:14]2[CH2:19][CH2:18][CH:17]([C:20]3[N:21]([CH3:36])[CH:22]=[C:23]([C:25]4[CH:30]=[CH:29][C:28]([F:31])=[C:27]([C:32]([F:35])([F:34])[F:33])[CH:26]=4)[N:24]=3)[CH2:16][CH2:15]2)=[CH:4][CH:3]=1.[CH3:38][O:39]C1C=CC(B(O)O)=CC=1>>[F:31][C:28]1[CH:29]=[CH:30][C:25]([C:23]2[N:24]=[C:20]([CH:17]3[CH2:18][CH2:19][N:14]([C:13]4[N:12]=[CH:11][N:10]=[C:9]([NH2:37])[C:8]=4[C:5]4[CH:6]=[CH:7][C:2]([O:39][CH3:38])=[CH:3][CH:4]=4)[CH2:15][CH2:16]3)[N:21]([CH3:36])[CH:22]=2)=[CH:26][C:27]=1[C:32]([F:33])([F:34])[F:35]
Reactant: COc1ccc(B(O)O)cc1
Reactant: Cn1cc(-c2ccc(F)c(C(F)(F)F)c2)nc1C1CCN(c2ncnc(N)c2-c2ccc(F)cc2)CC1
Product: COc1ccc(-c2c(N)ncnc2N2CCC(c3nc(-c4ccc(F)c(C(F)(F)F)c4)cn3C)CC2)cc1

Procedure:
The title compound was prepared in an analogous manner as 5-(4-Fluoro-phenyl)-6-{4-[4-(4-fluoro-3-trifluoromethyl-phenyl)-1-methyl-1H-imidazol-2-yl]-piperidin-1-yl}-pyrimidin-4-ylamine using 4-methoxyphenylboronic acid instead of 4-fluorophenylboronic acid. LC-MS: (M+1=527, obsd.=527).
Reaction SMILES: C(NC(C)C)(C)C.[Li]CCCC.[CH3:13][O:14][C:15]([C:17]1[S:18][CH:19]=[CH:20][C:21]=1[N:22]([CH:32]1[CH2:41][CH2:40][C:35]2([O:39][CH2:38][CH2:37][O:36]2)[CH2:34][CH2:33]1)[C:23]([C@H:25]1[CH2:30][CH2:29][C@H:28]([CH3:31])[CH2:27][CH2:26]1)=[O:24])=[O:16].[CH3:42][C:43]1([CH3:50])[CH2:48][CH2:47][C:46](=[O:49])[CH2:45][CH2:44]1>C1COCC1>[CH3:13][O:14][C:15]([C:17]1[S:18][C:19]([C:46]2([OH:49])[CH2:47][CH2:48][C:43]([CH3:50])([CH3:42])[CH2:44][CH2:45]2)=[CH:20][C:21]=1[N:22]([CH:32]1[CH2:41][CH2:40][C:35]2([O:39][CH2:38][CH2:37][O:36]2)[CH2:34][CH2:33]1)[C:23]([C@H:25]1[CH2:26][CH2:27][C@H:28]([CH3:31])[CH2:29][CH2:30]1)=[O:24])=[O:16]
Reactant: COC(=O)c1sccc1N(C(=O)[C@H]1CC[C@H](C)CC1)C1CCC2(CC1)OCCO2
Reactant: CC1(C)CCC(=O)CC1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: CC(C)NC(C)C
Product: COC(=O)c1sc(C2(O)CCC(C)(C)CC2)cc1N(C(=O)[C@H]1CC[C@H](C)CC1)C1CCC2(CC1)OCCO2
Temperature: -40 °C
Reaction time: 0.25 h

Procedure:
Diisopropylamine (5.75 g, 56.8 mmol) and dry THF (58 mL) were added to a dry 500 mL 3 neck round bottom flask under nitrogen. The solution was cooled to −40° C. and nBuLi (39 mL, 47.4 mmol) was added slowly while keeping the internal temperature at −40° C. After 15 min, a suspension of 3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(trans-4-methyl-cyclohexanecarbo-nyl)-amino]-thiophene-2-carboxylic acid methyl ester (10.0 g, 23.7 mmol) in THF (70 mL) was added dropwise while maintaining the internal temperature at −40° C. After 30 min at −40° C., 4,4-dimethyl-cyclohexanone (5.88 g, 47.7 mmol) was added in one portion and stirred at −40° C. for 30 min. The reaction mixture was quenched with saturated NH4Cl, partitioned and the aqueous phase extracted with EtOAc. The combined organic phase was washed with brine, dried over MgSO4, filtered and evaporated to obtain crude 3-[(1,4-dioxa-spiro[4.5]dec-8-yl)-(trans-4-methyl-cyclohexanecarbonyl)-amino]-5-(1-hydroxy-4,4-dimethyl-cyclohexyl)-thiophene-2-carboxylic acid methyl ester (14.4 g) which was used for the next step without any purification.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-:10])=[O:9])[C:3]=1[OH:11].[H-].[Na+].[C:14]([O:18][C:19]([N:21]1[C@H:25]([C:26]([O:28][CH2:29][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[O:27])[CH2:24]OS1(=O)=O)=[O:20])([CH3:17])([CH3:16])[CH3:15]>CN(C)C=O>[CH2:29]([O:28][C:26](=[O:27])[C@@H:25]([NH:21][C:19]([O:18][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:20])[CH2:24][O:11][C:3]1[C:4]([N+:8]([O-:10])=[O:9])=[CH:5][CH:6]=[CH:7][C:2]=1[CH3:1])[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1
Reactant: CC(C)(C)OC(=O)N1[C@H](C(=O)OCc2ccccc2)COS1(=O)=O
Reactant: Cc1cccc([N+](=O)[O-])c1O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1cccc([N+](=O)[O-])c1OC[C@H](NC(=O)OC(C)(C)C)C(=O)OCc1ccccc1
Reaction time: 1 h
Yield: 32.5 %

Procedure:
In an inert atmosphere and under exclusion of moisture, at 0° C. a solution of 1.5 g (10 mmol) of 2-methyl-6-nitro-phenol [Ger.Offen. 3536192] in 30 ml of N,N-dimethylformamide was treated portionwise with 0.42 g (18 mmol) of sodium hydride (55% dispersion in mineral oil). After complete addition, stirring was continued for 1 hour at 0° C. Thereafter, 3.85 g (11 mmol) of (S)-2,2-dioxo-2λ6-[1,2,3]oxathiazolidine-3,4-dicarboxylic acid 4-benzyl ester 3-tert-butyl ester was added and stirring continued at 0° C. for 3 hours, then at room temperature overnight. For the working-up, the solvent was evaporated under reduced pressure, the residue treated with 100 ml of hydrochloric acid (1 N), then extracted 3 times with 150 ml of ethyl acetate. The crude product (4.0 g) was obtained as a dark brown oil which was purified by flash-chromatography on silica gel using a gradient of a 100%:0%- to 50%:50%-mixture of heptane and ethyl acetate as the eluent. There were obtained 1.4 g (33%) of the title compound as an yellow oil, [α]589=−1.45° (c=1.0% in MeOH), MS m/e (%): 431.4 (M+H+, 13).
Reaction SMILES: [Cl:1][C:2]1[C:7]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([F:19])[CH:15]=3)[N:10]=[C:9]2[CH3:20])=[CH:6][CH:5]=[CH:4][N:3]=1.CO[CH:23](OC)[N:24]([CH3:26])[CH3:25]>CN(C)C=O>[Cl:1][C:2]1[C:7]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([F:19])[CH:15]=3)[N:10]=[C:9]2[CH:20]=[CH:23][N:24]([CH3:26])[CH3:25])=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: Cc1nc2ccc(F)cc2c(=O)n1-c1cccnc1Cl
Reactant: COC(OC)N(C)C
Solvent: CN(C)C=O
Product: CN(C)C=Cc1nc2ccc(F)cc2c(=O)n1-c1cccnc1Cl
Temperature: 25 °C
Yield: 87.3 %

Procedure:
A mixture of 3-(2-chloro-pyridin-3-yl)-6-fluoro-2-methyl-3,4-dihydro-quinazolin-4-one (3.5 g, 12.0 mmol) and dimethylformamide dimethyl acetal (3.2 mL, 24 mmol) in dimethylformamide (12 mL) was refluxed for 24 hours. The reaction was cooled to ambient temperature and concentrated at reduced pressure to afford an orange solid. The solid was triturated with ethanol and the yellow crystalline solid was collected and dried to give 3.61 g (87%) of 3-(2-chloro-pyridin-3-yl)-6-fluoro-2-(2-dimethylamino-vinyl)-3,4-dihydro-quinazolin-4-one, which had: mp 197-200° C.; H 1H NMR δ 8.46 (dd, J=1.5, 5 Hz, 1H), 7.85 (d, J=12.2 Hz, 1H), 7.70 (dd, J=3, 8.5 Hz, 1H), 7.68-7.65 (m, 1H), 7.45-7.38 (m, 2H), 7.31 (dt, J=3, 8.5 Hz, 1H), 3.87 (d, J=12.2 Hz, 1H), 2.80 (br s, 6H). Analysis calculated for C17H14ClFN4O: C, 59.22; H, 4.09; N, 16.25. Found: C, 59.14; H, 3.96; N, 16.25.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.C[O:18][C:19]([C:21]1[O:22][C:23]([CH2:26]Cl)=[CH:24][CH:25]=1)=[O:20]>>[N+:14]([C:11]1[CH:12]=[CH:13][C:8]([C:5]2[CH:4]=[CH:3][C:2]([O:1][CH2:26][C:23]3[O:22][C:21]([C:19]([OH:20])=[O:18])=[CH:25][CH:24]=3)=[CH:7][CH:6]=2)=[CH:9][CH:10]=1)([O-:16])=[O:15]
Reactant: COC(=O)c1ccc(CCl)o1
Reactant: O=[N+]([O-])c1ccc(-c2ccc(O)cc2)cc1
Product: O=C(O)c1ccc(COc2ccc(-c3ccc([N+](=O)[O-])cc3)cc2)o1

Procedure:
5-(4′-Nitro-biphenyl-4-yloxymethyl)-furan-2-carboxylic acid was prepared using general procedure A from 4-hydroxy-4′-nitrobiphenyl (available from TCI America, Portland, Oreg.) and 5-chloromethylfuran-2-carboxylic acid methyl ester (available from Aldrich, Milwaukee, Wis., or from Maybridge plc, Tintagel, UK). Yield: 40 mg. Mass spectrum (ES) MH+=340.
Reaction SMILES: C(N(CC)CC)C.[CH3:8][O:9][CH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1.[Cl:16][C:17]1[CH:18]=[C:19]([S:27](Cl)(=[O:29])=[O:28])[CH:20]=[CH:21][C:22]=1[S:23](=[O:26])(=[O:25])[NH2:24]>CC(C)=O>[Cl:16][C:17]1[CH:18]=[C:19]([S:27]([N:13]2[CH2:14][CH2:15][CH:10]([O:9][CH3:8])[CH2:11][CH2:12]2)(=[O:28])=[O:29])[CH:20]=[CH:21][C:22]=1[S:23]([NH2:24])(=[O:25])=[O:26]
Reactant: COC1CCNCC1
Reactant: NS(=O)(=O)c1ccc(S(=O)(=O)Cl)cc1Cl
Solvent: CC(C)=O
Solvent: CCN(CC)CC
Product: COC1CCN(S(=O)(=O)c2ccc(S(N)(=O)=O)c(Cl)c2)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 83.3 %

Procedure:
Triethylamine (4.2 ml) and 4-methoxypiperidine (3.15 g) were added to a solution of 3-chloro-4-sulphamoyl-benzene sulphonyl chloride (8.7 g) in acetone (100 ml). The mixture was stirred at room temperature for 1 hour and then poured into 50 ml of N-hydrochloric acid. The resulting product was removed by filtration, washed with water and recrystallized from isopropanol to give the desired compound (8.4 g), m.p. 165°-167°C.
Reaction SMILES: [CH3:1][CH:2]1[C:45](=O)[C:5]2=[CH:6][C:7]3[C:8]([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][CH3:44])([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[C:9]4[C:14]([C:15]=3[CH:16]=[C:4]2[CH2:3]1)=[CH:13][CH:12]=[CH:11][CH:10]=4.[BH4-].[Na+]>C1COCC1.C(O)C>[CH3:1][C:2]1[CH2:3][C:4]2[C:5]([CH:45]=1)=[CH:6][C:7]1[C:8]([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][CH3:44])([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH3:30])[C:9]3[C:14]([C:15]=1[CH:16]=2)=[CH:13][CH:12]=[CH:11][CH:10]=3
Reactant: CCCCCCCCCCCCCCC1(CCCCCCCCCCCCCC)c2ccccc2-c2cc3c(cc21)C(=O)C(C)C3
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCO
Product: CCCCCCCCCCCCCCC1(CCCCCCCCCCCCCC)c2ccccc2-c2cc3c(cc21)C=C(C)C3
Temperature: 25 °C
Reaction time: 12 h
Yield: 78.5 %

Procedure:
In a 500 mL round flask, 2-methyl-9,9-ditetradecyl-2,3-dihydrocyclopenta[b]fluoren-1(9H)-one (20 g, 31.9 mmol) was dissolved in 150 mL of THF and 150 mL of ethanol, and then stirred. Sodium borohydride (NaBH4) (1.8 g, 47.8 mmol) was added to the reactant in five lots, and then stirred for 12 hours. The resultant mixture, after removal of solvent, was dissolved in ethylacetate, and then washed with water three times. The organic layer was dried over magnesium sulfate, followed by removal of volatile materials. The dried reactant was dissolved in 150 mL of toluene, and then inputted to a round flask. After that, p-toluene sulfonic acid (0.08 g) was inputted thereto, and then water was completely removed under reflux with Dean-Stark. The resultant material was cooled to room temperature, and then an aqueous ammonium chloride solution (100 mL) and 200 mL of diethyl ether were injected thereto, followed by separation of the organic layer. The organic layer collected by extracting the residue with diethyl ether was dried over magnesium sulfate, followed by removal of volatile materials, and then purified by using silica gel column chromatography, to thereby obtain 15.3 g of 2-methyl-9,9-ditetradecyl-3,9-dihydrocyclopenta[b]fluorene (yield: 78.5%).