Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1]N1C(=O)CCC1=O.C([O:12][C:13]1[CH:22]=[C:21]2[C:16]([C:17](=[O:34])[C:18]([CH3:33])=[C:19]([CH:23]3[CH2:28][CH2:27][N:26]([C:29](=[O:32])[CH2:30][CH3:31])[CH2:25][CH2:24]3)[O:20]2)=[CH:15][CH:14]=1)C=C.O>CN(C)C=O>[Br:1][C:22]1[C:13]([OH:12])=[CH:14][CH:15]=[C:16]2[C:21]=1[O:20][C:19]([CH:23]1[CH2:28][CH2:27][N:26]([C:29](=[O:32])[CH2:30][CH3:31])[CH2:25][CH2:24]1)=[C:18]([CH3:33])[C:17]2=[O:34]
Reactant: C=CCOc1ccc2c(=O)c(C)c(C3CCN(C(=O)CC)CC3)oc2c1
Reactant: O=C1CCC(=O)N1Br
Solvent: O
Solvent: CN(C)C=O
Product: CCC(=O)N1CCC(c2oc3c(Br)c(O)ccc3c(=O)c2C)CC1
Temperature: 25 °C
Reaction time: 5 h
Yield: 53.9 %

Procedure:
N-Bromosuccinimide (171 mg, 0.96 mmol) was added to a solution of 7-hydroxy-3-methyl-2-(1-propanoylpiperidin-4-yl)-4H-chromen-4-one (304 mg, 0.96 mmol) obtained in Example 31-3 in N,N-dimethylformamide (5 mL), and the mixture was stirred at room temperature for 5 hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (dichloromethane/methanol=98/2→67/33) to obtain 204 mg of the title compound (yield: 54%).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[NH:7][N:6]=[C:5]2[C:12]([OH:14])=[O:13].[CH3:15][O:16][CH:17]([C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1)[CH3:18].C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.CCO>[Cl:11][C:10]1[CH:9]=[C:8]2[C:4]([C:5]([C:12]([OH:14])=[O:13])=[N:6][NH:7]2)=[CH:3][C:2]=1[C:22]1[CH:23]=[CH:24][C:19]([CH:17]([O:16][CH3:15])[CH3:18])=[CH:20][CH:21]=1
Reactant: O=C(O)c1n[nH]c2cc(Cl)c(Br)cc12
Reactant: COC(C)c1ccc(B(O)O)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: CCO
Product: COC(C)c1ccc(-c2cc3c(C(=O)O)n[nH]c3cc2Cl)cc1
Temperature: 100 °C
Yield: 10.6 %

Procedure:
A mixture of 5-bromo-6-chloro-1H-indazole-3-carboxylic acid (40.0 mg, 0.14 mmol), 4-(1-methoxyethyl)phenylboronic acid (27.4 mg, 0.152 mmol) and 2N aqueous potassium carbonate solution (0.2 mL, 0.4 mmol) in toluene (0.3 mL) and EtOH (0.7 mL) was purged with N2, and treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) under N2. The reaction mixture was heated to 100° C. for 48 hours, cooled to room temperature and concentrated in vacuo. The crude material was purified by reverse phase HPLC (Column: Waters Sunfire C18 19×100 mm, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); 95.0% H2O/5.0% MeCN linear to 0% H2O/100% MeCN in 7.0 min, HOLD at 0% H2O/100% MeCN to 8.5 min. Flow: 25 mL/min) to afford the title compound (4.9 mg, 11% yield). MS (ES+) 331.1 (M+H)+. Retention time=2.71 minutes (Column: Waters Atlantis dC18 4.6×50 mm, 5 μm; Mobile phase A: 0.05% TFA in water (v/v); Mobile phase B: 0.05% TFA in MeCN (v/v); Gradient: 95:5 A:B linear to 5:95 A:B in 4.0 min, hold at 5:95 A:B to 5.0 min. Flow: 2 mL/min).
Reaction SMILES: [OH-].[Na+].[Cl:3][C:4]1[CH:35]=[CH:34][CH:33]=[CH:32][C:5]=1[CH2:6][O:7][C:8]1[CH:17]=[C:16]([C:18](=[O:30])[NH:19][C:20]2[S:21][C:22]([C:25]([O:27]CC)=[O:26])=[CH:23][N:24]=2)[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH3:31])[CH:14]=2)[N:9]=1.Cl>C1COCC1.O>[Cl:3][C:4]1[CH:35]=[CH:34][CH:33]=[CH:32][C:5]=1[CH2:6][O:7][C:8]1[CH:17]=[C:16]([C:18](=[O:30])[NH:19][C:20]2[S:21][C:22]([C:25]([OH:27])=[O:26])=[CH:23][N:24]=2)[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH3:31])[CH:14]=2)[N:9]=1
Reactant: CCOC(=O)c1cnc(NC(=O)c2cc(OCc3ccccc3Cl)nc3ccc(C)cc23)s1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: Cc1ccc2nc(OCc3ccccc3Cl)cc(C(=O)Nc3ncc(C(=O)O)s3)c2c1
Temperature: 25 °C
Reaction time: 4 h
Yield: 32.7 %

Procedure:
Sodium hydroxide solution (0.3 ml of 2M, 0.6 mmol) was added to a stirred suspension of 2-(2-chlorobenzyloxy)-4-[N-(5-ethoxycarbonylthiazol-2-yl)carbamoyl]-6-methylquinoline (Method 1; 0.097 g, 0.202 mmol) in THF (5 ml) and water (2 ml), and the reaction mixture stirred at ambient temperature for 4 hrs. The reaction mixture was adjusted to pH 4–5 with aqueous hydrochloric acid (1M), and concentrated in vacuo. The solid thus precipitated was filtered, washed with water and dried to give the title compound as a colourless solid (0.030 g, 33%). NMR: 2.45 (3H, s), 5.60 (2H, s), 7.40 (3H, m), 7.50 (1H, m), 7.60 (1H, d), 7.65 (1H, m), 7.80 (2H, t), 7.90 (1H, d), 8.15 (1H, s); m/z
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:23])[C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:18]=[CH:17][C:16]([C:19]([CH3:22])(C)C)=[CH:15][CH:14]=2)=[N:7][CH:6]=1)[CH3:2].[CH3:24][CH:25]([CH3:37])[CH2:26]CCC1C=CC(C#C)=CC=1>>[CH2:1]([O:3][C:4](=[O:23])[C:5]1[CH:10]=[CH:9][C:8]([C:11]#[C:12][C:13]2[CH:14]=[CH:15][C:16]([CH2:19][CH2:22][CH2:24][CH:25]([CH3:37])[CH3:26])=[CH:17][CH:18]=2)=[N:7][CH:6]=1)[CH3:2]
Reactant: C#Cc1ccc(CCCC(C)C)cc1
Reactant: CCOC(=O)c1ccc(C#Cc2ccc(C(C)(C)C)cc2)nc1
Product: CCOC(=O)c1ccc(C#Cc2ccc(CCCC(C)C)cc2)nc1

Procedure:
Using the same general procedure as described for Compound 3, but using instead 4-(4-methylpentyl)phenylethyne (Compound 26), the title compound was synthesized as a yellow solid. PMR (CDCl3): & 0.91 (6 H, d, J-6.6 Hz), 1.20-1.30 (1H, m)., 1.47 (3H, t, J-7.2 Hz), 1.51-1.72 (3H, m), 2.63 (2H, t, J-7.8 Hz), 4.45 (2H, q, J-7.2 Hz), 7.22 (2H, d, J-8.4 Hz), 7.53-7.64 (3H, m), 8.30 (1H, dd, J-8.1 Hz, 2.1 Hz), 9.23 (1H, d, J-2.1 Hz).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][CH2:10][C:11]([OH:13])=O)=[CH:4][CH:3]=1.O.[NH2:16][NH2:17]>C(O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:9][CH2:10][C:11](=[O:13])[NH:16][N:17]=2)=[CH:4][CH:3]=1
Reactant: NN
Reactant: O=C(O)CCC(=O)c1ccc(F)cc1
Solvent: O
Solvent: CCO
Product: O=C1CCC(c2ccc(F)cc2)=NN1
Temperature: 80 °C
Yield: 86 %

Procedure:
In a round-bottomed flask, 4-(4-fluoro-phenyl)-4-oxo-butyric acid (4.90 g, 25.0 mmol) and hydrazine hydrate (1.70 ml, 35.0 mmol) were dissolved in ethanol (50 ml), and the reaction mixture was heated to about 80° C. for about ninety minutes. The mixture was allowed to cool to room temperature and then concentrated in vacuo. The resulting solids were suspended and stirred in ethanol (10 ml) for ten minutes and the mixture was then filtered to give pure product (4.14 g, 21.5 mmol, 86% yield). LRMS ([M+H]+)=193.2; m.p. 191-193° C.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C@@H:7]([NH2:11])[CH2:8][CH2:9][CH3:10])[CH:2]=1.[Cl:12][C:13]1[N:18]=[C:17](Cl)[C:16]([CH3:20])=[CH:15][N:14]=1.C(N(C(C)C)CC)(C)C>C(O)C>[Cl:12][C:13]1[N:18]=[C:17]([NH:11][C@H:7]([C:3]2[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=2)[CH2:8][CH2:9][CH3:10])[C:16]([CH3:20])=[CH:15][N:14]=1
Reactant: CCC[C@H](N)c1cccnc1
Reactant: Cc1cnc(Cl)nc1Cl
Solvent: CCO
Solvent: CCN(C(C)C)C(C)C
Product: CCC[C@H](Nc1nc(Cl)ncc1C)c1cccnc1

Procedure:
To a solution of (1S)-1-pyridin-3-ylbutan-1-amine (600 mg, 4.0 mmol) in ethanol (20 mL) was added 2,4-dichloro-5-methylpyrimdine (717 mg, 4.4 mmol) and diisopropylethylamine (1.4 mL, 8 mmol). The solution was heated at reflux for 24 h after which time the solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate (30 mL) and washed with H2O (2×15 mL), brine (15 mL) and dried (Na2SO4). The residue remaining after concentration in vacuo was chromatographed using ethyl acetate-hexanes (9:1) as eluant to separate the desired product (370 mg).
Reaction SMILES: O.O.[Sn](Cl)Cl.[N+:6]([C:9]1[C:10]([N+:17]([O-])=O)=[C:11]([O:15][CH3:16])[CH:12]=[CH:13][CH:14]=1)([O-])=O.[OH-].[Na+]>CCOC(C)=O>[NH2:6][C:9]1[C:10]([NH2:17])=[C:11]([O:15][CH3:16])[CH:12]=[CH:13][CH:14]=1
Reactant: COc1cccc([N+](=O)[O-])c1[N+](=O)[O-]
Agent: Cl[Sn]Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: O
Product: COc1cccc(N)c1N
Temperature: 25 °C
Yield: 71.1 %

Procedure:
Tin(II)chloride dihydrate (11.9 g, 52.6 mmol) was added to a solution of the above dinitroanisole (2.21 g, 8.76 mmol) in EtOAc (30 mL). The mixture was heated to reflux for 0.25 h upon which the solution became red in color. The solution was cooled to room temperature and poured into aqueous 2.0 M NaOH. The aqueous phase was extracted with EtOAc and the combined organic layers were washed with saturated aqueous NaHCO3. The organic layers were dried over sodium sulfate, eluted through a plug of silica gel (1% ammonium hydroxide in methylene chloride), and the filtrate was concentrated. The residue was dissolved in diethyl ether and extracted (3×) with 1.0 M HCl. The pH of the combined aqueous layers was adjusted to pH=12 with 2.0 M NaOH and extracted with methylene chloride. The combined organic layers were dried over sodium sulfate, filtered and concentrated to provide diaminoanisole (860 mg, 52%) as a red oil.
Reaction SMILES: [CH2:1]([C:5]1([N:28]([CH3:30])[CH3:29])[CH2:10][CH2:9][CH:8]([C:11]2[NH:12][C:13]3[C:18]([C:19]=2[CH2:20][CH2:21][CH2:22][CH2:23][O:24][C:25](=[O:27])[CH3:26])=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:7][CH2:6]1)[CH2:2][CH2:3][CH3:4].[Si]([Cl:35])(C)(C)C>C(OCC)(=O)C>[ClH:35].[C:25]([O:24][CH2:23][CH2:22][CH2:21][CH2:20][C:19]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[NH:12][C:11]=1[CH:8]1[CH2:9][CH2:10][C:5]([CH2:1][CH2:2][CH2:3][CH3:4])([N:28]([CH3:30])[CH3:29])[CH2:6][CH2:7]1)(=[O:27])[CH3:26]
Reactant: C[Si](C)(C)Cl
Agent: CCCCC1(N(C)C)CCC(c2[nH]c3ccccc3c2CCCCOC(C)=O)CC1
Solvent: CCOC(C)=O
Product: Cl
Reaction time: 1 h

Procedure:
Acetic acid 4-[2-(4-butyl-4-dimethylaminocyclohexyl)-1H-indol-3-yl]butyl ester (polar diastereomer) (124 mg, 0.3 mmol) was dissolved in ethyl acetate (50 ml). Me3SiCl (76 μl, 0.39 mmol) was then added dropwise at RT and the mixture was stirred for 1 h. A white precipitate precipitated out. The precipitate was filtered off with suction, washed with ethyl acetate (2×5 ml) and then dried. Example 176 (100 mg, m.p. 173-176° C., 74%) was obtained as a white solid.
Reaction SMILES: C[C:2]1(C)[O:9][C:7](=[O:8])[CH2:6][C:4](=[O:5])O1.N1C=CC=CC=1.[C:17]1([CH2:23]C(Cl)=O)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.Cl>C(Cl)Cl>[C:17]1([CH2:23][C:4](=[O:5])[CH2:6][C:7]([O:9][CH3:2])=[O:8])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: CC1(C)OC(=O)CC(=O)O1
Reactant: O=C(Cl)Cc1ccccc1
Agent: Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: COC(=O)CC(=O)Cc1ccccc1
Temperature: 0 °C
Yield: 91.6 %

Procedure:
In 70 ml of methylene chloride was dissolved 36.03 g (0.25 mol) of Meldrum's acid. Pyridine (38.17 g, 0.48 mol) was used as a base. To the solution was added dropwise 42.52 g (0.275 mol) of phenylacetyl chloride in an ice bath while stirring. After the reaction, ice-water and diluted hydrochloric acid were added to wash. Methylene chloride was evaporated, methanol was added, followed by refluxing, and the solvent was evaporated to give 44 g (91.7%) of methyl 4-phenyl-3-oxobutyrate.
Reaction SMILES: [C:1]1([CH3:11])[CH:6]=[CH:5][C:4]([S:7](Cl)(=[O:9])=[O:8])=[CH:3][CH:2]=1.[CH2:12]([OH:17])[CH2:13][CH2:14][C:15]#[CH:16].C(N(CC)CC)C>ClCCl>[CH3:11][C:1]1[CH:6]=[CH:5][C:4]([S:7]([O:17][CH2:12][CH2:13][CH2:14][C:15]#[CH:16])(=[O:9])=[O:8])=[CH:3][CH:2]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: C#CCCCO
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: C#CCCCOS(=O)(=O)c1ccc(C)cc1
Reaction time: 22 h
Yield: 87 %

Procedure:
p-Toluenesulfonyl chloride (21.4 g, 112 mmol) was added slowly to a stirred solution of 4-pentyn-1-ol (11.5 mL, 124 mL) and triethylamine (17.2 mL, 124 mmol) in dichloromethane (100 mL) at room temperature. After 22 hours, the solution was diluted with dichloromethane, washed with water, dried over sodium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography (silica gel, gradient elution from 95:5 to 85:15 hexanes/ethyl acetate) to afford the product pent-4-ynyl 4-methylbenzenesulfonate (23.4 g, 87%) as a colorless oil.
Reaction SMILES: [CH3:1][C@@:2]12[C:9]([CH3:11])([CH3:10])[CH:6]([CH2:7][CH2:8]1)[C:5](=[O:12])[CH2:4][C:3]2=[O:13].C(N(CC)CC)C.[N+:21]([C:24]1[CH:25]=[C:26]([N:30]=[C:31]=[O:32])[CH:27]=[CH:28][CH:29]=1)([O-:23])=[O:22].Cl>CN(C)C1C=CN=CC=1.ClCCl>[N+:21]([C:24]1[CH:25]=[C:26]([NH:30][C:31]([CH:4]2[C:5](=[O:12])[CH:6]3[C:9]([CH3:10])([CH3:11])[C@:2]([CH3:1])([CH2:8][CH2:7]3)[C:3]2=[O:13])=[O:32])[CH:27]=[CH:28][CH:29]=1)([O-:23])=[O:22]
Reactant: CC1(C)C2CC[C@]1(C)C(=O)CC2=O
Reactant: O=C=Nc1cccc([N+](=O)[O-])c1
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC1(C)C2CC[C@]1(C)C(=O)C(C(=O)Nc1cccc([N+](=O)[O-])c1)C2=O
Temperature: 30 °C
Reaction time: 8 h
Yield: 29 %

Procedure:
To an ice-cooled solution of (1S)-1,8,8-trimethylbicyclo[3.2.1]octane-2,4-dione (0.36 g, 2.0 mmole), triethylamine (0.20 g, 2.0 mmole) and 4-(dimethylamino)pyridine (0.24 g, 2.0 mmole) in dry dichloromethane (25 mL) was added a solution of 3-nitrophenyl isocyanate (0.33 g, 2.0 mmole) in dry dichloromethane (5 mL). The resulting mixture was allowed to stir overnight under a nitrogen atmosphere, during which time it came up to room temperature, and then was heated at 30° C. for 72 hours. The reaction mixture was treated with 2N aqueous HCl and the layers separated. The acidic aqueous layer was extracted with two additional portions of dichloromethane. The combined organic layers were dried over anhydrous sodium sulfate and concentrated on a rotary evaporator to give a yellow oil, which was purified by chromatography on silica gel (10% ethyl acetate/hexane) to yield an orange oil, which was crystallized from 95% ethanol to yield the title compound as a beige solid (0.20 g, 29% yield), mp=100–102° C.; MS (−) ESI m/z=343 (M−H)−; [α]D25=−26.3° (c=1, DMSO).
Reaction SMILES: [O:1]=[C:2]1[C:6]2([CH2:11][CH2:10][N:9]([CH2:12][CH2:13][CH2:14][C:15](=[O:22])[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:8][CH2:7]2)[N:5]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:4][N:3]1[CH2:29][C:30]1[CH:42]=[CH:41][CH:40]=[CH:39][C:31]=1[C:32]([O:34]C(C)(C)C)=[O:33]>Cl.O1CCOCC1>[O:1]=[C:2]1[C:6]2([CH2:7][CH2:8][N:9]([CH2:12][CH2:13][CH2:14][C:15](=[O:22])[C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[CH2:10][CH2:11]2)[N:5]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH2:4][N:3]1[CH2:29][C:30]1[CH:42]=[CH:41][CH:40]=[CH:39][C:31]=1[C:32]([OH:34])=[O:33]
Reactant: CC(C)(C)OC(=O)c1ccccc1CN1CN(c2ccccc2)C2(CCN(CCCC(=O)c3ccccc3)CC2)C1=O
Agent: Cl
Solvent: C1COCCO1
Product: O=C(CCCN1CCC2(CC1)C(=O)N(Cc1ccccc1C(=O)O)CN2c1ccccc1)c1ccccc1
Yield: 33.1 %

Procedure:
A solution of tert-butyl 2-((4-oxo-8-(4-oxo-4-phenylbutyl)-1-phenyl-1,3,8-triazaspiro[4.5]decan-3-yl)methyl)benzoate (268 mg, 0.472 mmol, 1 equiv) in 4M hydrogen chloride solution in dioxane was stirred at ambient temperature for 4 h. The mixture was concentrated in vacuo and purified using preparative thin layer chromatography in 7% methanol in dichloromethane. The pure extract was treated with 4M hydrogen chloride solution in dioxane to afford the hydrogen chloride salt of the title compound as a white powder (80 mg, 30%); 1H NMR (400 MHz, DMSO-d6): δ2.01 (d, 2H, J=14.4 Hz); 2.09 (t, 2H, J=7.2 and 7.6 Hz); 3.02 (t, 2H, J=12.4 and 10.4 Hz); 3.18 (bs, 2H); 3.23 (t, 2H, J=7.2 and 6.8 Hz); 3.65-3.7 (m, 4H); 4.69 (s, 2H); 4.94 (s, 2H); 6.81 (t, 1H, J=7.2 and 7.6 Hz); 7.04 (d, 2H, J=8.4 Hz); 7.24 (t, 2H, J=7.6 and 8 Hz); 7.33 (d, 1H, J=8 Hz); 7.43 (t, 2H, J=7.6 Hz); 7.53-7.61 (m, 3H); 7.66 (t, 1H, J=7.6 Hz); 7.93 (dd, 1H, J=1.2 and 1.6 Hz); 7.99-8.01 (m, 2H); 10.5 (bs, 1H); 13.2 (bs, 1H); MS for C31H33N3O4 m/z 512.4 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[N:10]1[CH2:15][CH2:14][CH2:13][C:12]2=[C:16]([C:20]([CH2:24][CH2:25][CH3:26])=[CH:21][CH2:22][CH3:23])[N:17]([CH3:19])[N:18]=[C:11]12>C(O)(=O)C.[Pd].C(OCC)(=O)C>[Cl:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[N:10]1[CH2:15][CH2:14][CH2:13][C:12]2=[C:16]([CH:20]([CH2:24][CH2:25][CH3:26])[CH2:21][CH2:22][CH3:23])[N:17]([CH3:19])[N:18]=[C:11]12
Reactant: CCC=C(CCC)c1c2c(nn1C)N(c1c(C)cc(C)cc1Cl)CCC2
Agent: [Pd]
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: CCCC(CCC)c1c2c(nn1C)N(c1c(C)cc(C)cc1Cl)CCC2
Reaction time: 12 h
Yield: 24.4 %

Procedure:
7-(2-Chloro-4,6-dimethylphenyl)-2-methyl-3-(1-propylbut-1-enyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine (41.5 mg) was dissolved in acetic acid (1 mL) and 12 mg of 10% palladium on carbon was added. The mixture was stirred under hydrogen at one atmosphere for 12 h. The mixture was diluted with ethyl acetate and filtered through diatomaceous earth which was then washed with ethyl acetate. The ethyl acetate filtrate was washed with aqueous sodium bicarbonate, dried with magnesium sulfate, and concentrated. The residue was chromatographed on silica gel eluting with an acetone/hexane gradient to provide 10.2 mg of 7-(2-chloro-4,6-dimethylphenyl)-2-methyl-3-(1-propylbutyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridine, as a crystalline film, ms m/z 374 (MH+).
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11].[CH2:13]1[C:18](=O)[CH2:17][C:15](=[O:16])[CH2:14]1.[NH2:20][C:21]1[N:25]([CH3:26])[NH:24][C:23](=[O:27])[CH:22]=1>>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]2[C:22]3[C:23](=[O:27])[NH:24][N:25]([CH3:26])[C:21]=3[NH:20][C:18]3[CH2:13][CH2:14][C:15](=[O:16])[C:17]2=3)=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11]
Reactant: O=C1CCC(=O)C1
Reactant: Cn1[nH]c(=O)cc1N
Reactant: O=Cc1ccc(Cl)c([N+](=O)[O-])c1
Product: Cn1[nH]c(=O)c2c1NC1=C(C(=O)CC1)C2c1ccc(Cl)c([N+](=O)[O-])c1
Yield: 55.4 %

Procedure:
4-Chloro-3-nitrobenzaldehyde (0.27 g, 1.5 mmol), 1,3-cyclopentadione (0.15 g, 1.5 mmol), and 5-amino-1-methyl-1,2-dihydropyrazol-3-one (0.17 g, 1.5 mmol) were processed as described in Example 1 to provide 0.3 g of the title compound. 1H NMR (300 MHz, DMSO-d6) δ 2.3 (t, 2H), 2.68 (m, 2H), 3.5 (s, 3H), 4.81 (s, 1H), 7.48 (dd, 1H), 7.6 (d, 1H), 7.78 (d, 1H), 9.61 (bs, 1H), 10.49 (s, 1H); MS (ESI−) m/z 359 (M−H)−; Anal. calcd for C16H13N4ClO4: C, 53.27; H, 3.63; N, 15.53. Found: C, 53.16; H, 3.88; N, 14.83.
Reaction SMILES: [C:1]1([P:7]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:20][CH2:21][CH:22]=[CH:23][C:24]#[C:25][Si:26]([CH3:29])([CH3:28])[CH3:27]>C1(C)C=CC=CC=1.C(OC)(C)(C)C>[Br-:20].[CH3:27][Si:26]([CH3:29])([CH3:28])[C:25]#[C:24]/[CH:23]=[CH:22]/[CH2:21][P+:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1
Reactant: C[Si](C)(C)C#CC=CCBr
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: Cc1ccccc1
Solvent: COC(C)(C)C
Product: C[Si](C)(C)C#C/C=C/C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Product: [Br-]
Temperature: 25 °C
Yield: 80.8 %

Procedure:
Triphenylphosphine (64.1 g, 0.244 mol) was added to a solution of 1-bromo-5-trimethylsilylpent-2-en-4-yne (44.26 g, 0.204 mol) in toluene (204 mL). The mixture was stirred at ambient temperature under a nitrogen atmosphere. After 3 days the suspension was diluted with methyl tert-butyl ether (408 mL), stirred for 1 hour at ambient temperature, and the precipitate was collected by filtration. The filter cake was washed with methyl tert-butyl ether and dried under vacuum at 30° C. to get 79 g of 2E-5-trimethylsilylpent-2-en-4-ynyltriphenyl-phosphonium bromide, a compound of formula (Q), as an off-white powder: 1H-NMR (300 mHz, CDCl3) δ 0.14 (s, 9H), 5.08 (dd, 2H), 5.91 (dt, 1H), 6.22 (dd, 1H), 7.6-8.0 (m, 15H); Anal. Calculated for C26H28BrPSi requires C, 65.13; H, 5.89; Br, 16.66; P, 6.46. found C, 64.95; H, 5.78; Br, 16.96; P, 6.31.
Reaction SMILES: [CH2:1]1[S:5][C@@H:4]([CH2:6][CH2:7][CH2:8][CH2:9][C:10]([O:12]C2C([N+]([O-])=O)=CC=CC=2)=O)[C@H:3]2[NH:22][C:23]([NH:25][C@@H:2]12)=[O:24].[CH3:26][O:27][CH:28]([O:31][CH3:32])[CH2:29][NH2:30].CCN(CC)CC>CC#N>[CH3:26][O:27][CH:28]([O:31][CH3:32])[CH2:29][NH:30][C:10](=[O:12])[CH2:9][CH2:8][CH2:7][CH2:6][C@H:4]1[C@@H:3]2[C@@H:2]([NH:25][C:23]([NH:22]2)=[O:24])[CH2:1][S:5]1
Reactant: O=C1N[C@H]2[C@H](CS[C@H]2CCCCC(=O)Oc2ccccc2[N+](=O)[O-])N1
Reactant: COC(CN)OC
Solvent: CCN(CC)CC
Solvent: CC#N
Product: COC(CNC(=O)CCCC[C@@H]1SC[C@@H]2NC(=O)N[C@@H]21)OC
Temperature: 25 °C
Reaction time: 16 h
Yield: 91 %

Procedure:
To a suspension of D-(+)-biotin 2-nitrophenyl ester (365 mg, 1.00 mmol) in MeCN (20 mL) was added aminoacetaldehyde dimethyl acetal (130 μL, 1.20 mmol) and Et3N (170 μL, 1.20 mmol). The suspension was gently heated until a solution was obtained; the solution was then stirred for 16 h at ˜25° C. The reaction mixture was evaporated to dryness under reduced pressure and the material left was purified by silica gel chromatography using a gradient of MeOH (0→10%) in CH2Cl2 as the eluent. Fractions containing the product were collected and evaporated to dryness under low pressure affording 9 (300 mg, 910 μmol) as a solid in a yield of 91%. 1H NMR (300 MHz, DMSO-d6): δ 7.87 (t, J=5.8 Hz, 1H), 6.43 (s, 1H), 6.37 (s, 1H), 4.32 (t, J=5.5 Hz, 1H), 4.28 (d, J=5.5 Hz, 1H), 4.12 (ddd, J=7.6, 4.4, 1.8 Hz, 1H), 3.25 (s, 6H), 3.13 (t, J=5.7 Hz, 2H), 2.82 (dd, J=12.3, 12.3 Hz, 1H), 2.56 (d, J=12.3 Hz, 1H), 2.07 (t, J=7.4 Hz, 2H), 1.66-1.22 (m, 7H). 13C NMR (75 MHz, DMSO-d6): δ 172.2, 162.6, 102.0, 61.0, 59.1, 55.4, 53.1, 40.2, 39.8, 34.9, 28.1, 28.0, 25.2. +ESI-HRMS: Calcd for C14H25N3O4S [M+H]+ 332.1639. found 332.1641.
Reaction SMILES: Cl[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10](/[C:13](/[C:23]2[CH:28]=[CH:27][C:26]([I:29])=[CH:25][CH:24]=2)=[C:14](\[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)/[CH2:15][CH3:16])=[CH:9][CH:8]=1.[CH3:30][NH:31][CH3:32].CCOCC>CO>[CH3:30][N:31]([CH3:32])[CH2:2][CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10](/[C:13](/[C:23]2[CH:28]=[CH:27][C:26]([I:29])=[CH:25][CH:24]=2)=[C:14](\[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)/[CH2:15][CH3:16])=[CH:9][CH:8]=1
Reactant: CNC
Reactant: CC/C(=C(\c1ccc(I)cc1)c1ccc(OCCCCCl)cc1)c1ccccc1
Solvent: CCOCC
Solvent: CO
Product: CC/C(=C(\c1ccc(I)cc1)c1ccc(OCCCCN(C)C)cc1)c1ccccc1
Temperature: 100 °C

Procedure:
A mixture of E-1-(4-(4-chlorobutoxy)phenyl)-1-(4-iodophenyl)-2-phenyl-1-butene (0.429 g, 0.83 mmol) and dimethylamine in methanol solution (30 ml, 30%) was heated In a sealed bomb at 100° C. for 2 h, then poured into ether (75 ml), and washed with brine (100 ml) and water (2×100 ml). The organic layer was dried (Na2SO4), and concentrated in vacuo. The residues were purified by flash chromatography (silica; eluant:0-10% methanol in ether) to give the title compound as an off white solid (0.391 g, 89%) mp 74°-77° C.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([OH:16])=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.[C:17](Cl)(=[O:26])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25].CN(C1C=CC=CN=1)C>O.C(Cl)Cl.C(N(CC)CC)C>[C:17]([O:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([OH:16])=[O:15])=[CH:10][CH:9]=2)=[CH:6][CH:7]=1)(=[O:26])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25]
Reactant: CCCCCCCCC(=O)Cl
Reactant: O=C(O)c1ccc(-c2ccc(O)cc2)cc1
Agent: CN(C)c1ccccn1
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: O
Product: CCCCCCCCC(=O)Oc1ccc(-c2ccc(C(=O)O)cc2)cc1
Temperature: 25 °C
Yield: 83.2 %

Procedure:
To 13 ml of methylene chloride, were dissolved 1.25 g of 4'-hydroxybiphenyl-4-carboxylic acid and 0.52 g of triethyl amine. To the solution was added 10 ml of methylene chloride solution of 1.2 g of nonanoyl chloride dropwise with stirring at an ambient temperature. Further, 0.2 g of dimethylamino pyridine was added and the solution was stirred for a whole day and night at an ambient temperature. After the termination of the reaction, the solution was concentrated under a reduced pressure, the reaction liquid was poured into water and neutralized, and the precipitate thus formed was separated by filtration, and washed with hexane, and dried under a reduced pressure to obtain 1.72 g of the desired compound.