Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[CH:9]=[C:8]([C:15]([CH3:21])([CH3:20])[C:16]([O:18]C)=[O:17])[CH:7]=[CH:6][C:5]2=1.C[Si](C)(C)[O-].[K+].Cl>C1COCC1.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[CH:9]=[C:8]([C:15]([CH3:21])([CH3:20])[C:16]([OH:18])=[O:17])[CH:7]=[CH:6][C:5]2=1
Reactant: COC(=O)C(C)(C)c1ccc2c(c1)[nH]c1ccc(Cl)cc12
Agent: C[Si](C)(C)[O-]
Agent: Cl
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)(C(=O)O)c1ccc2c(c1)[nH]c1ccc(Cl)cc12
Temperature: 50 °C

Procedure:
To a solution of methyl 2-(6-Chloro-9H-carbazol-2-yl)-2-methyl-propionate in THF (1.5 mL) was added potassium trimethylsilanolate (189 mg, 2.5 eq) and the mixture heated to 50° C. for 3 hrs. The solution was diluted with EtOAc and acidified to ˜pH 3 with 2M HCl. The organic layer was separated and the aqueous phase extracted with EtOAc. The combined organic phases were dried (MgSO4), filtered and evaporated to dryness to afford the desired acid, 2-(6-chloro-9H-carbazol-2-yl)-2-methyl-propionic acid, as a colorless solid. 1H NMR (500 MHz, MeOD) δ 7.98 (1H, d, J=1.8 Hz), 7.96 (1H, d, J=8.1 Hz), 7.47 (1H, d, J=1.5 Hz), 7.37 (1H, d, J=8.6 Hz), 7.29 (1H, dd, J=8.6, 2.1 Hz), 7.21 (1H, d, J=8.4, 1.7 Hz), 1.63 (6H, s).
Reaction SMILES: [CH:1]1[C:6]([OH:7])=[CH:5][CH:4]=[C:3]([CH3:8])[CH:2]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18].O>CC(C)=O>[CH3:8][C:3]1[CH:4]=[CH:5][C:6]([O:7][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:1][CH:2]=1
Reactant: CCOC(=O)CBr
Reactant: Cc1ccc(O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CC(C)=O
Product: CCOC(=O)COc1ccc(C)cc1
Temperature: 25 °C

Procedure:
A stirred mixture of p-cresol (14.6 g, 0.135 mole) and anhydrous potassium carbonate (37.2 g, 0.27 mole) in dry acetone (200 ml) was heated under reflux for 30 minutes. The mixture was then cooled to room temperature and ethyl bromoacetate (16.6 ml, 0.15 mole) added. The mixture was heated upto reflux again and maintained at this temperature for 41/2 hours, then allowed to cool before pouring into water (1000 ml). The aqueous mixture was extracted with ether (2×250 ml) and the organic solution washed with dilute hydrochloric acid (1×200 ml) and water (1×200 ml), then dried (MgSO4) and evaporated to dryness to give a quantitative yield of the title compound as a yellow oil.
Reaction SMILES: Br[C:2]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:3]=1[NH2:4].[C:13]([O:17][C:18]([N:20]1[CH2:25][CH:24]=[C:23](B2OC(C)(C)C(C)(C)O2)[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:15])[CH3:14]>O1CCOCC1>[C:13]([O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([C:2]2[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[CH:5][C:3]=2[NH2:4])[CH2:22][CH2:21]1)=[O:19])([CH3:16])([CH3:14])[CH3:15]
Reactant: Nc1ccc(C(F)(F)F)cc1Br
Reactant: CC(C)(C)OC(=O)N1CC=C(B2OC(C)(C)C(C)(C)O2)CC1
Solvent: C1COCCO1
Product: CC(C)(C)OC(=O)N1CCC(c2cc(C(F)(F)F)ccc2N)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 92.7 %

Procedure:
A 4.5 L reactor was charged with 2-bromo-4-trifluoromethyl aniline (100 g), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (124 g, prepared as described in WO 2006/003494), 1,4-dioxane (2500 ml) and the solution was degassed for 30 minutes with argon. Dichloro-bis(triphenylphosphine)-palladium (5.6 g) was added and the resulting solution was stirred for 30 minutes at ambient temperature under an argon atmosphere. A degassed solution of sodium carbonate (127 g) in water (1200 ml) was added and the mixture was stirred at 60° C. for 3 hours. The mixture was cooled to ambient temperature and extracted with ethyl acetate (3×300 ml). The combined organic layers were washed with water (3×400 ml), brine then dried over sodium sulfate and concentrated in vacuo. The residue was dissolved in heptane (200 ml) and cooled to −70° C. and then allowed to warm to 0° C. The solid was collected by filtration and rinsed with cold heptane to afford 4-(2-amino-5-trifluoromethyl-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (128 g) as a brown solid. MS (ES+) 214/215; 243/244 (MH+-BOC); 287/288; 343 (MH+); 1H NMR (400 MHz, CDCl3) 1.5 (s, 9H), 2.4 (m, 2H), 3.65 (t, 2H), 4.05 (m, 2H), 5.8 (m, 1H), 6.7 (d, 1H), 7.2 (d, 1H), 7.3 (dd, 1H).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([CH3:10])=[O:9])=[C:4]([CH3:11])[CH:3]=1.[OH-].[Na+].[CH:14](=O)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.Cl>CO.O>[CH3:11][C:4]1[CH:3]=[C:2]([CH3:1])[CH:7]=[CH:6][C:5]=1[C:8](=[O:9])[CH:10]=[CH:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: O=Cc1ccccc1
Reactant: CC(=O)c1ccc(C)cc1C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: Cc1ccc(C(=O)C=Cc2ccccc2)c(C)c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 83.8 %

Procedure:
2,4-Dimethylacetophenone (44ak, 1.48 g, 10.0 mmol) and sodium hydroxide (0.54 g, 13.5 mmol) were combined in methanol (30 ml) and stirred for 30 min at room temperature. A solution of benzaldehyde (1b, 1.02 ml, 10.0 mmol) and methanol (30 ml) was added dropwise and the mixture stirred for 18 hr at room temperature. Water (25 ml) was added and the mixture neutralized with hydrochloric acid (1 N). The mixture was extracted into ethyl acetate, washed with saturated sodium chloride, dried over magnesium sulfate, filtered and evaporated to afford an oil. The crude oil was distilled bulb to bulb to give 1.98 g (84%) of a yellow oil: [expected mp 68° C.]; 1H NMR δ 2.37 (s, 3H), 2.44 (s, 3H), 7.05 (m, 2H), 7.16 (d, 1H, J=16.1 Hz), 7.38 (m, 3H), 7.49 (d, 1H, J=15.9 Hz), 7.54 (m, 3H); 13C NMR: δ 20.4, 21.4, 126.0, 126.6, 128.2, 128.5, 128.8, 130.4, 132.2, 134.7, 136.1, 137.4, 140.8, 145.0, 195.6.
Reaction SMILES: [CH3:1][CH:2]([CH2:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH2:3][OH:4]>C1CCCCC1.ClC(Cl)C.[Fe](Cl)Cl>[CH3:1][CH:2]([CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:2]([CH3:5])([CH3:3])[CH3:1])=[CH:8][CH:7]=1)[CH2:3][OH:4]
Reactant: CC(CO)Cc1ccccc1
Agent: Cl[Fe]Cl
Solvent: C1CCCCC1
Solvent: CC(Cl)Cl
Product: CC(CO)Cc1ccc(C(C)(C)C)cc1
Yield: 84 %

Procedure:
DE 29 52 719 likewise describes the iron chloride-catalyzed Friedel-Crafts alkylation of 2-methyl-3-phenylpropanol. In cyclohexane or dichloroethane solvent, a yield of 84-86% of 2-methyl-3-(4-tert-butylphenyl)propanol was obtained. The formation of the misomeric compound, (2-methyl-3-(3-tert-butylphenyl)propanol), was not demonstrated.
Reaction SMILES: C[O:2][C:3](=O)[C@H:4]([CH2:13][O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[NH:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].[H-].C([Al+]CC(C)C)C(C)C.Cl>C1(C)C=CC=CC=1>[C:6]([NH:5][C@H:4]([CH:3]=[O:2])[CH2:13][O:14][CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)([O:8][C:9]([CH3:11])([CH3:10])[CH3:12])=[O:7]
Reactant: COC(=O)[C@H](COCc1ccccc1)NC(=O)OC(C)(C)C
Agent: CC(C)C[Al+]CC(C)C
Agent: Cl
Agent: [H-]
Solvent: Cc1ccccc1
Product: CC(C)(C)OC(=O)N[C@H](C=O)COCc1ccccc1
Temperature: -70 °C

Procedure:
N-Boc-O-benzylserine methyl ester (9.5 g, 32 mmol) was dissolved in dry toluene (distilled from sodium) (100 ml). The solution was cooled to -70° C., and a solution of diisobutylaluminium hydride in toluene (1.2M, 53 ml, 64 mmol) was added dropwise over a period of 45 minutes under vigorous stirring under nitrogen. The mixture was stirred for an additional 20 minutes and was then allowed to reach -50° C. Hydrochloric acid (2M, 150 ml) was carefully added and the resulting reaction mixture was allowed to reach -10° C. The organic layer was separated and the aqueous layer was extracted with ethylacetate (2×100 ml). The combined organic solution was dried with sodium sulphate and evaporated to dryness below 40° C. (bath temperature). The N-Boc-O-benzylserinal was isolated as a colourless oil. Yield 8.6 g (96%). The structure was confirmed by 1HNMR and 13CNMR.
Reaction SMILES: Cl.Cl.[NH2:3][CH2:4][CH2:5][CH2:6][S:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1.C(N(CC)CC)C.[CH3:21][O:22][C:23]1[CH:24]=[C:25]([CH:29]=[C:30]([O:32][CH3:33])[CH:31]=1)[C:26](Cl)=[O:27]>C(Cl)Cl>[CH3:33][O:32][C:30]1[CH:29]=[C:25]([CH:24]=[C:23]([O:22][CH3:21])[CH:31]=1)[C:26]([NH:3][CH2:4][CH2:5][CH2:6][S:7][C:8]1[CH:13]=[CH:12][N:11]=[CH:10][CH:9]=1)=[O:27]
Reactant: NCCCSc1ccncc1
Reactant: COc1cc(OC)cc(C(=O)Cl)c1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1cc(OC)cc(C(=O)NCCCSc2ccncc2)c1
Yield: 87.7 %

Procedure:
To a solution of 1.00 g (4.15 mmol) of 4-(3-aminopropylthio)pyridine dihydrochloride and 2.77 ml (19.8 mmol) of triethylamine in 40 ml of methylene chloride was added 995 mg (4.96 mmol) of 3,5-dimethoxybenzoyl chloride under ice-cooling with stirring and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was washed with an aqueous saturated sodium bicarbonate solution and water and dried. The solvent was distilled off. The residue was purified by column chromatography (eluent: ethyl acetate) to obtain 1.21 g of the desired compound (87.7% pale yellow powder), mp: 110.0°-111.0° C.
Reaction SMILES: [NH2:1][C:2]1[C:3]([NH:31][CH3:32])=[CH:4][C:5]([C:10]2[CH:26]=[CH:25][C:13]([O:14][CH2:15][CH2:16][NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[C:12]([C:27]([F:30])([F:29])[F:28])[CH:11]=2)=[N:6][C:7]=1[C:8]#[N:9].Cl.[N:34]([O-])=O.[Na+]>O1CCOCC1.O>[C:8]([C:7]1[C:2]2[N:1]=[N:34][N:31]([CH3:32])[C:3]=2[CH:4]=[C:5]([C:10]2[CH:26]=[CH:25][C:13]([O:14][CH2:15][CH2:16][NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[C:12]([C:27]([F:28])([F:29])[F:30])[CH:11]=2)[N:6]=1)#[N:9]
Reactant: CNc1cc(-c2ccc(OCCNC(=O)OC(C)(C)C)c(C(F)(F)F)c2)nc(C#N)c1N
Reactant: O=N[O-]
Agent: Cl
Agent: [Na+]
Solvent: C1COCCO1
Solvent: O
Product: Cn1nnc2c(C#N)nc(-c3ccc(OCCNC(=O)OC(C)(C)C)c(C(F)(F)F)c3)cc21
Temperature: 25 °C
Reaction time: 1 h

Procedure:
tert-Butyl 2-(4-(5-amino-6-cyano-4-(methylamino)pyridin-2-yl)-2-(trifluoromethyl)phenoxy)ethylcarbamate (1.130 mmol, 0.51 g) was dissolved in 1M Hydrochloric Acid (2.259 mmol, 2.259 ml) and dioxane (5 ml). Sodium nitrite (1.582 mmol, 0.109 g) in water (5.00 ml) was added to the reaction mixture and it was stirred at room temperature for 1 hr. The reaction mixture was filtered and the solid washed with water to afford tert-butyl 2-(4-(4-cyano-1-methyl-1H-[1,2,3]triazolo[4,5-c]pyridin-6-yl)-2-(trifluoromethyl)phenoxy)ethylcarbamate. (0.61 g)
Reaction SMILES: [I:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][CH:3]=1.[F:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=1[N:20]=[C:21]=[O:22].CCCCCC>ClCCCl>[F:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=1[NH:20][C:21]([NH:6][C:5]1[CH:7]=[CH:8][C:2]([I:1])=[CH:3][CH:4]=1)=[O:22]
Reactant: Nc1ccc(I)cc1
Reactant: O=C=Nc1cc(C(F)(F)F)ccc1F
Solvent: CCCCCC
Solvent: ClCCCl
Product: O=C(Nc1ccc(I)cc1)Nc1cc(C(F)(F)F)ccc1F
Temperature: 0 °C
Yield: 81.6 %

Procedure:
To a solution of 4-iodoaniline (438 mg, 2.0 mmol) in 15.0 mL 1,2-dichloroethane at rt was added 2-fluoro-5-(trifluoromethyl)phenyl isocyanate (0.304 mL, 2.1 mmol). After 50 minutes 3 mL hexane was added, the mixture cooled to 0° C., the precipitant filtered and rinsed with 10% EtOAc/hexane to give the title compound as a light purple solid (692 mg, 82%). 1H NMR (DSMO-d6) δ: 9.26 (s, 1H), 8.90 (d, J=2.9 Hz, 1H), 8.59 (dd, J=7.3, 2.3 Hz, 1H), 7.60-7.65 (m, 2H), 7.46-7.54 (m, 1H), 7.36-7.43 (m, 1H), 7.29-7.34 (m, 2H).
Reaction SMILES: [C:1]1([C:7]([C:9]2[NH:17][C:12]3=[CH:13][N:14]=[CH:15][CH:16]=[C:11]3[CH:10]=2)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:18]([NH:21][NH2:22])([NH2:20])=[NH:19].[ClH:23].Cl.CCOCC>C(O)C.CO>[ClH:23].[ClH:23].[C:1]1([C:7](=[N:22][NH:21][C:18]([NH2:20])=[NH:19])[C:9]2[NH:17][C:12]3=[CH:13][N:14]=[CH:15][CH:16]=[C:11]3[CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: N=C(N)NN
Reactant: O=C(c1ccccc1)c1cc2ccncc2[nH]1
Agent: Cl
Solvent: CCOCC
Solvent: CO
Solvent: CCO
Product: N=C(N)NN=C(c1ccccc1)c1cc2ccncc2[nH]1
Temperature: 25 °C
Reaction time: 3 h
Yield: 154.7 %

Procedure:
To a solution of phenyl(1H-pyrrolo[2,3-c]pyridin-2-yl)methanone (Example 35) (0.15 g, 0.67 mmol) in ethanol (6.7 mL) were added aminoguanidine hydrochloride (0.09 g, 0.81 mmol) and 6 N HCl (0.56 mL). The reaction mixture was heated to reflux under N2. After 3 h, heating was terminated and the reaction mixture was slowly cooled to room temperature overnight. The reaction mixture was concentrated to dryness. The residue was dissolved in water and washed with diethyl ether. The aqueous layer was made basic with 15% NaOH solution and extracted with ethyl acetate (2×). The organic extracts were combined and washed with water and saturated NaCl, and dried over Na2SO4. Filtration and concentration provided the crude residue, which was dissolved in methanol. To the methanol solution was added 2 N HCl in Et2O (0.67 mL, 1.34 mmol). The mixture was concentrated to dryness and the resulting solid was crystallized from EtOH/Et2O (9:1) to provide [[phenyl (1H-pyrrolo[2,3-c]pyridin-2-yl)methylene]amino]guanidine dihydrochloride (0.22 g, 93%) as an off-white solid: mp 306-310° C.; 1H NMR (300 MHz, CD3OD) δ6.71 (1H, s), 7.57-7.74 (5H, m), 8.07 (1H, d, J=6.5 Hz), 8.24 (1H, d, J=6.4 Hz), 9.10 (1H, s); ESI MS m/z 279 [C15H14N6+H]+; HPLC (Method A) >99% (AUC) tR=12.9 min.
Reaction SMILES: [OH2:1].[N+:2]([CH:5]([CH:8]=O)[CH:6]=O)([O-:4])=[O:3].[Na].C(O)=O.[CH2:14]([NH2:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CO.O>[CH2:14]([N:21]1[CH:8]=[C:5]([N+:2]([O-:4])=[O:3])[CH:6]2[N:21]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[CH:8]1[C:5]([N+:2]([O-:3])=[O:1])=[CH:6][N:21]2[CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: NCc1ccccc1
Reactant: O
Reactant: O=CC(C=O)[N+](=O)[O-]
Agent: [Na]
Solvent: CO
Solvent: O=CO
Product: O=[N+]([O-])C1=CN(Cc2ccccc2)C2C([N+](=O)[O-])=CN(Cc3ccccc3)C1N2Cc1ccccc1
Reaction time: 48 h
Yield: 65.1 %

Procedure:
A yellow-orange suspension of sodium nitromalonaldehyde monohydrate (63 mg, 0.40 mmol) in methanol (760 uL), water (32 uL) and 96% formic acid (3.2 uL, 0.084 mmol) was stirred at room-temperature and benzylamine (91.7 uL, 0.84 mmol) was added dropwise over a 5 min period during which the reaction solids dissolved, subsequently the crude product then quickly crystallized. The orange reaction mixture was stirred about 2 days at room-temperature. Filtration gave a yellow powder (63 mg) of which 59 mg was recrystallized from absolute ethanol (˜10 mL) yielding 25 mg (26%) of the title compound BC1 as a yellow, microcrystalline solid: mp 184-185° C.; FIRMS calcd for C27H26N5O4 (M+H+) 484.1985, obsd 484.18924; 1H NMR (300 MHz, DMSO-d6) δ 3.004 (s, 2H), 4.789-5.002 (q, 4H), 5.350 (s, 2H), 6.631-6.659 (d, 2H), 7.035-7.136 (m, 3H), 7.36-7.37 (br s, 10H), 8.800 (s, 2H); 1H NMR (300 MHz, CDCl3) δ 2.948, 2.955 (d, 2H), 4.581, 4.630 (d, 2H), 4.974, 5.023 (d, 2H), 5.308 (s, 2H), 6.714, 6.737 (d, 2H), 7.090, 7.116, 7.170-7.20 (m, 3H), 7.289, 7.298, 7.310, 7.321, 7.335, 7.342, 7.353, 7.363, 7.375 (complex m, 10H), 8.358 (s, 2H); 13C NMR (75 MHz, DMSO-d6) δ 145.704, 135.410, 135.380, 128.787, 128.382, 128.199, 127.879, 127.230, 120.561, 64.383, 57.309, 52.166; Anal. Calcd for C27H25N5O4 (483.52): C, 67.07; H, 5.21; N, 14.48. Found: C, 66.80; H, 5.13; N, 14.45.
Reaction SMILES: C1N2CCN(CC2)C1.[CH2:9]([N:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][N:24]=2)[C:19](Cl)=[C:18]([S:27]([CH3:30])(=[O:29])=[O:28])[C:17]1=[O:31])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[N:32]1([C:38]([C:40]2[S:41][CH:42]=[CH:43][CH:44]=2)=[O:39])[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1>CN1CCCC1=O.O>[CH2:9]([N:16]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][N:24]=2)[C:19]([N:35]2[CH2:36][CH2:37][N:32]([C:38]([C:40]3[S:41][CH:42]=[CH:43][CH:44]=3)=[O:39])[CH2:33][CH2:34]2)=[C:18]([S:27]([CH3:30])(=[O:29])=[O:28])[C:17]1=[O:31])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: O=C(c1cccs1)N1CCNCC1
Reactant: CS(=O)(=O)c1c(Cl)c2cccnc2n(Cc2ccccc2)c1=O
Agent: C1CN2CCN1CC2
Solvent: CN1CCCC1=O
Solvent: O
Product: CS(=O)(=O)c1c(N2CCN(C(=O)c3cccs3)CC2)c2cccnc2n(Cc2ccccc2)c1=O
Temperature: 110 °C
Yield: 74.7 %

Procedure:
DABCO (0.57 g, 5.0 mmol) was added to a solution of 1-benzyl-4-chloro-3-(methylsulfonyl)-[1,8]-naphthyridin-2(1H)-one (115) (0.88 g, 2.5 mmol) and piperazine-1-yl-thiophene-2-yl-methanone (0.60 g, 3.08 mmol) in N-methylpyrrolidone at room temperature. The solution was heated at 110° C. for 15 min. The solution was cooled and poured into ice cold 10% ammonium chloride solution in water. The solids formed were filtered, washed by water, and dried to yield 0.95 g (74%) of 1-benzyl-3-methanesulfonyl-4-[4-(thiophene-2-carbonyl)-piperazin-1-yl]-1H-[1,8]-naphthyridin-2-one (116) as yellow solids MP: 223° C.; 1H-NMR (DMSO-d6): δ 3.37 (s, 3H), 3.59 (m, 4H), 3.93 (b, 4H), 5.59 (s, 2H), 7.2 (m, 6H), 7.38 (m, 1H), 7.47 (dd, J=1.2, 3.6 Hz, 1H), 7.81 (dd, J=1.2, 5.2 Hz, 1H), 8.46 (dd, J=1.6, 8.0 Hz, 1H), 8.70 (dd, J=1.6, 4.4 Hz, 1H); EIMS m/z 509 (M+1).
Reaction SMILES: C(C1C=CC=C(CCCC)C=1O)CCC.C([C:20]1[CH:21]=[C:22]([C:31]2[CH:36]=[C:35](C(C)(C)C)[C:34]([OH:41])=[C:33](C(C)(C)C)[CH:32]=2)[CH:23]=[C:24](C(C)(C)C)[C:25]=1[OH:26])(C)(C)C>>[CH:23]1[C:22]([C:31]2[CH:36]=[CH:35][C:34]([OH:41])=[CH:33][CH:32]=2)=[CH:21][CH:20]=[C:25]([OH:26])[CH:24]=1
Reactant: CC(C)(C)c1cc(-c2cc(C(C)(C)C)c(O)c(C(C)(C)C)c2)cc(C(C)(C)C)c1O
Agent: CCCCc1cccc(CCCC)c1O
Product: Oc1ccc(-c2ccc(O)cc2)cc1

Procedure:
In producing p,p'-biphenol from a mixture of 2,6-di-butylphenol and 3,3',5,5'-tetra-t-butyl-4,4'-diphenoquinone or a mixture of 2,6-di-butylphenol, 3,3',5,5'-tetra-t-butyl-4,4'-diphenoquinone and 3,3',5,5'-tetra-t-butyl-4,4'-dihydroxybiphenyl in the process of the present invention, the reaction for the synthesis of 3,3',5,5'-tetra-t-butyl-4,4'-dihydroxybiphenyl and the reaction for the dealkylation of 3,3',5,5'-tetra-t-butyl-4,4'-dihydroxybiphenyl are performed at a reaction temperature of 120°-180° C. in the presence of a specified solvent and acid catalyst. Since p,p'-biphenol is directly obtained in one step without separating the 3,3',5,5'-tetra-t-butyl-4,4'-dihydroxybiphenyl that has been formed at the first stage, the present invention offers a simplified process for the production of p,p'-biphenol.
Reaction SMILES: C(O[C:5](=[O:7])C)(=O)C.Cl.[NH2:9][CH:10]1[CH2:18][C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11]1.C([O-])(=O)C.[Na+]>C(O)=O>[CH:5]([NH:9][CH:10]1[CH2:18][C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[CH2:11]1)=[O:7]
Reactant: CC(=O)OC(C)=O
Reactant: NC1Cc2ccccc2C1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: O=CO
Product: O=CNC1Cc2ccccc2C1
Temperature: 0 °C

Procedure:
Acetic anhydride (40 ml) and formic acid (20 ml) were mixed and heated at 50° for 15 minutes with stirring. 2-Aminoindane hydrochloride (25 g) (see J. Med. Chem., 1980, 23, page 745) and sodium acetate (20 g) were added to this mixture which was then stirred at room temperature for 24 hours. The reaction mixture was poured into ice/water and extracted three times with methylene chloride. The combined organic layers were washed with water and aqueous sodium carbonate, dried (MgSO4) and evaporated in vacuo to give the title compound, yield 17.6 g, m.p. 72°-74°.
Reaction SMILES: [CH3:1][O:2][CH2:3][CH2:4][NH2:5].[CH2:6]1[O:14][CH:7]1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>>[OH:14][CH:7]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[CH2:6][NH:5][CH2:4][CH2:3][O:2][CH3:1]
Reactant: COCCN
Reactant: c1ccc(C2CO2)cc1
Product: COCCNCC(O)c1ccccc1

Procedure:
To 157 g of refluxing 2-methoxyethylamine is added dropwise 25 g styrene oxide during a period of 15 minutes. After addition of the amine, the mixture is allowed to reflux for another two hours.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:6]=[C:7]([NH:11][C:12]2[N:17]=[C:16]([NH:18][CH2:19][CH:20]3[CH2:25][CH2:24][CH2:23][NH:22][CH2:21]3)[C:15]([C:26]([NH2:28])=[O:27])=[CH:14][N:13]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:3])[CH3:2].CCN(C(C)C)C(C)C.[C:38](OC(=O)C)(=[O:40])[CH3:39]>C(Cl)Cl>[C:1]([NH:4][C:5]1[CH:6]=[C:7]([NH:11][C:12]2[N:17]=[C:16]([NH:18][CH2:19][CH:20]3[CH2:25][CH2:24][CH2:23][N:22]([C:38](=[O:40])[CH3:39])[CH2:21]3)[C:15]([C:26]([NH2:28])=[O:27])=[CH:14][N:13]=2)[CH:8]=[CH:9][CH:10]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)OC(C)=O
Reactant: CC(=O)Nc1cccc(Nc2ncc(C(N)=O)c(NCC3CCCNC3)n2)c1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(=O)Nc1cccc(Nc2ncc(C(N)=O)c(NCC3CCCN(C(C)=O)C3)n2)c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 11.3 %

Procedure:
To a mixture of 2-(3-acetamidophenylamino)-4-(piperidin-3-ylmethylamino)pyrimidine-5-carboxamide (40 mg, 0.104 mmol) and DIEA (0.100 mL, 0.575 mmol) in CH2Cl2 (2 mL), acetic anhydride (0.040 mL, 0.423 mmol) was added. The mixture was stirred at room temperature for 4 h. It was then purified by HPLC to give the titled compound (5 mg). MS 426.5 (M+H); UV 248.6 nm.
Reaction SMILES: Cl[C:2]1[C:7]([NH:8][C:9]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[CH:10][C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.C1N2CCN(CC2)C1.CO.C(Cl)(Cl)Cl.C>CN(C)C=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C:10]2[C:2]3=[N:3][CH:4]=[CH:5][CH:6]=[C:7]3[NH:8][C:9]=2[C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[CH:12][CH:13]=1
Reactant: Fc1ccc(C=C(Nc2cccnc2Cl)c2ccncc2)cc1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: C1CN2CCN1CC2
Solvent: ClC(Cl)Cl
Solvent: CN(C)C=O
Solvent: CO
Product: Fc1ccc(-c2c(-c3ccncc3)[nH]c3cccnc23)cc1
Temperature: 120 °C
Reaction time: 4 h
Yield: 98.5 %

Procedure:
To a solution of (2-chloropyridin-3-yl)-[2-(4-fluorophenyl)-1-(pyridin-4-yl)-vinyl]amine (6.0 g, 18.5 mmol) and DABCO® (6.2 g, 55 mmol) in dimethylformamide (75 ml) was added bis(triphenylphosphine)palladium(II) chloride (650 mg, 0.926 mmol) and the reaction mixture was heated at 120° C. under an argon atmosphere. After 4 h, dimethylformamide was removed in vacuo and the residue was heated in ethyl acetate/methanol mixture. The product was filtered off to give a green solid which was redissolved in boiling methanol/chloroform mixture and treated with charcoal. The solution was filtered through a pad of Celite and the filtrate was concentrated to give 3-(4-fluorophenyl)-2-(pyridin-4-yl)-1H-pyrrolo[3,2-b]pyridine as a pale yellow solid (5.27 g).
Reaction SMILES: C([Li:5])CCC.[CH2:6]([NH:10][CH2:11][CH:12]([CH3:14])[CH3:13])[CH:7]([CH3:9])[CH3:8]>CCCCCC>[CH2:6]([N-:10][CH2:11][CH:12]([CH3:14])[CH3:13])[CH:7]([CH3:9])[CH3:8].[Li+:5]
Reactant: [Li]CCCC
Reactant: CC(C)CNCC(C)C
Solvent: CCCCCC
Product: CC(C)C[N-]CC(C)C
Product: [Li+]
Temperature: 20 °C
Reaction time: 0.25 h

Procedure:
4 ml n-butyl-lithium solution and 1.38 ml di-i-butylamine are added to 1 l n-hexane and the mixture is stirred for 15 minutes at 20°C with exclusion of air and moisture. A solution of lithium di-i-butylamide is obtained.