Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [S].[BH4-].[Na+].[CH2:4]([O:7][C:8]1[CH:9]=[C:10]([N:18]([CH3:20])[CH3:19])[CH:11]=[C:12]([F:17])[C:13]=1[N+:14]([O-])=O)[CH:5]=[CH2:6].C(N(CC)C(C)C)(C)C.[Cl:30][C:31]1[N:36]=[C:35](Cl)[C:34]([Cl:38])=[CH:33][N:32]=1>O1CCCC1.CCOCC>[CH2:4]([O:7][C:8]1[CH:9]=[C:10]([N:18]([CH3:20])[CH3:19])[CH:11]=[C:12]([F:17])[C:13]=1[NH:14][C:33]1[C:34]([Cl:38])=[CH:35][N:36]=[C:31]([Cl:30])[N:32]=1)[CH:5]=[CH2:6]
Reactant: Clc1ncc(Cl)c(Cl)n1
Reactant: C=CCOc1cc(N(C)C)cc(F)c1[N+](=O)[O-]
Agent: [BH4-]
Agent: [Na+]
Agent: [S]
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Solvent: CCOCC
Product: C=CCOc1cc(N(C)C)cc(F)c1Nc1nc(Cl)ncc1Cl
Temperature: 60 °C
Reaction time: 0.33 h

Procedure:
Sulfur (1.2 g, 38 mmol) was added to Sodium tetrahydroborate (0.48 g, 13 mmol) in Tetrahydrofuran (20 mL). After 20 min, a solution of (3-Allyloxy-5-fluoro-4-nitro-phenyl)-dimethyl-amine (0.61 g, 2.5 mmol) in Tetrahydrofuran (20 mL) was added, and after 20 min the mixture was heated at 60° C. for an additional 2.5 h. The mixture was cooled, quenched with 100 mL satd. sodium bicarbonate and extracted with EtOAc (3×50 mL). The organic extract was washed with brine, dried over sodium sulfate and conc. in vacuo. The residue was dissolved in N-Methylpyrrolidinone (10 mL) and N,N-Diisopropylethylamine (0.65 mL, 3.7 mmol) and 2,4,5-Trichloro-pyrimidine (0.60 mL, 5.2 mmol) were added. The mixture was heated under an atmosphere of Nitrogen at 80° C. After 2 h, the solution was cooled, diluted with 100 mL Ether and washed with water (3×20 mL) and brine (50 mL). The aq. extract was back extracted with DCM (2×50 mL), which was then diluted with 100 mL ether and washed with water (50 mL) and brine (50 mL). The organic extracts were combined, dried over sodium sulfate and diluted with an equal volume of hexane before filtering through a 2″h×3″w circular pad of silica gel to remove baseline colored impurities. The filtrate was conc. and chromatographed (ISCO 80 g silica gel, 0-20% EtOAc:Hex), with the product eluting at 20%. Following conc., 2-Allyloxy-N(1)-(2,5-dichloro-pyrimidin-4-yl)-6-fluoro-N(4),N(4)-dimethyl-benzene-1,4-diamine was isolated as a green film (140 mg, 15% over two steps). 1H-NMR (CDCl3): 8.11 (s, 1H), 6.62 (s, 1H), 6.12 (d, 1H, J=13.1 Hz), 5.97 (s, 1H), 5.95 (m, 1H), 5.32 (d, 1H, J=17.2 Hz), 5.23 (d, 1H, J=9.4 Hz), 4.55 (m, 2H), 2.96 (s, 6H); 19F-NMR (CDCl3): −118.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7](Br)[CH:6]=[CH:5][C:4]=1[N+:10]([O-:12])=[O:11].O.[CH2:14](O)[CH2:15]C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH:14]=[CH2:15])[CH:6]=[CH:5][C:4]=1[N+:10]([O-:12])=[O:11]
Reactant: CCCO
Reactant: COc1cc(Br)ccc1[N+](=O)[O-]
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Solvent: O
Product: C=Cc1ccc([N+](=O)[O-])c(OC)c1
Temperature: 100 °C
Yield: 58 %

Procedure:
To 5-bromo-2-nitrophenyl methyl ether (8.0 g, 34.47 mmol) in 80 mL of n-propanol was added, PdCl2(dppf)*DCM (0.5 g, 0.69 mmol), potassium ethenyl(trifluoro)borate (6.47 g, 48.3 mmol), and TEA (3.48 g, 34.47 mmol). The mixture was heated to 100° C. for 3 h. The mixture was poured into 250 mL of H2O and extracted with DCM, dried (Na2SO4), filtered, and rotovaped down, and purified by flash chromatography to give the title compound of step B (3.58 g, 19.98 mmol, 58%). 1H NMR (400 MHz, CDCl3) δ ppm 7.82-7.87 (m, 1H), 7.02-7.07 (m, 2H), 6.70 (dd, J=17.58, 10.80 Hz, 1H), 5.87 (d, J=17.58 Hz, 1H), 5.46 (d, J=10.99 Hz, 1H), 3.97 (s, 3H).
Reaction SMILES: [O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][N:11]3[CH2:15][CH2:14][C:13](=O)[CH2:12]3)=[CH:9][C:4]=2[O:3][CH2:2]1.C(OP([CH2:25]/[CH:26]=[CH:27]/[C:28]([O:30][CH2:31][CH3:32])=[O:29])(OCC)=O)C.[H-].[Na+]>COCCOC>[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([CH2:10][N:11]3[CH2:15][CH2:14]/[C:13](=[CH:25]\[CH:26]=[CH:27]\[C:28]([O:30][CH2:31][CH3:32])=[O:29])/[CH2:12]3)=[CH:9][C:4]=2[O:3][CH2:2]1
Reactant: CCOC(=O)/C=C/CP(=O)(OCC)OCC
Reactant: O=C1CCN(Cc2ccc3c(c2)OCO3)C1
Agent: [H-]
Agent: [Na+]
Solvent: COCCOC
Product: CCOC(=O)/C=C/C=C1\CCN(Cc2ccc3c(c2)OCO3)C1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 16.1 %

Procedure:
To a solution of ketone 274 (0.65 g, 2.96 mmol) and (E)-ethyl 4-(diethoxyphosphoryl)but-2-enoate (1.0 mL, 4.33 mmol) in ethyleneglycol dimethylether (50 mL) at 0° C. was added NaH (0.26 g, 6.58 mmol) and the mixture was stirred at 0° C. for 30 min then at room temperature for 2 h. The reaction mixture was quenched with acetone (2 mL) then diluted with DCM and washed with saturated NaHCO3, dried over MgSO4, filtered and concentrated. The residue was purified by flash column chromatography (eluent: 50% AcOEt in DCM) to provide title compound 275 (0.15 g, 16% yield) as a mixture of cis/trans isomers.
Reaction SMILES: Cl[CH2:2][CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([O:15][C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][C:17]=3[C:23]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:24])=[CH:10][CH:11]=[N:12]2)=[CH:7][C:6]=1[O:31][CH3:32].[CH2:33]([NH:35][CH2:36][CH3:37])[CH3:34].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[CH2:33]([N:35]([CH2:36][CH3:37])[CH2:2][CH2:3][O:4][C:5]1[CH:14]=[C:13]2[C:8]([C:9]([O:15][C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][C:17]=3[C:23]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:24])=[CH:10][CH:11]=[N:12]2)=[CH:7][C:6]=1[O:31][CH3:32])[CH3:34]
Reactant: COc1cc2c(Oc3ccc(C)cc3C(=O)c3ccccc3)ccnc2cc1OCCCl
Reactant: CCNCC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: CCN(CC)CCOc1cc2nccc(Oc3ccc(C)cc3C(=O)c3ccccc3)c2cc1OC
Temperature: 80 °C
Reaction time: 8 h
Yield: 12.9 %

Procedure:
(2-{[7-(2-Chloroethoxy)-6-methoxy-4-quinolyl]oxy}-5-methylphenyl)(phenyl)methanone (50 mg), diethylamine (24 mg), and potassium carbonate (76 mg) were suspended in N,N-dimethylformamide (3 ml), and the suspension was stirred at 80° C. overnight. The reaction solution was cooled to room temperature, water was then added to the cooled reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed therefrom by distillation under the reduced pressure, and the residue was purified by thin layer chromatography using methanol-chloroform to give the title compound (7 mg, yield 13%).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.Cl[S:15]([OH:18])(=[O:17])=[O:16]>C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([S:15]([OH:18])(=[O:17])=[O:16])=[CH:10][CH:9]=2)=[CH:6][CH:7]=1
Reactant: O=S(=O)(O)Cl
Reactant: Clc1ccc(-c2ccccc2)cc1
Solvent: ClC(Cl)Cl
Product: O=S(=O)(O)c1ccc(-c2ccc(Cl)cc2)cc1
Temperature: 25 °C
Reaction time: 6 h

Procedure:
To a solution of 4-chlorobiphenyl (15 g, 79.8 mmol) in chloroform (150 mL) is added dropwise chlorosulfonic acid (11.2 g, 96 mmol). A white solid precipitate forms during the addition. The reaction is stirred at room temperature for 6 hr, at which time the precipitate is collected by filtration and the precipitate is then washed with cold chloroform. The product is dried under vacuum to give a white solid product. The product is used without further purification.
Reaction SMILES: [NH2:1][C@@H:2]([C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][CH:13]=1)[CH2:10][C@@H:9]([NH:14][C:15](=[O:29])[C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][C@@H:24]3[CH2:28][CH2:27][CH2:26][O:25]3)=[CH:18][CH:17]=1)[CH2:8][CH2:7]2)[CH3:3].Br[CH2:31][CH2:32][CH:33]([CH3:37])[CH2:34][CH2:35]Br.C(N(C(C)C)C(C)C)C>C(#N)C>[CH3:37][CH:33]1[CH2:34][CH2:35][N:1]([C@@H:2]([C:4]2[CH:5]=[C:6]3[C:11](=[CH:12][CH:13]=2)[CH2:10][C@@H:9]([NH:14][C:15](=[O:29])[C:16]2[CH:21]=[CH:20][C:19]([O:22][CH2:23][C@@H:24]4[CH2:28][CH2:27][CH2:26][O:25]4)=[CH:18][CH:17]=2)[CH2:8][CH2:7]3)[CH3:3])[CH2:31][CH2:32]1
Reactant: CC(CCBr)CCBr
Reactant: C[C@@H](N)c1ccc2c(c1)CC[C@H](NC(=O)c1ccc(OC[C@@H]3CCCO3)cc1)C2
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: CC1CCN([C@H](C)c2ccc3c(c2)CC[C@H](NC(=O)c2ccc(OC[C@@H]4CCCO4)cc2)C3)CC1
Temperature: 40 °C

Procedure:
A mixture of N-[(S)-6-((R)-1-aminoethyl)-1,2,3,4-tetrahydronaphthalen-2-yl]-4-[(S)-1-(tetrahydrofuran-2-yl)methoxy]benzamide (50 mg), 1,5-dibromo-3-methylpentane (31 mg), ethyldiisopropylamine (0.10 ml) and acetonitrile (1 ml) was heated to 40° C. for 8 hours. The cooled reaction mixture was concentrated and the residue was purified by preparative HPLC. The product was thus obtained with the molecular weight of 476.66 (C30H40N2O3); MS (ESI): 477 (M+H+).
Reaction SMILES: [ClH:1].[CH:2]1([CH:5]([OH:16])[C@H:6]([NH:8]C(=O)OC(C)(C)C)[CH3:7])[CH2:4][CH2:3]1>C(Cl)Cl>[ClH:1].[NH2:8][C@H:6]([CH3:7])[CH:5]([CH:2]1[CH2:4][CH2:3]1)[OH:16]
Reactant: C[C@@H](NC(=O)OC(C)(C)C)C(O)C1CC1
Agent: Cl
Solvent: ClCCl
Product: C[C@@H](N)C(O)C1CC1
Temperature: 25 °C
Reaction time: 4 h
Yield: 100 %

Procedure:
HCl (4M in 1,4-dioxane) (15 mL, 60.0 mmol) was added in one portion to a solution of tert-butyl (2R)-1-cyclopropyl-1-hydroxypropan-2-ylcarbamate (745 mg, 3.46 mmol) in DCM (Volume: 10 mL). The reaction mixture was then allowed to stir at rt for 4 hrs before evaporating in vacuo. to give (2R)-2-amino-1-cyclopropylpropan-1-ol hydrochloride (525 mg, 3.46 mmol, 100% yield). 1H NMR (500 MHz, CD3OD) δ 3.78-3.72 (m, 1H), 3.25 (t, J=7.1 Hz, 3H), 3.05 (dd, J=8.3, 3.6 Hz, 1H), 2.87 (t, J=7.8 Hz, 2H), 1.39-1.32 (m, 3H), 0.89 (qt, J=8.1, 5.0 Hz, 1H), 0.67-0.51 (m, 2H), 0.46-0.32 (m, 2H).
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:18]3[CH2:23][CH2:22][C@@H:21]([N:24]4[CH2:29][CH2:28][N:27]([CH3:30])[CH2:26][CH2:25]4)[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.F[C:32]1[CH:39]=[CH:38][CH:37]=[C:36]([S:40][C:41]2[CH:46]=[CH:45][C:44]([CH3:47])=[CH:43][CH:42]=2)[C:33]=1[C:34]#[N:35].C(=O)([O-])[O-].[K+].[K+].[OH-].[Na+]>CN(C)C=O.C(OCC)(=O)C>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:18]3[CH2:23][CH2:22][C@@H:21]([N:24]4[CH2:25][CH2:26][N:27]([CH3:30])[CH2:28][CH2:29]4)[CH2:20][CH2:19]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([O:17][C:32]4[CH:39]=[CH:38][CH:37]=[C:36]([S:40][C:41]5[CH:42]=[CH:43][C:44]([CH3:47])=[CH:45][CH:46]=5)[C:33]=4[C:34]#[N:35])=[CH:13][CH:12]=3)[C:3]=12
Reactant: CN1CCN([C@H]2CC[C@@H](n3nc(-c4ccc(O)cc4)c4c(N)ncnc43)CC2)CC1
Reactant: Cc1ccc(Sc2cccc(F)c2C#N)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: Cc1ccc(Sc2cccc(Oc3ccc(-c4nn([C@H]5CC[C@@H](N6CCN(C)CC6)CC5)c5ncnc(N)c45)cc3)c2C#N)cc1
Temperature: 120 °C

Procedure:
A solution of cis-4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenol (0.300 g, 0.736 mmol) in dimethylformamide (20 mL), was treated with 2-fluoro-6-[(4-methylphenyl)sulfanyl]benzonitrile (0.447 g, 1.84 mmol) and potassium carbonate (0.203, 1.47 mmol). The reaction mixture was stirred at 120° C. over night under a nitrogen atmosphere. Ethyl acetate (150 mL) and 1 N sodium hydroxide solution were added to the reaction solution. The layers were partitioned, and the organic layer was washed with 1 N sodium hydroxide solution (300 mL). The organic layer was washed with water and brine (400 mL each), dried over magnesium sulfate, filtered, and evaporated under reduced pressure. The crude product was purified by flash silica gel column chromatography using 10% methanol in dichloromethane as the mobile phase. The light brown solid was triturated with ethyl acetate and filtered to give 0.050 g (11%) cis-2-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenoxy)-6-[(4-methylphenyl)sulfanyl]benzonitrile. A warm solution of cis-2-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenoxy)-6-[(4-methylphenyl)sulfanyl]benzonitrile (0.050 g, 0.079 mmol) in ethyl acetate/methanol was treated with a warm solution of maleic acid (0.028 g, 0.240 mmol) in ethyl acetate. A precipitate immediately formed and was filtered under a nitrogen atmosphere to give 0.028 g of cis-2-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenoxy)-6-[(4-methylphenyl)sulfanyl]benzonitrile tris-maleate. 1H NMR (DMSO-d6, 400 MHz) δ 8.251 (s, 1H), 7.72-7.70 (d, 2H, J=8 Hz), 7.55-7.48 (m, 3H), 7.37-7.33 (m, 4H), 6.96-6.93 (d, 1H, J=12 Hz), 6.74-6.72 (d, 1H, J=8 Hz), 6.18 (s, 6H), 4.85 (m, 1H), 3.15-2.90 (m, 4H), 2.85-2.75 (m, 3H), 2.38 (s, 3H), 2.05-1.99 (m, 2H), 1.90-1.60 (m, 5H); HPLC Waters 2690 Alliance HPLC (Symmetry Shield RP18 3.5 μm, 2.1×50 mm; 5%-95% acetonitrile-0.1 M ammonium acetate over 15 min, 0.5 mL/min) Rt 6.359 min (100%).
Reaction SMILES: [C:1]([Si:5]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH:17]=[CH2:18])([CH3:7])[CH3:6])([CH3:4])([CH3:3])[CH3:2].[C:19]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])(=[O:22])C=C>>[Si:5]([O:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16]/[CH:17]=[CH:18]/[C:19]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])([C:1]([CH3:3])([CH3:4])[CH3:2])([CH3:6])[CH3:7]
Reactant: C=CCCCCCCCCO[Si](C)(C)C(C)(C)C
Reactant: C=CC(=O)OC(C)(C)C
Product: CC(C)(C)OC(=O)/C=C/CCCCCCCCO[Si](C)(C)C(C)(C)C
Yield: 95 %

Procedure:
The representative procedure was followed using tert-butyl(dec-9-enyloxy)dimethylsilane (135 mg, 0.50 mmol), tert-butyl acrylate (128 mg, 1.00 mmol) and Grubbs-2 catalyst (8.5 mg, 0.01 mmol). Column chromatography on silica gel (eluting with 2% EtOAc/hexanes) afforded the product as a colorless oil (176 mg, 95%).
Reaction SMILES: [CH3:1][C:2]1([CH3:9])[CH2:7][C:6](=O)[O:5][C:3]1=[O:4].[NH2:10][C:11]1[CH:12]=[CH:13][C:14]([C:21]#[N:22])=[C:15]([C:17]([F:20])([F:19])[F:18])[CH:16]=1>>[CH3:1][C:2]1([CH3:9])[CH2:7][C:6](=[O:5])[N:10]([C:11]2[CH:12]=[CH:13][C:14]([C:21]#[N:22])=[C:15]([C:17]([F:18])([F:19])[F:20])[CH:16]=2)[C:3]1=[O:4]
Reactant: N#Cc1ccc(N)cc1C(F)(F)F
Reactant: CC1(C)CC(=O)OC1=O
Product: CC1(C)CC(=O)N(c2ccc(C#N)c(C(F)(F)F)c2)C1=O

Procedure:
2,2 Dimethyl succinic anhydride (2.0 g, 15.6 mmol) and 4-amino-2-trifluoromethyl-benzonitrile 1a (2.91 g, 15.6 mmol) was heated at 220° C. for 2 hrs. The resulting solid (4.59 g, 99%) was used as such in the next step. 1H NMR (400 MHz, Acetone-d6) δ: 1.44 (s, 6H), 2.84 (s, 2H), 7.97 (dd, 1H, J1=6.74 Hz, J2=1.63 Hz), 8.08 (s, 1H), 8.24 (d, 1H, J=8.32 Hz).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[CH3:25][CH:26]([CH2:37][CH3:38])[CH2:27][C:28]1[CH:36]=[CH:35][C:31]([C:32](Cl)=[O:33])=[CH:30][CH:29]=1.C1(C)C=CC=CC=1>N1C=CC=CC=1>[CH2:15]([O:14][C:11]1[CH:12]=[CH:13][C:8]([C:5]2[CH:4]=[CH:3][C:2]([O:1][C:32](=[O:33])[C:31]3[CH:35]=[CH:36][C:28]([CH2:27][CH:26]([CH3:25])[CH2:37][CH3:38])=[CH:29][CH:30]=3)=[CH:7][CH:6]=2)=[CH:9][CH:10]=1)[CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24]
Reactant: CCC(C)Cc1ccc(C(=O)Cl)cc1
Reactant: CCCCCCCCCCOc1ccc(-c2ccc(O)cc2)cc1
Solvent: c1ccncc1
Solvent: Cc1ccccc1
Product: CCCCCCCCCCOc1ccc(-c2ccc(OC(=O)c3ccc(CC(C)CC)cc3)cc2)cc1
Temperature: 25 °C
Yield: 39.1 %

Procedure:
This 4-hydroxy-4'-n-decyloxybiphenyl (0.5 g) was dissolved in dry pyridine (20 ml), followed by dropwise adding to the solution, commercially available (+)-p-(2-methylbutyl)benzoyl chloride (0.4 g), further pouring dry toluene (15 ml) in the mixture, sufficiently shaking at room temperature, further heating on a water bath at 60° C. for 3 hours, cooling down to room temperature, adding toluene (50 ml), twice washing with 6N hydrochloric acid (100 ml), further twice washing with a 2N alkali aqueous solution, several times washing with saturated NaCl aqueous solution to make the liquid neutral, drying over sodium sulfate, distilling off toluene, filtering through active carbon on heating using a mixed solvent of ethanol (20 ml) and ethyl acetate (20 ml), recrystallizing, filtering crystals deposited in a refrigerator, and drying to obtain the objective 4-n-decyloxy-4'-(p-(2-methylbutyl)benzoyloxy)biphenyl (0.3 g). Its phase transition points are shown in Table 3, sample No. 10. Further, its values of elemental analysis accorded well with its theoretical values as follows:
Reaction SMILES: [CH2:1]([NH:17][C:18]1[CH:26]=[CH:25][C:21]([C:22]([OH:24])=[O:23])=[CH:20][CH:19]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].[H-].[Na+].Cl[CH2:30][CH:31]([OH:34])[CH2:32][OH:33]>CN(C)P(N(C)C)(N(C)C)=O>[CH2:1]([NH:17][C:18]1[CH:19]=[CH:20][C:21]([C:22]([O:24][CH2:30][CH:31]([OH:34])[CH2:32][OH:33])=[O:23])=[CH:25][CH:26]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]
Reactant: CCCCCCCCCCCCCCCCNc1ccc(C(=O)O)cc1
Reactant: OCC(O)CCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Product: CCCCCCCCCCCCCCCCNc1ccc(C(=O)OCC(O)CO)cc1
Temperature: 60 °C
Reaction time: 1 h

Procedure:
A solution of 7.20 g of 4-(n-hexadecylamino)benzoic acid in 25 ml of hexamethylphosphoramide is added to a stirred mixture of 0.800 g of sodium hydride (57% in mineral oil) and 25 ml of hexamethylphosphoramide. The solution which forms after one hour is treated with 11.0 g of 1-chloro-2,3-propanediol and is then stirred at 60° C. for 18 hours. Dilution with water followed by filtration affords a white solid which is crystallized from ethanol to yield 2,3-dihydroxypropyl 4-(n-hexadecylamino)benzoate melting at 112°-113° C.
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]([CH2:14][CH3:15])[CH2:12][CH3:13])=[C:4](Cl)[N:3]=1.C(O)CCC.[I:22][C:23]1[CH:24]=[C:25]([CH2:29][NH2:30])[CH:26]=[CH:27][CH:28]=1>C(O)(C)C>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]([CH2:14][CH3:15])[CH2:12][CH3:13])=[C:4]([NH:30][CH2:29][C:25]2[CH:26]=[CH:27][CH:28]=[C:23]([I:22])[CH:24]=2)[N:3]=1
Reactant: CCC(CC)n1cnc2c(Cl)nc(Cl)nc21
Reactant: NCc1cccc(I)c1
Solvent: CC(C)O
Solvent: CCCCO
Product: CCC(CC)n1cnc2c(NCc3cccc(I)c3)nc(Cl)nc21
Reaction time: 22 h

Procedure:
The operation is carried out as in Stage 2 of Example 3 starting from 200 mg of the product obtained in Stage 1 of Example 3 and 4 ml of butanol and using 0.123 ml of 3-iodo-benzenemethanamine in place of the benzylamine. Agitation is carried out at ambient temperature then the reaction medium is taken to a temperature of 80 to 85° C. for 22 hours, left to return to ambient temperature, diluted with 4 ml of isopropanol, left for three hours at a temperature of approximately 0° C., followed by separating, washing with 10 ml of isopropanol and drying at a temperature of approximately 50° C. After purification on silica eluting with cyclohexane/ethyl acetate/ methylene chloride in a proportion of 70/15/15, 235 mg of expected product is obtained in the form of white crystals.
Reaction SMILES: [CH2:1]([O:3][C:4]([N:6]1[CH2:20][CH2:19][C:18]2[C:9](=[N:10][C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:16]=3[C:17]=2[Cl:21])[CH2:8][CH2:7]1)=[O:5])[CH3:2].[OH:22]O>>[CH2:1]([O:3][C:4]([N:6]1[CH2:20][CH2:19][C:18]2[C:9](=[N+:10]([O-:22])[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:16]=3[C:17]=2[Cl:21])[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: CCOC(=O)N1CCc2nc3ccccc3c(Cl)c2CC1
Reactant: OO
Product: CCOC(=O)N1CCc2c(Cl)c3ccccc3[n+]([O-])c2CC1
Yield: 29 %

Procedure:
11-Chloro-1,2,4,5-tetrahydro-3-azepino[4,5-b]quinoline-carboxylic acid ethyl ester-6-oxide was prepared from 11-chloro-1,2,4,5-tetrahydro-3-azepino[4,5-b]quinoline-carboxylic acid ethyl ester and 30% hydrogen peroxide analogous to Example 163. Yield: 29% of theory; m.p. 170° C.
Reaction SMILES: [SH2:1].O=[C:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1>C(O)(C)C>[S:1]=[C:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1
Reactant: S
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Solvent: CC(C)O
Product: CC(C)(C)OC(=O)N1CCC(=S)CC1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
Hydrogen sulfide gas was bubbled into a solution of tert-butyl 4-oxopiperidine-1-carboxylate (2 g, 10.05 mmol, 1.00 equiv) in isopropanol (20 mL) contained in a 100-mL 3-necked round-bottom flask. The resulting solution was stirred at room temperature for 2 h. The reaction mixture was concentrated and the crude product was used in the next step directly without purification.
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.C(OCC)C.C([Li:19])CCC>O1CCCC1>[CH:1]1([Li:19])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1
Reactant: [Li]CCCC
Reactant: C1=Cc2ccccc2C1
Solvent: CCOCC
Solvent: C1CCOC1
Product: [Li]C1C=Cc2ccccc21

Procedure:
Ten mL (85.7 mmol) of indene, which is a cyclopentacarbyl compound, was added to a container that contained 150 mL of diethyl ether and 15 mL of tetrahydrofuran to form a first mixture. This first mixture was then reacted with 53.6 mL (85.7 mmol) of n-butyllithium (1.6M in hexane) to form indenyllithium, which is a cyclopentacarbyl metal compound. This reaction took place at -78° C. A yellow solution was formed. This yellow solution was then stirred at room temperature (about 25° C.) for four hours and then cooled again to -78° C. An equivalent quantity of 1-bromopropene, a haloalkene compound, was added dropwise to the yellow solution to form a second mixture. This second mixture was then stirred overnight at room temperature (about 25° C.). Thereafter, this second mixture was then hydrolyzed with 50 mL of water to form an organic phase and a water phase. The organic phase was dried over sodium sulfate and then the solvent was evaporated under a vacuum to produce a third mixture. This third mixture was then distilled using a high vacuum (10-2 torr) to obtain a product. The product obtained was allyl-1-indene, which is an (omega-alkenyl) cyclopentacarbyl compound.
Reaction SMILES: CO.C(O)(C)C.[OH-].[Na+].[C:9](I)([C:12]([C:15]([C:18]([C:21]([C:24]([F:27])([F:26])[F:25])([F:23])[F:22])([F:20])[F:19])([F:17])[F:16])([F:14])[F:13])([F:11])[F:10]>O>[CH:9]([C:12]([C:15]([C:18]([C:21]([C:24]([F:25])([F:26])[F:27])([F:22])[F:23])([F:19])[F:20])([F:17])[F:16])([F:14])[F:13])([F:11])[F:10]
Reactant: FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)I
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CC(C)O
Solvent: CO
Product: FC(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F
Temperature: 25 °C
Reaction time: 1 h
Yield: 90.6 %

Procedure:
Into a 1 l four-necked flask equipped with a stirrer, a reflux condenser, a dropping funnel and a thermometer, 256 g of methanol, 3 g of isopropyl alcohol and 46.4 g (1.16 mol) of sodium hydroxide were charged. The reactor was heated to bring the internal temperature to 60° C. Then, 223 g (0.5 mol) of C6F13I was dropwise added thereto over a period of one hour. After completion of the dropwise addition, heating and refluxing were continued for 6 hours. The conversion was more than 99.9%. The reactor was cooled to room temperature, and then, 300 g of water was added to dissolve precipitated sodium iodide. The crude reaction solution was separated into two layers, and the fluorocarbon layer (lower layer) was further washed twice with 300 g of water to obtain 145 g (purity: 99.9%) of C6F13H. In the reactor, no formation of tar was observed.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:4]([C:13]([NH:15][CH2:16][CH2:17][NH:18]C(=O)OC(C)(C)C)=[O:14])=[N:3]1.FC(F)(F)C(O)=O.[ClH:33]>>[ClH:33].[NH2:18][CH2:17][CH2:16][NH:15][C:13]([C:4]1[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)=[CH:6][N:2]([CH3:1])[N:3]=1)=[O:14]
Reactant: Cn1cc(-c2ccccc2)c(C(=O)NCCNC(=O)OC(C)(C)C)n1
Agent: Cl
Solvent: O=C(O)C(F)(F)F
Product: Cn1cc(-c2ccccc2)c(C(=O)NCCN)n1
Yield: 90.4 %

Procedure:
In an analoqous manner to that described in Examples 16 and 17, from 4.6 g (13.4 mmol) of t-butyl [2-(1-methyl-4-phenyl-3-pyrazolecarboxamido)ethyl]carbamate there were obtained, after cleavage of the t-butoxycarbonyl group with trifluoroacetic acid and working-up, 4.8 g of the crude hydrochloride. Recrystallization from ethanol/diethyl ether yielded 3.4 g (90%) of N-(2-aminoethyl)-1-methyl-4-phenyl-3-pyrazolecarboxamide hydrochloride as white crystals, melting point 182°.