Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([N:10]2[CH2:15][CH2:14][C@:13]([CH2:22][C:23]([OH:26])([CH3:25])[CH3:24])([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[O:12][C:11]2=[O:27])[CH3:9])=[CH:4][CH:3]=1.[CH3:28][O:29][C:30]1[N:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1>>[OH:26][C:23]([CH3:25])([CH3:24])[CH2:22][C@@:13]1([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[O:12][C:11](=[O:27])[N:10]([C@H:8]([C:5]2[CH:6]=[CH:7][C:2]([C:33]3[CH:34]=[N:35][C:30]([O:29][CH3:28])=[CH:31][CH:32]=3)=[CH:3][CH:4]=2)[CH3:9])[CH2:15][CH2:14]1
Reactant: C[C@@H](c1ccc(Br)cc1)N1CC[C@](CC(C)(C)O)(c2ccccc2)OC1=O
Reactant: COc1ccc(B(O)O)cn1
Product: COc1ccc(-c2ccc([C@H](C)N3CC[C@](CC(C)(C)O)(c4ccccc4)OC3=O)cc2)cn1

Procedure:
The title compound was prepared from (S)-3-((S)-1-(4-bromophenyl)ethyl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one and 6-methoxypyridine-3-boronic acid following procedures analogous to those described in Example 75 Step 1. LC-MS Method 2 tR=1.989 min, m/z=403.1; 1H NMR (CDCl3) 1.10 (s, 3H), 1.17 (s, 3H), 1.52 (d, 3H), 2.13-2.28 (m, 6H), 2.47 (m, 1H), 2.87 (m, 1H), 3.95 (s, 3H), 5.70 (m, 1H), 6.79 (d, 1H), 7.02 (d, 2H), 7.21-7.38 (m, 6H), 7.58 (d, 1H), 8.27 (d, 1H).
Reaction SMILES: [NH:1]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=2[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:12]([C:14]1[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][C:15]=1[CH3:23])#[N:13].C(N(CC)CC)C>ClCCl.CN(C)C1C=CN=CC=1>[CH3:23][C:15]1[CH:16]=[C:17]([C:18]([N:1]2[CH2:2][CH2:3][CH2:4][CH2:5][C:6]3[CH:11]=[CH:10][CH:9]=[CH:8][C:7]2=3)=[O:19])[CH:21]=[CH:22][C:14]=1[C:12]#[N:13]
Reactant: c1ccc2c(c1)CCCCN2
Reactant: Cc1cc(C(=O)O)ccc1C#N
Agent: CN(C)c1ccncc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1cc(C(=O)N2CCCCc3ccccc32)ccc1C#N

Procedure:
To a solution of 2,3,4,5-tetrahydro-1H-1-benzazepine (0.80 g, 5.4 mmol) in dichloromethane (40 ml) were added 4-cyano-3-methylbenzoic acid from Example C (0.96 g, 6.0 mmol), triethylamine (0.75 ml, 5.4 mmol), 4-dimethylaminopyridine (0.66 g, 5.4 mmol) and WSCDI (2.2 g, 11 mmol). The mixture was stirred at reflux for 18 h, cooled and evaporated in vacuo. The residue was partitioned between EtOAc and 1M KHSO4. The organic layer was washed with saturated sodium bicarbonate solution and brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by flash chromatography on silica (eluant EtOAc:pet. ether 30:70); yield 1.1 g, 70%.
Reaction SMILES: Cl[C:2]1[S:6][N:5]=[C:4]([CH2:7][Cl:8])[N:3]=1.CCN(C(C)C)C(C)C.[CH3:18][O:19][C:20]1[CH:27]=[C:26]([O:28][CH3:29])[CH:25]=[CH:24][C:21]=1[CH2:22][NH2:23]>C(Cl)Cl>[Cl:8][CH2:7][C:4]1[N:3]=[C:2]([NH:23][CH2:22][C:21]2[CH:24]=[CH:25][C:26]([O:28][CH3:29])=[CH:27][C:20]=2[O:19][CH3:18])[S:6][N:5]=1
Reactant: ClCc1nsc(Cl)n1
Reactant: COc1ccc(CN)c(OC)c1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: COc1ccc(CNc2nc(CCl)ns2)c(OC)c1
Reaction time: 8 h

Procedure:
A solution of 5-chloro-3-chloromethyl-[1,2,4]thiadiazole (3 g, 18 mmol, [74461-64-6]) in DCM (20 mL) was treated with DIPEA (1 eq), followed by 2,4-dimethoxybenzylamine (1 eq). After stirring overnight, the mixture was concentrated and purified by silica gel chromatography (10% MeOH/EtOAc) to afford (3-chloromethyl-[1,2,4]thiadiazol-5-yl)-(2,4-dimethoxy-benzyl)-amine, which was used directly in the next step.
Reaction SMILES: [F:1][C:2]1[C:3]([Cl:12])=[C:4](Br)[C:5]2[O:9][CH:8]=[CH:7][C:6]=2[CH:10]=1.[CH3:13][C@H:14]1[CH2:19][NH:18][CH2:17][CH2:16][NH:15]1>>[ClH:12].[F:1][C:2]1[C:3]([Cl:12])=[C:4]([N:18]2[CH2:17][CH2:16][NH:15][C@@H:14]([CH3:13])[CH2:19]2)[C:5]2[O:9][CH:8]=[CH:7][C:6]=2[CH:10]=1
Reactant: Fc1cc2ccoc2c(Br)c1Cl
Reactant: C[C@H]1CNCCN1
Product: C[C@H]1CN(c2c(Cl)c(F)cc3ccoc23)CCN1
Product: Cl

Procedure:
Beginning with 0.27 gm (1.11 mMol) 5-fluoro-6-chloro-7-bromobenzofuran and 0.11 gm (1.11 mMol) 2(S)-methylpiperazine, the title compound was prepared essentially as described in GENERAL PROCEDURE IV.
Reaction SMILES: [N:1]1([C:6]2[CH:13]=[CH:12][C:11](B3OC(C)(C)C(C)(C)O3)=[CH:10][C:7]=2[C:8]#[N:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:23][C:24]1[N:29]=[C:28](Cl)[CH:27]=[CH:26][N:25]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:23][C:24]1[N:29]=[C:28]([C:11]2[CH:12]=[CH:13][C:6]([N:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)=[C:7]([CH:10]=2)[C:8]#[N:9])[CH:27]=[CH:26][N:25]=1
Reactant: CC1(C)OB(c2ccc(N3CCCC3)c(C#N)c2)OC1(C)C
Reactant: Clc1ccnc(Cl)n1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: N#Cc1cc(-c2ccnc(Cl)n2)ccc1N1CCCC1
Temperature: 100 °C
Yield: 381.1 %

Procedure:
Pyrrolidin-1-yl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzonitrile (200 mg, 0.67 mmol), 2,4-dichloropyrimidine (120 mg, 0.81 mmol), tetrakis(triphenylphosphine)palladium(0) (78 mg, 0.07 mmol, 10 mol %) and sodium carbonate (213 mg, 2.01 mmol) were diluted with 1:1 1,4-dioxane-H2O (4.0 mL). The mixture was then heated at 100° C. in the microwave (300 W, stirring) for 10 minutes. The reaction was repeated four more times. The reaction mixtures were combined and the solvents evaporated in vacuo (Genevac™). The residue was partitioned between DCM (150 mL) and H2O (50 mL). The organic phase was washed with water (50 mL) and saturated brine solution (75 mL). The organic phase was then dried (MgSO4), filtered and the solvent evaporated in vacuo. The crude product was purified by column chromatography (40-63 mesh silica gel, 70% isohexane-EtOAc) to provide the title compound as a yellow solid (727 mg, 76%); LC-MS, Rt=2.80 min (MeOH-FA method), m/z 285, 287 (MH+).
Reaction SMILES: C1(O)C=CC=CC=1.[Cl:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH2:19][N:20]3[CH2:24][CH2:23][C@H:22]([NH:25][S:26]([C:29]4[CH:38]=[CH:37][C:36]5[C:31](=[CH:32][C:33]([O:39][CH3:40])=[CH:34][CH:35]=5)[CH:30]=4)(=[O:28])=[O:27])[C:21]3=[O:41])[CH:17]=2)[CH:12]=[CH:11][N:10]=1.C([O-])(=O)C.[NH4+:46]>CCOCC>[ClH:8].[NH2:46][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([CH2:19][N:20]3[CH2:24][CH2:23][C@H:22]([NH:25][S:26]([C:29]4[CH:38]=[CH:37][C:36]5[C:31](=[CH:32][C:33]([O:39][CH3:40])=[CH:34][CH:35]=5)[CH:30]=4)(=[O:28])=[O:27])[C:21]3=[O:41])[CH:17]=2)[CH:12]=[CH:11][N:10]=1
Reactant: COc1ccc2ccc(S(=O)(=O)N[C@H]3CCN(Cc4ccc5ccnc(Cl)c5c4)C3=O)cc2c1
Reactant: [NH4+]
Agent: CC(=O)[O-]
Solvent: CCOCC
Solvent: Oc1ccccc1
Product: COc1ccc2ccc(S(=O)(=O)N[C@H]3CCN(Cc4ccc5ccnc(N)c5c4)C3=O)cc2c1
Product: Cl
Temperature: 115 °C
Reaction time: 0.08 h
Yield: 53.5 %

Procedure:
In a round-bottomed flask fitted with a cold finger condenser, phenol (0.569 g, 6 mmol) and 7-methoxynaphthalene-2-sulfonic acid [1-(1-chloro-isoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]-amide (0.2 g, 0.4 mmol) is melted at 70° C. The mixture is stirred for 5 minutes, then ammonium acetate (0.462 g, 6 mmol) is added and heated at 115° C. for 2 hours. After this time, additional ammonium acetate (0.462 g, 6 mmol) is added. After 2 hours the reaction mixture is cooled to room temperature then partitioned between EtOAc and 0.5N NaOH. The organic layer is separated and washed with water and brine, then dried over Na2SO4, filtered and concentrated. The resulting residue is partially purified by RP-HPLC eluting with a gradient of 10% CH3CN/H2O (0.1% TFA) to 100% CH3CN. The appropriate fractions are concentrated in vacuo. The solid which precipitates out from the solution is then filtered, dried and purified again by column chromatography eluting with 5% MeOH/CH2Cl2. This product is then triturated with cold MeOH and the collected solid is suspended in MeOH and cooled to 0° C. HCl(g) is bubbled through the slurry for a few minutes during which time all the solid dissolves into the solution. The solvent is removed in vacuo and the title product (0.11 g, 0.214 mmol) is washed with ether and dried.
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][C:11]1[S:15][C:14]2[CH:16]=[CH:17][CH:18]=[CH:19][C:13]=2[C:12]=1Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN(CCN(C)C)C.[Li]C(CC)C.[C:34]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=1)#N.C1C[O:45]CC1>C1(C)C=CC=CC=1>[CH2:1]([O:8][CH2:9][CH2:10][C:11]1[S:15][C:14]2[CH:16]=[CH:17][CH:18]=[CH:19][C:13]=2[C:12]=1[C:34]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=1)=[O:45])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: N#Cc1ccccn1
Reactant: C1CCOC1
Reactant: Brc1c(CCOCc2ccccc2)sc2ccccc12
Agent: CN(C)CCN(C)C
Agent: [Li]C(C)CC
Solvent: Cc1ccccc1
Product: O=C(c1ccccn1)c1c(CCOCc2ccccc2)sc2ccccc12
Reaction time: 0.08 h
Yield: 41 %

Procedure:
To a cooled solution (−78° C.) of 2-(2-benzyloxy-ethyl)-3-bromo-benzo[b]thiophene (9.6 g, 27.6 mmol) in anhydrous THF (200 mL), TMEDA (4.14 mL, 27.6 mmol) was added and the mixture was stirred for 5 min. After dropwise addition of sec-BuLi (23.3 mL, 30.3 mmol), while keeping the temperature below −60° C., the mixture was stirred for an additional 30 min at −78° C. A solution of 2-cyanopyridine (3.16 g, 30.34 mmol) in toluene (30 mL) was added and after stirring for 30 min at −78° C. the reaction was quenched by dropwise addition of 6N HCl (66 mL) in MeOH (134 mL), while keeping the temperature below −60° C. After stirring overnight while allowing the mixture to reach room temperature, the mixture was concentrated in vacuo. The residue was dissolved in dichloromethane (100 mL) and NH4OH (100 mL) was added. The organic layer was separated and the aqueous layer was further extracted with dichloromethane. The combined organic layers were dried (Na2SO4), concentrated and subjected to silica gel column chromatography (eluent: EtOAc/Hex=1/4 up to EtOAc/Hex=1/1) to afford 4.2 g of [2-(2-benzyloxy-ethyl)-benzo[b]thiophen-3-yl]-pyridin-2-yl-methanone (41% yield).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[C:11]([O-:13])[O+:10]=[N:9]2)=[CH:4][CH:3]=1.C(Cl)(=O)C.[CH3:18][S:19](C)=O>>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:12]([S:19][CH3:18])=[C:11]([O-:13])[O+:10]=[N:9]2)=[CH:6][CH:7]=1
Reactant: [O-]c1cn(-c2ccc(F)cc2)n[o+]1
Reactant: CS(C)=O
Solvent: CC(=O)Cl
Product: CSc1c([O-])[o+]nn1-c1ccc(F)cc1
Reaction time: 8 h

Procedure:
Using the procedure of Masada and Okutani (Tetrahedron 30, 409-414 (1974)) the crude 3-(4-fluorophenyl)-3H-1,2,3-oxadiazol-1-ium-5-olate (1.95 g, 10.82 mmol) was dissolved in anhydrous DMSO (27 mL) and cooled in ice. Acetyl chloride (2.0 g, 25.5 mmol) was added dropwise. The reaction mixture was allowed to come to room temperature. After stiffing overnight, the mixture was partitioned between ether and saturated NaHCO3 solution. The organic layer was washed several times with water, dried and evaporated to dryness to afford 3-(4-fluorophenyl)-4-(methylthio)-3H-1,2,3-oxadiazol-1-ium-5-olate.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:7])[CH:4](Br)[CH3:5].[O-:8][C:9]#[N:10].[K+].[CH3:12][OH:13]>>[CH3:1][O:2][C:3](=[O:7])[CH:4]([NH:10][C:9]([O:13][CH3:12])=[O:8])[CH3:5]
Reactant: N#C[O-]
Reactant: CO
Reactant: COC(=O)C(C)Br
Agent: [K+]
Product: COC(=O)NC(C)C(=O)OC
Yield: 59 %

Procedure:
From the reaction of 11.69 grams of 2-bromopropionic acid methyl ester with 8.52 grams of potassium cyanate and 7.85 grams of methanol under the conditions described in Example 1 there were isolated 6.66 grams (59%) of 2-methoxycarbonylaminopropionic acid methyl ester with a boiling point of 65°-67° C./0.0013 mbar.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH2:8][O:9][CH2:10][O:11][CH3:12])=[CH:4][C:3]=1[CH3:13].CN(C)[CH:16]=[O:17].O.Cl>O1CCCC1.C([Li])CCC.CCCCCC>[CH3:12][O:11][CH2:10][O:9][CH2:8][C:5]1[CH:6]=[CH:7][C:2]([CH:16]=[O:17])=[C:3]([CH3:13])[CH:4]=1
Reactant: CN(C)C=O
Reactant: COCOCc1ccc(Br)c(C)c1
Agent: Cl
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Solvent: O
Product: COCOCc1ccc(C=O)c(C)c1
Temperature: -65 °C
Reaction time: 0.5 h

Procedure:
4.00 g of 1-bromo-4-[(methoxymethoxy)methyl]-2-methylbenzene was dissolved in 40 mL of tetrahydrofuran, to which 11.5 mL of a solution of n-butyllithium in n-hexane (1.56 M) was added dropwise at −65 to −60° C., and then this mixture was stirred for 30 minutes at −65° C. Then, 20 mL of N,N-dimethylformamide was added dropwise thereto at −65 to −40° C., and a temperature of this reaction mixture was raised to room temperature over one hour and was stirred for another one hour at room temperature. Water was added to the reaction mixture and adjusted to pH 5 with 6M hydrochloric acid, followed by addition thereto of ethyl acetate, and then the organic phase was separated therefrom. After the resultant organic phase was washed with water and a saturated sodium chloride solution successively, the washed phase was dried over anhydrous magnesium sulfate, and the solvent was distilled out under reduced pressure. The resultant residue was purified by silica gel column chromatography [eluent; hexane:ethyl acetate=5:1] to yield 1.54 g of 4-[(methoxymethoxy)methyl]-2-methylbenzaldehyde as colorless oil.
Reaction SMILES: [CH:1]1[C:2]2[N:3]([CH:8]=[N:9][CH:10]=2)[C:4](=[S:7])[NH:5][N:6]=1.C[O-].[Na+].I[CH2:15][CH3:16]>CO>[CH2:15]([N:5]1[C:4](=[S:7])[N:3]2[CH:8]=[N:9][CH:10]=[C:2]2[CH:1]=[N:6]1)[CH3:16]
Reactant: CCI
Reactant: S=c1[nH]ncc2cncn12
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: CCn1ncc2cncn2c1=S

Procedure:
To a mixture of 3.04 g of imidazo[1,5-d]-as-triazine-4(3H)-thione and 30 ml of methanol is added a solution of 1.08 g of sodium methoxide in 10 ml of methanol. The resulting solution is treated with 1.70 ml (3.28 gm) of iodoethane. Upon evaporation, the residue is purified by preparative thin layer chromatography on silica gel. Recrystallization from acetone gives the desired product, m.p. 143°-144.5° C.
Reaction SMILES: C(OC(=O)[NH:7][CH:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]#[N:27])[CH:24]=3)[CH:19]=[CH:18][C:17]2=[O:28])[CH2:10][CH2:9]1)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[NH2:7][CH:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][N:16]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:26]#[N:27])[CH:24]=3)[CH:19]=[CH:18][C:17]2=[O:28])[CH2:10][CH2:9]1
Reactant: CC(C)(C)OC(=O)NC1CCN(CCn2c(=O)ccc3ccc(C#N)cc32)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: N#Cc1ccc2ccc(=O)n(CCN3CCC(N)CC3)c2c1

Procedure:
A solution of tert-butyl{1-[2-(7-cyano-2-oxoquinolin-1(2H)-yl)ethyl]piperidin-4-yl}carbamate (Intermediate 15) (6.57 g, 16.57 mmol) in dichloromethane (100 mL) was treated with trifluoroacetic acid (40 mL) at 0° C. for 30 minutes. The solvent was removed under reduced pressure and the residue codistilled once with dichloromethane, then taken up in dichloromethane (200 mL) and washed with saturated sodium hydrogencarbonate solution (50 mL, pH adjusted to 10 with sodium hydroxide). The aqueous phase was back-extracted three times with dichloromethane (3×100 mL) and dried over sodium sulfate. The solvent was removed under reduced pressure to give the product as off-white solid, 5 g, mp 138° C.
Reaction SMILES: C(CC1[N:5]=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[NH:7]C=1C)#N.[CH3:16][C:17]1([OH:30])[C:21]([CH3:23])([OH:22])NC(C2C=CC=CC=2)=N1>O>[C:6]([NH2:7])(=[NH:5])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[C:21]([C:17]([CH3:16])=[O:30])([CH3:23])=[O:22]
Reactant: Cc1[nH]c(-c2ccccc2)nc1CC#N
Reactant: CC1(O)N=C(c2ccccc2)NC1(C)O
Solvent: O
Product: CC(=O)C(C)=O
Product: N=C(N)c1ccccc1

Procedure:
An alternative method of preparing the preferred compound, 4-cyanomethyl-5-methyl-2-phenylimidazole (X), is from the precursor, 4,5-dimethyl-2-phenylimidazoline-4,5-diol (VII), preferably in the form of a mineral acid addition salt. The precursor (VII), which is described by O. Diels and K. Schleich, Ber. 49, 1711 (1916), may be obtained by the reaction of benzamidine with biacetyl in water. By heating (VII) in a strong non-oxidizing mineral acid, preferably dilute HCl, under reflux conditions (about 95° C) for about 1-2 hours, and then cooling the reaction mixture to about 0° C for maximal precipitation conditions, there is obtained 5(4)-methyl-2-phenylimidazole-4(5)-methanol (VIII), the hydroxy function of which is then transformed successively to the chloride (IX) and then to the nitrile (X), as previously described, to yield the desired 4-cyanomethyl-5-methyl-2-phenyl-imidazole. The foregoing reactions may be illustrated by the following schematic flow chart: ##STR3##
Reaction SMILES: C(NC(C)C)(C)C.C([Li])CCC.[CH2:13]([N:20]1[CH2:25][CH2:24][C:23](=[O:26])[CH2:22][CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[OH-:27].[Na+].[O:29]1[CH2:33][CH2:32]CC1>C(O)(=O)C>[CH2:13]([N:20]1[CH2:25][CH2:24][C:23]([CH2:32][C:33]([OH:29])=[O:27])([OH:26])[CH2:22][CH2:21]1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: O=C1CCN(Cc2ccccc2)CC1
Reactant: [OH-]
Reactant: C1CCOC1
Agent: [Li]CCCC
Agent: [Na+]
Solvent: CC(C)NC(C)C
Solvent: CC(=O)O
Product: O=C(O)CC1(O)CCN(Cc2ccccc2)CC1
Temperature: 25 °C

Procedure:
A mixture of 2.12 g diisopropylamine and 15 ml tetrahydrofuran is stirred under argon at 0°. To this solution is added over two minutes 14 ml of 1.5 M n-butyllithium. To this solution at 0° is added 0.6 g acetic acid. The mixture is stirred five minutes at 20° and then cooled to -70°. To this mixture is added a solution of 1.89 g N-benzyl-4-piperidone in 4 ml tetrahydrofuran. The mixture is allowed to warm to room temperature and poured into 50 ml 1% sodium hydroxide. This mixture is extracted with three 50 ml portions of diethyl ether. The aqueous phase is adjusted to pH 7.0 with 3 N hydrochloric acid and is extracted with five 40 ml portions of dichloroethane. Evaporation of the dichloromethane affords (1-benzyl-4-hydroxypiperidin-4-yl)acetic acid.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=3)[C:3]=12.[N+:23]([C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1)([O-:25])=[O:24].ClC(Cl)C.ClCCl>N1C=CC=CC=1.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[CH:18]1([N:8]2[C:4]3=[N:5][CH:6]=[N:7][C:2]([NH2:1])=[C:3]3[C:10]([C:11]3[CH:12]=[CH:13][C:14]([O:17][C:30]4[CH:29]=[CH:28][CH:27]=[C:26]([N+:23]([O-:25])=[O:24])[CH:31]=4)=[CH:15][CH:16]=3)=[N:9]2)[CH2:22][CH2:21][CH2:20][CH2:19]1
Reactant: O=[N+]([O-])c1cccc(B(O)O)c1
Reactant: Nc1ncnc2c1c(-c1ccc(O)cc1)nn2C1CCCC1
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: CC(Cl)Cl
Solvent: c1ccncc1
Solvent: ClCCl
Product: Nc1ncnc2c1c(-c1ccc(Oc3cccc([N+](=O)[O-])c3)cc1)nn2C1CCCC1
Temperature: 25 °C
Yield: 11.8 %

Procedure:
A mixture of 4-(4-amino-1-cyclopentyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenol (0.202 g, 0.684 mmol, 1 equiv), 3-nitrophenylboronic acid (0.571 g, 3.42 mmol, 5.0 equiv), copper (II) acetate (0.186 g, 1.02 mmol, 1.5 equiv), and 4 Å molecular sieves in pyridine (0.28 mL) and dichloroethane (6.8 mL) was heated at reflux for 24 h. The reaction mixture was allowed to cool to ambient temperature. Dichloromethane (25 mL) was added to the residue and the resulting solid was removed by filtration through a pad of Celite with the aid of MeOH (20 mL). The filtrate was concentrated to afford a brown liquid which was purified by column chromatography over silica gel (elution with 400 mL of heptane, 400 mL of 10% EtOAc/heptane, 400 mL of 20% EtOAc/heptane, and 800 mL of MeOH) to afford a red oil which was further purified by preparative RP-LC/MS (Gilson-Micromass C18, 5 μm, 130 Å, 21 cm, 0%-100% acetonitrile-0.1M ammonium acetate over 9 min, 25 mL/min). The acetonitrile was removed in vacuo and the aqueous mixture was lyopholyzed to give 1-cyclopentyl-3-[4-(3-nitrophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine as a pale yellow solid (0.034 g, 0.081 mmol): 1H NMR (d6 DMSO, 400 MHz): δH 8.22 (1H, s), 7.28-7.74 (6H, m), 7.18 (2H, d, J=8.6 Hz), 7.7 (2H, bs), 5.13-5.26 (1H, m), 2.02-2.10 (4H, m), 1.89-1.91 (2H, m), 1.68-1.70 (2H, m); RP-HPLC (Hypercil C18, 5 μm, 100 Å, 15 cm; 5%-100% acetonitrile-0.1M ammonium acetate over 15 min, 1 mL/min) Rt 19.98 min.
Reaction SMILES: [Br:1][C:2]1[C:3]([OH:19])=[C:4]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[N:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:6]=1[Br:7].[CH3:20][C:21](C)([O-])[CH3:22].[K+].BrC(C)C>CS(C)=O>[Br:1][C:2]1[C:3]([O:19][CH:21]([CH3:22])[CH3:20])=[C:4]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[N:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:6]=1[Br:7]
Reactant: CCOC(=O)c1c(O)c(Br)c(Br)n1-c1ccccc1
Reactant: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(C)Br
Solvent: CS(C)=O
Product: CCOC(=O)c1c(OC(C)C)c(Br)c(Br)n1-c1ccccc1
Temperature: 25 °C

Procedure:
Ethyl 4,5-dibromo-3-hydroxy-1-phenyl-1H-pyrrole-2-carboxylate (4.0 g, 0.010 moles) is dissolved in DMSO (20 mL) under argon. Potassium tert-butoxide (1.2 g, 0.011 moles) is added, followed after 15 minutes by 2-bromopropane (2.6 g, 0.021 moles), and the mixture is stirred at room temperature. After 24 hours the mixture is stirred into ice water (300 mL) and extracted with CH2Cl2 (3×125 mL). The combined extracts are washed with saturated brine (2×100 mL) and dried over MgSO4. Removal of the solvent under reduced pressure left the product (4.1 g) as an oil, sufficiently pure for further use.
Reaction SMILES: [C:1](Cl)(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(=O)(=O)(O)O.C(=O)(O)[O-].[Na+].[C:20]([O-:28])(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[CH3:29][CH2:30][O:31][CH2:32][CH3:33]>O.N1C=CC=CC=1>[C:20]([O:28][C@@H:4]1[CH2:3][C@@H:2]2[C@@H:7]([CH2:6][CH2:5][C:1]2=[O:8])[C@H:29]1[CH2:30][O:31][CH2:32][C:33]1[CH:6]=[CH:7][CH:2]=[CH:3][CH:4]=1)(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1
Reactant: O=C([O-])c1ccccc1
Reactant: CCOCC
Reactant: O=C(Cl)c1ccccc1
Agent: O=C([O-])O
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: c1ccncc1
Solvent: O
Product: O=C(O[C@@H]1C[C@H]2C(=O)CC[C@H]2[C@H]1COCc1ccccc1)c1ccccc1
Reaction time: 4 h

Procedure:
A solution of 0.55 g. of the alcohol of formula XIX in 4 ml. of pyridine is combined with 0.5 ml of benzoyl chloride. The mixture is agitated for 4 hours at 25°, combined with 0.4 ml of water agitated for 2 hours, diluted with ether, and the mixture is shaken in succession with water, 5% sulfuric acid, water, 4% sodium bicarbonate solution, and three times with water. After drying over magnesium sulfate the mixture is evaporated under vacuum, thus obtaining 720 mg. of the benzoate as a colorless oil.
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH:8]=2)[C:3]=1[C:24]([NH2:26])=[O:25].[C:27](=O)([O-])[O-].[K+].[K+].CI.O>CN(C)C=O>[CH3:27][O:1][C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[C:7]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH:8]=2)[C:3]=1[C:24]([NH2:26])=[O:25]
Reactant: CCCCCCCCCCCCc1ccc2c(C(N)=O)c(O)ccc2c1
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CI
Solvent: CN(C)C=O
Product: CCCCCCCCCCCCc1ccc2c(C(N)=O)c(OC)ccc2c1
Yield: 82.8 %

Procedure:
3.6 g of 2-hydroxy-6-n-dodecyl aminocarbonylnaphthalene obtained in example 2 was dissolved in 36 g of dimethylformamide. To this solution, 1.7 g of potassium carbonate and 2.2 g of methyl iodide were added, and allowed to react at 40° C. for 8 hours. The reaction liquid was poured to 180 g of water, and then precipitate was filtrated, washed thoroughly with methanol and water, dried to give 3.1 g of 2-methoxy-6-n-dodecyl aminocarbonylnaphthalene (Decomposition point: 324° C.). The infrared absorption spectrum (KBr) of the compound is shown in FIG. 3. The triboelectric charge was measured by blow-off method as described in example 1. The triboelectric charge of the compound was +17.6 μC/g.