Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]1[CH2:4][CH:3]([N:5]([CH2:12][C:13]2[CH:14]=[N:15][C:16]([C:19]3[S:27][C:26]4[C:21](=[N:22][CH:23]=[CH:24][C:25]=4[O:28][C:29]4[CH:34]=[CH:33][C:32]([NH:35][C:36]([NH:38][CH:39]5[CH2:41][CH2:40]5)=[O:37])=[CH:31][C:30]=4[F:42])[CH:20]=3)=[CH:17][CH:18]=2)[CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])[CH2:2]1.[CH2:43]([N:45]=[C:46]=[O:47])[CH3:44]>C1COCC1>[CH:39]1([NH:38][C:36](=[O:37])[NH:35][C:32]2[CH:33]=[CH:34][C:29]([O:28][C:25]3[CH:24]=[CH:23][N:22]=[C:21]4[CH:20]=[C:19]([C:16]5[N:15]=[CH:14][C:13]([CH2:12][N:5]([CH:3]6[CH2:2][N:1]([C:46](=[O:47])[NH:45][CH2:43][CH3:44])[CH2:4]6)[CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:18][CH:17]=5)[S:27][C:26]=34)=[C:30]([F:42])[CH:31]=2)[CH2:40][CH2:41]1
Reactant: CCOC(=O)CN(Cc1ccc(-c2cc3nccc(Oc4ccc(NC(=O)NC5CC5)cc4F)c3s2)nc1)C1CNC1
Reactant: CCN=C=O
Solvent: C1CCOC1
Product: CCNC(=O)N1CC(N(CC(=O)OCC)Cc2ccc(-c3cc4nccc(Oc5ccc(NC(=O)NC6CC6)cc5F)c4s3)nc2)C1
Temperature: 25 °C
Reaction time: 1 h
Yield: 87.3 %

Procedure:
To a suspension of 432 (0.135 mmol) in THF (5 mL) were added TEA (0.094 mL, 0.675 mmol) and ethyl isocyanate (0.032 mL, 0.405 mmol) and stirred at RT for 1 h. The mixture was then concentrated, water was added to form a precipitate that was collected by filtration, rinsed with water, air-dried to afford the title compound 433 (78 mg, 88% yield for 2 steps) as a beige solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.71 (s, 1H), 8.55 (d, J=1.6 Hz, 1H), 8.52 (d, J=5.6 Hz, 1H), 8.34 (s, 1H), 8.25 (d, J=8.4 Hz, 1H), 7.88 (dd, J=8.0, 2.0 Hz, 1H), 7.73 (dd, J=13.6, 2.4 Hz, 1H), 7.38 (t, J=9.0 Hz, 1H), 6.65 (dd, J=5.6, 0.8 Hz, 1H), 6.57 (bd, J=2.8 Hz, 1H), 6.27 (t, J=5.6 Hz, 1H), 4.06 (q, J=7.2 Hz, 2H), 3.84-3.75 (m, 5H), 3.69-3.61 (m, 2H), 3.02-2.94 (m, 2H), 2.59-2.51 (m, 1H), 1.18 (t, J=7.2 Hz, 3H), 0.97 (t, J=7.2 Hz, 3H), 0.68-0.62 (m, 2H), 0.45-0.40 (m, 2H). MS (m/z): 662.60 (M+H).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[O:10][CH2:11][C:12](=[O:19])[C:13]=2[C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:4][CH:3]=1.[NH:20]1[C:28]2[C:23](=[CH:24][CH:25]=[CH:26][N:27]=2)[C:22]([CH:29]=O)=[CH:21]1.N1CCCCC1>C(O)C>[NH:20]1[C:28]2=[N:27][CH:26]=[CH:25][CH:24]=[C:23]2[C:22]([CH:29]=[C:11]2[O:10][C:9]([NH:8][C:5]3[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=3)=[C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[C:12]2=[O:19])=[CH:21]1
Reactant: O=Cc1c[nH]c2ncccc12
Reactant: CCOC(=O)C1=C(Nc2ccc(Br)cc2)OCC1=O
Solvent: C1CCNCC1
Solvent: CCO
Product: CCOC(=O)C1=C(Nc2ccc(Br)cc2)OC(=Cc2c[nH]c3ncccc23)C1=O
Temperature: 25 °C
Yield: 35.9 %

Procedure:
To a solution of ethyl 2-[(4-bromophenyl)amino]-4-oxo-4,5-dihydrofuran-3-carboxylate (0.15 g, 0.46 mmol) which similarly prepared according to the procedure described in the Example 4, First step and 7-azaindole-3-carboxaldehyde (0.067 g, 0.46 mmol) in ethanol (5.0 mL), piperidine (0.85 mL, 0.92 mmol) was added at ambient temperature. The mixture was refluxed for 24 h. Cooled to ambient temperature, the precipitate was collected by filtration, washed with ethanol then dried to afford the titled compound (0.075 g, y. 36%).
Reaction SMILES: [CH3:1][CH:2]([CH:6]=[CH2:7])[C:3]([OH:5])=[O:4].[Cl:8][CH2:9][CH2:10]O>C(OCC)C.CC1C=CN=C(N)C=1C>[Cl:8][CH2:9][CH2:10][O:4][C:3](=[O:5])[CH:2]([CH3:1])[CH:6]=[CH2:7]
Reactant: OCCCl
Reactant: C=CC(C)C(=O)O
Agent: Cc1ccnc(N)c1C
Solvent: CCOCC
Product: C=CC(C)C(=O)OCCCl
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 85.1 %

Procedure:
45.1 g (0.45 mol) of 2-methyl-3-butenoic acid, 45.33 g (0.56 mol) of 2-chloroethanol and 4.1 g (34 mmol) of dimethyl-aminopyridine were placed in 450 ml of diethyl ether under argon. 102.2 g (0.495 mol) of N,N-dicyclohexylcarbodiimide were added thereto in 5 portions at 0° C. within 30 minutes, the mixture was stirred at room temperature for a further 2 hours and the separated urea was filtered off. The filtrate was washed in succession with 200 ml of 0.5N aqueous hydrochloric acid, 100 ml of saturated sodium bicarbonate solution and 100 ml of saturated sodium chloride solution. The organic solution was dried over anhydrous sodium sulphate and, after concentration, the product was distilled on a Vigreux column (20 cm) at 80-81° C./10 mbar. This gave 62.3 g (83% yield) of 2-methyl-but-3-enoic acid 2-chloroethyl ester as a colourless oil with a content of 97.5% according to GC.
Reaction SMILES: [CH:1]([N:4]1[C:8]2=[N:9][C:10]([C:14]3[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=3)=[N:11][C:12](O)=[C:7]2[CH:6]=[N:5]1)([CH3:3])[CH3:2].P(Cl)(Cl)([Cl:25])=O>>[Cl:25][C:12]1[N:11]=[C:10]([C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-:22])=[O:21])=[CH:16][CH:15]=2)[N:9]=[C:8]2[N:4]([CH:1]([CH3:3])[CH3:2])[N:5]=[CH:6][C:7]=12
Reactant: O=P(Cl)(Cl)Cl
Reactant: CC(C)n1ncc2c(O)nc(-c3ccc([N+](=O)[O-])cc3)nc21
Product: CC(C)n1ncc2c(Cl)nc(-c3ccc([N+](=O)[O-])cc3)nc21
Temperature: 25 °C
Yield: 100 %

Procedure:
A suspension of 1-isopropyl-6-(4-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ol (0.76 g, 2.5 mmol) in phosphorus oxychloride (20 mL) was heated a sealed tube with a heat gun until all of the starting material was dissolved. After allowing the mixture to cool to room temperature it was concentrated to dryness under reduced pressure, leaving a pale yellow solid which was then triturated with water and collected by Buchner filtration. The solid was further washed with water and dried under house vacuum to provide 4-chloro-1-isopropyl-6-(4-nitrophenyl)-1H-pyrazolo[3,4-d]pyrimidine (0.90 g, >100%) as a pale yellow solid. MS (ES+): 317.7, 319.8 (M+H)+
Reaction SMILES: [H-].[Na+].[CH3:3][C:4]1[CH:9]=[CH:8][C:7]([S:10]([NH:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][NH:21][S:22]([C:25]2[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=2)(=[O:24])=[O:23])(=[O:12])=[O:11])=[CH:6][CH:5]=1.[H][H].[C:34]([O:38][C:39]([N:41]([CH2:52][CH2:53][CH2:54][CH2:55]Cl)[S:42]([C:45]1[CH:50]=[CH:49][C:48]([CH3:51])=[CH:47][CH:46]=1)(=[O:44])=[O:43])=[O:40])([CH3:37])([CH3:36])[CH3:35]>CN(C)C=O>[C:34]([O:38][C:39]([N:41]([S:42]([C:45]1[CH:50]=[CH:49][C:48]([CH3:51])=[CH:47][CH:46]=1)(=[O:44])=[O:43])[CH2:52][CH2:53][CH2:54][CH2:55][N:13]([S:10]([C:7]1[CH:6]=[CH:5][C:4]([CH3:3])=[CH:9][CH:8]=1)(=[O:11])=[O:12])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][N:21]([S:22]([C:25]1[CH:26]=[CH:27][C:28]([CH3:31])=[CH:29][CH:30]=1)(=[O:23])=[O:24])[CH2:55][CH2:54][CH2:53][CH2:52][N:41]([C:39]([O:38][C:34]([CH3:35])([CH3:37])[CH3:36])=[O:40])[S:42]([C:45]1[CH:50]=[CH:49][C:48]([CH3:51])=[CH:47][CH:46]=1)(=[O:44])=[O:43])=[O:40])([CH3:37])([CH3:36])[CH3:35]
Reactant: [H][H]
Reactant: Cc1ccc(S(=O)(=O)NCCCCCCCNS(=O)(=O)c2ccc(C)cc2)cc1
Reactant: Cc1ccc(S(=O)(=O)N(CCCCCl)C(=O)OC(C)(C)C)cc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1ccc(S(=O)(=O)N(CCCCCCCN(CCCCN(C(=O)OC(C)(C)C)S(=O)(=O)c2ccc(C)cc2)S(=O)(=O)c2ccc(C)cc2)CCCCN(C(=O)OC(C)(C)C)S(=O)(=O)c2ccc(C)cc2)cc1
Temperature: 0 °C
Reaction time: 8 h

Procedure:
Suspend sodium hydride (4.8 g, 0.2 mol) in anhydrous dimethylformamide (100 mL), cool to 0° C. and place under a nitrogen atmosphere. Add, by dropwise addition, a solution 1,9-bis[(4-methylphenyl)sulfonyl]-1,9-diazanonane (43.8 g, 0.1 mol) in dimethylformamide. Stir until evolution of hydrogen ceases. Add, by dropwise addition, a solution of N-(t-butyloxycarbonyl)-N-[(4-methylphenyl)sulfonyl]-4-chlorobutylamine (72.4 g, 0.2 mol) in dimethylformamide (100 mL). Stir overnight at room temperature then carefully quench with saturated ammonium chloride. Extract into ethyl acetate, dry (MgSO4) and evaporate the solvent in vacuo. Purify by silica gel chromatography to give the title compound.
Reaction SMILES: C(N([CH2:6][CH3:7])CC)C.[C:8]1([SH:14])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.[OH2:15]>CN(C)C=O>[C:8]1([S:14][CH2:9][C@H:8]([C:7]2([OH:15])[CH2:6][CH2:12][CH2:11][CH2:10]2)[CH3:13])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1
Reactant: CCN(CC)CC
Reactant: O
Reactant: Sc1ccccc1
Solvent: CN(C)C=O
Product: C[C@H](CSc1ccccc1)C1(O)CCCC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a mixture of 4a (3.65 g, 11.9 mmol) and triethylamine (2.5 mL) in N,N-dimethylformamide (18 mL) was added thiophenol (1.8 mL) in one portion. The mixture was stirred at ambient temperature overnight. The mixture was poured into water, and extracted with diethyl ether. The combined organic layers were washed with sodium bicarbonate solution and brine, and dried over sodium sulfate. Filtration and concentration gave 3.26 g of an oily material, which was purified by column chromatography (silica gel 40 g, ethyl acetate in n-hexane, 2.5-20%) to give 2.06 g (73.3%) of 5a, as a pale yellow oil. 1H-NMR δ (CDCl3, 500 MHz); 1.24 (3H, d, J=6.3 Hz), 1.53 (1H, br s), 1.56-2.04 (9H), 2.85 (1H, dd, J=12.9 and 10.2 Hz), 3.44 (1H, dd. J=12.9 and 2.8 Hz), 7.28 (1H, t, J=8.0 Hz), 7.39 (2H, t, J=8.0 Hz), 7.46 (2H, d, J=8.0 Hz)
Reaction SMILES: [N+]([C:4]1[CH:33]=[CH:32][CH:31]=[CH:30][C:5]=1[C:6]([NH:8][CH:9]([C:11]1[N:16]=[N:15][C:14]([NH:17][C:18]2[CH:23]=[C:22]([O:24][CH3:25])[C:21]([O:26][CH3:27])=[C:20]([O:28][CH3:29])[CH:19]=2)=[N:13][CH:12]=1)[CH3:10])=[O:7])([O-])=O.NC(C1N=NC(NC2C=C(OC)C(OC)=C(OC)C=2)=NC=1)C.C(N(CC)CC)C.[F:63][C:64]([F:75])([F:74])C1C=C(C=CC=1)C(Cl)=O>ClCCl>[F:63][C:64]([F:75])([F:74])[C:33]1[CH:4]=[C:5]([CH:30]=[CH:31][CH:32]=1)[C:6]([NH:8][CH:9]([C:11]1[N:16]=[N:15][C:14]([NH:17][C:18]2[CH:19]=[C:20]([O:28][CH3:29])[C:21]([O:26][CH3:27])=[C:22]([O:24][CH3:25])[CH:23]=2)=[N:13][CH:12]=1)[CH3:10])=[O:7]
Reactant: COc1cc(Nc2ncc(C(C)NC(=O)c3ccccc3[N+](=O)[O-])nn2)cc(OC)c1OC
Reactant: O=C(Cl)c1cccc(C(F)(F)F)c1
Agent: COc1cc(Nc2ncc(C(C)N)nn2)cc(OC)c1OC
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1cc(Nc2ncc(C(C)NC(=O)c3cccc(C(F)(F)F)c3)nn2)cc(OC)c1OC

Procedure:
In a similar manner as described for Intermediate 10, 6-(1-aminoethyl)-N-(3,4,5-trimethoxyphenyl)-1,2,4-triazin-3-amine (Intermediate 9) (0.085 g, 0.28 mmol), triethylamine (0.10 mL, 0.72 mmol) and 3-(trifluoromethyl)-benzoyl chloride (0.065 g, 0.31 mmol) in dichloromethane (5 mL) gave 3-(trifluoromethyl)-N-(1-{3-[(3,4,5-trimethoxyphenyl)amino]-1,2,4-triazin-6-yl}ethyl)benzamide (0.12 g) as a yellow oil. MS m/z 478 (M+1).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:4]=1[CH:5]=O.[CH2:13]([NH2:16])[C:14]#[CH:15].[BH4-].[Na+]>CO>[CH3:1][O:2][C:3]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[CH:7][C:4]=1[CH2:5][NH:16][CH2:13][C:14]#[CH:15]
Reactant: COc1ccc(C=O)c(OC)c1
Reactant: C#CCN
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: C#CCNCc1ccc(OC)cc1OC
Temperature: 0 °C
Reaction time: 2 h

Procedure:
Meanwhile, 2,4-dimethoxybenzaldehyde (1 eq) and propargylamine (1.2 eq) were stirred in MeOH at RT under a N2 atmosphere for 1.5 h and then cooled to 0° C. NaBH4 (1.8 eq) was added in three portions over 15 min. The mixture was stirred for additional 2 h at RT and then quenched with 1 N NaOH solution. The product was extracted with DCM (3×) and then the combined organic layers were washed with brine, dried (Na2SO4) and evaporated under reduced pressure to yield N-(2,4-dimethoxybenzyl)prop-2-yn-1-amine as an orange oil that was used as such in the next step without purification. 1H NMR (400 MHz, DMSO-d6) δ: 7.15 (1H, d, J=8.3 Hz), 6.52 (1H, d, J=2.3 Hz), 6.46 (1H, dd, J=8.3, 2.3 Hz), 3.76 (3H, s), 3.74 (3H, s), 3.63 (2H, s), 3.28 (2H, d, J=3.3 Hz), 3.04 (1H, t, J=2.4 Hz), 2.1 (1H, bs).
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[CH:6]=[C:7]([OH:14])[C:8]([OH:13])=[C:9]([CH:12]=1)[C:10]#[N:11])=O.[C:15]1([NH:21][C:22]([NH2:24])=[S:23])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[ClH:25]>CN(C)C=O>[ClH:25].[NH:21]([C:22]1[S:23][CH:2]=[C:3]([C:5]2[CH:6]=[C:7]([OH:14])[C:8]([OH:13])=[C:9]([CH:12]=2)[C:10]#[N:11])[N:24]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: NC(=S)Nc1ccccc1
Reactant: N#Cc1cc(C(=O)CBr)cc(O)c1O
Agent: Cl
Solvent: CN(C)C=O
Product: N#Cc1cc(-c2csc(Nc3ccccc3)n2)cc(O)c1O
Reaction time: 5 h

Procedure:
3.8 g of 5-(bromoacetyl)-2,3-dihydroxybenzonitrile dissolved in 25 ml of N,N-dimethylformamide are treated with N-phenylthiourea and stirred at 100° for 5 hours. Thereafter, the solvent is removed by evaporation. The residue is treated with 200 ml of 1N sodium carbonate solution and extracted three times with 100 ml of methylene chloride each time. The combined organic phases are washed with water, dried over sodium sulfate and evaporated. The residue is chromatographed on 30 g of silica gel with ethyl acetate. The thus-obtained crude product is treated with 40 ml of 1N hydrochloric acid, evaporated and crystallized from acetone. There is obtained 5-(2-anilino-4-thiazolyl)-2,3-dihydroxybenzo- nitrile hydrochloride of m.p. 245°-247°.
Reaction SMILES: Cl.[NH2:2][C:3]1[C:11]([OH:12])=[C:10]2[C:6]([CH2:7][CH2:8][CH:9]2[CH2:13][CH2:14][NH:15][C:16](=[O:18])[CH3:17])=[CH:5][CH:4]=1.[CH2:19]([N:21]([CH2:24]C)[CH2:22]C)C.C(=O)([O-])O.[Na+]>ClCCl.C(OCC)(=O)C>[CH3:19][N:21]([CH3:24])[C:22]1[O:12][C:11]2[C:10]3[CH:9]([CH2:13][CH2:14][NH:15][C:16](=[O:18])[CH3:17])[CH2:8][CH2:7][C:6]=3[CH:5]=[CH:4][C:3]=2[N:2]=1
Reactant: CC(=O)NCCC1CCc2ccc(N)c(O)c21
Reactant: CCN(CC)CC
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCOC(C)=O
Product: CC(=O)NCCC1CCc2ccc3nc(N(C)C)oc3c21
Reaction time: 0.25 h
Yield: 7 %

Procedure:
N-[2-(6-Amino-7-hydroxy-2,3-dihydro-1H-inden-1-yl)ethyl]acetamide hydrochloride (100 mg, 0.369 mmol) was suspended in dichloromethane (3.7 mL), triethylamine (51.5 μg, 0.369 mmol) was added at room temperature, and the mixture was stirred for 15 min. Thereto was added dichloromethylenedimethyliminium chloride (59.9 mg, 0.369 mmol), and the mixture was heated under reflux for 1 hr. To the reaction solution was added saturated aqueous sodium hydrogencarbonate solution. The mixture was diluted with ethyl acetate, washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/methanol=100/0→90/10) to give the title compound (7.4 mg, yield 7%).
Reaction SMILES: [CH:1](=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[N:4][CH:3]=1.[C:9]([O:13][CH2:14][CH3:15])(=[O:12])[CH:10]=[CH2:11]>C1N2CCN(CC2)C1>[CH2:14]([O:13][C:9](=[O:12])[C:10]([CH:1]([OH:8])[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1)=[CH2:11])[CH3:15]
Reactant: O=Cc1cccnc1
Reactant: C=CC(=O)OCC
Agent: C1CN2CCN1CC2
Product: C=C(C(=O)OCC)C(O)c1cccnc1
Reaction time: 8 h
Yield: 95.6 %

Procedure:
To a solution of nicotinaldehyde (10.0 g, 93.4 mmol) in ethyl acrylate (20 mL, ˜200 mmol) at room temperature was added DABCO (0.5 g, 4.5 mmol) and the mixture was stirred overnight. Excess ethyl acrylate was removed in vacuo. The resulting crude solid was washed with hexane to give the title compound (18.5 g, 95%) as an off-white solid. δH (CDCl3) 8.62 (d, J 1.7 Hz, 1H), 8.53 (dd, J 4.8, 1.3 Hz, 1H), 7.81 (d, J 7.9 Hz, 1H), 7.28 (s, 1H), 6.42 (s, 1H), 5.93 (s, 1H), 5.63 (s, 1H), 4.18 (m, 2H), 3.20 (br s, 1H), 1.27 (t, J 7.1 Hz, 3H). LCMS (ES+) 208.2 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1([CH3:32])[CH2:11][CH:10]=[C:9]([C:12]2[CH:17]=[CH:16][C:15](C)=[CH:14][CH:13]=2)[C:8]2[CH:7]=[C:6]([C:19]#[C:20][C:21]3[CH:31]=[CH:30][C:24]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:23][CH:22]=3)[CH:5]=[CH:4][C:3]1=2.CC1(C)CC=C(OS(C(F)(F)F)(=O)=O)C2C=C(C#CC3C=CC(C(OCC)=O)=CC=3)C=CC1=2>>[CH3:32][C:2]1([CH3:1])[CH2:11][CH:10]=[C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:8]2[CH:7]=[C:6]([C:19]#[C:20][C:21]3[CH:22]=[CH:23][C:24]([C:25]([O:27][CH2:28][CH3:29])=[O:26])=[CH:30][CH:31]=3)[CH:5]=[CH:4][C:3]1=2
Reactant: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(c2ccc(C)cc2)=CCC3(C)C)cc1
Agent: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(OS(=O)(=O)C(F)(F)F)=CCC3(C)C)cc1
Product: CCOC(=O)c1ccc(C#Cc2ccc3c(c2)C(c2ccccc2)=CCC3(C)C)cc1

Procedure:
Employing the same general procedure as for the preparation of ethyl 4-[(5,6-dihydro-5,5-dimethyl-8-(4-methylphenyl)-2-naphthalenyl)ethynyl]benzoate (Compound 1), 203.8 mg (0.43 mmol) of ethyl 4-[(5,6-dihydro-5,5-dimethyl-8-(trifluoromethylsulfonyl)oxy-2-naphthalenyl)ethynyl]benzoate (Compound G) was converted into the title compound (colorless solid) using 58.2 mg (0.36 ml, 0.69 mmol) of phenyllithium (1.8M solution in cyclohexane/Et2O), 116.1 mg (0.85 mmol) of zinc chloride and 13.8 mg (0.01 mmol) of tetrakis(triphenylphosphine)palladium(0). PMR (CDCl3): δ 1.36 (6H, s), 1.40 (3H, t, J=7.1Hz), 2.37 (2H, d, J=4.7 Hz), 4.38 (2H, q, J=7.1 Hz), 6.02 (1H, t, J=4.7 Hz), 7.20 (1H, d, J=1.5 Hz), 7.27 (1H, m), 7.39 (6H, m), 7.52 (2H, d, J=8.2 Hz), 7.98 (2H, d, J=8.2 Hz).
Reaction SMILES: CN(C)[CH:3]=[O:4].[C:6]([O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20]1[C:25]([O:26]C2CCCCO2)=[C:24]([O:33][CH3:34])[C:23]([O:35][CH3:36])=[CH:22][C:21]=1C)(=[O:8])[CH3:7]>O=O.C1C=C(C=NCCN=CC2C([O-])=CC=CC=2)C([O-])=CC=1.[Co+2]>[C:6]([O:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][C:20]1[C:25](=[O:26])[C:24]([O:33][CH3:34])=[C:23]([O:35][CH3:36])[C:3](=[O:4])[C:21]=1[CH3:22])(=[O:8])[CH3:7]
Reactant: CN(C)C=O
Reactant: COc1cc(C)c(CCCCCCCCCCOC(C)=O)c(OC2CCCCO2)c1OC
Agent: [Co+2]
Agent: O=O
Agent: [O-]c1ccccc1C=NCCN=Cc1ccccc1[O-]
Product: COC1=C(OC)C(=O)C(CCCCCCCCCCOC(C)=O)=C(C)C1=O

Procedure:
To a dimethylformamide solution (20 ml) of 6-(10-acetoxydecyl)-2,3-dimethoxy-5-methyl-1-tetrahydropyranyloxybenzene (240 mg) is added bis(salicylidene)ethylenediiminocobalt(II) (14 mg), followed by stirring in oxygen streams at atmospheric temperature and pressure for 72 hours. The reaction product is isolated in the same manner as Example 7 and recrystallized from hexane. The above procedure yields 6-(10-acetoxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone (110 mg) as orange-yellow needles melting at 37° C.-38° C.
Reaction SMILES: F[C:2](F)(F)[C:3]([NH:5][C:6]1[CH:11]=[CH:10][N:9]2[CH:12]=[C:13]([CH3:15])[N:14]=[C:8]2[C:7]=1I)=O.[C:19]1(C#C)[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C>[CH3:15][C:13]1[CH2:12][N:9]2[CH:10]=[CH:11][C:6]3[C:7]([CH:2]=[C:3]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)[N:5]=3)=[C:8]2[N:14]=1
Reactant: Cc1cn2ccc(NC(=O)C(F)(F)F)c(I)c2n1
Reactant: C#Cc1ccccc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC1=Nc2c3cc(-c4ccccc4)nc-3ccn2C1
Temperature: 115 °C
Reaction time: 48 h
Yield: 56.2 %

Procedure:
A mixture of 28 (200 mg, 0.54 mmol), phenylacetylene (83 mg, 0.81 mmol), [Cu(Phen)(PPh3)2]NO3 (45 mg, 54.0 μmol), K3PO4 (230 mg, 1.08 mmol) and anhydrous DMF (5 mL) was flushed with argon and stirred for 2 days at 115° C. After removal of the solvent, the residue was diluted with H2O (25 mL) and extracted with CH2Cl2 (5×20 mL). The CH2Cl2 extracts were dried (Na2SO4), filtered and evaporated. The residue was purified by chromatography using CH2Cl2/EtOAc (4/1, v/v) as eluent to afford compound 29 (75 mg, yield: 56%); mp 222° C.; IR (KBr) 3026, 3057, 2944, 2824, 1641, 1604, 1535 cm−1; 1H NMR (400 MHz, DMSO-d6) δ 2.3 (s, 3H), 6.96 (d, 1H, J=7.2 Hz), 7.15 (s, 1H), 7.29 (t, 1H, J=7.4 Hz), 7.46 (t, 2H, J=7.8 Hz), 7.50 (s, 1H), 7.85 (d, 2H, J=8.4 Hz), 8.06 (d, 1H, J=7.2 Hz), 11.98 (s, 1H); 13C NMR (100 MHz, DMSO-d6) δ 14.2, 98.1, 100.6, 109.3, 114.2, 120.9, 124.5, 127.1, 128.9, 131.4, 131.9, 135.7, 139.1, 140.7. Anal. Calcd for C16H13N3: C, 77.71; H, 5.30; N, 16.99. Found: C, 77.69; H, 5.41; N, 16.94.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[CH:10][C:11](=[O:14])[NH:12][N:13]=2)[CH:5]=[CH:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:21](Br)[CH3:22].N1N[C:26](=O)[CH:27]=CC=1>C(O)C>[CH2:26]([O:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[CH:10][C:11](=[O:14])[N:12]([CH2:21][CH3:22])[N:13]=2)[CH:5]=[CH:6][CH:7]=1)[CH3:27]
Reactant: O=c1cccn[nH]1
Reactant: O=c1ccc(-c2cccc(O)c2)n[nH]1
Reactant: CCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: CCOc1cccc(-c2ccc(=O)n(CC)n2)c1
Reaction time: 6 h

Procedure:
To a 2 liter 4-neck round bottom flask, stirring under a nitrogen atomsphere, was charged 50.0 g (1.0 eq., 0.266 moles) of 6-(3-hydroxyphenyl)-3(2H)-pyridazinone in 500 ml of ethanol followed by 73.4 g of potassium carbonate (2.0 eq., 0.53 moles) and 58.0 g of ethyl bromide (2.0 eq., 0.53 moles) in 50 ml of ethanol. The reaction was stirred at reflux, 70° C.-72° C. for 6 hr. with monitoring by glc. After 6 hr. 5.8 g of ethylbromide was added (0.2 eq., 53 mmoles) and after stirring for an addtional 15 hr. at reflux glc indicated all the starting pyridazinone was consumed. The reaction was worked up by vacuum filtering the mixture while still warm and washing the solid with 2×150 ml of ethanol. The filtrate was concentrated by evaporation under reduced pressure to afford 67.3 g of 6-(3-ethoxyphenyl)-2-ethyl-3(2H)-pyridazinone as a brown oil which solidified.
Reaction SMILES: [C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]#[CH:15])=[CH:10][C:9]=1[N+:16]([O-:18])=[O:17])([CH3:4])([CH3:3])[CH3:2].Br[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=1>>[C:1]([O:5][C:6](=[O:19])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]#[C:15][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][N:22]=2)=[CH:10][C:9]=1[N+:16]([O-:18])=[O:17])([CH3:4])([CH3:2])[CH3:3]
Reactant: C#Cc1ccc(NC(=O)OC(C)(C)C)c([N+](=O)[O-])c1
Reactant: Brc1ccccn1
Product: CC(C)(C)OC(=O)Nc1ccc(C#Cc2ccccn2)cc1[N+](=O)[O-]
Yield: 86.3 %

Procedure:
Prepared from (4-ethynyl-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example F2) (262 mg, 1.0 mmol) and 2-bromopyridine (0.15 mL, 1.6 mmol) according to the general procedure F. Obtained as a yellow solid (293 mg).
Reaction SMILES: S(=O)(=O)(O)[OH:2].[NH2:6][C:7]([CH3:13])([CH:10]([CH3:12])[CH3:11])[C:8]#[N:9].N>C1COCC1>[NH2:6][C:7]([CH3:13])([CH:10]([CH3:12])[CH3:11])[C:8]([NH2:9])=[O:2]
Reactant: O=S(=O)(O)O
Reactant: CC(C)C(C)(N)C#N
Agent: N
Solvent: C1CCOC1
Product: CC(C)C(C)(N)C(N)=O
Temperature: 100 °C
Reaction time: 1 h

Procedure:
Concentrated sulfuric acid (29.7 ml) is cooled with stirring in an ice-acetone cooling bath. To the acid is added 11.8 g (-)-2-amino-2,3-dimethylbutyronitrile with [α]D25 =-7.31° (c=0.0368 g/ml THF) at such a rate that the temperature does not go above 25° C. After the addition, the temperature of the reaction mixture is slowly raised to 100° C. and held at that temperature for one hour. After cooling the mixture in an ice-acetone bath, 85 ml concentrated ammonia is added at such a rate that the temperature does not exceed 75° C. The mixture is extracted five times with methylene chloride, the combined extracts dried and concentrated. This gives 11.95 g of white solid, mp 79°-81° C. and [α]D25 =+57.43° (c=0.0213 g/ml THF). This solid is recrystallized from methylene chloride-hexane to give 11.2 g of (+)-2-amino-2,3-dimethylbutyramide, mp 81°-82° C. [α]D25 =+59.38° (c=0.0162 g/ml THF).